st The 1 Annual Meeting The Middle-Eastern Association for Cancer Research December 27-28, 2011 Tanta University Egypt 1 The 1st Annual Meeting of the Middle-Eastern Association for Cancer Research (MEACR) “Cancer Research from Bench to Clinic” اﻟﻤﺆﺗﻤﺮ اﻟﺴﻨﻮى اﻷول ﻟﻼﺗﺤﺎد اﻟﺸﺮق اﻷوﺳﻄﻰ ﻷﺑﺤﺎث اﻟﺴﺮطﺎن ”“اﻟﺠﺪﯾﺪ ﻓﻰ أﺑﺤﺎث اﻟﺴﺮطﺎن ﻣﻦ اﻟﺒﺤﺚ إﻟﻰ اﻟﺘﻄﺒﯿﻖ اﻟﺴﺮﯾﺮى Tanta University, Egypt (December 27 – 28, 2011) ORGANIZED BY TANTA UNIVERSITY MEACR UNDER THE PATRONAGE OF MINISTER OF HIGHER EDUCATION PROF. DR. HUSSAIN KHALID VICE-PRESIDENT OF POSTGRADUATE STUDIES PROF. IBRHAIM A. SALEM 2 HONORARY CHAIRS Prof. Mostafa El-Sheikh Dean, Faculty of Science, Tanta University Prof. Ayman EL-Saied Dean, Faculty of Medicine, Tanta University EXECUTIVE CHAIRS Egyptian-CHAIR Prof. Mohamed L. Salem Tanta University MEACR-CHAIR Prof. Ala-Eddin Al Moustafa CEO, MEACR 3 GENERAL SECRETARY PROF. YOUSRY AL-SENOOSY VICE-DEAN, FACULTY OF MEDICINE TANTA UNIVERSITY PROF. TAREK FAYED VICE-DEAN, FACULTY OF SCIENCE TANTA UNIVERSITY PROF. ASHRAF BARAKAT HEAD, ONCOLOGY DEPARTMENT FACULTY OF MEDICINE COORDINATORS PROF. MAHMOUD ABDEL AZIZ PROF. OF OTORHINOLARYNGOLOGY TANTA UNIVERSITY PROF. SAID HAMAD PROF. OF CLINICAL PATHOLOGY TANTA UNIVERSITY DR. MOHAMED ALM ELDIN LECTURER OF ONCOLOGY TANTA UNIVERSITY INTERNATIONAL COMMUNICATION MEDICAL SCIENCE SECTION DR. MOHAMED EL-SHANSHOORY, MD, PHD PROF. OF PEDIATRICS, TANTA UNIVERSITY BASIC SCIENCE SECTION DR. EHAB TOUSON, PHD FACULTY OF SCIENCE, TANTA UNIVERSITY DR. ELSAYED SALEM, PHD FACULTY OF SCIENCE, TANTA UNIVERSITY 4 Welcome 6 Scientific Program 7 Plenary Session 1 (day 1, 27th) 8 A- Special Session 1 (Prof. General Omar heikal) 8 B- Plenary Session 1 9 Parallel Sessions 1 (Oral presentations, day 1) 14 Poster Session 1 (poster abstracts, day 1) 34 Plenary Sessions 2 (day 2, 28th) 46 A- Special Session 1 (Prof. Mostafa Elsayed) 47 B- Plenary Session 2 49 Parallel Sessions 2 (Oral presentations, Day 2) 53 Poster Session 2 (Poster abstracts, Day 2) 78 5 It is our great pleasure that the Middle Eastern Association for Cancer Research (MEACR) and the University of Tanta, Egypt host the first Annual meeting from December 27th to 28th, 2011 at the Conventional Center of the Medical campus of Tanta University. Tanta is the capital of Al-Gharbiah provience which is located about 80 km north to Cairo, the capital city of Egypt and is famous with the great mosque of sidi Ahmed ElBadawi and magnificent traditional and country side surroundings. The burden of cancer has rapidly increased in Egypt and the in the Middle East. The MEACR conference 2011 will focus on sharing experiences of cancer research activities from different resource settings. collaboration are Regional challenges and to be international forced. The conference will offer a good opportunity to exchange knowledge, form networks and also discover the culture, cuisine and scenic surroundings in dynamic Egypt starting from Tanta. We take this opportunity to welcome all participants and invite them to enjoy fruitful interpretations in cancer esearch. Chair of the MEACR conference 6 7 Day 1: December 27, 2011 A. Special Session 1 Hepatocellular Carcinoma in Egypt Dr. Omar Heikal, General, MD President of Military Medical Academy Prof. of Medicine, G.I.T and Hepatology Tel. (202) 2620371 – 22615943 (Office) Fax :(202)2613421, Mobile: +2 – 010 -1721265 E-mail: [email protected] Biography Prof. Omar Heikal (MD) is the Prof. of Medicine, GIT and Hepatology, at Military Medical Academy, Cairo, Egypt since 1999. He has been a Fellow at Royal Free Hospital (GIT, HEPTO) since 1990 School of Medicine London University. He Is the Chief of Military Medical Academy since July 2007 till now. He was graduated (MB Bch) from Faculty of Medicine, Ain Shams University in 1971. He was then spent his Residence of Internal Medicine (1973 – 1976) at Kobry El-Kobba Military Medicine Hospital and Master Degree (MSc; General Medicine) from Faculty of Medicine, Ain Shams University in 1979. Prof. Omar served as the Chairman of Internal Medicine Department, Hepatology unit in Air Force Hospital, 1993, and Chairman of Internal Medicine and GIT Unit, Ghamra Military Hospital, 1994-1995, Chairman of Internal Medicine in Kobry Elkobba Military Hospital, 1996 – 2001. He has also served as a Commando of Specialized Medical Hospital in K.K 2002 – 2006, Chairman of Internal Medicine Council, Military Medical Academy, Cairo, Egypt. Prof. Omar is a member in the Egyptian Society of Hepatology, Member of Medical Sector of High Supreme Council since 2007, Kasr Ainy, Faculty of Medicine council, Ain Shams, Faculty of Medicine council, the Egyptian Medical Council – EMC, Higher Committee for Organ Transplantation. He is the Vice president of the Egyptian Society of Hepatology Gasroenerology and Infectious Diseases and Vice president of the Egyptian group for study of GIT and Hepatology and the Dean of Arab Society of Proper use Antimicrobial from 2002 – 2005. Dr. Omar research focuses on hepatocellular carcinoma and the role of hepatitis virus C infection in the development of this disease. Abstract: Liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Hepatocellular carcinoma (HCC), which accounts for 80% - 90% of primary liver malignancy, is characterized by a very poor prognosis and is associated with high mortality. Nowadays, more than half a million cases are diagnosed every year on a worldwide basis. The peak age of incidence is 50-70 years, with a male predominance of 4:1. There has been a remarkable increase of the proportion of HCC among chronic liver disease patients from 4.0% 8 to 7.2% over a decade. For patients at risk of developing HCC, the aim of imaging is lesion detection, lesion characterization and determination of the stage. The European Association for the study of the Liver has documented the diagnostic criteria for HCC. Nodules larger than 2 cm with an arterial hypervascular pattern by two imaging techniques or by imaging technique associated with an AFP level higher than 400 ng/ml was considered to be HCC in cirrhotic patients without needing confirmation by a positive biopsy. The epidemiology of HCC in Egypt and the world will be presented. B. Plennary Session 1 (Cancer Research from Bench to Clinic) 01 From bench to bedside: The use of arabinoxylan rice bran (MGN-3/Biobran) in cancer medicine Mamdooh Ghoneum, Ph.D. Faculty Executive Board (FEB), Charles Drew University of Medicine & Science, Department of Otolaryngology, Associate Professor III, Chief of Research, Department of Neurobiology, UCLA, School of Medicine, USA Contact: Phone (323) 563-5953, [email protected] Biography Dr. Ghoneum is currently Associate Professor and Chief of Research at Charles Drew University of Medicine and Science, Department of Otolaryngology, Head and Neck Surgery, Los Angeles, CA. He is also Research Associate at Department of Neurobiology, School of Medicine, University of California Los Angeles (UCLA). Dr. Ghoneum earned his Ph.D. at the University of Tokyo, Japan in the field of radioimmunology (1976-1980) and did his postdoctoral at UCLA, School of Medicine (1983) in the field of cellular and molecular immunology. He has published 90 articles and 130 abstracts, including 8 books in Japanese and in English related to cancer immunology. He holds 3 patents for inventing 3 biological response modifiers for the treatment of cancer. He currently serves on the Editorial Board of the International Journal of Occupational Medicine, Immunology and Toxicology and Ejorsa "Egyptain Journal of Radiation sciences and Application.” In addition to his expertise in immune suppression by chemical carcinogens, aging and stress, Dr. Ghoneum is an internationally recognized immunologist who is an expert in the area of Cancer Immune therapy. Dr. Ghoneum’s contribution to immunotherapy is introducing and patenting several new nontoxic biological response modifiers (BRMs) that activate NK cells and induce apoptosis of cancer cells. These BRMs include: arabinoxylan rice bran (MGN-3), marina crystal minerals (MCM), active hemicellulose compound (AHCC), gross thymic extract (Thymax) etc. Results of his studies have been published in several peer review journals and are currently applied in major clinical trials around the world. He received several international awards from; The American Cancer Society. 1993. Japan Functional Food Research Association (JAFRA) Tokyo, Japan. 2002. The Filipino-Chinese Medical Society. Manila, Phillipines, 2005. In 2007 he was nominated for the annual $1 million prestigious Gotham Prize in Cancer Research. He created a video to educate the public about a new cancer therapy. The video was created in collaboration with Dr. Susan Kelly and Dr. Keith Norris. He had special accelerated promotion. He has been awarded numerous research grants from NIH-MBRS and major 9 research institutions in Japan. He has been a reviewer for the NIH Study Section Member. He has been an organizer for annual workshops between the Japanese Immunology Society and Drew University since 1990. He is a member of several Scientific Societies, including the American Association for Cancer Research (AACR). Abstract: This study describes how bench research on arabinoxylan rice bran (MGN-3 /Biobran) has translational potential. Although conventional therapeutics for cancer have proven to be initially effective, many patients relapse over time. Tumor relapse may be due to the development of therapeutic resistance, motivating the need to study novel treatments that target drug resistant cells. The current study explains the potential of MGN-3 as a chemo-sensitizer and as a novel adjuvant for the treatment of cancer. MGN-3 is an arabinoxylan with a xylose in its main chain and an arabinose polymer in its side chain. MGN-3 has attracted the attention of many scientists and health professionals from around the globe for its ability to fight cancer. In a recent study, a three-year randomized clinical trial of the anticancer activity of MGN-3 against hepatocellular carcinoma (HCC) was carried out in the Military Central Hospital, Vietnam. 68 patients with HCC (stages I and II) were divided into two groups: 38 patients were treated with conventional therapy (CT) plus MGN-3, and 30 patients were treated with CT alone. CT included transarterial oily chemoembolization (TOCE) and pericutaneous ethanol injection therapy (PEIT). Results showed a synergistic effect of CT and MGN-3. Patients in the MGN-3 group showed: i) reduced tumor size, ii) lower alpha fetoprotein (AFP) level, iii) lower alanine transaminase (ALT) level, iv) less recurrence of cancer, and v) higher survival rate. In a major clinical study that was conducted at Sano Clinic, Japan, 205 progressive and partially metastasized cancer patients were treated with chemotherapy plus MGN-3 or chemotherapy alone. Patients in the MGN-3 group demonstrated: i) prolonged life expectancy, ii) an improved quality of life (QOL) as characterized by a decrease in pain, nausea, and malaise and an increase in appetite. In another study at the Mayo Clinic, Florida, doctors described a case report as follows: “the lung masses steadily decreased in size, and at 34 months after the initiation of [MGN-3] therapy, the tumor was undetectable.” Extensive basic research examined the mechanisms by which MGN-3 synergized with chemotherapy and exerted anti-cancer activity. Results demonstrated that MGN-3 sensitized cancer cells to chemotherapy by modulating drug transport. In addition, MGN-3 modulated host immune responses by i) activating dendritic cells, NK cells, and T cells, and ii) inducing the production of cytokines such as interleukin-2 and interferon-gamma. We conclude that MGN-3 may be useful for the treatment of HCC and needs to be studied in clinical trials. 10 02 Id Genes and Proteins as Novel Therapeutic Targets for Metastatic Cancer Pierre-Yves Desprez, Ph.D Senior Scientist, California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, San Francisco, CA 94107, USA E-mail: [email protected]" <[email protected] Biography Dr. Pierre-Yves Desprez joined the University of California at Berkeley at the end of 1991 after completion of his doctoral thesis at the University of Lyon in France. Dr. Desprez has been a Principal Investigator and a Staff Scientist at the California Pacific Medical Center Research Institute in San Francisco since 1996. The main focus of his laboratory is the regulation of tumor cell behaviors by transcriptional regulators. Dr. Desprez¹s laboratory was one of the pioneer groups to show that the expression of Id-1 protein was upregulated in multiple types of cancer and that it may therefore represent a new marker that indicates the progression of some cancers on their way towards their final, untreatable stages. Moreover, the laboratory was the first one to show that Id genes and proteins were promising targets for the suppression of breast invasive and metastatic cancers. Recently, the discovery by Dr. Desprez and his colleague Dr. McAllister that a cannabinoid compound represented the first nontoxic agent that decreased Id-1 expression, and consequently breast tumor aggressiveness and metastasis, was reported worldwide by several news agencies. Abstract: During normal development and embryogenesis, helix-loop-helix Id proteins regulate the differentiation programs of many tissues. Moreover, recent studies have shown that dysregulated Id expression contributes to cancer progression and metastasis. Specifically, we found high levels of one of the Id family members, Id-1, in breast, prostate and brain tumor biopsies from human patients with aggressive cancer and low levels of Id-1 in non-invasive tumors. Ectopic expression of Id-1 in non-aggressive human cancer cells rendered them highly proliferative and invasive, and induced high levels of matrix metalloproteinase (MMP) expression. Conversely, human metastatic cancer cells became significantly less proliferative and invasive in culture when Id-1 protein expression was decreased by antisense RNA directed against the Id-1 gene. Next, we asked whether Id-1 could be exploited as a therapeutic target to treat metastatic cancers. Using tumor-bearing animals and non-viral systemic gene targeting technique, we showed that reduction of Id-1 levels, and consequently MMP expression, could significantly decrease the metastatic spread of cancer cells. These results suggested that Id-1 gene and/or protein could be a promising target for development of therapeutic strategies to reduce cancer metastasis. Since Id-1 expression is scarce in most mature adult tissues, a majority of normal cells would not be affected by systemic therapy targeting this gene. We recently determined that cannabinoid compounds could specifically inhibit the expression of the Id-1 gene and, as a result, cancer cell proliferation and invasion in culture and tumor metastasis in vivo. 11 03 Nanodiagnostic Assays for In Vitro Detection of Cancer Hassan M. E. Azzazy, PhD, DABCC, FACB Professor of Chemistry Leader, Novel Diagnostics & Therapeutics Research Group Yousef Jameel Science & Technology Research Center The American University in Cairo, Egypt E-mail: [email protected] Biography Dr. Hassan M. E. Azzazy received his B.Sc. and graduate diploma in Biochemistry from Alexandria University, Egypt. In 1994, he received his PhD in Biochemistry and Molecular Biology from University of North Texas Health Science Center at Fort Worth, TX, USA. He was a postdoctoral fellow then an assistant professor at the Pathology and Medical & Research Technology departments at University of Maryland School of Medicine in Baltimore, MD. He is also an adjunct professor with the Graduate School of Management and Technology, University of Maryland University College, Adelphi, MD. He has board certifications in Clinical Chemistry and Molecular Diagnostics from the American Board in Clinical Chemistry, Washington DC. Dr. Azzazy currently serves as professor of Chemistry at the American University in Cairo. In 2009, he has founded the Novel Diagnostics and Therapeutics group at Yousef Jameel Science & Technology Research Center, AUC. He is interested in developing novel bionanotechnology-based diagnostics and identifying therapeutic candidates. He actively collaborates with researchers in Japan, the Netherlands, Qatar, Portugal, and USA. Recently, Dr. Azzazy has received Excellence in Research & Creative Endeavors Award, Excellence in Teaching Award from AUC and the State Prize in Advanced Technological Sciences from the National Academy for Scientific Research & Technology. He has over 120 publications including journal articles, conference abstracts, book chapters, and monographs. Abstract: Current cancer detection techniques are costly, time-consuming, often unable to distinguish between benign and malignant tumors, and have variable sensitivity and specificity. Nanoparticles have been proposed as promising tools to address these limitations. They have unique optophysical properties which enable sensitive detection of cancer, and are easily amenable to modification for use in different assay formats. Additionally, their synthesis and functionalization are relatively simple and inexpensive and their detection methods are quite versatile. This presentation serves as a guide for utilization of nanoparticles to develop assays for detection of cancer cells and biomarkers in biological fluids. The following assay prototypes will be discussed: (1) conjugation of magnetic and fluorescent nanoparticles to high affinity aptamers for collection and detection of acute leukemia cells in mixed cells and whole blood samples; (2) immobilization of epidermal growth factor peptide on nanoparticles for detection of circulating tumor cells in peripheral blood of patients with squamous cell carcinoma; (3) employing magnetic and gold nanoparticles in a bio-barcode assay for ultrasensitive detection of prostatespecific antigen after radical prostatectomy; (4) employing positively charged gold nanoparticles to develop a colorimetric assay for measuring hyaluronidase activity in urine of patients with bladder cancer; (5) using magnetic nanoparticles conjugated to antibodies for mixing reagents and detection of tumor markers in microfluidic ELISA; (6) using gold nanorods as biosensors for label-free detection of tumor markers based on antibody-antigen interaction and the resonant Rayleigh scattering spectrum of individual gold nanorods; (7) using gold nanoparticles labeled with antibody and luminal to develop a chemiluminescent immunoassay for detection of carcinoembryonic antigen in serum; and (8) conjugating gold nanoparticles to telomere strand primers for detection of telomerase activity and initial screening of telomerase inhibitors. 12 04 Gene Expression profile of Egyptian hepatocellular carcinoma Abdel-Rahman N. Zekri, PhD Prof Molecular Virology and Immunology Head of Virology and, Immunology Department National Cancer Institute, Cancer Biology Unit, Cairo University, Cairo, Egypt E-mail: [email protected] Biography Dr. Zekri is the Prof. of Molecular Virology and Immunology at Cancer Biology Department, National Cancer Institute, Egypt. He obtained his B.Sc. in Microbiology in May 1982, M.Sc. in Microbiology in October 1987 and Ph.D. in Virology and Immunology from National Cancer Institute, Cairo Univ in November 1991. He was granted a Doctoral Fellowship from National Institute of Health, Centers of Disease Control, USA in 1990 and a 2-year (1992-1993) Post Doctoral Fellowship from University of Amsterdam, The Netherlands and from the National Institute of Health, USA (19951996) and a visiting scientist fellowship from the Fox Chase Cancer Center, USA (1996-1998). Dr. Zekri research focuses on the development of novel cell-based therapy against hepatitis C virus-induced liver cancer. He has been using stem cells and mesenchymal stem cells to treat patients with HCC who fail the standard therapy. He has published several articles that indicate to the beneficial effects of such treatment regimen. His research also focuses on the development of novel immunotherapeutic approaches against HCV. Abstract: The incidence rate in Hepatocellular carcinoma (HCC) has increased worldwide leading to high mortality among cancer patients. This situation calls for more studies at the molecular level. In continuation of our previously published preliminary work, we performed cDNA microarray on 15K to give an insight on the genetic profile of Egyptian HCC using 25 K c-DNA microarray as a confirmatory study. The study included 31 patients with HCC who were studied for gene expression profile by 25 K c-DNA microarrays. In addition, another set of 30 HCC patients were used to confirm the array data. Those were tested by RT-PCR for selected 7 genes involved in immunoregulation and lipid metabolism pathways. Out of the 25,000 studied cDNAs, 958 transcripts were differentially expressed; 503 were up regulated and 455 were down regulated. Only 19 pathways were specifically up regulated (P<0.05) by 27 genes and 13 pathways are specifically down regulated (P<0.05) by 19 genes. Thrity seven genes showed significant difference in their expression between HCC cases with high and low AFP. The confirmatory HCC cases showed down regulation of the following genes: PPP3CA (75%), ATG5 (85%), BACE (62%), and up regulation of ABCG2 (90%), RXRA (80%), ELOVL2 (65%), CXR3 (80%) genes. This is the first study on the global gene expression profile in Egyptian HCC. The identified genes could provide a panel of new diagnostic, prognostic as well as for molecular target therapy for HCC in the future. Contributing authors: Abeer A. Bahnassy1, Hanaa M Al-el-Din2 Mohamed Abouelhod3 Mohamed M Hafez3, Zeinab K Hassan1, Ahmed Ali4 1 Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt, 2Center of Informatics Sciences, Nile University, 3Clinical Pathology Department, Faculty of Medicine, Beni-Suef University, 4Biostatistic and Epidemiology Department, National Cancer Institute, Cairo University, Cairo, Egypt. 13 14 Session 1: Therapy (Human studies): O 1.1 Therapy (Human studies) Bryostatin-1, Fenretinide and 1α,25(OH)2D3 induce growth inhibition, apoptosis and differentiation in T and B cell-derived Acute Lymphoblastic Leukemia cell lines Ali M. Ardekani1*, Shahrzad Soleymani Fard1, Mahmoud Jedi Tehrani2, Ramin Ghahremanzade3 1Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IRAN; 2. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, IRAN. 3Nanotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IRAN Corresponding Author: Dr. Ali M. Ardekani. Editor-in-Chief: Avicenna Journal of Medical Biotechnology, Reproductive Biotechnology Research Center, Avicenna Research Institute Tel/Fax: 66409980- 6649365; E-mail: [email protected] Abstract Background: In much acute leukemia, normal differentiation does not occur. However, in many cell lines derived from hematologic malignancies, differentiation or apoptosis can be induced by variety of agents. Despite advances in the treatment of acute lymphoblastic leukemia (ALL), in most patients long-term survival rates remain unsatisfactory, especially in T-cell derived ALL. Aim: Thus we studied the anti-cancer effects of fenretinide, 1α,25(OH)2D3, and bryostatin-1 in CCRF-CEM (T-cell derived) and Nalm-6 (B-cell derived) ALL cell lines. Methods: MTT proliferation assay was used to assess proliferative response of the tumor cell lines under the effects of the studied compounds. Results: Using MTT assays, both cell lines were shown to exhibit increased inhibition of proliferation at micro and nanomolar concentrations and induce apoptosis via activation of caspase-3 pathway. Furthermore, for the first time we are reporting consistent anti-proliferative and apoptotic effects of Bryostatin-1 in ALL T-cell derived cell line with the lowest ED50. To evaluate the differentiation induction by fenretinide, 1α,25(OH)2D3, and bryostatin-1 in ALL cell lines, we assayed for the expressions of CD19, CD38 markers on Nalm-6 and CD7 marker on CCRF-CEM cell line. The flow cytometric analysis showed a significant increase in expression of CD markers in response to anticancer drug treatments. Conclusion: Overall results demonstrate that the anticancer agents used in this study are strong inhibitors of ALL cell proliferation and inducers of apoptosis and differentiation in vitro. These findings may be quite significant if these drugs are to be used for differentiation therapy of ALL patients in the clinic in the future. Further studies are warranted to establish the in vivo effect of these drugs particularly in patients with T-cell derived ALL. Key words: Acute lymphoblastic leukemia, anti-cancer compounds, apoptosis, differentiation 15 O 1.2 Therapy (Human studies) Concurrent radiotherapy and chemotherapy for locally advanced squamous cell carcinoma of the head and neck 1-Elsayed Mostafa Ali 2-Ahmad Gaber Abdelraheem 1-Lecturer of Clinical Oncology, Faculty of Medicine, Sohag University, Sohag 2-Lecturer of ENTsurgery, Faculty of Medicine, South Valley University, Egypt Correspondence: Dr. Elsayed Mostafa Ali E-mail: [email protected], Phones: 0101638744 / 0932308901 Abstract Background: Concurrent chemoradiation is the standard of treatment for patients with advanced head and neck squamous cell carcinoma (HNSCC). Aim: The present study was carried out with objective of assessing the feasibility and efficacy of low dose gemcitabine as radiosensitizer when used during radical therapeutic management of patients with locally advanced HNSCC. Patients and methods: From July 2008 to December 2010, 52 patients with locally advanced HNSCC (stage III 50%, stage IVa 50%) were enrolled. All received course of radiotherapy (70 GY over 7 weeks) concurrent with weekely infusions of gemcitabine at 50 mg/m2. Results: All patients were available for toxicity and response. Severe mucositis (grade 3-4) was observed in 76% of patients. Severe hematological toxicity was uncommon. Xerostomia was the most common late toxicity in 34 patients (65.4%). The rate of complete and partial response rate was 67.3% and 21.1% respectively, with an overall response rate of 88.45%. 2 years disease free survival was 38.46%. Conclusion: using low dose gemcitabine concurrent with radiotherapy is maintaining high response rate with low systemic toxicity, in spite of severe mucositis in a high percentage of patients. Key words: chemoradiation, gemcitabine, head and neck cancer, locally advanced, radiotherapy, squamous cell carcinoma O 1.3 Therapy (Human studies) Role of chemotherapy in the treatment of uterine leiomyosarcoma: About ten cases and literature review Imane Ouafki, H.El Yacoubi, M.Benameur, S.Boutayeb, H.M’Rabti, H.Errihani Department of Medical Oncology, INO, CHU Rabat, Morocco E-mail: [email protected] Abstract Introduction: Uterine leiomyosarcoma is a rare malignancy, developed at the expense of mesenchymal components of myometrium. It represents 1.3% of all cervical cancers and 40 to 50% of uterine sarcomas. Materials and methods: This is a retrospective study of ten cases treated in the Nationnal Institute of Oncology in Rabat (Morocco), from 2004 to 2011, and review of the literature focuses on uterine leiomyosarcomas. Results: The average age of patients at diagnosis was 50 years. The circumstances of discovery were pelvic pain, abdominal distention, and bleeding. The diagnosis rarely discussed before 16 surgery, is usually made on histological examination of the operative specimen. The outcome is related to the mitotic activity of the tumor and to the infiltration of nearly structures. Treatment was multidisciplinary based on surgery, radiotherapy and chemotherapy for metastatic patients. Discussion: The uterine leiomyosarcoma is a rare entity, occurring in middle-aged women between 45 and 55. Its absolute frequency is 0.67 per 100 000 women per year aged over 20 years. Clinically it is manifested by pelvic pain, abdominal mass or vaginal bleeding. On CT, large areas of necrosis or cystic transformation may suggest the diagnosis which is often made on the part of hysterectomy performed for uterine fibroids. Treatment is primarily surgical and should be complete at the outset, consisting of a hysterectomy with annexectomy. Radiotherapy reduces the incidence of local recurrence but does not improve survival. Chemotherapy is indicated in locally advanced or metastatic uterine leiomyosarcoma. The most active drugs are doxorubicin, ifosfamide, docetaxel and gemcitabine. The recurrence rate varies from 35 to 70%. The 5-year survival is 25 to 40%. The presence of metastases influence survival: 19 months for lung metastases and 12 months if multiple metastases. Conclusion: Uterine leiomyosarcoma is a rare cancer with poor prognosis. Preoperative diagnosis is rarely made . Management of locally disease remains surgical.Chemotherapy improves progression-free survival and quality of life in metastatic patients. O 1.4 Therapy (Human studies) A case of primary pleural leiomyosarcoma treated by chemotherapy Imane Ouafki, H.El yacoubi, T.Sghiri, S.Boutayeb H.M’Rabti, H.Errihani Department of Medical Oncology, INO, CHU Rabat; Morocco E-mail: [email protected] Abstract Introduction: Primary sarcomas of the thorax are rare. They occur in the lung, mediastinum, pleura, and chest wall. Angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, and mesothelioma (sarcomatoid variant) are the most common primary intrathoracic sarcomas. Primary leiomyosarcoma of the chest wall is a rare neoplasm and is reported to occur in approximately 1-4 % of the patients with primary soft tissue sarcomas of the chest wall.We here present a case of locally advanced pleural leiomyosarcoma. Case report: We report a case of a 64-year-old man with locally advanced primary pleural leiomyosarcoma which was treated by chemotherapy in October 2011. The circumstance of discovery was an intrathoracic mass, gradually increasing in volume, operating in a context of fever and altered general condition. Abdominal computed tomography showed a huge lesional process thickened wall and pseudo-necrotic center, substernal seat, occupying the right thoracic base, measuring 14 x 9 cm long axis, forcing the heart cavity with discrete pericardial effusion. This tumor has a bottom development exerting a mass effect on segment VIII and IV of liver. Surgical exploration revealed a very locally advanced pleural tumor invading the mediastinum. A simple biopsy was performed. In the histological study, the tumor was diagnosed as a high-grade leiomyosarcoma. Our patient received a doxorubicin-based chemotherapy at a dose of 60 mg / m², administered every 21 days. Evaluation after 6 cycles of 17 chemotherapy found a clinical benefit and a radiological partial response estimated at 30%. Currently, he is in good control. Discussion: The pleural leiomyosarcoma is an exceptional disease. It usually occurs in the sixth decade or later with a male predominance. Clinically, it is characterized by a painful retrosternal mass, as may be asymptomatic in early stages. Radiologically it appears as a necrotic process exerting a mass effect on adjacent structures. The initial diagnosis is often difficult because the clinical and imaging are not specific. The diagnosis is confirmed by biopsy and pathological study with immunohistochemistry. For which is the surgical treatment, in many previous reports, it is recommended that the resection should include all of the involved soft tissues and bones with an adequately ensured margin of normal tissue around. Indeed such wide chest wall resection contributes to decreasing local recurrences, but it does not lead to prolonged survival. Also Gordon et al. mentioned that the factors affecting prognosis were histological tumor grade and development of metastasis, but not margin status. To the contrary, Perry et al. reported that the most important factor affecting overall survival was margin status. Whichever may be true, at least it is important that resected margins are tumor-negative. Chemotherapy is indicated for locally advanced or metastatic pleural leiomyosarcoma. It is essentially based on doxorubicin at a dose of 60 mg / m² on day 1 and ifosfamide 5 g / m² on day 1 administered every 21 days . Metastatic disease is transmitted by the blood and is mostly liver and lung. Conclusion: Pleural leiomyosarcoma is an extremely rare entity. Its diagnosis is pathological. Extended surgery with clear margins remains the treatment of choice. Chemotherapy has its place before surgery, or in case of metastatic disease. O 1.5 Therapy (Human studies) Bladder leiomyosarcoma: A case report Imane Ouafki, H.El Yacoubi, M.Benameur, S.Boutayeb, H.M’Rabti, H.Errihani Department of Medical Oncology, INO, CHU Rabat; Morocco E-mail: [email protected] Abstract Introduction: The bladder leiomyosarcoma is a rare tumor. The clinical characteristics and the methods of therapeutic management remain uncodified. The treatment is essentially surgical excision often associated with adjuvant chemotherapy. The poor prognosis of this tumor appears to be related to high grade of the tumor, with rapid local recurrence and the occurrence of distant metastases. Case report: We report a case of a 52-year-old man who consulted for intermittent terminal hematuria with urinary frequency. Clinical examination was normal. Renal and vesico-prostatic ultrasound objectified a right lateral bladder process with a right. 18 O 1.6 Therapy (Human studies) Comprehensive management of peritoneal carcinomatosis as a new emerging specialty Ayman Elnemr, MD, PhD1, Yutaka Yonemura, MD, PhD2 1 Surgical Oncology Unit, Tanta University, Tanta, Egypt NPO Organization to support Peritoneal Surface Malignancy Treatment, Osaka, Japan, Correspondence: Ayman Elnemr, M.D,Ph.D Head of Surgical Oncology Unit, Department of Surgery, Tanta University, mobile: +20(10)624-5403; home: (040)536-0910, E-mail: [email protected] 2 Abstract In this presentation we will provide the full description of the comprehensive management of peritoneal carcinomatosis (PC) as a new emerging specialty. Approaches to this malignancy differ completely form those used for the treatment of cancers affecting the individual organs in the peritoneal cavity. The current state-of-the-art treatment for PC consists of a cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). The complete cytoreduction rate depends on the selection criteria for the CRS and the ability and experiences of the surgeons. This cytoreductive approach may require six peritonectomy procedures to resect or strip cancer from all intra-abdominal surfaces. These are greater omentectomy-splenectomy; left upper quadrant peritonectomy; right upper quadrant peritonectomy; lesser omentectomy-cholecystectomy with stripping of the omental bursa; pelvic peritonectomy with sleeve resection of the sigmoid colon; and antrectomy. No survival benefit has been reported by cytoreductive surgery alone. In contrast, CRS plus hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) confers a prolonged survival period. In this work, the current investigational modalities, quantitative estimators of PC, our surgical techniques for the complete CRS and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) will be presented. Session 2: Anti-tumor Immunity O 2.1 Anti-tumor Immunity Improvement of conventional cancer therapies by immunological microenvironment manipulating tumor Shengdian Wang, MD, PhD Professor/Deputy Director; CAS Key Lab of Infection and Immunity Institute of Biophysics, Chinese Academy of Sciences Tel +86-10-64888493(Office); 64886603(Lab), Fax: +86-10-64846538, E-mail [email protected] 19 Biography 1998, Ph.D. degree from Chinese Academic Medical Science and Beijing Union Medical College; 19982003, postdoctoral fellow in Department of Immunology, Mayo Medical School, Mayo Clinic, Rochester, MN, USA; 2003~2005, Research Associate in Mayo Medical School, Mayo Clinic and Johns Hopkins University; 2005, Professor, Institute of Biophysics, CAS., supported by CAS Hundred Talent Program. T lymphocytes play critical roles in host immune response against viral infection and cancer and are involved in the progression of autoimmune diseases. Activation and differentiation of lymphocytes are regulated by co-signaling pathways. We combined our basic study with clinical resource and requirement to mainly study the cellular and molecular mechanisms of co-signaling pathways, trying to elucidate the regulation of T cell responses during viral infection and in the progression of cancer and autoimmune diseases, to develop new approach for immunotherapy. In recent years, we established a series of mouse models of chronic hepatitis B, tumor metastasis and the transplant of human cancer tissue. We found that co-signaling molecules of CD24, B7-H1/PD-1, CD137/CD137L have a important roles in initiation and development of chronic hepatitis B and hepatocellular carcinoma. Our study demonstrated that T cell responses are important for the anti-HER2/neu antibody-mediated tumor therapy, and B7-H1/PD-1 inhibitory co-signaling pathway play critical role in dysfunction of anti-tumor immune responses in tumor microenvironment, which will promote the tumor therapy. Abstract: Although it has been well known that the immune system plays a critical role in occurrence and development of cancer, the contribution of immune system has been neglected in conventional cancer therapies. Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumor effects of conventional chemo- and radio-therapies. We have recently demonstrated that the therapeutic effect of anti-HER2/neu antibody also depends on both innate and adaptive immunity. Antibody mediated blockade of HER2/neu signaling and induction of ADCC cause tumor cell death and the release of danger signals, such as HMGB1, that initiate tumor specific CTL responses by triggering an innate MyD88-dependent pathway. Intriguingly, the addition of chemotherapeutic drugs shortly after anti-HER2/neu antibody, although capable of enhancing the reduction of tumor burden, could abrogate antibody-initiated immunity leading to decreased resistance to rechallenge or earlier relapse. Although the antitumor T cell responses could be induced by immunogenic death of cancer cells, and really made crucial contributions to therapeutic effects in conventional cancer therapies, combination of immunotherapies aimed to promoting specific antitumor T cell responses could not dramatically improve the conventional therapies. Our analysis on the tumor microenvironment showed that tumor tissues were heavily infiltrated by tumor-associated macrophages with M2 phenotypes and CD8+ T cells highly expressing inhibitory co-signaling receptor PD-1 with the development of tumor. Amelioration of tumor immunosuppressive microenvironment dramatically improves the therapeutic effects of anti-HER2/neu. O 2.2 Anti-tumor Immunity Genetic engineering of poorly immunogenic cancer cells with a xenogenic antigen ncreases their responses to chemotherapy and formation of anti-tumor immunity 1* 1 Mohamed Labib Salem, 1Sabr Ali EL-Naggar and 2Abeer Hasan Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Egypt Zoology Department, Faculty of Science, Cairo University, Egypt * Correspondence: Prof. Mohamed Labib Salem, Prof. of Immunology E-mail: [email protected], Tel. (+20) 01274272624 2 20 Abstract Background: Although some cancers can respond to chemotherapy, several types of cancers do not. Moreover, the growth of the cancer that responds to tumor recurs resulting in failure of treatment and tumor progression due to the lack of anti-tumor immunity. Therefore, this failure poses a challenge toward cancer treatment. Aim: The main aim behind designing this study was to determine whether poorly immunogenic tumor that fails to respond to chemotherapy can be genetically engineered to be immunogenic and respond to chemotherapy and form immunity. Methods: The EL4 thymoma cancer cell line on C57BL/6 (H2 b) background was used. This cell line is known to be poorly immunogenic and does not respond in vivo to treatment with the anticancer drug cyclophosphamide (CTX). This cell line was genetically engineered to express and secrete ovaalubmin (OVA), which is a xenogenic antigen to C57BL/6 mice. The OVA-transfected EL4 cell line was termed EG7. As control, the B16 melanoma cell line, also on C57BL/6 (H2b) background, was used and transfected with OVA gene to form B16-OVA cell line, which express, but not secrete, OVA protein. The cell lines were injected (2 x 105/mouse) via subcutaneous injection into the left flank of wild type or splenectomized mice and then treated once with intraperotoneal injection of 4mg/mouse CTX. The mice were re-challenged with the tumor 1-2 months after the primary tumor challenge. The tumor size was monitored by measuring the length and width of the tumor using Caliper twice a week. The tumor surface area was calculated by multiplying the two diameters and expressed as mm 2. Results: Treatment of EL4-bearing mice at any time point after tumor challenge did not affect the tumor growth rate and the mice succumbed the tumor and dies after 3 weeks. Treatment of EG7-bearing mice with CTX, however, resulted in cure of the tumor even when the treatment was delayed until the tumor reached an advanced size (about 100mm 2). Interestingly, these tumor-free mice immediately rejected the second and the third challenge with EG7, but not the B16-OVA or EL4, tumor injected 1 month after the 1ry prior tumor injection. Finally, the absence of spleen (using spelenctomized mice) had no effect on the responses of EG7 to CTX and the formation of anti-tumor immunity. Conclusion: Engineering poorly immunogenic tumor to secrete xenogenic antigen is a reliable means to increase its immunogenicity and responses to chemotherapy. The data also indicate to the importance of secretion but not expression of the antigen. These data has potential implication in cancer chemotherapy and immunotherapy. Keywords: Cyclophosphamide, Cancer, B16, Chemotherapy, EL4, EG7, Thymoma O 2.3 Anti-tumor Immunity Immunotoxicity investigation of representative heterocyclic drugs Mohamad A. Fararjeh PhD. Department of immunology and Medical Laboratory Technology, Hashemite University. Zarqa, Jordan Fax: +962 5 3750573. Mobile +962 79 5590491; E-Mail: [email protected] 21 Abstract Heterocyclic drugs are a group of antiprotozoal and antibacterial agents. These drugs are widely used and are used repeatedly because of reinfections. The bone marrow suppression by metronidazole has been previously shown in different studies. The objective of this study was to determine the immunomodulatory effects of MTZ at plasma concentration and higher in vitro and in vivo using animal model. Doses were selected according to plasma concentration of drug in human. For in vitro studies, parenteral solution of drug was used, and different concentrations of MTZ (5, 10, 50, and 200 μg/ml) were used. For in vivo study, immunotoxicological screening tests were conducted, we examined the effects of subtheraputic, therapeutic and high dose exposure to intraperitoneally (i.p.) administered MTZ at doses of 14, 28, 42, 57, and 114 mg/kg body weight which were equals to (0.5x, 1.0x, 1.5x, 2.0x, and 4.0x) human therapeutic dose respectively, using healthy female Balb/c mice (6-8 weeks old; 19-21g weights) for 14 days. At the end of treatment, peripheral blood samples from the retro-orbital plexus were collected, and then animals were sacrificed by cervical dislocation. Spleen, thymus, liver, lymph nodes, and kidneys were collected and weighed. Functional tests including, percent body weight gain, organ body weight ratio, spleenocytes phenotypes determination by flow cytometry were performed to assess the effect of the drug on the cell mediated immune response. In order to test innate immune response, in vitro TNF-α production by activated peritoneal macrophages were determined. IFN-γ and IL-2 spleenocytes production in vitro were also tested using sandwich ELISA. Results showed that high as well as therapeutic doses of MTZ suppressed humoral as well as cell mediated immune responses. MTZ at low dose (14 mg/kg) showed significant changes in humoral immune system. It seems that MTZ has suppressive effects on mice immune system. The effectiveness of MTZ in the treatment of diseases should be counterbalanced by the increasing evidence of its immunotoxicity. Statistical analysis was done using oneway analysis of variance (ANOVA). All analyses were made using GraphPad Prism 4.03 statistical software package. O 2.4 Anti-tumor Immunity The toll-like receptor 3 agonist polyinosinic-cytidylic acid (poly(I:C)) targets natural killer cells with NK1.1+CD11b+CD11c+Ly6G-B220+ phenotype 1, 3 Mohamed L. Salem, 1,2Sabry A. EL-Naggar, and 3David J. Cole 1 Immunology and Biotechnology Unit, Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt 2 Department of Biology, Faculty of Science, Al-Jouf University, Sakakah, KSA; 3Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA Correspondence: Pof. Mohamed Labib Salem, Prof. of Immunology; [email protected]; [email protected] Tel: +20-01274272624, Fax: +20-40-3350804 22 Abstract Background: Natural killer (NK) cells are traditionally considered to be one of the major arms of the innate immune system. These cells are capable of killing virally infected and tumor targets while spare most normal cells. We have reported recently that in vivo administration of the TLR3L poly(I:C), a synthetic double stranded RNA (dsRNA) that mimics viral dsRNA, into naïve mice induces rapid increases in the frequencies of NK cells mainly in the liver. Aim: In order to get more insight into the phenotype of the NK cells targeted by poly(I:C), we performed a detailed phenotypic analyses on the NK cells in blood, spleen and liver after treatment with poly (I:C). Results: We found that poly(I:C) targeted NK cells expressing the phenotype NK1.1highCD11bhighCD11chighLy6Glow B220low. These cells did not express the typical costimulatory molecules CD40 and CD80. Using CR3 -/- knockout mice and NK-depleted mice (by injection of anti-asialo GM1 polyclonal antibody) demonstrated absolute requirement of CD11b and NK1.1 molecules, respectively to mediate the effects of poly(I:C) on NK cells. We further found that the effects of poly(I:C) on NK cells is partly mediated by the presence of its specific TLR3. Conclusion: Taken together, our data show that a subset of NK cells expressing the myeloid markers CD11b and CD11c are the target of the TRL3L poly(I:C) under partial effect of TLRs. These results are of paramount significance for the rationale clinical application of this biological response modifier toward viral infection and cancer diseases. Keywords: Poly(I:C), TLR3 agonist, TLR3 ligand, natural killer cells, attrition, PBL, expansion, Liver. O 2.5 Anti-tumor Immunity Intermittent prolonged fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects Mo’ez Al-Islam” E. Faris1*, Ref’at A. Al-Kurd1, Mohamed L. Salem2, Safia T. Kacimi3,Yasser K. Bustanji2, Mohammad K. Lahham2, Mohamad K. Fararjeh4 1 Department of Nutrition, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan Zoology Department, Faculty of Science, Tanta University, Egypt 3 Dept of Clin. Pharmacy and Biopharmaceutics, Fac. of Pharmacy, University of Jordan, Amman, Jordan. 4 Faculty of Medical Laboratory and Technology, Hashemite University, Zarka, Jordan. Corresponding author: Dr. Moez Faris <[email protected]> 2 Abstract Inflammation has long been associated with carcinogenesis, especially in the promotion phase. Intermittent fasting has been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. In the holy month of Ramadan, adult healthy Muslims are refrained for 29-30 days from eating and drinking from down to sunset (about 14-15 hours a day). This makes Ramadan fasting a unique model of prolonged intermittent fasting. The current study aimed to investigate the impact of Ramadan intermittent fasting (RIF) on selected inflammatory cytokines. Fifty healthy volunteers (21 males and 29 females), were recruited for the investigation of circulating proinflammatory cytokines (IL-1β, IL-6, and TNF-α), immune cells (total leucocytes, monocytes, granulocytes, and lymphocytes), anthropometric and dietary assessments. 23 The investigations were conducted one week before Ramadan fasting, on the third week of Ramadan, and one month after the cessation of Ramadan. The proinflammatory cytokines IL-1β, IL-6, and TNF-α, systolic and diastolic blood pressures, body weight, and body fat percentage were significantly lower (P< 0.05) during Ramadan as compared to before Ramadan or after the cessation of Ramadan fasting. Immune cells significantly decreased during Ramadan but still remained within the reference ranges. Conclusion: These results indicate that RIF attenuates inflammatory status of the body by inhibiting proinflammatory cytokine expression and decreasing body fat and circulating leucocytes. Further, these data showing that the anti-inflammatory effect on RIF are expected to be of a paramount significance to patients with inflammatory diseases that have been found to progress into cancer with the increase of inflammation. As such, Ramadan fasting can be considered as adjuvant regimen during anti-cancer treatment Key words: Interleukin-1β, Interleukin-6, Leucocytes, Prolonged Intermittent Fasting, Ramadan, Tumor Necrosis Factor-α. O 2.6 Anti-tumor Immunity Survivin expression increases during aging and enhances the resistance of aged human fibroblasts to genotoxic stress 1Huda H. Al-Khalaf and 2Abdelilah Aboussekhra 1 The Joint Centre for Genomics Research, King Abdulaziz City for Science and Technology, Riyadh 11211, KSA. 2 King Faisal Specialist Hospital and Research Centre, Department of Biological and Medical Research, MBC # 03, PO BOX 3354, Riyadh 11211, KSA Correspondence: Dr. Huda H. Alkhalaf: Tel: 996-1-4647272 Ext: 32962; Mobile: 996-50350-7881; email: [email protected] Abstract Background: Cancer is principally an age-related disease. Survivin, an important antiapoptotic protein is highly expressed in most cancers. Aim: We examined age-related modulation of survivin level. Results: We have shown accumulation of surviving and phospho-survivin (Thr34) in aged normal human skin fibroblasts and mice organs. This age-related accumulation of survivin was due to protein stabilization through association with the molecular chaperone Hsp90 protein, which was also up-regulated during aging. Interestingly, Hsp90 binds preferentially to phospho-survivin, which explains its higher stability. In addition, we provide clear evidence that aged cells exhibit apoptosis resistance when challenged with UV light, cisplatin, γ-rays or H2O2 as compared to their younger counterparts. In response to γ-rays and H2O2, the levels of Bcl-2 and both forms of survivin were upregulated in old cells, but not in their corresponding young ones. This repression of survivin and phospho-survivin in young cells is p53-dependent. Importantly, surviving inhibition/down-regulation with flavopiridol or specific shRNAs increased the apoptotic response of old fibroblasts to various genotoxic agents, and restored the pro-apoptotic Bax/Bcl2 ratio and the increase in the levels of cleaved capsase-3 and PARP in old cells. Conclusion: These results show the role of survivin in 24 the age-dependent resistance of human fibroblasts, and provide new insights into the molecular mechanisms that underlie the complex relationship between aging, apoptosis and cancer. Session 3: Tumor Markers O 3.1 Tumor Markers Comparison of gross cystic dosease fluid primary and metastatic breast carcinoma protein 9 (GCDFP-15) expression in Imrana Basher, Samina Mansoor; Shaukat Khanum Cancer Hospital and Research Centre, Lahore Pakistan. <[email protected]> Correspondence: Dr. Imrana Tanvir Abstract Aim: The objectives of the study is to evaluate the concordance of staining pattern of Gross cystic disease fluid protein -15 (GCDFP-15) in primary and metastatic breast carcinoma as to assess its utility as a diagnostic marker for unknown primary breast cancer. Method: Between 17 June 2006 to 19 December 2006, Fifty cases of cancer breast found suitable by inclusion criteria were invited for the study. An informed consent was obtained from all of them. The data regarding age, socio-economic status, duration and symptoms of illness, clinical examination and investigation were collected from the hospital record. The received mastectomy specimens were fixed in 10%buffered neutral formalin. Representative sections were processed and stained with hematoxylin and eosin to see the tumor morphology. The immunohistochemical stain GCDFP-15 was performed simultaneously on primary and metastatic tumors. Two pathologists assessed the immunohistochemical stains independently. Information obtained was recorded on the performa. The expression of (GCDFP-15) in primary tumors was compared with the expression of this biomarker in metastatic carcinoma. Results: GCDFP-15 Expression was compared and positivity was observed in 92% of primary tumors which was reduced to 88% in metastatic. Gross cystic disease fluid protein showed 96% concordance in primary and metastatic tumor. Conclusion: GCDFP-15 showed significant concordance of staining pattern between primary and metastatic tumors. 96% concordance is observed in primary and metastatic tumors, which proves its utility as a diagnostic marker. Keywords: CYSTIC DISEASE; 9GCDFP-15; METASTATIC; BREAST CARCINOMA 25 O 3.6 Tumor Markers Clinical evaluation of spermidine andsSpermine in breast cancer patients and follow up the progress of disease Alaa K. Jabbar and Raad K. Muslih College of Pharmacy , Al- Mustansiryia University, Baghdad , Iraq Correspondence: Prof. Alaa K. Jabbar; E-mail: [email protected] Abstract Practical evidence was suggested an important role of Spermidine and Spermine concentration levels in breast cancer development. Spermidine and Spermine have been determined in human serum samples of 25 primary invasive breast cancer patients and 9 serum samples from breast cancer patients ( stage three) in different ages .Statistical analysis was performed in order to determine the concentration level values in different ages . The concentration levels of Spermidine and Spermine in breast cancer patients were significantly higher than the primary invasive breast cancer patients. They correlated especially with markers of tumor of high stages of cancer patients. Spermidine and Spermine concentration levels were identical between cancer patients controls. The knowledge of the Spermidin and Spermine concentration levels pattern in breast cancer become importance in clinical practice particularly of Spermidine and Spermine is target as a therapeutic approach. O 3.3 Tumor Markers Plasma analysis of non-smokers, smokers and lung cancer patients for patternbased differentiation profiling of proteins and peptides by magnetic bead technology with MALDI-TOF MS Syed Ghulam Musharraf *a, b, Naghma Hashmi b, Muhammad Iqbal Choudhary Rizvic, Ahmed Usmanc, and Atta-ur-Rahman a,b, a,b , Nadeem a. Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan; b. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; c. Jinnah Postgraduate Medical Center (JPMC), Karachi-75510, Pakistan *Corresponding author. Tel.: +92 213 4824924-5; 4819010; fax: + 92 213 4819018-9. E-mail address: [email protected] Abstract Lung cancer is among the most lethal diseases accounting for millions of death, and smoking is the major contributor. Current study focused on the correlation between the proteomic profiling of lung cancer patients, healthy nonsmokers and smokers. Patternbased diagnostic peptide profiling of 186 plasma, comprising lung cancer (LC) patients, healthy non-smokers (NS) and smokers (S) was performed through RPC-18 magnetic bead fractionation with MALDI-TOF-MS analysis. Statistics were investigated by ClinProTools (CPT) software in four groups, I (NS vs. LC), II (S vs. LC), III (NS vs. S), and IV (NS vs. S vs. LC). Support vector machine (SVM) algorithm was employed for 26 groups I, II and III, while supervised neural network (SNN) was used for group IV. 100% recognition capability and 96.70, 94.30 % cross validation were found for groups I and II, while groups III and IV showed 85.60, 87.80 % cross validation and 96.70, 94.90 % recognition capability, respectively. Unique peptides at m/z 1760, 5773, and 5851 Da were expressed only in cancerous subjects while peaks at m/z 2940 and 7172 Da showed gradual decrease in intensity from NS < S < LC. Developed diagnostic model was externally validated with 100 % sensitivity and 71-77 % specificity. Pattern based diagnostic profiling of plasma peptides in lung cancer patients, smokers and non-smokers by above mentioned technique have been developed. Up- or down-regulated biomarker peaks with high diagnostic capability were identified and can serve as a potential tool for the detection and the screening of lung cancer. Details will be discussed in the oral presentation. O 3.4 Tumor Markers Lymphatic invasion as a possible route for peritoneal dissemination: a new concept Ayman Elnemr MD, PhD1,4, Yutaka Yonemura MD, PhD1, Masahiro Miura MD, PhD, Eisei Nishino MD, PhD3 1 NPO Organization to Support Peritoneal Surface Malignancy Treatment, Japan Department of anatomy, Oita Medical University, Oita, Japan 3 Department of Pathology, Kishiwada Tokushukai hospital, Kishiwada, Osaka, Japan 4 Department of Surgery, Faculty of Medicine, Tanta University, Egypt Correspondence: Ayman Elnemr, M.D,Ph.D Head of Surgical Oncology Unit, Department of Surgery, Tanta University, mobile: +20(10)624-5403; home: (040)536-0910, E-mail: [email protected] 2 Abstract Background: It is well known that cancer cells disseminate inside the peritoneum by seeding and direct attachment to peritoneal mesothelium closer to blood vessels, followed by angiogenic switch and neovascularization. This is the first study to demonstrate the lymphatic invasion in peritoneal dissemination using the monoclonal antibody (Mab) D240 to identify the lymphatic endothelium. Methods: A total of 10 consecutive patients with 90 resected peritoneal specimens of the different zones in cases of peritoneal surface malignancy were investigated. Expression of D2-40 in lymphatic endothelial cells was examined immunohistochemically in the formalin-fixed and paraffin-embedded specimens. D2-40-positive lymphatic vessel distribution and density (LVD) at the different peritoneal zones were quantitatively evaluated. CEA Mab was used to identifying the invading cancer cells. Results: Lymphatic endothelial cells in all examined tissues expressed D2-40. Its positive staining delineated flattened channels or open spaces lined by a single layer of endothelial cells. Lymph vessels lined with D2-40 were visualized just below the mesothelial layer of the peritoneum especially in the area of falciform ligament, followed by the right subdiaphragmatic peritoneum and paracolic gutters. Clusters of cancer cells were identified in the lymph vessels of the submesothelial layer. The frequency of the invasion to the submesothelial layer lymph vessels correlated 27 with presence of microscopic invasion. Conclusion: There were lymph vessels in the submesothelial layer of the peritoneum, and cancer cells can spread through these channels, and permeate to the deep large lymph vessels. We conclude that our concept of lymphatic invasion as possible route for peritoneal dissemination could be supported by using Mab D2-40, as a new selective marker of lymphatic endothelium. O 3.5 Tumor Markers A step in new tumor markers for HCC Mohamed Fathey Elgazzar M.D. Internal Medicine; Tawhid Mohamad Mowafy, Professor of Internal MedicineNabil Atia Khatab Professor of internal medicine; Abd elaziz Zydan Professor of clinical Pathology; Magda Hamed Bakr Professor of pathology Corresponding author: Mohamed Fathey Elgazzar M.D. Internal Medicine. Consultant of Internal medicine, Banha University, 3Kornish st., Stad area, Tanta, Egypt [email protected], Telephone: 01000128881 Abstract: Background: AFP is considered as the reference biological marker for HCC; however the lack of increase of AFP in some cases justifies the search for new markers. Hepatic tumor cells produce and release t-PA, fibrinogen and PAI-1. Aims: to determine the reliability of t-PA, fibrinogen and PAI-1 in detection of primary liver cancer as compared to or combined with the established tumor marker AFP. Patients and methods: We performed a comparative study of plasma level of PAI-1 antigen, t-PA antigen, fibrinogen antigen and alpha fetoprotein in twenty cirrhotic patients of post viral hepatitis, 45 HCC patients with a history of pre-existing cirrhosis with only one focal lesion without metastasis, divided into subgroup A tumor size <5cm and subgroup B with tumor size >5cm. Group III consists of 10 normal control persons. Results: PAI-1 was significantly increased in HCC patients than cirrhotics and normal control groups. t-PA level was significantly elevated in cirrhotics than normal group. Fibrinogen level was significantly elevated in HCC than cirrhotic and normal groups. Alpha fetoprotein level was significantly elevated in HCC than cirrhotic and control groups. Plasma levels of PAI-1, fibrinogen and t-PA antigens were higher in patients with tumor size >5cm than <5 cm tumor sized patients. Conclusion: PAI-1, AFP and fibrinogen can be used as markers for detection of HCC especially when combined with each others and they have competitor cost effectiveness. Plasma PAI-1antigen, t-PA, fibrinogen and AFP can be used in follow up of HCC progression, its response to treatment and its relapse. Key words: HCC, tumor markers, PAI-1, t-PA, fibrinogen. 28 Abstract 5.1 O 3.6 Tumor Markers Cancer Genetics Correlations of genetic mutations of Fibroblast Growth Factor Receptor 3 in schistosomal bladder cancers with the expression profile of Epidermal Growth Factor Receptor Elsayed I. Salim, Ph.D. (D.M.Sc.) Ass. Professor of Toxicological Pathology & Molecular Carcinogenesis. Zoology Department, Faculty of Science, Tanta University, Tanta-31527- Egypt Asian Pacific Organization for Cancer Prevention (APOCP). E-mail: [email protected]; [email protected] Telefax: (+20) 040 3350804; Cell: (+20) 01220177760 Abstract We have recently proposed a molecular mechanism of induction of Schistosomal bladder cancer due to increased levels of oxidative stress accompanied by DNA damage and repair (Salim et al., Int. J. Cancer, 1;123(3):601-8.2008). The present study analyzed the possible prognostic value of the fibroblast growth factor receptor (FGFR3) genetic mutations in bladder cancer accompanied or not with Schistosomiasis in Egyptian patients. FGFR3 belongs to a family of structurally related tyrosine kinase receptors, the FGFR family, which are regulating cell proliferation, differentiation, migration and angiogenesis. A FGFR3 mutation, evaluated by a PCR-single-stranded conformation polymorphism (PCR-SSCP) analysis was found in 6 out of 17 (35.3%) Schistosomal squamous cell carcinomas (SCCs), all had G→A transition in exon 7. Also one out of four tumors (25%) of superficial urothelial carcinomas (UCs) had a mutation of A→G transition in exon 15. In addition, the immunohistochemical expression status of FGFR3 and EGFR-1 were significantly higher in superficial Schistosomal SCCs and UCs in comparison to invasive UCs and bilharzial cystitis cases. In conclusion, the results show that Schistosomal SCCs and Papillary UCs have higher prognostic levels than invasive tumors and bilharzial cystitis in bladder cancer patients. Session 4: Stem cells O 4.1 Apoptosis from Basics to Therapy Stem Cells Faris Q. Alenzi, PhD Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, AlKharaj, Saudi Arabia Tel: 00966 1 5454518, Fax: 966 1 5454586, E-mail: [email protected] Abstract It is increasingly clear that apoptosis plays a central role in the pathogenesis of several human diseases. For instance, an increase in apoptosis leads to cell loss accompanied by 29 neurodegenerative diseases, whereas we know that genetically determined defects of apoptosis result in deregulated cell proliferation, typical of cancer. Hence, apoptosis may be relevant as therapeutic targets for many human diseases. M y t a l k reviews briefly the regulation and the clinical relevance of apoptotic mechanisms in several different human diseases. O 4.2 Stem cell origin of gastric cancer Stem Cells Sherif M. Karam Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al-Ain, United Arab Emirates; E-mail: [email protected] Abstract In the stomach, the epithelial stem cells undergo perpetual proliferation and differentiation to maintain the steady state of four main cell lineages secreting mucus, acid, pepsinogen and various hormones. Alteration of the gastric stem cell differentiation program in genetically engineered mouse models induced some events that occur during gastric carcinogenesis, e.g. loss of parietal and zymogenic cell lineages. In addition, the gastric epithelial stem/progenitor cells were amplified. These hyperplastic stem cells expressed glycoconjugates specific for adhesins of Helicobacter pylori. With age, these mice developed gastric adenocarcinoma suggesting a role for stem cells in the origin of cancer. To examine whether the stem cells also play a similar role in the human stomach, we have recently assembled an array of gastric mucosal tissues obtained from informed patients undergoing endoscopy (due to upper gastrointestinal symptoms) and gastrectomy (for gastric adenocarcinoma). Tissues were processed for histological and immunohistochemical analysis. Some tissues were frozen and later processed for Western blotting using stem cell-specific antibodies (anti-Oct4). Eighty nine biopsies were examined and categorized as: normal (33%), mild superficial gastritis (34%) and severe atrophic gastritis (33%). About 5% of the latter exhibited evidence of intestinal metaplasia. Cancer tissues obtained from three patients were examined in three regions: safe resected margin, tumor edge and tumor center. Progressive changes in mucosal thickness, dysplasia and cellular transformation were observed, and when compared with alterations in biopsies, all appeared to represent a continuum of progression toward invasive adenocarcinoma. Interestingly, epithelial stem/progenitor cells were amplified during the early stages of gastric carcinogenesis. In conclusion, our studies on mice and humans provide some evidence in support of the stem cell origin of cancer and would help in designing new modalities for early detection and/or prevention of gastric cancer. (Funded by Terry Fox Foundation for Cancer Research). 30 O 4.3 Stem Cells The CD34+ blood stem cells in the umbilical cord: cell aging, chromosomal instability, telomerase, and telomerase functions Akram M. Abouzied Zoology Dept., Faculty of Science, Suez Canal University, Ismailia, Egypt. E-mail: [email protected] Abstract Stem cells refer to the cells that have a capacity to divide, self renewal and multipotency. Umbilical cord blood is attractive as a stem cell source for the following reasons: (a) it is a resource that is usually being discarded; (b) it is rich in stem cells of fetal origin with considerable proliferative potential; (c) the stem cells have reduced immuno-competence making them permissible; (d) the cells are usually more readily available. However, the disadvantages of using cord blood include the relatively small size and a longer time of collection causing an increase risk for infections, cell viability and genomic instability. Hematopoietic stem cells (HSCs) give rise to lineage restricted stem cells, which can further differentiate into numerous blood cell types. Chromosomes are essential for cell viability and directly involved in shaping the karyotypes of stem cells. Therefore, structures, numbers and chromosome ends are required for chromosome stability. Stem cells require active telomere elongation mechanisms to grow indefinitely. On the basis of our experimental data, this could vary with respect to the source (e.g. bone marrow peripheral blood, cord blood, age, pathology, treatment, processing procedure and so on). Our objective in this review is to summarize the knowledge about CD34+ cells isolated from umbilical cord and focus mainly on cell aging, chromosomal instability and telomerase functions. The status of CD34+ cells from umbilical cord may show the same number but could give unsatisfactory results in a promising stem cell research and clinical practice. Key Words: Human; CD34+; Umbilical cord; Stem cells; Chromosome ; Telomerase; Cell aging; Chromosome instability O 4.4 Stem Cells Brief in vitro triggering of toll-like receptor signaling in fresh bone marrow cells induces acquisition of dendritic cell-like phenotype and effective antigen presentation capability Mohamed Labib Salem and Sabry EL-Naggar Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Egypt Correspondence: Prof. Mohamed Labib Salem (PhD): e-mail: [email protected] Tel. 0127 427 2624 Abstract Background: Stem cell based therapy has been explored as a promising means to overcome obstacles that meet the conventional therapy. Bone marrow (BM) is one of the main sources of the adult hematopoietic stem cells. Treatment with chemotherapeutic 31 drug, in particular cyclophosphamide (CTX), alone or in combination with mobilizing growth factors is known to increase the numbers of stem cells in the circulation. We have reported recently the effectiveness of CTX to induce BM to yield higher numbers of dendritic cell in vitro upon treatment the fresh cells in vitro with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days. Although this beneficial effect of CTX to yield high numbers of dendritic cells is considered as a significant advantage, the technology of the generation of dendritic cells in 7-10 days in vitro is laborious and expensive. Aim: In this study we aimed to generate cells expressing dendritic cell phenotype from BM after brief stimulation with toll-like receptor ligands (TLRLs). Methods: Naïve mice were treated with an intraperitoneal injection of a single dose of PBS or 200mg/Kg (4mg/mouse) of CTX. Mice were sacrificed after 2 days, the time point we have reported to mobilize stem cells, and bone marrow was harvested and cultured overnight after lysis of RBCs. The cultured cells were left alone or stimulated with 5-10ug/mL of TLR2/6L (zymosan), TLR3L (poly(I:C)), TLR4L (lipopolysaccharide; LPS) , TLR6L (pam3), TLR7/8L (imiquimod) or TLR9L (unmethylated ODN DNA; CPG) alone or in combination. The cells were harvested and analyzed by flow cytometry for surface markers. The antigen presenting function of the harvested cells was assessed in vitro after their pulsing with the MHC class-I OVA peptide (SIINFEKL) after co-cultured with OT-1 CD8+ T cells that are genetically engineered to specifically recognize this antigen. Results: BM harvested from CTX-treated mice should higher numbers of cells expressing the myeloid markers CD11c, Ly6G and CD11b than PBS-treated mice. Stimulating BM cells with different TLRLs induced much higher numbers of the cells to co-express CD40, CD80, and CD86, the typical markers of the activated dendritic cells. The TLR9L showed the highest effect, followed by the tLR3L and TLR7/8L in particular in combination. Of more interest, the BM from CTX treated mice conditioned with TLRLs showed superior antigen presenting function as evidenced by their capability to induce OT-1 cells to proliferate in vitro and produce IFN-g. Conclusion: BM cells from a host treated with chemotherapeutic drug can function as antigen presenting cells upon brief stimulation with TLRls. These data have a significant implication in immunotherapy against cancer and viral diseases. O 4.5 Stem Cells The differentiation of mesenchymal stem cell derived from the human umbilical cord blood into heptocyte-like cells Khalil A. Elhalfawy1, Medhat S. Hdwidy2, Ezzat A.El-Drieny3, Ehab M.M. Ali4, Batoul M. Izzularab5 1. Professor of Genetic Engineering, Iinstitute of Genetic Engineering, Minoufiya University, Egypt 2. Professor of Obstetric and Gynacology, Faculty of Medicine, Tanta University, Egypt 3. Professor of Histology, Faculty of Medicine, Tanta University, Egypt 4. Professor of Biochemistry, Faculty of Science, Tanta University, Egypt 5. PHD student (Biochemistry Division), Faculty of Science, Tanta University, Egypt Corresponding author: Batoul M. Izzularab: E-mail: [email protected] 32 Abstract: The capacity of mesenchymal stem cell (MSCs) in the differentiation into specific cell type make them very promising in tissue regeneration and repair. In this study characterization of hepatocyte cell differentiated from human umbilical cord blood (HUCB) mesenchymal stem cell in relation to their molecular expression and morphological structure .MSCs were isolated from the cord blood by easy step technology. Cultured cells were treated with fibroblast growth factor (FGF-4), hepatocyte growth factor (HGF), Oncostain M (OSM), leukemia inhibitory factor (LIF) and stem cell factor (SCF). Approximately 90%of cells were differentiated into hepatocyte on day 28 by immunostaining with CK8-18.Conventional and real time PCR showed that the differentiated cells expressed number of hepatocyte specific genes. Electron microscopic examination showed that the differentiated cells are structurally similar to hepatocytes. HUCB-derived MSCs are a new source of cell type for cell transplantation and therapy. Key words: Mesnchymal stem cell, Human umbilical cord blood, Differentiation, Hepatocyte 33 34 1. Therapy (Human Studies) P 1.1 Therapy (Human Studies) Paratesticular rhabdomyosarcoma of the young adult in a case report Imane Ouafki, H. El yacoubi, T.Sghiri, S.Boutayeb , H.Mrabti , H.Errihani Department of Medical Oncology, INO, CHU Rabat, Morocco. [email protected] Abstract Introduction: The paratesticular rhabdomyosarcoma (RMS) is a rare tumor, observing at any age, but especially in children and young adult. It develops from the mesenchymal tissues of spermatic cord, epididymis and testicular tunics. It is characterized by its rapid evolution with a poor prognosis. Case report: We report a case of embryonal paratesticular rhabdomyosarcoma, in a young adult of 19 years, treated with chemotherapy at the National Institute of Oncology (INO) in Rabat in 2010. The fact discovery was a spontaneous right large purse, having gradually increased in volume,accompanied by severe pain radiating along the spermatic cord.Clinical examination revealed a painful scrotal lobed mass of 6 cm in diameter,with inguinal extension and seems independent of the testicle. The testicular ultrasound showed a homogenous echotexture of right testicle with a large heterogeneous mass fluid measuring 58mm x 56mm in diameter and lateralized to the right, pushing back the right testicle, the left testicle is normal. Abdominal ultrasound showed no deep pyelocaliceal expansion. Cystoscopy confirmed the presence of a tumor occupying the entire right side. Transurethral resection of bladder tumor was incomplete. Pathological examination was in favor of a bladder leiomyosarcoma. The uroscan showed a process of bladder filling peri-vesical fat and invading the right ureteral meatus, measuring 39.7 x 27.6 x 39 mm. The treatment consisted of a radical cystoprostatectomy with urinary diversion type Briker and bilateral ilio-obturator lymph node dissection. Pathological examination of the specimen revealed the presence of a high-grade bladder leiomyosarcoma. The limits of resection were healthy. Lymph nodes were invaded.Our patient had adjuvant chemotherapy based on six cycles of doxorubicin and ifosfamide. It is in good control with a decline of 6 months. Discussion: The bladder leiomyosarcoma is a relatively rare tumor, representing less than 1% of bladder cancers. It occurs in patients between the sixth and eighth decade with a male predominance. Its prevalence is higher among patients treated with cyclophosphamide with an increased risk x 9. The mode of revelation is a macroscopic hematuria in 80% of cases, less frequently on the occasion of obstructive symptoms or abdominal mass. Diagnosis is based on pathological examination with immunohistochemical study. A review of the experience of the MD Anderson study reported 14 patients with bladder leiomyosarcoma. They had undergone 35 radical cystectomy with urinary diversion Briker type, followed by adjuvant doxorubicin and dacarbazine or vincristine, doxorubicin and cisplatin. The overall survival at 5 years was 59% with a median survival of 6 years. Conclusion: The bladder leiomyosarcoma is a rare disease .His prognosis seems increasingly improved with the advent of chemotherapy, ensuring completion of surgery in advanced or metastatic tumors, and reducing the risk of local recurrence or metastatic disease after adjuvant therapy lymphadenopathy, the tumor markers (hCG, LDH, α FP) was normal. The scans of the chest, abdomen and pelvis were without abnormalities.He underwent an inguinal orchiectomy with ligation of the spermatic cord. Histological examination of the specimen was in favor of an embryonal rhabdomyosarcoma confirmed by immunohistochemical study. The patient was reoperated 10 days later, a right hemiscrotectomy is performed, histologic examination showed no scrotal invasion.Chemotherapy Based on six cycles of doxorubicin 60 mg / m² and Ifosfamide 9 mg / m² is established one month postoperatively. The patient is in good control. Conclusion: The paratesticular RMS is a rare tumor, which requires early diagnosis and accurate staging. The treatment is now well codified and thanks to the combination surgery, chemotherapy and radiotherapy the prognosis has improved significantly. Adequate long-term monitoring must be introduced to detect relapses which are generally fatal. P 1.2 Therapy (Human Studies) Tamoxifen resistance in breast cancer: cCytochrome p450 2D6 gene copy number in Iranian patients Keivan Majidzadeh-A, MD, MPH, Ph.D; Rezvan Esmaeili, Ph.D candidate; Mahta Mazaheri, MD, Ph.D; Leila Farahmand, Pharm D., Ph.D; Sahar Motamedi, Msc Cancer Genetics Research Group (CGRG), Iranian Center for Breast Cancer (ICBC), Academic Center for Education, Culture and Research (ACECR), Iran e-mail: Dr. Keivan Majidzadeh <[email protected] Abstract Background: Tamoxifen is one of the most effective adjuvant breast cancer therapies available. The rate of metabolism of this medicine is mainly determined by the amount of cytochrome p450 2D6 (CYP2D6) enzyme expressed in the liver, which is highly variable due to its extensive genetic polymorphisms and copy number variation. So copy number variation maybe one of the most important mechanisms of resistance to Tamoxifen. Aim: Since there is limited information about CYP2D6 in resistant patients, we aimed to determine copy number of this gene in Tamoxifen resistant Iranian breast cancer patients. Materials and Methods: Samples: A total of 23 unrelated Iranian Tamoxifen resistant and 56 sensitive breast cancer patients as the control group were obtained from Iranian Center for Breast cancer Bio-Bank (ICBC-BB). DNA extraction was done using phenol chloroform method and the extracted DNA concentration was quantified using spectrophotometery. Copy number analysis: Establishment of standard curves for copy number determination was done by cloning of CYP2D6 fragment as the gene of interest 36 and albumin gene as a copy number control in TA cloning vector. PCR Primers were designed using primer express V.3.0 software. Real-time PCR was performed using the ABI 7500 system apparatus. Amplification reactions (20 ul) were carried out in triplicate with 40 ng of template DNA, SYBR Green Master Mix buffer (PrimerDesign Ltd, UK) and 300 nM of each primer. Each sample was run triplicate with 4 fold serial dilutions in the same plate. Samples with standard deviation greater than 0.5 from the mean threshold cycle of the triplicates were excluded from the analysis. Copy number calculation was done using applied biosystems SDS software ver2.0. Result: Primer efficiency for CYP2D6 and Albumin was 104 % and 97% respectively. The copy number range was 0.4 to 3 and no significant difference was seen between resistance and nonresistance group in this phase of study. Conclusion: Although no significant difference was detected between two groups in this phase of the study, it does not mean that copy number variation play no role in resistant group in the samples. Further analysis including genotyping and multivariate analysis considering other factors for tamoxifen resistance and also increasing sample size must be done in order to decide about CYP2D6 status in tamoxifen response in Iranian samples. Key words: CYP2D6, copy number, tamoxifen P 1.3 Therapy (Human Studies) A case of orbital rhabdomyosarcoma in adults Imane Ouafki, H.El Yacoubi, T.Sghiri, S.Boutayeb ,H.M’Rabti, H.Errihani Department of Medical Oncology, INO, CHU Rabat, Morocco. E-mail: [email protected] Abstract Introduction: Rhabdomyosarcoma is a malignant mesenchymal tumor, the most common. It represents 60-70% of mesenchymal tumors and 5% of all malignancies. It is the primary malignant orbital tumor most common in children, but it can occur at any age. This is an emergency diagnostic and therapeutic care that is based on a multidisciplinary approach. The originality of our case is related to patient age and tumor histology. Case report: We report the case of a patient of 26 years, presented in August 2009 with a unilateral right rapidly progressive proptosis. Radiological assessment showed an intraorbital expansive process of the lacrimal gland without invasion of the optic nerve. A biopsy of the tumor was performed. Pathological examination was in favor of embryonal rhabdomyosarcoma. Neoadjuvant chemotherapy (VAC) was administred which allowed a reduction in tumor size by 40%. After six cycles the patient underwent right exenteration, but the surgical limits were invaded. Two months later, he relapsed locally and bone. He received first line chemotherapy: etoposide plus cisplatin with stabilization after six cycles. Three months later, brain CT has objectified a right large intraorbital tumor process with intracranial extension and significant lesion progression by 114.2 x79, 9 mm long axis (vs. 37 x 25).A second-line chemotherapy (high dose ifosfamide) was administered, with a complement of local radiotherapy.Discussion: Rhabdomyosarcoma is a rare malignant tumor with an average age of discovery of 8 37 years, with a slight male predominance:sex ratio of 1,4. Its occurrence in adults is exceptional. The clinic is non-specific. This may be a unilateral exophthalmos, not axial, irreducible and rapidly progressive, with local inflammatory signs, an ophthalmoplegia or swelling of eyelid. The MRI and CT allow oculo-orbital study of the anatomical relationship of the tumor and staging. The CT scan appearance is fairly limited tissue mass, making the contrast; if tumor extended, we have a total filling of the orbit. The tumor extension is towards the ethmoid, nasal cavity and the cavernous sinus. However, the CT is limited by the fact that it does not differentiate between tumor and sinus retention. In addition, MRI can properly analyze periorbital extensions. Histologically, the embryonal type is the most common and usually occurs in young children. After 10 years, the alveolar type is most often found. In addition to the atypical age of our patient, histological type is unusual. The diagnosis of rhabdomyosarcoma is based on pathological examination. The local expansion is specified mainly by CT, MRI secondarily. The treatment is based on chemotherapy with or without radiotherapy. Monitoring is done by the clinic and imaging. It allows early detection of possible local recurrence in 70 to 80%, or metastatic in 30%. The risk of recurrence decreases over 3 years to become lower after 6 years.Conclusion: Although exceptional in adults, the diagnosis of rhabdomyosarcoma should be considered in orbito-palpebral rapidly progressive swelling. The diagnosis and treatment of this disease should be initiated early to improve prognosis. The frequency of metastases and / or recurrence requires a prolonged clinical and radiological surveillance. P 1.4 Therapy (Human Studies Assessing the response of radiotherapy in treating the patients with lung cancer Yasha Makhdoumi1, Mehrdad Soltani Delgosha2, Amir Houshang Youssefi3, Isa Bilejani3 Mashhad university of Medical science1, Reza Oncology Centre2, Tabriz University of Medical science3, IRAN. Correspondence: Dr. Mehrdad Soltani Delgosha. [email protected] Abstract Introduction: Lung cancer is the deadliest type of cancer. Each year, more people die of lung cancer. Lung cancer is more common in older adults. There are many different types of treatment like surgery, chemotherapy and Radiotherapy. Treatment depends on the stage of cancer. One of the main ways of treatment is radiotherapy. Aim: In this study, we investigate the effect of radiotherapy on survival rate of patients with lung cancers. Material& Methods: in this retrospective study, we assessed 111 patients with lung cancers who were admitted in Imam Khomeini hospital in Tabriz. All the patients got radiotherapy as main treatment. For each patient total radiotherapy dosages, fractions, duration of therapy and survival were determined and analyzed. Results: the mean age of patient was 60. 80.2% patients were male and 19.8% were female. 25.2% were operated, 18% were got chemotherapy.Total dosages were used from 1000CGy to 9000CGy.The range of fractions was between 2 and27 in which the mean was 19. Duration of radiotherapy was 4 to 5 weeks.The survival rate of patients was 0 to 48 months in which 38 there wasn't significant difference between SCLC and NSCLC (p=0.05,t-test).By correlation test we found out there was significant correlation between radiotherapy dosage and survival rate of patients. There was no significant relationship between the fractions of radiotherapy and survival rate. Conclusion: increasing the dosages and fractions in the appropriate range will significantly improve the survival rate of patients with lung cancers, in our study the mean of survival was 6.32 months which 8.8% of patients survived more than 1year. Key words: Radiotherapy, lung cancer, survival. P 1.5 Therapy (Human Studies Protective effect of carvedilol on Adriamycin-induced left ventricular dysfunctionvin children with Acute Lymphoblastic Leukemia Nagla A. El-Shitanya,Osama A. Tolbab, Mohamed R El-Shanshoryc, EslamE. El-Hawaryc a Department of Pharmacology and Toxicology, College of Pharmacy, Tanta University, Tanta, Egypt Pediatric Department, College of Medicine, Cardiology Unit, Tanta University, Tanta, Egypt. c Pediatric Department, College of Medicine, Hematology and Oncology Unit, Tanta University, Tanta, Egypt. Correspndence: Dr. Nagla Fouad El-Shitany; Asociate Prof of Pharmacology And Toxicology (e-mail: [email protected] b Abstract Adriamycin (ADR) is a potent chemotherapeutic agent widely used in the treatment of childhood acute lymphoblastic leukemia (ALL); its clinical use is limited for its marked cardiotoxicity. The present study aimed to investigate the possible protective role of carvedilol on ADR-induced left ventricular dysfunction in children with ALL.Fifty newly diagnosed ALL children were included in this study. They were divided into two equal groups; 1- ADR group, 2- carvedilol + ADR group. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2-D), pulsed tissue Doppler (PTD), and 2-D longitudinal strain echocardiography (2-DS) before and after therapy. Plasma troponin I, LDH and CPK levels were also determined before and after therapy.ADR treatment induced left ventricular systolic dysfunction as assessed by significant decrease in fractional shortening (FS) (2-D) and global peak systolic strain (GLPSS) (2-DS). In addition, ADR treatment significantly increased plasma troponin I and LDH. Pretreatment of ADR-treated patients with carvedilolresulted in significant increase in FS (2-D), and GLPSS (2-DS). Alsocarvedilolpretreatment inhibited ADRinduced increase in the plasma troponin I and LDH.These results suggested that, carvedilolcould be used to protect the heart against the cardiotoxic effect of ADR. Large scale studies are recommended, to allow further assessment of the protective role of carvedilolin ADR-induced cardiotoxicity in cancer patients. 39 2. Anti-Tumor Immunity P 2.1 Anti-tumor Immunity Dendritic cell-based vaccine in cancer: total RNA vs cancer testis chimeric antigens RNA in esophageal squamous cell carcinoma Mohammad Reza Abbaszadegan, Ph.D.1, Mehran Gholamin, Ph.D.1, Mohammad Mahdi Forghanifard, Ph.D.1, Omeed Moaven, M.D.1, Moein Farshchian, M.Sc.1, Bahram Memar, M.D.4, Mohammad Naser Forghani, M.D.3 1 Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran 2 Department of Pathology, Omid Hospital, MUMS, Mashhad, Iran 3 Department of Surgery, Omid Hospital, MUMS, Mashhad, Iran Correspondence: Dr. Mohammad Reza Abbaszadegan (PhD); [email protected] Abstract Introduction: Esophageal cancer is the seventh most common cause of cancer deaths worldwide and the fifth leading cause of cancer-related death in Iran. Squamous cell type of the cancer (ESCC) consists 95% of all cases. The high incidence areas of Iran include Golestan and Khorasan Provinces in northeastern Iran with incidence rate of ASR of 43.4 per 100,000 for men and 36.3 for women. These regions of Iran are located in a high risk area designated as “Central Asian Esophageal Cancer Belt”. Most cases of ESCC are diagnosed in advanced stages. Surgical treatment and adjuvant therapeutic modalities such as chemo- and radiotherapy have only a minimal effect on patient outcome and the overall 5-years survival rate is less than 25%. Development of vaccines against ESCC may improve the therapeutic modality as a neo-adjuvant. Methods: We evaluated the capability of autologous Dendritic cells (DCs) transfected with total tumor and normal RNA as compared with mRNA of chimeric tumor antigen epitopes (ChiTA) to induce cytotoxic CTL as the preliminary step to design a DC-based vaccine in the ESCC. Monocytes-derived DCs were electroporated with either total tumor or normal RNA or ChiTA mRNA. T cells were then primed with tumor or ChiTA RNA transfected DCs and lytic effects of the generated CTL were measured with Calcein-AM cytotoxicity assay and IFN-γ Release Elispot assay. Results: Cytotoxicity was induced against DCs loaded with tumoral RNA (%24.8 ± 5.2 SEM) while in normal RNA- loaded DCs, it was minimal (%6.1 ± 2.4 SEM) and significantly lower (p < 0.05). INF-γ secretion was more than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNAloaded DCs (p < 0.05). Significantly higher differences were obtained in lyses of cells loaded with chimeric mRNA vs Mock cells by ChiTA-stimulated lymphocytes, using cyotoxicity test, %65 vs %4 (P < 0.05). Conclusion: Stimulation of immune system using pulsed DC with ChiTA mRNA which has tumoral antigens epitopes as compared to total tumoral RNA may have a better advantage to develop DC-vaccine as a new therapeutic modality against ESCC. Key words: Dendritic Cell, Vaccine, Chimeric, Tumor antigen, Esophageal cancer, RNA 40 P 2.2 Anti-tumor Immunity In vivo generation of splenic dendritic cell subsets by Berberis Vulgaris extract Doaa A. Ghareeb1, Eiman H. El-Wakeel2, Maha A. El-Demellawy3, Marwa Abo Sariaa3, Mohamed Abd El Sallam4, Mina Saad1, Noha Habachi1, Amel Abd Elmagied1, Hend M. Hussein5 1Biochemistry Department, Faculty of Science, Alexandria University, Egypt 2 Microbiology and Botany Department, Faculty of Science, Alexandria University, Egypt 3 Biomedical technology Department, City of Scientific Research and Applied Technology, Egypt 4 Pharmacognosy Department, Faculty of Pharmacy, Alexandria University, Egypt 5 Faculty of Pharmacy, Faros University, Alexandria, Egypt Correspondence: Dr. Doaa A. Ghareeb, e-mail: [email protected] Abstract Dendritic cells (DCs) are unique antigen presenting cells that are immature prior to their encounter with an antigen. The efficient capacity of DCs to initiate and regulate lymphocyte-mediated immunity has led to the study of DCs as cellular vaccine. In this study, we demonstrated a novel approach for implementing and characterizing an efficient DCs-base immunization. DCs were expanded in vivo by intraproteneal and intravenous injection of mice with Berberis vulgaris crude ethanolic extract (BRB) at dose of 30 and 60 mg/kg for IV and at 100 and 200 mg/kg for IP administration route. Spelenocytes were isolated then splenic DCs were purified with magnetic micro beads. Our results showed that IP BRB administration increased enriched DC population by 10 and 15 % while IV injection increased it by 18 and 25% respectively that combined with a significant increase in Interleukin 12 (IL12) secretion by four fold at IV BRB injection (60 mg/kg), in comparison to a negative control. Therefore, BRB can be used to increased DC production that will open a new hope in HCV treatment as it is well known that DC and IL 12 are progressively decreased in HCV patients. P 2.3 Anti-tumor Immunity Recombinant human anti – ALCAM (Activated leukocyte cell adhesion molecule) antibody scFv fragment production in bacterial host Leyla Farahmand, Ph.D Candidate; Keivan Majidzadeh-A, MD, MPH, PH.D; Alireza M. Ansari, Ph.D Candidate; Nasrin Abdoli, MSc Cancer Genetics Research Group (CGRG), Iranian Center for Breast Cancer (ICBC), Academic Center for Education, Culture and Research (ACECR), Iran E-mail: Kkeivan Majidzadeh" <[email protected]> Abstract Background: Recent studies demonstrated that cancer may arise from stem cells known as cancer stem or tumor initiating cells (TICs) which might be in charge of primary and metastatic tumor growth. So stem cells are considered as potential therapeutic and diagnostic targets for many types of cancers such as breast cancer. Cancer stem cell marker profiles have been suggested for many tumors, with several markers such as 41 Activated leukocyte cell adhesion molecule (ALCAM) (CD166). ALCAM is a cell adhesion molecule which play critical role in cell migration and cancer progression. Aim: The molecular methods developments and the evaluation of the structure and function of the antibodies have made it possible to create new generation of antibodies, known as recombinant human antibodies. These antibodies and their derivatives have emerged as an important targeted therapy and diagnostic agents and fast growing group within biotech-pharma research. Materials &methods: DNA fragments encoding the light and heavy variable (VL, VH) regions were obtained by amplification of germ line antibody variable segments using polymerase chain reaction (PCR). Amplified sequences were mutated to encode the anti – ALCAM (VL, VH) regions. VL and VH were operatively joined together by a linker to generate scFv (single-chain variable fragment) and inserted into a dicistronic expression vector. Expression cassette transformed to the bacterial host and was cultured in LB medium. Produced antibody was assayed by conventional methods. Results: Dicistronic expression vectors were constructed for the antibody scFv fragment and Expression of antibody fragment was processed successfully. Whole cell harvested from induced cultures electrophoretically separated by Laemmli gel. Assembled antibody was observed under Non-reducing condition. Other conventional assays showed other related results, respectively. Conclusion: ALCAM is classified as an adhesion molecule so anti ALCAM antibodies can suppress cell migration, cancer growth and metastasis. Despite vital role of antibodies in therapeutic regimens, cost of producing recombinant antibodies at large scale is a big problem. Bacterial hosts, such as Escherichia coli, are an alternative route and potentially more economical expression system for production aglycosylated antibodies and their fragments. P 2.4 Anti-tumor Immunity Molecular immunological studies on a novel zymosan-binding protein (ZBP-240) Soha Gomaa1, Miki Nakao2 1 Labortory of Biotechnology and Immunity, Tanta University Egypt, Biotechnology, Kyushu University, Japan Correspondence: Soha Gomaa; E-mail: [email protected] 2 Division of Bioscience and Abstract C3 has been recognized as a major serum protein with binding ability to zymosan, crude yeast cell wall component. Unlike zymosan-binding proteins (ZBPs) of other vertebrates tested to date, tilapia ZBPs contained a novel major polypeptide with molecular mass of 240 kDa, designated as ZBP-240, in addition to the iC3b fragment. ZBP-240 was purified from tilapia serum by three chromatographic separations on Q-Sepharose HP, Superdex 200, and hydroxylapatite and digested chemically using CNBr or enzymatically by lysyl endopeptidase releasing 2-3 digested peptides which are separated by RP-HPLC. On the Superdex 200 column, ZBP-240 migrated as a ~400 kDa protein, suggesting that it is 42 present as a dimer in serum. ZBP-240 was also characterized for its binding ability to various microbial targets like (gram-positive and gram-negative bacteria, different yeasts, YCW and zymosan). Furthermore, ZBP-240 was demonstrated to show a significant opsonic activity, like complement C3, for tilapia kidney phagocytes enhancing phagocytosis. ZBP-240 also enhanced binding of C3 to the microbial targets, probably resulting in further increase of C3-mediated target opsonization. More over, functional assays of C3 and a novel ZBP-240 at the protein level demonstrated their binding and opsonization of microbial targets, suggesting their unique coordination in pathogen recognition and elimination. Based on the previous study, we may use this novel ZBP240 in cancer immunotherapy by studying its receptors on different cells as this protein may enhance phagocytic cells through toll like receptors (TLR), how it activates different cells like dendritic and T-cells and finally anti-tumer immunity. 3. Tumor Markers P 3.1 Tumor Markers Assessment of ki67 frequency in breast cancer patients without axillary lymph nodes involvement and its relation with disease free survival condition Fatemeh Homaei Shandiz, M.D.*1; Nourieh Sharifi, M.D.2; Monavar Afzalaghaee, M.D.3; Emane Roshanzamir, M.D.4; Hossein Shabahang, M.D.5; Alireza Tavasoli, M.D.6; Shadi Emami, M.D.; 7Javad Aghamohammadian 1Associated professor of Radiation Oncology, Cancer Research Center of Mashhad University Medical of Sciences, Omid and Ghaem Hospitals, Iran; 2 Associated Professor of Pathology, Mashhad University Medical of Sciences; 3Assistant professor of Epidemiology, Mashhad University Medical of Sciences; 4 Mashhad University of Medical Sciences; 5 Associated professor of Surgery, Mashhad University of Medical Sciences; 6 Associated professor of Surgery, Mashhad University of Medical Sciences; 7Mashhad University of Medical Sciences; 7Assistant professor of Pathology, Mashhad University of Medical Sciences * Corresponding author: Dr. Fatemeh Homaei Shandiz, Associated professor of Radiation Oncology, Cancer Research Center, Omid Hospital, Alandasht Sq., Mashhad, Iran, Tel: +98-511-8428621 / 8445647 , Fax: +98-511-8428622 , E-mail: [email protected] Abstract Introduction: The aim of this study was to assess ki67 frequency in breast cancer patients without axillary lymph nodes involvement and evaluating of its prognostic value in disease free survival and relation with other prognostic factors such as age, size of tumor, pathologic subgroup, ER, PR, P53 and HER-2. Methods: Ki67 levels were measured by IHC and compared with prognostic factors of tumor in lymph node negative 43 invasive breast cancer and its effect on disease free survival. Results: We assessed 106 women with the mean age 49. 94.3% of patients were invasive ductal carcinoma of breast and mean of tumor size at diagnosis was 2.8 centimeter. 50.9% of patients were ER positive and 47.2% of them were PR positive and P53 was positive in 48.1% cases. According to IHC methode, only 8.5% of our patients were Her2/neu positive. Ki67 by IHC method was positive in 66 (62.3%) patients. There was a meaningful relation between ki67 positive cases and age (p=0.0229) and positive Her2/neu status (KAPPA=0.043) and positive P53 cases (KAPPA=0.265). In positive ki67 cases, the mean of age was less than negative ki67. After mean of 40 months follow up 13 patients (12.3%) had recurrence. The most common kind of recurrence was systemic and in the relapsing cases, 10 patients (77%) were Ki67 positive (p=0.0235) that was significance. The 3 year disease free survival in Ki67 positive and negative patients were 89% and 85% (p=0.556). Conclusion: It is suggested to carry out survival study on more cases to find out the relation between Ki67 positivity and cancer recurrence. Key words: breast cancer; ki67 proliferative factor; negative Axillary lymph node; disease free survival; Iran P 3.2 Tumor Markers A comparative immunohistochemical study of benign prostate hyperplasia (BPH) and prostate cancer (PCa) in Sulaimani province using Prostate- Specific Antigen (PSA) as a tumour marker Sirwan Mustafa Muhammad*; Intissar Numman Waheed ** *Department of Biology\ College of Science\ University of Sulaimania; **School of Pharmacy\ Faculty of Medical Sciences\ University of Duhok, Iran Correspondence: Dr. Intissar Numman Waheed E- mail: [email protected] Abstract Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two common diseases in aging males and their prevalence increases exponentially with age. The current study was applied to evaluate the significance of serum Prostate- Specific Antigen (PSA) as a screening tool for the PCa and the role of percent free - to- total PSA ratio in the discriminating between BPH and PCa as well as to experience immunohistochmical expression of PSA in human prostate tissue specimens and scoring the staining intensity. Prostatic biopsies and blood were collected from (62) patients aged between (50-89) years. Also eleven healthy men with negative digital rectal examination, (median age, 60.6yr) were enrolled in this study as a control group. The commonest diseases encountered were BPH (59.7%), BPH with prostatitis (19%), adenocarcinoma (17.7%), and transitional cell carcinoma (3.2%). The intensity of PSA staining was scored as (0, 1, 2, and 3). 27% of BPH cases demonstrated strong staining scores of (3) and 47% of them showed scores of (1), whereas 50 % of PCa cases showed scores of (1) with no cases of PCa and prostatitis revealed staining scores of (3). 54% of BPH cases had tPSA level < 4 ng/ml as well 13.5% of them having tPSA>10, while 15.3% of Malignant cases had tPSA 44 level < 4 ng/ml and 84.7% of them having tPSA>10. The statistical analysis showed a significant difference between (BPH and PCa ); (PCa and control cases) and (prostatitis and control) in regard to tPSA. Regarding to % cPSA the entire cases of PCa showed levels >60% aligned with only 75%, 27%, 16% in prostatitis, control and BPH groups successively. The mean comparison showed statistically significant differences between the PCa patients and control cases and between prostatitis and control cases, while no significant differences between BPH and control group. Regarding to % FPSA, 53.8 % of PCa cases showed ≤15, along with 16.6 % of prostatitis showed ≤15, while no cases of both BPH and control revealed FPSA ≤15. Comparison of the means showed a statistically large difference between the (PCa and BPH), (PCa and control) and (prostatitis and control) cases. While no significant differences between (BPH and control) cases. In conclusion PSA staining intensity was increased and expressed in a strong and uniform pattern in BPH tissue sections in comparison with the PCa tissue sections, in which the staining intensity was decreased. Combinational use of tPSA with other molecular forms of PSA especially proportion of FPSA provide higher diagnostic and differentiative accuracy than the tPSA alone. 45 46 Day 2 December 28, 2011 A- Special Session Beating cancer cells to death with gold nanoparticles in more than one way Mostafa E l-Sayed, PhD Professor, Juilius Brown Chair and Regent Professor, Director, Laser Dynamics Lab, Georgia Institute of Technology (http://ldl.gatech.edu), Atlanta, Georgia,, USA, E-mail: [email protected] Biography Mostafa El-Sayed was born in Egypt where he received his B.Sc. He received his Ph.D.at Florida State University with Professor Michael Kasha. After doing postdoctoral work at Yale, Harvard and Caltech, he joined the faculty at UCLA. In 1994, he moved to Georgia Tech and became the Julius Brown Chair, Regent Professor and Director of the Laser Dynamic Lab. El-Sayed and his group (over 70 Ph.D. students and over 40 Postdoctoral Fellows) have contributed to many areas of physical and material chemistry research. They have been involved in the development of new techniques such as magneto photo selection, picoseconds Raman spectroscopy and phosphorescence microwave double resonance spectroscopy. Using spectroscopic techniques, they have been able to answer fundamental questions regarding ultra-fast dynamical processes involving molecules, solids and photo biological systems. Since he moved to Georgia Tech, El-Sayed and his group became active in the study of the physical, chemical and photo thermal processes of metallic and semiconductor nano structures of different shapes and compositions. The shape dependent applications of the metallic nanoparticles in nano catalysis, nano motors as well as nano medicine (in Cancer diagnoses and photo-thermal therapy) have been demonstrated. El-Sayed has published over 520 peer-reviewed papers, gave over 45 special named lectures and over 250 invited talks at National and International meetings. He has served on numerous international and national committees such as the Advisory Boards of NSF and Basic Energy Sciences of DOE and the National Research Council Board of Chemical Sciences. Prof. El-Sayed has served as the Editor-in-chief of the 47 Journal of Physical Chemistry (1980-2004) and as the U.S. Editor of the International Reviews in Physical Chemistry. El-Sayed is an elected member of the U.S. National Academy of Science, and elected Fellow of the American Academy of Arts and Sciences, the AAAS and the American Physical Society. He has also received the 1990 King Faisal International Prize in Science and an Honorary Doctor of Philosophy degree from the Hebrew University. He has received a number of national awards such as the Fresenius, the Tolman, the Richard's medal, as well as other numerous local ACS section awards. In 2002, he received the ACS-APS Langmuir National Award in Chemical Physics. In 2007, he was named the Distinguished Professor of the year at Georgia Tech and was offered the Miller Visiting Professorship at the University of California at Berkeley. Abstract: Gold nanoparticles have a number of properties that are used in cancer diagnosis and therapy: 1) they can scatter light very strongly and if bound to cancer cells they enable us to detect cancer (used in diagnosis). 2) Depending on their size and shape, they can also absorb light very strongly and convert it into localized photothermal heat that can melt attached cancer cells (used for photo-thermal therapy). 3) Because of their large size compared to molecules, each can carry thousands and thousands of drug molecules, transport them to sick cells and enhance drug effectiveness (used in drug delivery). 4) Because of their small size compared to the size of the cell components, we can bind them to its nucleus which stops cell division and convinces the cancer cells to commit suicide (apoptosis). 5) Using the strong scattering and toxic properties of silver nanoparticles, the interesting behavior of community of dying cancer cells was captured in time on vedio. References: 1. Xiaohua Huang; Ivan H. El-Sayed; Wei Qian and Mostafa A. El-Sayed, “Cancer Cell Imaging and Photo thermal Therapy in Near-Infrared Region by Using Gold Nanorods,” Journal of American. 2. Chem. Soc., 128, 2115-2120, (2006) [most cited paper in the field of chemistry, Sept-Oct 2007, most cited paper in JACS in 2007] 3. Xiaohua Huang, Prashant K. Jain, Ivan H. El-Sayed, Mostafa A. El-Sayed, “Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy,” Invited Review, Nanomedicine, 2(5), 681-693, (2007). #1 most cited Nanomedicine article to date (Oct 27, 2009) 4. Dreaden, E. C.; Mwakwari, S. C.; Sodji, Q. H.; Oyelere, A. K.; El-Sayed, M. A., Tamoxifen-PEG-Thiol Gold Nanoparticle Conjugates: Enhanced Potency and Selective Delivery for Breast Cancer Treatment. Bioconjugate Chemistry, 20, 2247– 2253 (2009). 5. Kang, B.; Mackey, M.A.; El-Sayed, M.A., Nuclear Targeting of Gold Nanoparticles in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis. Journal of the American Chemical Society Communication, 132, 1517–1519 (2010) 6. L Austin, B Kang And El-Sayed, J. Am. Chem. Soc., Comm , 2011 , 133 (44), pp 17594–17597 48 B- Plennary Session 2 01 Role of plasminogen activators (PAs) system in hormone dependent malignancies: diagnostic, prognostic and therapeutic implications Shafaat A. Rabbani, MD Professor, McGill University Health Centre Department of Medicine , 687 Pine Avenue West, Montreal, Quebec, Canada H3A1A1. Tel: 1-514-843-1632, Fax: 1-514-843-1712 E. mail: [email protected] Biography Dr Shafaat A. Rabbani received his medical degree from KingEdward Medica, College, Lahore, Pakistan. He did his research fellowship at McGill University, Montreal, Canada, where he was awarded the Medical Research Council of Canada Fellowship. His research interests include skeletal metastasis in hormone dependent malignancies, role of proteases in tumor progression and epigenetic regulation of gene transcription in cancer. Studies carried out in the laboratory of Dr Rabbani led to invitations to national and international conferences, scientific panels and patents related to his area of research. Over the years he served as a consultant and scientific advisor to several biotechnology and multinational pharmaceutical companies in the area of oncology. He was also awarded the Medical Research Council of Canada and Canadian Cancer Research Society Scholar award. More recently he received the Outstanding Achievement Award from the Society of American AsianScientists in Cancer Research (SAASCR). Dr Rabbani is a Full Professor in the Department of Medicine and is an Associate Member in the Departments of Physiology and Oncology at McGill University Health Centre in Montreal, Canada. Abstract: Hormone dependent malignancies (breast, and prostate) are unique due to their propensity to develop skeletal metastases, which results in a high incidence of tumor associated morbidity and mortality. In the multi-step process of tumor progression, a number of growth factors and proteases play a crucial role in promoting tumor cell invasion, migration and metastasis to non skeletal and skeletal sites. Members of the PA system; urokinase type plasminogen activator (uPA), its receptor (uPAR) and PA inhibitors 1 and 2 (PAI-1, 2) are expressed by several tumors including breast and prostate cancer. uPA is a member of the serine protease family and plays a key role in tumor progression due to its ability to break down different components of the extracellular matrix to promote tumor invasion and metastasis. These proteolytic effects of uPA are localized via uPAR, which is anchored to the tumor cells via its glycophosphatidylinositol (GPI) anchor and can also form a complex with integrins and vitronectin. While PAIs regulate the activity of uPA and tissue type plasmingon activator (tPA), high levels of PAI-1 is associated with the progression of several malignancies including breast cancer. Long term studies in patients with different cancers have shown increased expression of uPA, uPAR, and PAI-1 with advanced stage cancer. Determination of the levels of expression of uPA, uPAR, and PAI-1 in these patients by immunohistochemistry and ELISA can serve as useful clinical tools to predict disease status and response to therapy. We have shown that uPA 49 and PAI-1 are abundantly expressed in highly invasive, hormone insensitive breast and prostate cancer cells. This selective expression of uPA and PAI-1 at late stages of cancer was shown to occur via the epigenetic regulation by DNA methylation of these pro-metastatic genes. Determination of the promoter methylation status of these key genes in patients with various cancers, including breast and prostate cancer, was shown to correlate with their expression and disease stage, where they can serve as a reliable and early method to predict disease progression. Using current molecular and cell biology techniques and our established in vivo models of breast and prostate cancer associated with skeletal metastasis, we have developed and validated various therapeutic strategies to block uPA, uPAR transcription, expression and activity. Results from these studies, which show the effectiveness of these approaches and their current state of clinical development, will be presented and discussed. 02 Prostate-Specific Antigen: Where we are and where we are going Kailash C. Chadha, PhD Associate Member & Associate Professor of Oncology Department of Molecular & Cellular Biology, State University of New York at Buffalo, Roswell Park cancer institute, Buffalo, NY, USA Tel: 716-845-3101, Fax; 716-845-1275 e-mail:[email protected] Biography Kailash Chadha is the Associate Member and Associate Professor of Oncology in the Department of Molecular and Cellular Biology at Roswell Park Cancer Institute, and Department of Medicine, State University of New York at Buffalo, NY, USA. He got his Ph.D. degree in Virology from the University of Guelph, Guelph, Ontario, Canada. After his graduation he spent two years as a fellow of National Research Council of Canada. Following that he joined Roswell Park Cancer Institute in Buffalo, New York as a Cancer Research Scientist in the Department of Medical Viral Oncology. His research interests are in the area of cell and molecular biology of Herpes viruses, interferon and prostate cancer. He has published well over 125 publications, written several book chapters and currently holds four U.S. patents. He has been invited to participate in numerous national and international scientific meetings and has often chaired sessions on several international meetings. He is currently on the editorial board of J. Medicine and Indian J. Medical Microbiology, The Open Prostate Cancer Journal, International J Nephrology & Urology, World Journal of Clinical Urology and member of several professional organizations including New York Academy of Sciences; American Association for the Advancement of Science; Society for Experimental Biology & Medicine; American Association for Cancer Research; International Society for Interferon & Cytokine research and The Society of Basic Urologic Research etc. Recently, he has completed editing a book on interferons entitled “Interferons: Current Status, published by Research Signpost (ISBN 81-7736256-9). His immediate research interest is in developing new ”biomarkers” for early detection and management of prostate cancer and in studying physiological role of prostate-specific antigen (PSA) in regulating prostate tumor growth and in-particular role of PSA in “angiogenesis”. His research is being supported by National Cancer Institute, American Cancer Society, National Multiple Sclerosis Society, and EMD Serono Inc. Abstract: Prostate cancer has the highest incidence of any non-cutaneous malignancy in the western world and is the second leading cause of cancer related deaths in men. Prostate-Specific 50 Antigen (PSA) is an androgen regulated serine protease of the tissue kallikrein family, and a well recognized biomarker for the early diagnosis and management of prostate cancer. However, PSA test is neither disease specific nor tissue specific and test results are >70% false positive and 30% false negative. Therefore, one of the major goal is to identify additional circulating biomarkers that will either alone or in combination with PSA test will significantly improve the sensitivity and specificity in the early diagnosis and in management of prostate cancer. At present, we are investigating the relevance of IL-8, TNF-α and sTNFR1 etc as potentially new biomarkers. Our data strongly suggests that serum levels of IL-8, TNF-α and sTNFR1 will provide powerful tools in differentiating between the benign and malignant tumors; which is the major disadvantage of currently available PSA test. PSA has been documented to have anti-tumorigenic and anti-angiogenic activities. We have shown that intact PSA has anti-angiogenic activity in vitro based on inhibition of tube formation by human umbilical vein endothelial cells (HUVEC) in Matrigel. PSA is also known to regulate expression, in endothelial cells and in prostate cancer epithelial cells of pro-angiogenic growth factors/cancer genes/proteins including VEGF, IL-8, EphA2, CYR61, Bcl2, Pim-1 oncogene, uPA, and up regulate expression of anti-angiogenic genes/proteins, including interferons and interferon related genes. Furthermore, exogenously administered PSA inhibited growth of PC-3M prostate tumor xenografts in nude mice. In preliminary studies, we have shown that PSA significantly decreased micro vessel density (MVD) in xenografts of human prostate cancer tissue harvested from animals treated with PSA; compared to animals treated with vehicle. These observations validate both the potential therapeutic importance of PSA and the utility of primary xenograft model for evaluation of anti-angiogenic therapeutics. Impact of our research: The physiological role of PSA in prostate tissue microenvironment, in prostate tumor growth and progression, and in prostate cancer metastasis is not known. Attenuation of PSA levels with age, disease progression, or during androgen deprivation therapy, however, removes this important regulator of angiogenesis, and by extension results in tumor progression. Re-introduction of human PSA into the prostate tissue microenvironment may suppress tumor angiogenesis through either the inhibition of expression of pro-angiogenic genes or induction of expression of anti-angiogenic genes, or via inhibition of signaling mechanisms associated with angiogenesis that are independent of gene transcription. Validation of an antiangiogenic effect of PSA on the human tissue vasculature in a pre-clinical model of primary xenografts of human prostate and prostate cancer tissue will provide compelling evidence that PSA has therapeutic potential against prostate cancer. Precursor Lesions & Predictive markers of Oral Cancer Shahid Pervez, PhD Professor & Consultant Histopathology, Department of Pathology & Microbiology, Aga Khan University Hospital, Stadium Road P.O. Box 3500, Karachi 74800, Pakistan Phone: 92 21 4861554; [email protected] 51 Biography Dr Shahid Pervez obtained M.B., B.S. from Pakistan in 1982, Diploma in Clinical Pathology, University of London and Ph.D. in histopathology, University of London in 1990, and the F.C.P.S (fellowship in Histopathology), Pakistan, 1993. He currently works as a Professor and Consultant Section of Histopatholgy, Department of Pathology and Microbiology, Faculty of Health Sciences, Medical College, the Aga Khan University Hospital, Karachi, Pakistan. His major research interests are in Head & Neck cancer, Breast Cancer and Lymphomas. He is Vice President of the ‘Middle Eastern Association for Cancer Research (MEACR)’ and supervised several PhD students. He published over 160 research papers, contributed several chapters and edited a Histopathology Atlas. He is also on the editorial board of several international journals. Abstract: In southern Pakistan ‘Oral Cancer (OC)’ is 2nd most common malignancy in both males and females with highest reported incidence in the world. In contrast to Europe, Australia, South America and Africa where smoking and alcohol are the prime risk factors, in subcontinent including Pakistan alternate chewing habits along with smoking are the main culprits. A common precursor lesions in our practice therefore is ‘Oral submucosal fibrosis’ aetiologically strongly associated with chewing of areca nut, which is recently being categorized by IARC as a human carcinogen. Biopsies usually are characterized by epithelial atrophy, keratosis & fibrosis. Dysplasia may or may not be associated. Other common precursor lesion encountered includes ‘Leukoplakia’. Recently it has been shown that ‘Human papillomavirus (HPV’ plays a significant role in carcinogenesis of OC and incidence of HPV association in white Americans is 9 times higher than black Americans. Interestingly HPV association with OC has been shown to be associated with good response to chemotherapy and radiation and prolonged overall survival, hence disparity in survival of white & black Americans. A similar study was conducted in Karachi, Pakistan however we did not find survival advantage although 2/3rd of the 140 cases contained predominantly HPV 16 genome. In view of the evidence from US studies that HPV status may be used as a prognosticator & predictor to stratify patients for treatment options, there is a compelling need for better understanding of the molecular pathogenesis in a large cohort of patients who are particularly at great risk. Preparing Scientific Manuscripts for Publication – Focus on the APJCP Malcolm Moore Ph.D Prof., Head, UICC Asian Regional Office, Chief Editor, Asian Pacific Journal of Cancer Prevention, Chief Editor APJCP, Head UICC Asian Regional Office, [email protected] Abstract: It is essential for the success of cancer control programs in the Middle East for scientists to be able to publish their research findings in the international literature, where they can be accessed though PubMed and other citation systems. To help younger scientists in particular, the Asian Pacific Organization of Cancer Prevention, and its official journal the Asian Pacific Journal of Cancer Prevention, have tried to promote a skeleton approach to writing papers, focusing on essential principles to maximise the ease of writing and hopefully impact of research results. Whether destined for submission to the APJCP, Clinical Cancer Investigation or any other international journal, it is of the essence that research projects and manuscripts are well designed, following instructions to authors and avoiding obvious pitfalls. My own 30 years experience of helping German, Japanese and now other Asia scientists write papers is here condensed to hopefully provide clues to acceptance by reputable journals specialising in the cancer field. 52 53 Day 2: Oral Presentations Session 1: Infection and Cancer O 1.1 Infection and Cancer Skin cancer and cutaneous blastomycosis Azhar A.F. Al-Attraqhchi*, Husam Hasson, Hiba Thamer Address: Al-Kadhimiyah/Baghdad/Iraq/College of medicine/Al-Nahrain University, Iraq Correspondence*:[email protected] Abstract Background: Blastomycosis is a pulmonary disease caused by inhaling spores of the dimorphic fungus Blastomyces dermatitidis, occasionally, the fungi spread hematogenously, causing extrapulmonary disease. Cutaneous blastomycosis are common on the face, extremities neck and scalp as the infection spreads from the lungs to other parts of the body. Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. Basal-cell carcinoma is the most common type of skin cancer. Aim: This study was conducted to relate between cutaneous blastomycoses and skin cancer, we found that there were two cases of blastomycoses with basal cell carcinoma. Materials and methods: Skin biopsies were obtained from one hundred patients with verrucous, ulcerative and noduler lesions. Controls included skin debris of 10 apparently healthy individuals. Bbiopsies were processed for histopathology or cultivated in agar. Results: According to the type of lesion, the patients distributed into three groups of clinical presentations which are: 1) verrucous lesions; 2) ulcerative lesions; and 3) noduler lesions. According to histopathology only eight samples (8%) out of 100 were positive, revealed (budding yeasts), which were the same of that culture results. A 51 and 75 years old males with verrucous and ulcerative lesions, respectively, one in the face and the other on his leg, both showed skin cancer (basal cell carcinoma) superimposed with blastomycosis. Key words: Blastomycosis, skin cancer O 1.2 Infection & Cancer Studies on the genomic association between Schistosomiasis and HCV infection Akram M. Abouzied1, Rasha H. Soliman2, Tarek M. El-Beltagy1, Hekmat M. Tantawy1. 1 Zoology Department, Faculty of Science, Suez Canal University, Ismailia, Egypt Department of Parasitology and Laboratory Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt 2 Correspondence: Dr. Akram K. Abouzied Faculty of Science, Suez Canal University, Ismailia, Egypt, e-mail: [email protected] 54 Abstract Background: Hepatitis C virus (HCV) infection and schistosomiasis are major public health problems in the Nile Delta of Egypt. Studies done in Egypt found the highest risk of HCV infection in whom infested with schistosomiasis. Moreover, HCV-Ab prevalence reported to be more than 70% in adults suffering from schistosomiasis. HCV is a leading stage cause of end-stage liver disease. Co-infection with schistosomiasis leads to faster progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). Aim: The overall aims of the studies described in this work were: 1) to gain knowledge of whether HCV infections could be trasmitted by Schistosoma mansoni to human and 2) to assess whether or not a genomic association between schistosomiasis and HCV infection. Methods: We screened the genomic DNA libraries of Schistosoma mansoni based on PCR by using two oligonucleotide specific primers of HCV RT-PCR diagnostic kits. Results and Conclusion: This work increases our knowledge of the existence of HCV genome in the genomic DNA of Schistosoma mansoni. In addition, it highlights the genomic association between schistosomal infestation and HCV infection. O 1.3 Infection & Cancer Hepatitis B and C viral forms in a group of patients with hepatocellular carcinoma in hepatitis C hyper endemic region, Egypt Abdel Raouf Abou El Azm MD1, Hassan El-Batae MD 1, LobnaAbou Ali MD 1, Maali MabroukMD 2, Hussien Ghorabah PhD3 , Amr El Badry MD 4. Department of Tropical Medicine and Infectious Diseases 1, Clinical Pathology 2, Pathology3, Radiology4, Faculty of Medicine, Tanta University, Egypt Corresponding author: Prof. Dr Abdel RaoufAbou El Azm. E-mail: [email protected] Abstract Background: The rate of hepatocellular carcinoma (HCC) is increasing worldwide. The major risk factors are chronic hepatitis B and C (HBV and HCV). Co-infection and occult-B are generally believed to be factors favoring progression of liver fibrosis towards cirrhosis and HCC. Occult HCV infection is a new form of HCV. Egypt is highly endemic with HCV. Aim: to investigate the incidence of HBV, and HCV viral forms associated with HCC and their carcinogenic potential in our area. Patients and methods: Sixty three consecutive patients with HCC and 54 with cirrhosis were selected in addition to 54 apparently healthy controls. Sera were tested for HBsAg and HCV-antibodies by ELISA, HCV-RNA and HBV-DNA for patients negative for HBsAg using(PCR) and occult-C by liver biopsy. Results: HCC patients proved 100% HCV infection (positive serum RNA in 85.7% and 14.3% occult-C), HBV co-infection 38.1% of which 28.57% occult-B. Cirrhotic patients showed 11.11% non-viral cirrhosis, 88.89% HCV (positive serum RNA 77.77%, and Occult-C 11.11%), of which 16.66% co-infection while occultB 11.11%. Controls showed 5.56% HCV RNA. There was an insignificant increase in coinfection, occult-C and occult-B in HCC patients as compared to cirrhosis and significant increase in HCC and cirrhosis as compared to control. Conclusion: HCV infection alone or in co-infection is the main cause of HCC in our region. Occult-B seemed higher 55 prevalence andamplify HCC risk than occult-C. HBV is under estimated. The study can give a better strategy for primary, secondary prevention of HCC and control of both viruses. O 1.4 Infection & Cancer Hepatocellular carcinoma is it a preventable disease? Abdel RaoufAbou El-Azm Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, EGYPT Prof. Abdel RaoufAbou El-Azm, e-mail: [email protected] Abstract Liver cancer incidence rates have been rising rapidly in the past decade. There are several reasons for this spike in prevalence, many of which are preventable.HCC has a poor prognosis. Itcauses death 6 months-1 year from diagnosis and is considered a preventable disease rather than a curable one. It can be prevented by public health measures that reduce exposure to known risk factors for this disease.HCC prevention appears to be a cost-effective public health strategy in at-risk populations and is preferable to HCC surveillance as a cancer control. HCC is a disease of multi-factorial etiology and developed in multistep process. It is the result of an accumulation of risks which will be discussed. O 1.5 Infection and Cancer Increases in the frequency of myeloid-derived immunosuppressor cells in Egyptian patients with chronic hepatitis C virus 1 2 Mohamed Labib Salem (PhD), 2Abdel Raouf Abou Al-Azm (MD), 3Maha Aldemelaawy (PhD), Hasan Albate (MD), 4Mohamed Attia, 1Mohamed Abou Senna (BSc) 1,4 Zoology Department, Faculty of Science, Tanta University, Egypt Department of Tropical Medicine, Faculty of Medicine, Tanta University, Egypt 3 Biomedical technology Department, City of Scientific Research and Applied Technology, Egypt 4 Department of Clinical Pathology, Faculty of Medicine, Tanta University, Egypt Correspondence: Prof. Mohamed L Salem, [email protected] (01274272624) 2 Abstract Background: Clearance of hepatitis C virus (HCV) infection depends on functional immune cells, including myeloid cells. Suppression of immunity results in progression of the disease and the development of liver cancer. We have reported recently that cancer progression correlate with the emergence of an immunosuppressive population called myeloid-derived suppressor cells (MDSC). Similarly, HCV infection may also induce expansion of MDSC from myeloid precursors. Aim: the main aim of this study was to etermine whether the failure of chronic HCV patients to IFN-α therapy correlates with increases in the numbers of MDSC. Methods: about 25 patients were recruitedin this study in addition to 5 healthy controls. The patients were selected among those admitted at Tropical Medicine & Infectious Diseases, Tanta University, Tanta, Egypt. Patients were determined positive for HCV by measuring the HCV RNA level in their plasma 56 using commercial kit. A clinical protocol was approved by the Protocol Review Committee of the Faculty of Medicine, Tanta University Institutional Review Board and a written consent was obtained from subjects. Peripheral blood samples were collected from the patients before treatment with IFN-α or at multiple time points during the treatment. The frequency of the MDSCs in the PBMCs was analyzed by flow cytometry and characterized as Lin-HLA-DR-CD11b+CD22+ after staining with anti-human Lin, HLA-DR, CD11b, and CD33 mAbs. Results: The results clearly showed increases in the number of MDSCs in the PBMCs of about 8 patients. The increases in the numbers of these cells were independent of the number of weeks after IFN- α treatment. Conclusion: These data indicate to the role of MDSCs in the failure of the HCV patients from the treatment with IFN-α. These results open a new avenue to target these cells to improve the efficacy of IFN-α treatment. Keywords: HCV, IFN-a, MDSC, myeloid suppressive cells. O 1.6 Infection & Cancer High-risk HPV/Oncogene interaction & cancer progression Amber Yasmeen1,2, Andrew Darnel1,2, Amal Kassab1, Pierre-Yves Desprez3 & Ala-Eddin Al Moustafa*1,2,4,5 1 Segal Cancer Centre, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada; 2Department of Oncology, McGill University, Montreal, Quebec, Canada; 3California Pacific Medical Center Research Institute, San Francisco, CA 94115, USA; 4Department of Mechanical Engineering, Concordia University, Montreal, Quebec, Canada; and 5Syrian Research Cancer Centre of the Syrian Society against Cancer, Aleppo, Syria *Correspondence: DR. Ala-Eddin Al Moustafa; E-mail: [email protected] Abstract Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with more than 120 different types identified to date. HPVs are classified as high or low risk (HR or LR) depending on their potential to provoke cancer. Persistent infections with HR types of HPVs could present a major risk factor for the development of a variety of human cancers including cervical, colorectal, head and neck as well as breast cancers. However, HPV infection alone, with one type of HR-HPV, is not sufficient to induce neoplastic transformation of normal human cells; HPV-infected cells must undergo additional genetic alterations. Therefore, we investigated the association between E6/E7 oncoproteins of HR-HPVs and several oncogenes such as ErbB-2, Id-1 and Src in human head and neck, breast and cervical cancer. Our data showed that E6/E7 cooperate with these oncogenes to enhance tumor progression of these human carcinomas. Moreover, we reported the E-cadherin/catenin complex, which is an important regulator of normal adhesion in epithelial cells, is a major target of E6/E7/ErbB2, Id-1 and Src cooperation. Thus, in my presentation, I will talk about the interaction between E6/E7 of HR-HPV and 57 ErbB-2, Id-1 as well as Src and their outcome on the E-cadherin/catenin complex in human head and neck, breast and cervical cancers. Key words: HPV, ErbB-2, Id-1, Src, E-caderin/catenin complex, head and neck cancer, breast cancer, and cervical cancer Session 2: Theray (Preclinical Studies) \\\ O 2.1 Therapy (Prelinical Studies) In vitro and in vivo antitumor activity of novel 3D-organotin supramolecular coordination polymers based on CuCN and pyridine bases Safaa El-din H. Etaiw*(1), Ahmed S. Sultan (2) and Mohamed M. El-bendary (1) Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt (1) Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt (2) *Corresponding author. Dr. Mohamed M. El-bendary. E-mail address: [email protected], [email protected]. Tel: +01008043708 Abstract Two novel organotin supramolecular coordination polymers (SCP), namely, [Me3SnCu(CN)2.(EN)2], 1 and [Ph3SnCu(CN)2.(3-mpy)2], 2 are obtained by the reactions of K3[Cu(CN)4], ethyl nicotinate (EN) or 3-methylpyridine (3-mpy) and Me3SnCl or Ph3SnCl in H2O/acetonitrile solution at room temperature. 2D-layers are constructed via H-bonds between the parallel 1D-puckered chains which contain nanometer-sized [CN(R3Sn)NC-] spacers connecting the tetrahedral (T-4) copper sites. The network structures of 1 and 2 consist of infinite layers connected by interlayer H-bonds forming 3D-framworks. 2 is the first compound in this family containing the Ph 3Sn cation. The electronic absorption spectra of 1 and 2 reveal a broad band at 320 nm due to CT transition while the emission spectra exhibit high energy bands at 400-460 nm due to metal-centered (MC) transitions and low energy bands at 485-530 nm corresponding to MLCT. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the in vitro antitumor effects of the SCP 1 and 2 on human breast cancer cell line, ZR-75-1. Cell cycle analysis revealed that the SCP 1 and 2 induced apoptosis in ZR-75-1 breast cancer cell line through activating caspase-3. Moreover, in vivo model, the compound SCP 2 suppressed tumor growth developed mammary carcinoma by 52.3%. Taken together, our novel compounds selectivity exhibit specific in vivo and in vitro antitumor effects. Key words: Organotin supramolecular coordination polymer, Copper Cyanide, pyridine bases, Hydrogen bonds, in vitro/ in vivo antitumor activity. 58 O 2.2 Therapy (Prelinical Studies) Targeting Clusterin by small interference RNA sensitizes cervical cancer cells to hyperthermia 1 1 Mohamed K. Hassan,1 Ali Hussein Abo-Almaati, 2Hidemichi Watari, 2Noriaki Sakuragi. Biotechnology program, Zoology Department, Port Said University, Egypt Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University Sapporo, Japan. Correspondence: E-mail: [email protected] 2 Abstract The cytoprotective chaperone protein, Clusterin (CLU), has been reported to be involved in carcinogenesis and tumor growth, including apoptotic cell death, cell cycle regulation, DNA repair, cell adhesion, tissue remodeling, lipid transportation. Here, we investigated how human cervical cancer cells escaped from hyperthermia. Treating Hela cell line with hyperthermia (42.5oC) induced cytostatic arrest in the G2/M phase without prominent apoptosis. Hela cells, which have negative P53, expressed quite large amounts of wild type Bax which up-regulated after hyperthermia. Western blotting analysis indicated that Clusterin expression was up-regulated upon hyperthermia treatment and that upregulation was maximum one-day after hyperthermia treatment. Transfection of siRNA specifically targeted CLU into Hela cells resulted in Bax-induced apoptosis by hyperthermia 2-3 times more than control siRNA transfectant as detected by FACS and Annexin V staining independent of P53. Interestingly CLU-KD cells did not show the same cytostatic arrest as well as control cells but were directed into cytotoxic G1 arrest followed by apoptosis. Taken together, our data indicate that CLU-based cellular protection from heating is cell cycle dependent. Disturbing this protection mechanism is a possible approach to enhance the therapeutic efficacy of hyperthermia. Abstract 2.3 Therapy (Prelinical Studies) Vitamin C and diallyl sulfide as chemo-sensitizers to cisplatin in treating hepatocellular carcinoma Abdel-Hamid, NM *1, Nazmy, MH 1and Nazmy, WH 2 1 Biochemistry Department, Faculty of Pharmacy and 2Physiology Department, Faculty of Medicine, Minia University, Egypt Correspondence: Prof. Abdel-Hamid,Nabil Mohie.PhD , Department of Biochemistry, Faculty of Pharmacy, Minia Univ, Egypt.. Mobiles: +201006426998, +201227300491 and +201121830691. Land Phone: +20506913997. E-mail: [email protected] Abstract Background: The resistance to chemotherapy is a major obstacle in the treatment of hepatocellular carcinoma (HCC), necessitating the discovery of additional agents. The use of natural products in this respect is extensively under investigation. Aim: This work aims to check if naturally occurring materials can help in improving response to CP chemotherapy and if ploylol profile can assist in more accurate HCC detection. Materials and Methods: Two hundred and ten male albino rats were used, divided into 14 groups. Selected groups were pre-treated with vitamin C (ascorbic acid, AA) and/or diallyl sulphide (DAS). Hepatocarcinogenesis was initiated by a single intra-peritoneal 59 (IP) injection of diethyl nitrosamine (DENA), diabetes was induced by a single IP injection of Streptozotocin (STZ). Other groups were treated with cisplatin (CP) alone or combined with AA and/or DAS for 14 weeks. Results: The results revealed that DENA significantly increased relative liver weight, serum ALT, AST and GGT activities, AFP, TNF-α and IL-6 levels, expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and Bcl2 proteins in the liver with decrease in body weight, expression of Bax protein and Bax/Bcl2 ratio in the liver. These effects were more pronounced in DENA+STZ group. These parameters showed relative correlation to AFP levels in HCC, in response to AA and/or DAS treatment except for SDH. Treatment with CP and/or AA and/or DAS significantly modulated most of these parameters except for SDH which showed no significant change in response to the suggested treatment. Conclusion: In conclusion, AA and/or DAS showed apparent chemo-sensitizing, anti-inflammatory, AR inhibitory, apoptotic inducing and anti-diabetic activities, indicating new aspects for use as adjuvant to chemotherapy. Induction of diabetes in hepatoma-bearing rats showed higher resistance to chemotherapy. The suggested biomarkers are useful prognostic tools in HCC patients with diabetic background. Keywords: Ascorbic acid, Chemo-sensitization, Diabetes, Diallyl sulphide, Hepatocellular carcinoma, Diethyl nitrosamine. O 2.4 Therapy (Prelinical Studies) Phosphonopeptides synthesis using α-aminophosphonates and their antimicrobial and anticancer activities Mohamed F. Abdel-Megeeda,*, Badr E. Badrb, Mohamed M. Azaama a Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt. Department of Botany, Faculty of Science, Tanta University, Tanta, Egypt. Correspondence: Dr. Mohamed F. Abdel-Megeed: Tel.: +20104694523; Fax: +23344352 E-mail address: [email protected] b Abstract A series f novel phosphenopeptides using α-aminophosphonates derivatives has been synthesized. The antimicrobial activities against Escherichia Coli (NCIM2065) as gramnegative bacteria, Bacillus Subtitles (PC1219) and Staphylococcus aureus (ATCC25292) as gram-positive bacteria, Candida albicans and Schccaromycies cerevisiae as fungi showed high activities at low concentrations (10, 50, 100µg/ml). Furthermore, anticancer activity against human colon carcinoma cell line (HCT116) was also carried out and all compounds showed significant cytotoxicity (IC50:13.7, 7.5, 5.9, 15.9, 9.1, and 9.4 µg/ml). The lethal dose of the synthetic compounds was also determined (1000, 843, 100, 67, 175 and 100µg/ml) which indicated that some of these compounds are safe and less toxic. 60 O 2.5 Therapy (Prelinical Studies) Anti-tumor activity of some 1, 3, 4-thiadiazoles and 1, 2, 4-triazine Derivatives against Ehelishs Ascites Carcinoma Ahmed EL-Barbary, L-Naggar and Shaimaa Talat Chemistry Department and Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt Correspondence: Prof. Ahmed EL-Barbary, Prof. of Organic Chemistry, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt. E-mail: [email protected] Abstract Recently, identifying new chemo-preventive agents to replace the current chemotherapies consider one of the most important approaches which could be crucial for cancer treatment. The present study was conducted to evaluate the anti-tumor activity of some newly synthesized heterocyclic 1, 3, 4-thiadiazoles and1, 2, 4-triazine derivatives. Different groups of mice were inoculated with Ehrlish Ascetic Carcinoma cells (EAC) intra-peritoneal (i.p) (2x10^5 cells mouse -1). After one day of inoculation, mice were treated either with cisplatin (reference drug) or with twenty five different new derivatives of 1, 3, 4-thiadiazoles or1, 2, 4-triazine. The anti-tumor activities of these derivatives against EAC-bearing mice were monitored through he changes in the total body weight. Total ascetic volume, the number of live and dead tumor cells, median cervical time (MST) and some biochemical parameters. The results showed that only five compounds of1, 3, 4-thiadiazoles significantly inhibited the tumor progression after 14 days of the treatment. Interestingly, two of these compounds increased the life span of tumored mice by 34 and 40% when compared with the untreated group.incontrast, all 1, 2, 4-triazine derivatives did not show any potential anti-tumor activity against EAC-model. In conclusion, screening of1, 3, 4-thiadiazoles derivatives did not show any marked antitumor activity. O 2.5 Therapy (Prelinical Studies) The curative effect of Cymbopogon citrates volatile oil against chlorambucil drug toxicity Islam M. El Garawani Researcher of Molecular Biology and Genetic Engineering, PhD. National Organization for Drug Control and Research, MHP e-mail: [email protected] Abstract Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer agent and as an immunosuppressant. Its chemical structure and clinical experience indicated its mutagenicity, teratogenicity and carcinogenicity. The aim of this study is to investigate the curative effect of oral treatment with lemongrass (Cymbopogon citratus) essential oil (75 mg/kg) against damage induced by chlorambucil (7.5 mg/kg) administration in rats. The results of our study revealed that the presence of good improvement in spleen genomic DNA and total protein evaluated by SDS-PAGE after 15 days. In addition, the excellent improvement also was evaluated by alkaline single cell gel electrophoresis 61 (SCGE)/comet assay for lymphocytes from rats' blood after 48 hours of treatments with the same doses of chlorambucil and Cymbopogon citratus. Our findings indicated that lemongrass essential oil provided a good curative effect against chlorambucil possible hazardous effects. Session 3: Medicinal Plants O 3.1 Medicinal Plants Gene profiling cDNA microarray analysis of rat colon carcinogenesis treated with crude Nigella sativa oil Elsayed I. Salim, Ph.D., D.M.Sc. Ass. Professor of Toxicological pathology & MolecularCarcinogenesis, Zoology Department, Faculty of Science, Tanta University, Tanta-31527- Egypt Asian Pacific Organization for Cancer Prevention (APOCP) E-mail: [email protected], [email protected] Telefax: (+20) 040 3350804, Cell: (+20) 01220177760 Abstract It was recently shown that Nigella sativa (N. Sativa) extracts can exert significant modulatory effects on different pathological, toxicological and cytotoxic protocols in vitro and in vivo. Studies from our laboratory and others have also shown inhibitory effects on tumor formation by N. sativa in different animal carcinogenesis bioassays including colon cancer. The present experiment was designated to evaluate the candidate genes possibly involved with N. sativa inhibitory effects on colon carcinogenesis in post initiation phase. 20 male rats were administered two consequent injections of 1,3dimethylhydrazine (DMH) (20 mg/kg b.wt) subcutaneously, once a week at the beginning. The first group (10 rats) received 200 mg/kg of fresh N. sativa oil daily by i.g. for eleven weeks after cessation of the carcinogen administration, while the second control group (10 rats) had no treatment after DMH administration. Repeated genetic 3DcDNA microarray analysis pointed out mainly to 19 genes to be significantly changed in the colonic mucosa after N. sativa treatment either by up or down-regulation. Interestingly, these genes encoding transcription factor activity, regulation of cell cycle, signal transduction, xenobiotic metabolism, apoptosis, DNA repair and lipid transport and metabolism. Real-time reverse transcription-PCR (RT-PCR) analysis confirmed the altered expressions of some dedicated genes after N. sativa treatment. These data point out to the involvement of N. sativa oil in many genetic pathways particularly those concerning cell cycle, apoptosis, DNA repair and xenobiotic metabolism in response to oxidative stress. These results could explain the genetic mechanism of action of N. sativa oil in inhibiting colon carcinogenesis in rats. 62 O 3.2 Medicinal Plants Cytotoxic effects of aqueous , methanolic and secondary metabolites extracts of Capparis spinosa fruit on tumor cell lines in vitro Asaad Abdulwahed, Bader, AL-Asady, Khesar, Husen, Khalil and Sa’adi Saleh Mohammed Barwari University of Duhok ,Faculty of Medicine , School of Medicine, Dept.of Anatomy Duhok, Iraq Correspondence: Dr. Asaad Abdulwahed [email protected] Abstract The present study aims to prepare two types of extracts; (methanolic and aqueous) crude extracts and (polyphenol and rutin) secondary metabolite extracts of immature fruit of Capparis spinosa to evaluate the cytotoxic effects of all these extracts on Human larynx carcinoma (Hep-2) and Human cervix adenocarcinoma (HeLa) tumor cell lines in vitro. The results of present study showed that the yield of extraction % of methanol and aqueous crude extracts;16.1% and 15%,respectively,whereas that of polyphenol and rutin secondary metabolite extracts were 12.7% and 12.1% ,respectively. The results revealed that the more effective extracts against the proliferation of Hep-2 tumor cell line was aqueous extract after 24 hrs treatment. After 48hrs treatment each of methanol, aqueous ,and rutin was more effective than polyphenol extract. All types of immature fruit extracts had CC50 values on Hep-2 cell line > 10000μg/ml for both periods of exposure. The present study revealed that the effect of both methanol and rutin on proliferation of HeLa cell line after 24 hrs treatment were more than that of aqueous and polyphenol extracts. After 48hrs treatment the activity of methanolic extract and aqueous against the proliferation of HeLa cell line more than that of polyphenol and rutin, the values of CC50 on HeLa cell line treated with methanol extract after 48hrs was 9700 μg/ml. Aqueous extract was more effective after 48hrs than 24 hrs. The present study shows that HeLa tumor cell line was more effective than Hep-2 tumor cell line. O 3.3 Medicinal Plants Oxidative stress biomarkers in young male rats fed with stevioside Hala A. Awney Lab. Environmental Toxicology, Department of Environmental Studies, Institute of Graduate Studies & Research, Alexandria University, 163 Horreya Ave., El-Shatby 21526, P O Box 832, Alexandria, EGYPT. Email: [email protected] Abstract Stevioside is a natural non-caloric sweetener refined from Stevia rebaudiana Bertoni leaves. The introduction of stevioside as a sugar substitute in the diets of diabetics and others on carbohydrate-controlled diets has been suggested, but safety issues have prevented implementation. The aim of this study was to examine antioxidant status changes in the sera, livers, kidneys and brains of young male rats fed with low doses of stevioside (SL) or high doses of stevioside (SH) for 12 weeks. We investigated oxidative stress biomarkers such as the levels of total antioxidant capacity (TAC), reduced 63 glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR). Our results show that SH treatment causes significant induction of TBARS in liver, kidney and brain, accompanied by a significant reduction in TAC, SOD, CAT, GR and GSH levels in the same organs. SL treatment causes insignificant changes in TAC, SOD and CAT, but significant reduction was observed in GR, GSH and TBARS in serum and all tested organs when compared with the control. In conclusion, features of oxidative stress were detected in the liver, kidney and brain of young male rats treated with SH for 12 weeks, whereas no significant changes in TAC, SOD and CAT were detected after SL treatment. Keywords: Stevioside; safety, sweeteners; food safety; oxidative stress biomarkers O 3.4 Medicinal Plants Berberis vulgaris new extract: A new solution for HCV genotype 4 infection Doaa A. Ghareeb1, Eiman H. El-Wakeel2, Maha A. El-Demellawy3, Marwa Abo Sariaa3 1Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt 2 Microbiology and Botany Department, Faculty of Science, Alexandria University, Alexandria, Egypt. 3 Biomedical technology Department, City of Scientific research and Applied Technology, Egypt Correspondence: Dr. Doaa A. Ghareeb, e-mail: [email protected] Abstract Hepatitis C virus (HCV) infection is a global public health problem that affects almost 3% of the world's population with a morbidity and mortality that are second only to HIV among the emerging infections. The conventional antiviral regimen is a combination therapy of pegylated Interferon (INFα) and the nucleoside analogue ribavirin, but only 40% to 50% of patients who can complete the 6- to 12-month treatment have a sustained virologic response. Also, it is too expensive for use in most underprivileged countries. Because, Berberis vulgaris has shown a number of beneficial effects including immunostimulation and macrophage activation, we screened Berberis vulgaris new extract (BCE) anti HCV activity in vitro comparing to its active ingredient Berberine chloride (BRB). Peripheral blood lymphocytes (PBLs) of healthy donors were isolated by Ficoll gradient centrifugation. Purified PBLs were co-cultured with HCV-infected serum in RPMI culture medium for 24 hours. To investigate in vitro interactions, BER or BCE was added at serial dilutions of 1-300 ug/ml. INFᵧ and interleukin 12 (IL12) levels in culture supernatants were measured by ELISA. Also, RNA was detected in PBLs lysates by nested HCV RT-PCR and the products were resolved on 2% agarose gel. The PBLs IC 50 of BRB and BCE were 600 ug, and 900 ug, respectively, after 24 hours incubation. Significant alterations in PBLs distribution were identified; where BRB and BCE enriched the PBLs count by 2, and 3 folds, at a dose of 100ug/ml. At the same dose in culture supernatants, BCE activated INFᵧ by 2 fold, and induced IL-12 secretion by 3 fold, while BER did not. mRNA expression revealed similar patterns. Furthermore, BCE treatment led to 174 bp band disappearances, which is an indication for viral RNA, while BER treatment did not.These findings suggest that BRB does not account as anti HCV, 64 while BCE successfully blocks viral entry into PBLs, which was indicated by 174 bp band disappearance. The mechanism by which BCE works,, is that it functions as a part of the host innate immune defense mechanisms Thus, further studies are needed to define the precise mechanisms of viral clearance. O 3.5 Medicinal Plants Interrelation of anticancer and antioxidant effects of some Egyptian plants and their phenolic constituents N. M. Abdel-Hady, Gouda T.M. Dawoud* and **A. A. El-Hela Pharmacognosy Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt * Phytochemistry Dept. Medicinal Plant Center, NODCAR **Pharmacognosy Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt Correspondence: Dr. Nevein Abdelhady: E-mail: [email protected] Abstract Cancer is a dreadful human disease, increasing with changing life style, nutrition, and global warming while current available potent anticancer drugs cause serious side effects in most instances. Plants are considered to be the most potential resource of anticancer agents; they are diverse, largely productive, biologically active and chemically unique offering great scope for discovery of new anticancer drugs. Several reports suggested that the relationship between their anticancer effect and their antioxidant character; they suggested that most of them act through promoting host resistance against various diseases, restabilizing body equilibrium and conditioning body tissues as well. Polyphenolic content of such plants is a determinant factor in evaluating their pharmacological effects as they displayed an array of pharmacological properties as antioxidant, immunostimulant and antitumour activities. This paper is conducted on this aspect with a view to provide more information about the anticancer effect of a chosen twenty-three Egyptian medicinal plants interrelated with their antioxidant effect and polyphenolic content screening for cheaper, safer and potent natural anticancer to challenge this dreadful human disease. O 3.6 Medicinal Plants The mushroom extract from Pleurotus ostreatus inhibits cell proliferation of HepG2 cells and protects rats from liver damage induced by dimethylnitrosamine carbontetrachloride Nihad Abdelmoneim1, Muhammad El-Saadani1, Eiman Aleem2, Ayman Daba3, Samar Saleh1 1 Alexandria University, Faculty of Science, Department of Biochemistry, 2Alexandria University, Faculty of Science, Department of Zoology, Division of Molecular Biology, Moharram Bey 21511, Alexandria, Egypt, 3City for Scientific Reseasrch and Technology Application (MuCSAT), Genetic Engineering and Biotechnology Research Institute, New Borg El Arab, Alexandria, Egypt Correspondence: Dr. Eiman Abdel Aleem, Department of Zoology, Division of Molecular Biology, Faculty of Science, Alexandria University, Alexandria, Egypt, E-mail: [email protected] Abstract Medicinal mushrooms have been shown to improve cardiovascular health and stimulate immune function. The oyster mushroom Pleurotus ostreatusis one of the widely cultivated edible mushrooms. The aim of the present study was to investigate the protective effect of polysaccharide-protein (PSP) complexes isolated from the oyster mushroom against Diethylnitrosamine/Carbon tetrachloride-induced hepatotoxicity in 65 vivo and its antiproliferative effects in vitro using HepG2 cells. We isolated and partially purified PSP from the culture broth of P. ostreatus mushroom and determined its chemical and physico-chemical properties Treatment of HepG2 cells with PSP inhibited cellproliferationwith an IC50 of 0.54 µg / ml.We induced liver injury in rats using DENA/CCl4 for 14 weeks. The rats were divided into the following groups and received: (I) only DENA/CCl4, (II) DENA/CCl4+PSP 30 mg/kg for 14 weeks, (III) DENA/CCl4 followed by PSP only at the last four weeks of the experiment, (IV) PSP only for 14 weeks, (V) PSP for the last 4 weeks, (VI) only saline. PPP protected and treated the rats against hepatic injury induced by DENA/ CCl 4and induced an increase in superoxide dismutase and glutathione-S-transferase, decrease in hepatic lipid peroxidation, and in the activity of liver enzymes, as well as total cholesterol in comparison to the group with liver toxicity. Furthermore, PSP treated the histopathological changes induced by DENA/ CCl4(fibrosis, necrosis, macrosteatosis and inflammation). We conclude that PSP extract from the oyster mushroom isanatural and inexpensiveway to improve the body’s defence against oxidative stress. Session 4: Epidemiology O 4.1 Epidemiology Is cancer a major problem in Egypt? Nadira Mansour Professor of Public Health and Community Medicine, Faculty of Medicine ,Tanta University Epidemiology can answer this question. It helps us in knowing the magnitude, distribution and determinants of this problem. Also, it is the first step that paved the way for the health planner to take the correct actions to solve the problem. The National population Based Cancer registry for Egypt and Gharbiah population based cancer registry are good efforts that can be used as guides in dealing with cancer problem in Egypt. O 4.2 Epidemiology Brief overview cancer epidemiology in the Middle-East – pointers to research priorities Malcolm Moore PhD, Head, UICC Asian Regional Office, Chief Editor, Asian Pacific Journal of Cancer Prevention; Chief Editor APJCP, Head UICC Asian Regional Office. Correspondence: Prof. Malcolm Moore <[email protected]> 66 Abstract South-West Asia, stretching from Lebanon and Syria in the north, through to Yemen in the south and Iraq in the east, and the North-Western and Central region of Asia, from Turkey through Iran to the Central Asian republics, are home to more than 500 million people. Cancer is already a major problem and will only become heavier over time, especially with aging of what are now still youthful populations. There are a number of active registries in the region and population-based data are now available for a considerable number of countries, highlighting both similarities and variation in the different cancer types. In males, the most prevalent cancers vary, with lung, urinary bladder or liver in first place in the Arab world and Turkey, but stomach in most of Iran and Central Asia, followed by the oesophagus. For females throughout the region breast cancer is the major problem, with cervical cancer relatively rare. In both sexes, nonHodgkins lymphomas and leukemias are important in Arabia. General tendencies for increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer point to change in environmental influence over time. Variation in risk factors depends to some extent on the level of economic development but also different cultural influences which have obvious interest for cancer epidemiology research. Overall the countries of the region face similar challenges in achieving effective cancer control, underlying the necessity for cooperation. Conclusion: Although the demographics and clinical characteristics of children with ALL are similar to those reported elsewhere but the outcome even at this early phase appears suboptimal. O 4.3 Epidemiology Lung cancer incidence in the Arab league countries: perspectives of risk factors and control Elsayed I. Salim1,2 Malcolm Moore2, Abdulrahman Jazieh3, 1 Ass. Professor of Toxicological Pathology & Molecular Carcinogenesis, Zoology Department, Faculty of Science, Tanta University, Tanta-31527- Egypt Asian Pacific Organization for Cancer Prevention (APOCP) E-mail: [email protected]; [email protected] Telefax: (+20) 040 3350804, Cell (+20) 01220177760 2 Asian Pacific Organization for Cancer Prevention (APOCP), UICC-ARO regional Office, [email protected]. 3 Oncology Dept., Cancer Center, King Abdulaziz Medical City-Riyadh. Saudi Arabia, [email protected] Abstract Lung cancer incidence, the most common cancer worldwide, is gradually increasing in the Arab world, 15 out of 22 Arab countries have lung cancer as the most common cancer in males. Also the forthcoming prediction of estimated numbers of new lung cancer cases in the Arab world shows a gradual increase every year. Population growth, aging, increased smoking prevalence particularly in youth and women, as well as increased 67 exposures to environmental pollutants in the region may play a critical role. Also the frequency of different histological types of lung cancer shows a shift towards squamous cell carcinomas in males and adenocarcinomas in females. This histological trend has changed in the last two decades in USA and Eastern Europe reflecting changes in patterns of tobacco consumption, the latter is increasing in the Arab world. The comparison between the tobacco prevalence and lung cancer incidences in the Arab populations reveals an obvious risk in most Arab countries for example in Bahrain, Tunisia, Algeria, Morocco and Libya for males, and Lebanon for both sexes, however, some Arab countries with high smoking prevalence had either low lung cancer incidence rates (Yemen, Sudan and Djibouti), or moderate incidence rates such as Egypt, Syria and most of the Gulf Cooperation Council (GCC) countries except Bahrain. In contrast to the high incidence and mortality rates of lung cancer in African Americans over Caucasians in the USA, the African Arabs in Mauritania, Somalia, Djibouti and Comros besides Yemen show the lowest incidence and mortality rates in the Arab countries. The underlying mechanisms for this trend warrant interest. There is a great need for networking all the cancer research data in the Arab region. This will be certainly of high advantage to the region and the world. O 4.4 Epidemiolog Health in the West Bank, occupied Palestinian Territory: Cancer mortality pattern assessment, 1999-2000 Niveen Abu-Rmeileh, PhD1, Emilio Antonio Luca Gianicolo, MS2, Suzan Mitwali, MPH1, Maurizio Portaluri3, Antonella Bruni, MS2, Jawad Bitar, MD4, Mutaem Hamad4,Maria Angela Vigotti2, Rita Giacaman1 1. Institute of Community and Public Health- Birzeit University, Occupied Palestinian Territory. 2. Institute of Clinical Physiology of the National Research Council, Italy. 3. Radiotherapy Dept. "Perrino" General Hospital, Brindisi, Italy 4. Health Information Management Centre- Ministry of Health, Occupied Palestinian Territory Correspondence: Dr. Niveen Abu-Rmeileh [[email protected]] Abstract Background: The burden of cancer is increasing worldwide, both in developed and developing world. The situation in the occupied Palestinian territory is not different. This study aims to study mortality patterns of cancer types in the different governorates in the West Bank. Methods: The study is based on death certificates collected for Palestinians living in the West Bank, occupied Palestinian territory for the period between 1999 to 2009 by the Palestinian Ministry of Health Information Centre. Results: The quality of data was judged based on the completeness and proportion of ill-defined diseases as cause of death. The most common cause of death out all cancer types was lung cancer among males and breast cancer among females followed by colo-rectal cancer in both males and females. There were regional variation in cancer specific causes of death. The central governorates had the lowest standardised mortality rate for most cancer types for both men and women. Lung cancer standardised mortality rate was highest in the north among men, prostate cancer standardise mortality rate was highest in north and south. Breast cancer standardized mortality rate was highest in the south, as was female genital organs standardized mortality rate. Conclusion: The study documents regional variation in deaths due to cancer. The observed variation might be explained by personal, 68 contextual and environmental factors that need to be investigated in depth to correctly inform policy maker. O 4.5 Epidemiology Is risk malignancy index a useful tool for predicting malignant ovarian masses in developing countries? Dr. Aliya Aziz, Dr. Nida Najmi Department of Obstetrics & Gynecology, Aga Khan University Hospital, Karachi, Pakistan Correspondence: Dr. Aliya Aziz, E-mail: [email protected] Abstract Introduction: Risk of malignancy index has been widely studied for prediction of malignant pelvic masses in western population, however, little is known regarding its implication in the developing countries. The objective of this study is to determine how accurately the RMI can predict the malignant pelvic masses. Materials & Methods: This was a retrospective review of charts conducted at The Aga Khan University Hospital, Karachi, Pakistan. Those patients who came to the Gynecological clinic between January 2004 to December 2008 with adnexal masses were identified by means of IDC-9CM coding system. The files of these patients were reviewed for collecting information related to demographic characteristics, ultrasound findings, menopausal status, CA 125 and histopathology. Patients with advanced stage disease were excluded. The RMI for each of these patients were calculated based on the standard formula. Results: A total of 283 women were included in the analysis. When analyzing the individual parameters of RMI, the best predictor for malignancy was ultrasound with the sensitivity, specificity and positive likelihood ratio of 78.3%, 81.5% and 4.2 respectively. The positive likelihood ratio of RMI at the standard cut off value of 250 was 8.1 while at the cut off of 200; it was 6.8 with comparable sensitivity and specificity. Conclusion: RMI is a sensitive tool in predicting malignant adnexal masses. A cut off of 200 may be suitable in developing countries for triaging and early referrals to tertiary care centers. O 4.6 Epidemiology Fertility preservation in young female cancer patients Mohamed Salama Gad Professor of Obstetrics and Gynecology Menoufiya University, Egypt E-mail: [email protected] Abstract For some patients, especially young women, loss of fertility after cancer treatment is almost as painful as facing the disease itself. Variables to be considered before treatment include patient’s age, cancer type and stage, proposed treatment regime and time before it is initiated, availability of partner sperm. All these data along with fertility preservation strategies, ovarian protection, and ovarian preservation will be discussed. 69 Session 5: Cancer Genetics Abstract 5.1 O 5.1 Cancer Genetics Cancer Genetics Molecular Mechanisms of Liver Cancer Mehmet Ozturk, PhD Prof., Department of Molecular Biology and Genetics Mehmet Ozturk, Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey INSERM-UJF Centre de Recherche U832, InstitutAlbert Bonniot, Grenoble, France Phone: (90)(312) 266 50 81 Fax: (90)(312) 266 50 97, Emails:[email protected],, [email protected] Biography Mehmet Öztürk, Professor of Molecular Biology and Director of Bilkent University Bilgen Genetics and Biotechnology Research Center in Ankara, is jointly affiliated with INSERM-UJF U832 Research Center as a Research Director. Profesor Öztürk, after graduating from Gazi University Faculty of Pharmacy, obtained a PhD degree in biochemistry from Paris XI University in 1985. From 1995 to 1992, he performed research on liver cancer in Harvard Medical School affiliated Massachusetts General Hospital in Boston. He became Assistant Professor of Biochemistry at Harvard Medical School in 1989. Profesor Öztürk was invited to create a molecular oncology unit Leon Berard Cancer Center in Lyon in 1992. He worked as an INSERM Research Director at this institution between 1992-1995. Upon invitation from Bilkent University, he moved to Ankara to create the Department of Molecular Biology and Genetics at this university. He worked as department head at Bilkent University until 2007, when he decided to take his present joint appointment position. The department he created was awarded in 2004 by Koc Foundation for its outstanding contributions to life sciences in Turkey. Profesor Öztürk is a molecular biologist working on genetic and biological foundations of cancer. He was awarded TUBITAK-TWAS Science Award, and elected as a member to Turkish Academy of Sciences, European Molecular Biology Organization and TWAS, The Academy of Sciences for the Developing World. He served as a UNESCO International Bioethics Committee Member between 1998-2001. Abstract: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancers. Worldwide, most HCCs are etiologically linked to chronic hepatitis due to Hepatitis B (HBV) and Hepatitis C (HCV) viruses. Chronic liver injury caused by viral infections or other factors such as alcohol appears as the driving cellular mechanism of hepatocellular carcinogenesis. Chronic liver injury is associated with different forms of cellular stress causing excessive hepatocyte death, and increased proliferation as a compensatory response. Chronic hepatitis, when it takes tens of years, drives liver tissue into a fibrotic process leading to cirrhosis. Cirrhotic hepatocytes display several landmark features of senescent cells such as shortened telomeres, increased levels of cyclindependent kinase inhibitors (CDKIs) and senescence-associated beta-galactosidase (SA-β-gal). More than 80% of liver cancers occur in cirrhotic patients. This suggests that liver cirrhosis is the primary cause of HCC. Tumor cells emerging from cirrhotic nodules display features indicative of their escape from senescence-mediated cell cycle arrest. Re-expression of telomere reverse transcriptase, inactivating mutations of p53, epigenetic silencing of CDKI p16, and lack of SA-βgal activity are the major indicators of senescence escape in HCC cells. Mechanisms of 70 uncontrolled proliferation of HCC cells are ill known. Oncogenic mutations of β-catenin gene associated with excessive cell proliferation are observed in a subset of HCCs. Increased phosphorylation of Akt suggests that tyrosine kinase receptors may also be activated. Therapeutic efficacy of Sorafenib, a protein kinase inhibitor drug, also suggests that tyrosine kinase signaling is overactive in these tumors. However, it is presently unknown whether this overactivity is due to a genetic mutation or not. Recent investigations aiming at finding additional mechanisms are being expanded to non-genetic mechanisms such as epigenetic aberrations. Experimental induction of liver cancer by methyl-deficient diet is a well-established concept. Recent investigations identified aberrant DNA methylation and histone changes in HCC. Most recently, inactivating mutations of ARID2, a chromatin remodeling gene, have been reported in one fifth of HCCs associated to HCV infection. Our unpublished data provide additional support for the implication of multiple epigenetic aberrations in liver cancer. Some of such epigenetic regulatory genes may serve as potential tumor markers, as well as drug targets for better management of liver cancer. O 5.2 Cancer Genetics Cellular and molecular analysis of human non-Hodgkin lymphoma subtypes Nasser Parsa, M.D., Ph.D. National Institutes of Health (NIH), Bethesda, MD. USA. Email: [email protected] Abstract Background: Non-Hodgkin’s Lymphomas (NHLs) are heterogeneous group of malignant tissues which originated from the lymphoid system. To evaluate the molecular and cellular alterations in malignant tissues, micro-array technology has been developed to provide us with a better understanding of pathogenesis of human cancers. Aim: Burkitt’s lymphomas (high grade) and Diffuse Large B-Cell Lymphomas (intermediate grade) were analyzed by microarray genomic profiling which led to an accurate reclassification of these Non-Hodgkin’s Lymphomas subtypes. Methods and Materials: Microarray based expression profiling was employed to examine approximately 100 Burkitt’s lymphoma specimens. With this technique, we can study the expression of thousands genes in one experiment. These tumors were already analyzed and reported by the conventional and pathological methods as high grade Burkitt’s lymphomas. Results: With the help of microarray which involves the hybridization of mRNA molecule to its cellular DNA (cDNA) template on a microchip, we were able to show a different gene expression which is only associated with DLBCL-lymphomas. After careful analysis of molecular and translational profiling of these tumors, we were able to demonstrate a different diagnosis which eventually will have an impact on the prognosis. Results: Specific genetic alterations associated with their protein expression led to the identification of several molecular markers to re-classify 75 out of 100 tumors from high grade Burkitt’s to intermediate grade of DLBCL-lymphomas. BCL2 and BCL-6 genes were two of the targeted genes that showed an over expression which is associated with DLBCL-lymphomas. DLBCL- patients respond to treatment remarkably and have a much better prognosis than the Burkitt’s lymphoma patients. Conclusions: Our knowledge of human cancers has originated from the developmental discoveries in cancer biology. The advanced molecular technology helped us to recognize the basic mechanisms of most molecular processes that govern the formation of a malignant tumor. 71 The RNA-microarrays and protein profiling of NHLs have revealed to us a better understanding of molecular pathogenesis of human lymphomas. Consequently, it provided us with an accurate diagnosis and followed by more specific and effective treatment. O 5.3 Cancer Genetics Application of interphase Flourescence In Situ Hybridization (FISH) in the aneuploidies studies of the spontaneous miscariages products Sarah Mellali (1), Latifa. Mohamadi (1), K. Haoud (1,2), S. Moulessehoul (1), Biotoxicology laboratory, Biology department, Science Faculty, University Djillali liabes Sidi bel abbes , Algeria. (2)Medical cytogenetic service, Medical University, Clermont-Ferrand; France Dr. Mohamdi Latifa: [email protected]; [email protected] Abstract The spontaneous miscarriage is one of the most common complications of pregnancy; actually this type of loss represents 10 to 20% of all recognized pregnancies. The genetic causes explain 2/3 of these pregnancies failures. Indeed the fetus karyotype abnormalities, mainly numerical, are present in nearly 70% of first trimester spontaneous abortions. This number drops to 20% in the second trimester. On account of the frequent culture failures and the long delays that reach 3 weeks, the molecular cytogenetic, specially hybridization in situ fluorescent (FISH) on Interphase nuclei, allowed as to study the karyotypes of miscarriages products in order to identify the chromosomal abnormalities that are the most often linked to this fetal losses. Our experimental works is based on the chorionic villi molecular cytogenetic analysis of curettage products of 15 patients suffering from spontaneous miscarriage, with gestation ages between 8 and 18 weeks. Interphase FISH technique has been applied to our samples in order to detect the most frequent aneuploidies that could be at the origin of these spontaneous miscarriages. We detected the presence of three pathological cases represented by two cases of Turner’s syndrome and one case of Down's syndrome. The other results was balanced for the chromosomes 13, 18, 21, X and Y however the probes used didn't allow as to exclude the involving possibility of other chromosomal abnormalities. Interphase FISH technique afford us a reliable, efficient and quick result (within 24 H), however this technique remains an exam of second intention (after the conventional Karyotype) since it is expensive and can only detected the targeted chromosomal abnormalities. A statistical study has been achieved on 946 patients having spontaneous miscarriages for the year 2009, at the Maternity center of Sidi Bel Abbes. The maternal age, first risk factor, showed a peak between 35 and 39 years. The frequency of spontaneous miscarriages was about 10% out of the total number of registered pregnancies, in which 2/3 occurring late. 4% of the recruited women experienced three successive miscarriages, which it is extensively over to the average recorded previously in published studies that is situated between 0.4 and 1% only. Keywords: Spontaneous miscarriage, Chromosomal abnormalities, Chorionic villi, Interphase FISH. O 5.4 Cancer Genetics Probing the methylation status of different tumor suppressor genes from bladder cancer patients of Pakistani origin Shumaila Bilgrami1, Shahid Pervez2, Sohail Qureshi3and Farhat Abbas4* 72 Office of Research and Graduate Studies1, Department of Microbiology and Pathology2, Department of Biology, School of Science and Engineering, Lahore University of Management Sciences, DHA, Lahore, Pakistan3 Department of Surgery4, Aga Khan University, Stadium Road, Karachi 74800, Pakistan *Correspondence: Farhat Abbas, MD E-mail: farhat.abbas @aku.edu ; Tel: +92-213-4402/4409; Fax: + 92-213-493-4294; Abstract Background: Bladder cancer is the second most common urological malignancy in men, with a high recurrence rate in superficial disease and a bad prognosis associated with the muscle invasive cancer at initial diagnosis. Promoter methylation induced silencing of tumor suppressor genes has been implicated for various genes in bladder cancer. Aim: We analyzed the promoter methylation in a panel of tumor suppressor genes involved in apoptosis, DNA repair, cell cycle control and progression in non-invasive and invasive bladder cancer. Methods: Promoter hypermethylation was investigated in the gene promoters of RASSF1a, APC, MGMT, p16 and p15 in 43 non-invasive and low grade, 33 invasive and high grade bladder cancer and 10 cases with normal bladder mucosa/benign urologic disease using real-time methylation-specific PCR with SYBR green. In addition to the 86 tissue samples, DNA methylation analyses were also carried out in 16 plasma samples from patients with invasive high grade bladder cancer. Results: Promoter hypermethylation was frequently observed in RASSF1a, APC and MGMT genes (pvalue<0.001) and was prominent in the invasive high grade bladder cancer tissues as compared to the non-invasive low grade group (p<0.001) and normal bladder mucosa (pvalues 0.040, 0.000 and 0.003 for RASSF1a, APC and MGMT, respectively). When the data from16 plasma samples were compared to the corresponding tissue samples, only APC (p-value 0.006) and p16 (p-value 0.011) showed significance in paired-T test. Conclusions: Our results suggest that promoter methylation analysis can serve as a valuable tool for monitoring progression of bladder cancers and assessing their spread. Although the data on plasma samples is preliminary, it has encouraged us to interrogate the DNA methylation status of an expanded panel comprised of oncogenes and tumorsuppressor genes in a larger number of samples. O 5.5 Cancer Genetics Methylation profile of cancer related genes in Tunisian patients with breast, gastrointestinal and nasopharyngeal carcinomas Raja Mokdad-Gargouri, Imen Miladi-Abdennadher, Dorra Ben Ayed-Guerfali, Sondes Karray-Chouayekh, Ali Fendri and Ali Gargouri Centre of Biotechnology of Sfax, University of Sfax Tunisia; [email protected] Abstract Epigenetic modification is one of the mechanisms leading to gene silencing in neoplastic cells. By methylation-specific PCR, we analyzed the promoter methylation profile of cancer-related genes in Tunisian patients with breast, gastrointestinal and nasopharyngeal carcinomas. These genes are involved in crucial cellular functions such as the tumor suppressor (RASSF1A), cell cycle control (P16INK4a), DNA repair (hMLH1), cell signalling (RARb2) and apoptosis (DAPKinase). The MSPCR was performed on tumor DNA as well as normal tissues. We showed that RASSF1A gene promoter is highly methylated in breast and nasopharyngeal carcinoma. However, the percentage of methylated RASSF1A is lower in colorectal (35%) and gastric (45%) adenocarcinomas. Moreover, we showed that aberrant methylation of p16INK4a and hMLH1 promoters 73 occur more frequently in colorectal than in breast carcinoma (47% vs 19 % for p16INK4a and 53% vs 24% for hMLH1). Significant associations were revealed between aberrant methylation status and clinico-pathological parameters. In fact, hypermethylation of hMLH1 is predictive of poor prognosis in breast and colorectal carcinomas while the methylated RASSF1A correlated with advanced TNM in nasopharyngeal carcinoma of Tunisian patients. Altogether, our data supports that the methylation profiles of CpGisland hypermethylation vary with tumour types. O 5.6 Cancer Genetics Centrosome-associated Nuak2 kinase regulates centrosome amplification and cell cycle progression of cancer cells Doaa H Zineldeen1,2 and Makoto Nakanishi 2 1 Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt, Department of Biochemistry & Cell Biology, Graduate School of Medicine, Nagoya City University, Nagoya, Japan. Correspondence: Dr. Doaa Zineldeen, e-mail: [email protected] 2 Abstract Centrosomal amplification is a common phenomenon in various human malignancies and may play a dominant role in tumor initiation and progression. Here, we report a novel function of the mammalian Nuak2 kinase by demonstrating that human Nuak2 directly contributes to centrosome amplification. A subpopulation of endogenous Nuak2 localized to the centrosomes in a cell-cycle dependent manner. Overexpression of Nuak2 resulted in centrosome overduplication in a kinase-activity dependent manner, while overexpression of its kinase- dead mutant negatively affected centrosome duplication and resulted in fragmented pericentriolar material and mitotic defects. Additionally, overexpressed wild type Nuak2 caused polyploidy and stabilization of the microtubules. Targeting Nuak2 kinase by its specific small interfering RNA (siRNA duplexes) arrested the cells at metaphase. Those cells showed defective centrosomal duplication together with variable spindle polar abnormalities and chromosomal misalignment. Furthermore, our data indicate that at interphase Nuak2 is required for duplication of centrosomes, thereafter centrosomal maturation, bipolar spindle assembly and normal mitotic progression. Overall, considering that centrosome overduplication is linked to cellular transformation, our observations may also provide a molecular link between mammalian Nuak2 kinase and cancer and provides a multimodal therapeutic target in a subset of malignancies. 74 Session 6: Tumor Markers O 6.1 Tumor Markers: Thyroid Screening of TPO gene c.1708C>T and c.1978C>G mutations in Iraqi patients with hypothyrodism and thyroid cancer Abdul-Hassan, I.A.1 , Al-Ramahi, I. J.2 , Al-Faisal, A.H.M.1 and Barusrux, S.3 1 Genetic Engineering and Biotechnology Institute(GEBI), Baghdad, Iraq. Al-Razi Centre for Medical Diagnostic kits Production, Ministry of Industry, Iraq. 3 Center for Research and Development of Medical Diagnostic Laboratories (CMDL) ,Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. Correspondence: Dr. Ismail A. Abdul-Hassan, Tel : +9647700011410, E-mail: [email protected] 2 Abstract Thirty seven patients (hypothyroidism, n=20 and thyroid cancer, n=17) and twenty five healthy individuals (control) were used in this study. These patients who attend the endocrinologist in Nuclear Medicine Hospital and Al Yarmouk Nuclear Medicine Department in Baghdad, were selected during a period from July to October 2009. Modified specific locked nucleic acid (LNA) primers were used for the detection of TPO gene mutations which include c.1708 C> T and c.1978 C>G. Seven mutations were found in TPO gene. Mutations involved transition cytosine by thymine at position 1708 of the exon 10 (c.1708C>T) were found in four thyroid cancer patients, while, transversion of cytosine by guanine at the position 1978 of exon 11 (c.1978C>G) were found in one thyroid cancer and two hypothyroidism patients. It can be conclude that the c.1708C>T and / or c.1978C>G mutant TPO in hypothyroidism and thyroid cancer patients studied is very likely to be properly expressed but lacks enzymatic activity. Key Wards: TPO, c.1708C>T, c.1987C>G, Mutations, LAN primers. O 6.2 Tumor Markers Histo-pathological study of mammary glands of benign tumors in the female rats Abdul –Hadi sallal Mohammad; Tawfeeq Jawad Ali; Atheer kadhim ibadi College of Health and Medical Technology; Community Health Department Kufa Technical Institute of Kufa; Iraq Correspondence: Prof. Abdul-Hadi Mohammad ([email protected]) Abstract The present study revealed the type of the benign tumours in the female albino rats at age (4) months, the common type of benign tumours in mammary glands was fibro adenoma which arise from connective tissue and epithelium, histologically, the fibro adenoma appear as duct like structure and thinner in ductular structure of mammary gland which occurred and over growth in the connective tissue masses. The female rats with benign breast tumour showed epithelial hyperplasia had a definitive increased risk of developing 75 mammary gland cancer, and the epithelial and connective tissue hyperplasia was related to mild increased risk. The complications of connective tissue can occur in the mammary glands such as lipomas and haemangiomas. Keywords: Histo-pathology; Mammary glands; Breast Tumors; Rats O 6.3 Tumor markers High Ezrin immunoreactivity is an indicator of poor survival in squamous cell carcinoma of uterine cervix Tahany M. Shams, M.D*; Hanaa O. Badr- El- Din, M.D** and Iman Loay, MD The Departments of Pathology* Faculty of Medicine, Suez Canal University; Obstetrics and Gynecology**, Faculties of Medicine, Al-Azhar University and Department of Pathology***, Cairo University, National Cancer Institute, Egypt Correspondence: Dr. Tahani Shams: E-mail: [email protected] Abstract Background and Aim: Ezrin; the membrane-linking protein is highly expressed in several types of human cancers and correlations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown. However, such studies have not yet been done on cervical cancer. So the aim of our study was investigate the expression of Ezrin in cases of cervical squamous cell carcinoma then correlate the data with disease specific survival and metastasis survival and also with other clinicopathological variables as age, grade, stage, lymph node or distant metastasis, tumor size and type. Material and Methods: We carried out Immunohistochemical analysis of Ezrin in 64 cases of cervical cancer and correlated it to clinicopathologic variables and disease outcome. Ezrin was scored as absent (0), weak (1), intermediate (2) and marked (3) staining. Results: Ezrin was identified in 50(78.1%) of 64 cervical cancer studied cases which classified as weak, moderate and marked in 16%, 28% and 56% respectively. In contrast to the predominantly membranous immunoreactivity in normal cervical epithelium, it was cytoplasmic in cancer cells. Ezrin expression significantly correlated with lymph node metastasis and distant metastasis at diagnosis (p <0.001), also there is significantly correlation with tumor grade and stage (p= 0.02 and 0.005 respectively but not correlated with other variables as (age, tumor size, histological type). For statistical analysis, we classified Ezrin expression into two group as (-&1) and (2&3); the last is considered as high Ezrin expression. Regarding outcome, high Ezrin expression was associated with short disease specific survival (DSS) and poor metastasis survival MS (P <0.001). In univariate analysis the patients with (-&1) Ezrin score had a significantly longer DSS and MS (P <0.001) so high Ezrin immunoreactivity can predict both 5 year DSS and MS but this prediction was lost in multivariate analysis. conclusion: Our results suggested that Ezrin expression may represent an effective prognostic marker and a potential target for treatment of invasion and metastasis in cervical cancer. Keywords: Ezrin, immunohistochemistry, squamous cell carcinoma, cervical cancer, clinicopathological, patient surviva 76 O 6.4 Tumor markers Detection of circulating tumour cells in prostatic cancer patients using polymerase chain reaction Ola Sharaki(1),Seif Elislam Mahmoud(2), Abla abou zeid(1), Nermine Hossam(1) and Rasha Nour(1) Clinical Pathology Department (1), Surgical Urology (2) Faculty of medicine, Alexandria University Correspondence: Dr. Nermine Hossam Eldin Zakaria Assistant Professor of Clinical Pathology Technical Manager of AUHL, Faculty of Medicine, Alexandria University, Egypt [email protected], Mob: 01223374277 Abstract The aim of this study was to determine the presence of hematogenous neoplastic cells in patients with prostate cancer. We used a reverse transcription (RT) polymerase chain reaction (PCR) of prostate- specific antigen (PSA) mRNA to detect the presence of circulating tumour cells in 34 clinicopathologically proven prostatic cancer patients, 19 of them were proven to have locally malignant tumour and 15 were diagnosed with metastatic prostate cancer. 26.3%(5/19) of patients with locally malignant tumour were positive for CTCs and 80%(12/15) of patients with metastatic disease were positive for CTCs . There was a statistically significant positive correlation between CTCs and tPSA, Gleason score and imaging studies. We recommend searching for CTCs to be done as a routine in all newly diagnosed non metastatic prostate cancer patients for the early detection of metastasis. Key words: prostate cancer, prostate specific antigen, PCR and circulating tumour cells. Abbreviations: RT reverse transcriptase, PCR polymerase chain reaction, PSA prostate specific antigen, CTCs circulating tumour cells. O 6.5 Tumor markers Quality Care Nursing: Educational issues in genetic testing Manal Tawfiq Deapartment of Obstetritcs and Gyencology, Faculty of Nursing, Tanta University, Egypt Abstract Fifteen years a major scientific revolution started with the establishment of the human genome project. Since that time a comprehensive sequence of the human genome has been defined. Individual, family and social goals conflict with current health care practices and polices when genetic testing is done. Current health polices do not fully address their concern. Unresolved issues include protection and privacy of individuals while considering genetic information needs family members, determination of a properiate monitoring of genetic test, assressing generic health care descripancies, and assuring appropriate nursing workforce preparation. Introducing genetic testing into health care requires that providers are knowlegable regarding ethical, policies, and practices, issues in order to minimize risk for any harm, protect the right of individuals and family and considered social context in the management of genetic test results. The understanding of these issues is a component of the gentic nursing competency that must be addressed at all levels of nursing education. 77 Day 2: Poster Session 2 1. Infection and Cancer O 1.1 Infection and Cancer Anti-schistosomal and anti-tumor responses to mutual interaction between cancer and infection Mohamed Labib Salem1, Afrah Fathi Salama2, Mohammed Mahmud Ali El-said3 Afnan Hamdy El-gowily4 Immunology and Biotechnology Unit, Zoology Department 1* and Biochemistry Department, Faculty of Science, Tanta University3, Biochemistry Department, Faculty of Science, Alexandria University, Egyp 4, *Corresponding to: Dr. Mohamed Labib Salem, Prof. of Immunology, [email protected]]; [email protected] Tel: +20-01274272624, Fax: +20-40-3350804 Abstract Background: Tumor can be developed in schistosoma-infected patients. Alternatively, patients with tumor can be subjected to schistosoma infection. It is not clear, however, whether there is a mutual effects of these diseases with or without treatment with the choice drugs. Aim: Determine the host responses to mutual interaction between cancer, represented by Ehrlich ascites, and infection, represented by Schistosomiasis.Method: For schistosmiasis infection, mice were infected with 70 cercariae by tail immersion. For tumor challenge, mice were injected with 1 million cells of Ehrlich ascites carcinoma cell line. The anti-schistosomal drug prazequintal (PZQ) and the anti-tumor drug cisplatin were used for intraperitoneal treatment at the indicated time points. Results: Mice infected with schistosoma and challenge wit tumor 4-5 weeks later showed the same antischistosomal (worm and egg burden) and antitumor (total tumor cell count and mouse survival) parameters when compared to mice infected with schistosoma alone group or challenged with tumor cells alone. As expected, combinatorial treatment with PZQ and cisplatin of schistosoma-infected mice that were challenged 4-5 weeks later with tumor cell line decreased the tumor burden as wells as the worm and egg burden after treatment as compared to the non-treated controls. Interestingly, however, the worm and egg burden in mice challenged with schistosoma alone or schistosoma and tumor cells showed more decreases after treatment with both cisplatin and PZQ. Conclusion: The results of this study showed that there is no mutual interaction between schistosomiasis infection and tumor burden. It also showed that PZQ has no effect on antitumor parameters while cisplatin even at low doses has anti-schistosomal effects. Keywords: Schistosomiasis, Breast Cancer, Ehrlich ascities; Prazequintel; Fibrosis; Worm Burden 78 O 1.2 Infection and Cancer Association of hepatitis virus on acute and chronic myeloid leukemias: A preliminary report A . Movafagh*1 ,N.Varma2 , F.Shaveisi Zadeh *1 For correspondence PhD; Associate Professor and Head Department of Medical Genetics,Shahid Beheshti University of Medical Sciences ,Tehran, Iran, Fax +98(21) 2240067 +98-21-23872572; E mail [email protected] 2 Postgraduate Institute of Medical Education and Research (PGI), Chandigarh, India Correspondence: Movafagh Abolfazl Head Department of Medical Genetics, Associate Professor,Department of Medical Genetics. Shahid Beheshti Medical Sciences University., Chamran Highway,EVIN AVE.Tehran Iran 0098 21 23872572, 0098 09121307881, Email [email protected] Abstract Background: More than 15% of human cancers can be attributed to virus infection. In this connection, Hepatitis B Virus (HBV) increases the risk of leukemia, especially acute myeloid leukemia. Materials and Methods: This prospective sectional study was conducted from 1996 to 2010 among patients with acute and chronic myeloid leukemia and controls. Cytochemical staining, immunophenotyping, cytogenetic /molecular cytogenetics, Elisa, enzyme immunoassay and Western blot, were the main subject of laboratory manipulation. Results: Hepatitis B virus was diagnosed in one control patient (%0.004) and four infected with leukemic patients (%3). The differences of leukemic patients revealed statistical significant when compared with controls (P=0.0047). Conclusion: In the preliminary results, the prevalence of HBV infection was higher in patients with leukemias than in patients as non malignant controls, but the number of cases is not large enough to draw firm conclusion. We suggest that this issue warrants further investigation by large consortium studies. Keywords: Leukemia, AML, CML, HBV, Association 2.Theray: Preclinical Studies P 2.1 Therapy (Preclinical Studies) Anti-angiogenic and apoptotic effect of novel synthetic Europium(III)-Acridine carboxylate complex against Ehrlich ascites tumor cells Abdullah I. El-Faloujia, Mona F. El-Azabb, Belal H. M. Husseinc and Hassan A. Azab c a Biotechnology Research Center, bDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, c Chemistry Department, Faculty of Science. Suez Canal University, Ismailia 41522, Egypt. Correspondence: Dr. Abdullah I. El-Falouji Biotechnology Research Center, Suez Canal University , Ismailia 41522 , Egypt . Tel.: +20-01115990299; fax: +2064-3200452., E-mail: [email protected] 79 Abstract New organometallic complex europium(III)-acridine-9-carboxylate complex was synthesized and characterized. Invivo anti-tumor and anti-angiogenic potencies of europium(III)-acridine-9-carboxylate complex against ehrlich ascites carcinoma (EAC) cells are described. The newly synthesized complex resulted in inhibition of proliferation of EAC cells and ascites formation. The anti-tumor effect was found to be through antiangiogenic activity as was evident by the reduction of microvessel density in EAC solid tumors. Their anti-angiogenic effect is mediated through, at least in part, the downregulation of VEGF receptor type-2 (Flk-1). Capillary electrophoresis (CE) method was used to monitor the progress of complexes to induced apoptosis of EAC cells by analyze DNA fragmentation. It was found that EAC cells had distinct DNA fragmentation patterns analyzed by CE. Keywords: Lanthanum complex, Antitumor activity, anti-angiogenesis, Apoptosis, DNA fragmentation. P 2.2 Therapy (Preclinical Studies) Discovery of carbon-nanotube genes’ target in human normal bronchial epithelial cells model Anas Alazzam1,2, Etienne Mfoumou1,2, Ion Stiharu1, Narayanswamy Sivakumar1 & Ala-Eddin Al Moustafa1,2,3 1 Department of Mechanical Engineering, Concordia University, Montréal, Quebec, Canada. 2Montréal Centre for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Canada; and 3Department of Anatomy, Faculty of Medicine/University of Aleppo, Aleppo, Syria Corresponding Author: Ala-Eddin Al Moustafa, email: [email protected] Abstract Carbon nanotubes (CNTs) offer exciting opportunities for science and applications. In recent years, CNTs research has been established as a highly interdisciplinary field to exploit their outstanding features. Great interest has been generated in fullerenes in general, but especially in CNTs and carbon nanohorns as biologically compatible materials and drug carriers mainly because of their distinct architecture, hollow interior and cagelike structures. However, the small size, large surface area, and high reactivity of these materials are the main factors for potential toxicity. Moreover, CNTs will have wide-spread applications in many technological fields, thus worker/consumer exposure is likely to occur, posing emerging health concerns. Initial toxicological studies demonstrated that pulmonary deposition of CNTs causes acute pulmonary inflammation as well as chronic responses such as fibrosis. However, the mechanisms by which CNTs provoke susceptibility to toxicity and pulmonary inflammation is not clear. Thus, genome-wide monitoring of gene expression is important to understand the extent of CNTs effect. To this end, we have carried out a cDNA array analysis using Affymetrix probe-sets complementary to approximately 54 675 human genes, to monitor the levels of expression within aggregates of human normal bronchial epithelial cells treated with 80 CNTs and their wild type cells. We identified a comprehensive list of genes that are differentially expressed between CNTs-treated and their control cells, the majority of them have been identified for the first time as targets of CNTs-effect. In addition to revealing the complex nature of the genetic changes after the accumulation of CNTs in human normal lung cells; we believe that our data can provide the possibility to use modified forms of CNTs as a potential therapeutic agent to treat lung cancer. Key words: Carbon Nanotubes, Human Bronchial Epithelial Cells, cDNA Microarray, Gene Expression. This work was published in the Nanomedicine journal (Alazzam et al., 2010) O 2.3 Therapy (Preclinical Studies) Anticancer peptides derived from animal venoms Mohamed A. Abdel-Rahman a* and Peter N. Strong b a Zoology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt b Biomedical Research Centre, Biosciences Division, Sheffield Hallam University, Sheffield S1 1WB, UK Correspondence: Dr. Mohamed A. Abdel Rahman, PhD Lecturer of Molecular Physiology & Toxinology, Editor of the Journal of Venom Research (JVR) Zoology Dept., Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt, Mobile: +20120862886, e-mail: [email protected], [email protected] Abstract Natural products have a rich history in the development of anti-cancer drugs. Venomous animals use their venoms, both to subdue prey and as defense mechanisms, and as a consequence these venoms contain a pharmacopeia of biologically active molecules which have been proven to either be of direct use as novel therapeutic agents or to provide a critical template for the design of others. Venoms of several animal species (such as snakes, scorpions, spiders, frogs, bees, wasps and ants) and specific proteins and peptides isolated from these venoms have shown therapeutic potential as anti-cancer agents. Several cytotoxic venom peptides have been shown to possess several distinct mechanisms of action including (i) ion channel blockade (ii) matrix metalloproteinase inhibition and (iii) induction of apoptosis. The first clinical trials of synthetic peptides derived from animal venoms are beginning to show positive results and the field is looking very promising. In this review, we present research highlights characterizing peptides of animal venoms which have anticancer activity. Our recent findings of the anticancer efficacy of Conus venom will also be discussed. Keywords: Venom, Cytotoxic Peptides, Cancer, Anti-tumor therapy. O 2.4 Therapy (Preclinical Studies) Combined effect of Cerastes cerastes snake venom and magnetic waves on Ehrlich tumor bearing mice H. M. SAYED AHMED 1, F.M. ALI2, H.A. ABD EI TAWAB3, E.M. ABD EL-KADER4 AND C. R. SHAKER 5 Department of Pharmacology1, Faculty of Pharmacy, Cairo University, Cairo, Egypt, Department of Biophysics 2, Faculty of Science, Cairo University, 81 Department of Pharmacology3, Faculty of Pharmacy, Cairo University, Cairo, Egypt , Department of Pharmacology4, Faculty of Pharmacy, Modern University for Technology and information, Cairo, Egypt and Holding company of biological products and vaccines VACSERA 5 ,Cairo, Egypt. Dr Nevein Abdel hady [email protected]> Abstract The use of chemotherapy for cancer treatment is a successful modality. However, this treatment has its side effects, which limits its applicability. This work was done to study the effect of snake venom and/or of exposure to extremely low frequency magnetic waves (ELF- MW) on liver of normal mice, and of Ehrlich carcinoma bearing mice. A total of 122 mice were used, divided into two groups, "A" and "B". Group A: normal mice were subdivided into 3 subgroups: A 1: control, was given saline 0.2 ml: A2: was given (0.75 μg / g b.w) snake venom; A3: was whole body exposed to 4.5 Hz square wave magnetic field of intensity 2 Gauss for a period of 7 days (d) at a rate of 2h/d. Group B: tumor bearing mice, were subdivided into 5 subgroups: B 1: was received no treatment; B2: was given (0.75 μg / g b.w) snake venom; B3: was whole body exposed to 4.5 Hz square wave magnetic field of intensity 2 Gauss for a period of 7 days (d) at a rate of 2h/d; B4: was given snake venom and exposed to MWs; B 5: was given 2.8 mg/kg methotrexate as standard chemotherapy. Histological examination of liver using hematoxylene and eosin (H& E), as well as blood analysis were performed. Results showed that crude snake venom did not satisfactorily control tumor growth; while exposure to ELF- MWs at resonance frequency 4.5 Hz, 2G was quite effective in limiting tumor growth and proliferation, with minimal effect on non- involved tissues. The use of magnetic waves at resonance frequency 4.5 Hz, 2G proves to be much safe for treatment of primary tumor site and to secondary sites. O 2.5 Therapy (Preclinical Studies) A novel hydrogen bonded bimetallic supramolecular coordination polymer [Me3Sn(bpe).Ag(CN)2.2H2O] as anticancer drug Safaa El-din H. Etaiw1, Ahmed S. Sultan2, Ahmed S. Badr El-din1 1 Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt Correspondence: Dr Ahmed Samara Ahmed Badr El-din Lecturer of Inorganic Chemistry, Chemistry Department, Faculty of Science, Tanta University, Egypt E-mail: [email protected]; [email protected]; Mobile: 002/0104363172 2 Abstract The reaction of Me3SnCl, K3[Ag(CN)4] and 1,2-bis(4-pyridyl)ethane (bpe) in water/CH3CN solution at room temperature affords the novel bimetallic supramolecular coordination polymer (SCP) [Me3Sn(bpe).Ag(CN)2.2H2O], 1. The structure of 1 consists of cationic {-Sn(Me3)-bpe-}+ chains that are neutralized by [Ag(CN)2]- anions. The dicyanoargentate(I) anions present discrete uncoordinated fragments between the cationic chains. The water molecules bind the cationic chains and the anions forming 3Dsupramolecular structure through hydrogen bonds. 1 exhibits strong fluorescence in the 82 solid state at room temperature. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the in vitro antitumor effects of the SCP 1 on human breast cancer cell line, T-47D. Cell cycle analysis revealed that the SCP 1 induced apoptosis in T-47D breast cancer cell line. Moreover, in vivo, the SCP 1 suppressed tumor growth in rats model developed mammary carcinoma by 44.8% compared to the vehicle treated control. Thus, the SCP 1 exhibits specific in vivo and in vitro antitumor effects. Keywords: Silver cyanide, Trimethyltin, 1,2-bis(4-pyridyl)ethane, Supramolecular Coordination polymer, Hydrogen bonds, Fluorescence, Antitumor activity. O 2.6 Therapy (Preclinical Studies) Synthesis, antimicrobial, and anticancer activities of new α- aminophosphonate derivatives using 3-acetylpyridine Mohamed F. Abdel-Megeeda,*, Badr E. Badrb, Mohamed M. Azaama a Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt. Department of Botany, Faculty of Science, Tanta University, Tanta, Egypt. Correspondence: Dr. Mohamed M. Azaam: Tel.: +20104694523; Fax: +23344352 E-mail address: [email protected] b Abstract A series of novel α-aminophosphonate derivatives using 3-acetyl pyridine has been synthesized. The antimicrobial activities against Escherichia coli (NCIM2065) as gramnegative bacteria, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as gram-positive bacteria, Candida albicans and Schccaromycies cerevisiae as fungi showed high activities at low concentrations (10, 50, 100 μg/ml). Furthermore, anticancer activities against two cancer cell lines [liver carcinoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF7)] were also carried out and all compounds showed significant cytotoxicity (IC 50: 17.3, 15.8, 13.3, 17.1, and 17.6 μg/ml for HepG2 and 18.2, 17.6, 20.2, 19.6, and 19.4 μg/ml for MCF7 respectively). The lethal dose of the synthesized compounds was also determined (915, 38, 83, 1000, and 843 μg/ml) which indicated that some of these compounds are safe and less toxic. Keywords: α-Aminophosphonate, 3-acetyl pyridine, anticancer, antimicrobial, lethal dose. P 2.7 Therapy (Preclinical Studies) Marine sponges: A potent source of anticancer metabolites Haiam M. Aboul-Ela The National Institute of Oceanography and Fisheries. Alexandria, Egypt e-mail: [email protected] Absract The search for pharmaceutically active compounds from natural sources is well established. With oceans covering 70% of the surface of the earth, coupled with the large and varied biodiversity of the marine environment, the oceans remain a largely unexplored, but extremely promising source of new drug candidates. Approximately half of the novel marine natural products reported in the literature are biologically active. This 83 occurrence can be contributed to the reliance of sessile, soft-bodied marine invertebrates on chemical defense for survival, as many lack the physical defense mechanisms of movement and camouflage. Among the most promising sessile marine organisms in this aspect are marine sponges. More than 15.000 marine products have been described up to now in which sponges are champion producers, concerning the diversity of products that have been found. They are responsible for more than 5300 different products and every year hundreds of new compounds are being discovered. Most bioactive compounds from sponges can be classified as antiinflammatory, antitumour, immuno- or neurosurpressive, antiviral, antimalarial, antibiotic or antifouling. The chemical diversity of sponge products is remarkable. In addition to the unusual nucleosides, bioactive terpenes, sterols, cyclic peptides, alkaloids, fatty acids, peroxides, and amino acid derivatives (which are frequently halogenated) have been described from sponges. A number of isolated sponge compounds are inhibitors of protein kinase C (PKC). PKC inhibitors have attracted interest worldwide, as there is evidence that too high levels of PKC enzyme are both involved in the pathogenesis of arthritis and psoriasis (due to regulation of phospholipase A2 activity), and in tumour development. The marine sponges continue to attract attention as rich sources of structurally novel anticancer secondary metabolites. P 2.8 Therapy (Preclinical Studies) Marine derived Fungi through the drug discovery and application in treatment of cancer and neurological disorders Asmaa N. Ali1, Nehad M. Abdel-Moneim2 and Ahmed M. Abdel-Azeem3 1 National Institute of Oceanography and fisheries, [email protected] Department of Biochemistry, Faculty of Science, Alexandria University 3 Department of Botany, Faculty of Science, Suez Canal University 2 Abstract Fungi derived from marine sources are considered to represent a huge reservoir of secondary metabolites, many of which are biologically active and have application. Marine fungi are highly potent producers of bioactive substances with antifungal, anti-cancer, anti-inflammatory and antioxidant activity. Tyrosine kinase inhibition, antioxidant and anti-inflammatory effect, indicate the powerful effect of fungal extract as a protective against many types of cancer and neurological disorder such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Our result recorded highly inhibition ratio by 91.98%, 91.09%, 93.55% of tyrosine kinase, in-vitro lipid per oxidation (TBARS inhibition assay) and acetylcholinestrase inhibition respectively. 84 3. Medicinal Plants P 3.1 Medicinal Plants Comparison of antitumor effects of garlic extracts against human laryngeal carcinoma Ahmad Ghorbani1,2, Jalil Tavakkol-Afshari3, Moosa-Alreza Hadjzadeh4, Mohammad Taghi Shakeri5, and Heydar Parsaei6 1 Neyshabur Faculty of Medical Sciences, Neyshabur, Iran Pharmacological Research Center of Medicinal Plants, Faculty of Medicine, Mashhad University of Medical Sciences, Iran 3 Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Iran 4 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran 5 Department of Social Medicine, Faculty of Medicine, Mashhad University of Medical Sciences Iran 6 Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran Correspondence: Dr. Ahmad Ghorbani: [email protected] 2 Abstract Experimental studies provide evidences that garlic (Allium sativum) is effective inhibitor of the tumor growth. In this study, we compared the antitumor effects of two types of garlic extracts, aqueous and ethanolic, against human laryngeal carcinoma (Hep2) cells. The cells were cultivated and incubated with concentrations of 0.5, 1, 4, 8 and 12 mg/ml of the extracts. They were assessed microscopically for signs of death such as morphological changes, granulation and anchorage independency from 24 to 72 h after treatment. Also, the antiproliferative properties of the extracts were determined by MTT colorimetric assay. After 24 h, the cytotoxic effect of garlic was started from concentrations of 4 and 8 mg/ml for ethanolic and aqueous extracts, respectively. For both extracts, the effect became more pronounced with time and with increase of concentration. According to MTT assay, the viability of Hep2 cells decreased to 10 and 80% of control with the addition of 12 mg/ml of ethanolic and aqueous extracts, respectively. Therefore, it seems that ethanolic extract of garlic had more potent antitumor property against human laryngeal carcinoma than its aqueous extract. P 3.2 Medicinal Plants Sophora pachycarpa and Salvia chorassanica: as promising antitumor medicinal plants Seyed Hadi Mousavi*, Mahsa Hossini Motaez, Hojat Soufi, Seyed Ahmad Emami, Zahra Tayarani-Najaran, * Seyed Hadi Mousavi, M.D., Ph.D., Pharmacological Research Centre of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Email: [email protected], [email protected] . Mobile: + 98-9155199598, Work: 0511 8002258 85 Abstract Here, we investigated the cytotoxic effects of methanol extract and obtained fractions from S. pachycarpa and Salvia chorassanica root extract as Iranian medicinal plants on different cancer cell lines including A549, HeLa, HL60, MCF-7, and PC3 cells, and lymphocytes as non-malignant cells. Meanwhile the role of apoptosis was explored in this toxicity. Malignant and non-malignant cells were cultured in RPMI 1640 medium and incubated with different concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak) and activity of caspase 3,8 and 9. The degree of DNA fragmentation was analyzed using agarose gel electrophoresis based on the formation of internucleosomal units. S. pachycarpa inhibited the growth of malignant cells in a dosedependent manner and the CH2Cl2 fraction showed the lowest IC50 values ranged from 30 to 50 μg/mL in various cell lines. The IC50 for methanol extract, n-hexan, CH2CL2 fractions for S. chorassanica were calculated 8.8, 5.45 and 2.38 µg/ml in HeLa cells. S. pachycarpa and S. chorassanica induced a sub-G1 peak in flow cytometry histogram of treated cells, DNA fragmentation and activation of caspase 3 and 8 acivity indicating apoptotic cell death is involved in S. pachycarpa and S. chorassanica -induced toxicity. In conclusion, S. pachycarpa and S. chorassanica exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. IC50 values show both plants could be considered as a potential and promising chemotherapeutic agent in cancer treatment. Keywords: apoptosis, Sophora pachycarpa, Salvia chorassanica, cytotoxicity P 3.3 Medicinal Plants Potential in vitro and in vivo antitumor effects of polyphenolic compounds on experimental tumor ascites 1 Mohamed Labib Salem, 2Abdel-Halim Abdel- Hady Mostafa, 3Ehab M. Mohamed, and 3Abeer Abdel-Hamid Ahmed Khamis 1 Zoology Department, Faculty of Science, Tanta University; 2Biochemistry Department, Faculty of Science, Ain Shams University; 3Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Egypt. Correspondence: Pof. Mohamed Labib Salem, Prof. of Immunology; [email protected]; [email protected]; Tel: +20-01274272624, Fax: +20-40-3350804 Abstract Background: Although several conventional anti-cancer drugs are available, most of them are toxic and intolerable after long-term use. Therefore, there has been a global increased interest to identify novel agents that can possess anti-tumor effects by itself or maximize the anti-tumor effects of low doses of conventional anti-cancer drugs. Aim: The primary aim of this study was to purify phenolic compounds from widely used medicinal plants extracts, including Camellia Sinensis, Nigella Sativa,Triticum Aesativum and Matricaria Chamomilla. The secondary aim was to investigate the anti-tumor effects 86 of a single or combinatorial treatment with extracts from these plants in vitro and in vivo. Methods: Ehrlich ascities carcinoma (EAC) cells were used as a breast cancer tumor model. For in vitro studies, 1 million EAC cells in PBS were incubated with varying concentration of phenolic extracts at 37 ◦C for 4h in CO2 incubator. The viability of the cells was determined by trypan blue exclusion method. For in vivo studies, was EAC cells were injected into Swiss albino mice followed by oral administration of the phenolic extracts at a dose of 100 mg/kg body weight every other day for 14 d. After 24h of the last treatment dose, the mice were left to monitor their survival or sacrificed to assess the tumor cell numbers. Results: The phenolic extracts from C. Sinensis, N. Sativa, T. Aesativum and M. Chamomilla caused significant (P<0.01) increases in the mean survival time (MST) and prolonged the life span of EAC tumor-bearing mice. The enhanced survival o was associated with decreases in the total numbers of tumor cells as well as the numbers of viable and dead tumor cells. Interestingly, the anti-tumor effects of combinatorial treatment of the extracts showed higher effects than treatment with single estract. Furthermore, addition of either of these phenolic extract with cisplatin, the drug of choice for EAC, induced higher anti-tumor responses than treatment with the extract or cisplatin alone. The phenolic extract of green tea showed the highest the anti-tumor effects as compared to the other extracts. Conclusion: The phenolic extracts of the studies plants have potential anti-tumor effects when used in combination and can enhance the anti-tumor effects of the conventional anti-cancer drugs. P 3.3 Medicinal Plants Outcome of Teucrium polium plant extract on human prostate and lung cancer Mustapha Kandouz1, Khadidja Haïdara1, Amal Alachkar2, Amber Yasmeen1 & Ala-Eddin Al Moustafa1,2,3,4 1 Segal Cancer Centre, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada; 2Syrian Research Cancer Centre of the Syrian Society Against Cancer & Aleppo University, Aleppo, Syria; 3Oncology Department, McGill University, Montreal, Quebec, Canada; and 4Department of Mechanical Engineering, Concordia University, Montreal, Quebec, Canada Correspondence: Dr. Ala-Eddin Al Moustafa, email: [email protected] Abstract Teucrium polium (TP) is a medicinal plant that has been used for more than two thousand years for treating many diseases such as abdominal pain, indigestion and diabetes in the Middle East. On the other hand, human prostate and lung metastatic cancers are the two major causes of cancer-related deaths especially in western countries. Nevertheless, the effect of TP plant extract on human metastatic cancer cells especially prostate and lung cancers has not been investigated yet. Hence, we examined the effects of TP extract on selected parameters in human prostate and lung cancer cell lines, PC3, DU145, H322 and A549. We found that TP plant extract induces cell death and provokes S cell cycle arrest and reduction of G0-G1 phase in these cell lines. We also reported that TP extract induces differentiation to an epithelial phenotype “mesenchymal-epithelial transition” which is an important process in cell invasion and metastasis; consequently TP plant extract provokes a dramatic decrease in cell invasion of PC3 and DU145 cancer cells in comparison with 87 untreated cells. These alterations are accompanied by a re-localization of the expression patterns of E-cadherin and catenins which can be induced by the conversion of catenin’s role from a transcriptional regulator to a cell-cell adhesion molecule via Src dephosphorylation. Our data reveal that TP plant extract regulates signaling pathways of cell death and cell adhesion, suggesting that this plant extract has therapeutic promise in the treatment of several human carcinomas including prostate and lung. Key words: Teucrium polium plant, prostate & lung cancers, cell death, cell invasion, E-caderin/catenin complex, Src P 3.4 Medicinal Plants Cytotoxic and apoptogenic properties of Sophora pachycarpa and Salvia chorassanica in human cancer cell lines Seyed Hadi Mousavi*, Mahsa Hossini Motaez, Hojat Soufi, Seyed Ahmad Emami, Zahra Tayarani-Najaran, * Seyed Hadi Mousavi (Pharmacological Research Centre of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran) Email: [email protected], [email protected]; + 98-9155199598, Work: 0511 8002258 Abstract Here, we investigated the cytotoxic effects of methanol extract and obtained fractions from S. pachycarpa and Salvia chorassanica root extract on different cancer cell lines including A549, HeLa, HL60, MCF-7, and PC3 cells, and lymphocytes as non-malignant cells. Meanwhile the role of apoptosis was explored in this toxicity. Malignant and nonmalignant cells were cultured in RPMI 1640 medium and incubated with different concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (subG1 peak) and activity of caspase 3,8 and 9. The degree of DNA fragmentation was analyzed using agarose gel electrophoresis based on the formation of internucleosomal units. S. pachycarpa inhibited the growth of malignant cells in a dose-dependent manner and the CH2Cl2 fraction showed the lowest IC50 values ranged from 30 to 50 μg/mL in various cell lines. The IC50 for methanol extract, n-hexan, CH2CL2 fractions for S. chorassanica were calculated 8.8, 5.45 and 2.38 µg/ml in HeLa cells. S. pachycarpa and S. chorassanica induced a sub-G1 peak in flow cytometry histogram of treated cells, DNA fragmentation and activation of caspase 3 and 8 acivity indicating apoptotic cell death is involved in S. pachycarpa and S. chorassanica -induced toxicity. In conclusion, S. pachycarpa and S. chorassanica exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. IC50 values show both plants could be considered as a potential and promising chemotherapeutic agent in cancer treatment. Keywords: apoptosis, Sophora pachycarpa, Salvia chorassanica, cytotoxicity 88 P 3.5 Medicinal Plants Quantitation of the antitumor Activity of Some Natural Compounds Afrah Fatthi Salama, Ahmad Ahmad ABarbary, Saad Mohamed El-Gendy, Shabaan El-Sayed Abdel-Azez Division of Biochemistry, Chemistry Department, Faculty of Science, Tanta University, Egypt and Department of Cancer Biology, National Cancer Institute, Cairo university, Egypt Corresponding author: Dr. Afrah Salam, [email protected] Abstract Background: There is a growing interest in investigating the anti-tumor effects of thymoquinone (TQ), the bioactive constituent of the volatile oil of black seed, and garlic. It is not known, however, whether their anti-tumor effects are due to apoptotic or necrotic effects. Aim: The goal of this study was to investigate the anti-neoplastic, cytotoxic or apoptotic effects using the hepatoma (Hep-G2 cells) and lung cancer (H460) cell lines. Methods: The anti-tumor effects of TQ and garlic were measured using sulphorodamine B (SRB) cytotoxicity, MTT, and flow cytometry assays. Results: Treatment of Hep-G2 and H460 cells with TQ (50, 100, 200, 300 and 400ug/ml) or garlic extracts (1, 2, 3 and 4 %) resulted in significant decreases in the proliferation and survival rates of Hep-G2 and H460 cells after 48 hours and completely inhibited the cell growth after 72 h of treatment as compared to the effect of cisplatin. Interestingly, the anti-tumor effects of these agents were found to be mediated though induction of potent apoptotic effects as compared to cisplatin, which induced both cell apoptosis and necrosis. Conclusion: Supplementation of TQ and garlic could be used as an adjuvant therapy during anticancer treatments. Keywords: Thymoquinone; Garlic extract; Apoptosis; Cell cycle; Anti-cancer; Hep-G2 cells; H460 cells P 3.6 Medicinal Plants Protective effect of Crocus sativus stigma extract and Crocin (trans-crocin 4) on methyl methanesulfonate–induced DNA damage in mice organs Elham Asadpour, Hamid R. Sadeghnia Neuroscience Research Center (NRC), Department of Pharmacology, Department of New Sciences and Technology, School of Medicine, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran Tel: +98 511 882 8566, Fax: +98 511 882 8567, E-mail:[email protected] Abstract This study was designed to examine the effect of aqueous extract of Crocus sativus stigmas (CSE) and crocin (trans-crocin 4) on methyl methanesulfonate (MMS)-induced DNA damage in multiple mice organs using comet assay. Adult male NMRI mice in different groups were treated with either physiological saline (10 mL/Kg, intraperitoneal [ip]), CSE (80 mg/Kg, ip), crocin (400 mg/Kg, ip), MMS (120 mg/Kg, ip), and CSE (5, 20, and 80 mg/Kg, ip) 45 min prior to MMS administration or crocin (50, 200, and 400 mg/Kg, ip) 45 min prior to MMS administration. Mice were scarified about 3 h after each different treatment, and the alkaline comet assay was used to evaluate the effect of these compounds on DNA damage in different mice organs. The percent of DNA in the comet tail (% tail DNA) was measured. A significant increase in the % tail DNA was seen in 89 nuclei of different organs of MMS-treated mice. In control groups, no significant difference was found in the % tail DNA between CSE- or crocin-pretreated and salinepretreated mice. The MMS-induced DNA damage in CSE pretreated mice (80 mg/Kg) was decreased between 2.67-fold (kidney) and 4.48-fold (lung) compared to those of MMS-treated animals alone (p<0.001). This suppression of DNA damage by CSE was found to be depended on the dose, which pretreatment with CSE (5 mg/Kg) only reduced DNA damage by 6.97%, 6.57%, 7.27%, and 9.90% in liver, lung, kidney, and spleen, respectively ( p>0.05 as compared with MMS-treated group). In the same way, crocin also significantly decreased DNA damage by MMS (between 4.69-fold for liver and 6.55-fold for spleen, 400 mg/Kg), in a dose-dependent manner. These data indicate that there is a genoprotective property in CSE and crocin measured by comet assay in vivo. Key Words: Crocus sativus, Crocin, Genotoxicity, Comet assay, DNA damage P 3.7 Medicinal Plants Biological and therapeutic effects of Berberis vulgaris and its active constituent, Berberine: antioxidants, anti-cholinergic, anti-diabetic and anticancer effect Doaa A. Ghareeb 1, Abeer ES Abd El Wahab 2, Eman Sarhan 1, Marwa M Abu-Serie 2, Maha A. El Demellawy 2. Biochemistry Department, Faculty of Science, Alexandria University 1, Medical Biotechnology Department, Genetic Engineering & Biotechnology Research Institute, City for Scientific Research & Technology Applications, Egypt 2 Correspondence: Prof. Maha A. El Demellawy, City for Scientific Research & Technology Applications, Phone: +203-459-3422, Fax: +203-459-3407, [email protected] Abstract: Berberis vulgaris is a well known plant with traditional herbal medical history. The aims of this study was to bioscreen and compare the in vitro biological activity (antioxidant, anticholinergic, antidaibetic and the anticancer) of barberry crude extract and berberine active compound. The effect of B. vulgaris extract and berberine chloride on thiobarbituric acid reactive substances (TBARS) and diphenyle –α-picrylhydrazyl (DPPH) radical scavenging), nitric oxide scavenging activity, superoxide dismutase (SOD) and glutathione peroxidase activity (GPx), acetylcholinesterase (AChE) and αgulcosidase activities were spectrophotometrically determined. On the other hand, the effect of extract and berberine as anticancer was estimated on three different cell lines which were MCF-7, HepG-2, and Caco-2 cells by using neutral red uptake assay. Our results showed that barberry crude extract contains 0.6 mg berberine/mg extract. Barberry extract showed potent antioxidative capacity through a decrease in thiobarbituric acid reactive species (TBARS) and NO and the oxidation of DPPH that associated with GPx and SOD hyper activation. Berberis crude extract α-glucosidase stimulatory effect was more potent than berberine chloride effect. Besides, different concentrations of both berberine chloride and barberry ethanolic extract showed to have no growth inhibitory effect on normal blood cells (PBMC). Otherwise, both berberine chloride and barberry ethanolic extract showed to have inhibitory effect on the growth of breast, liver and colon cancer cell lines (MCF7, HepG2 and CACO-2 respectively) at different incubation times 90 starting from 24 hrs up to 72 hrs and the inhibitory effect increased with time in a dose dependant manner. This work demonstrates the potential of the bioactive ingredients of barberry on suppressing lipid peroxidation, suggesting a promising use in the treatment of hepatic oxidative stress, Alzheimer and idiopathic male factor infertility. Beside, Berberis vulgaris ethanol extract can induce cancer cell death that could return to its powerful antioxidant activity. Keywords: Berberis vulgaris, berberine chloride, antioxidant, anticancer, α-glucosidase P 3.8 Medicinal Plants Evaluation of hepatoprotective and anticancer properties of aqueous olive leaf extract in chemically induced hepatocellular carcinoma in rats 1 1 Abdel-Hamid, NM, 2El-Moselhy, MA, 1Abdel-Baky, AE and 1Fawzy, MA Biochemistry Department, Faculty of Pharmacy, Minia University, Egypt. Pharmacology and Toxicology Department, Faculty of Pharmacy, Minia University, Egypt. Correspondence: Dr. Mohammed Ahmed M. El-Moselhy, PhD Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University Tel: Mob.: 0101748182, Work: +2 086 2347759, Fax: +2 086 2369075 E-mail: [email protected] 2 Abstract Objectives: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. The study aimed to investigate the role of aqueous olive leaf extract (AOLE) in modulating metabolic disorders occurring in hepatic malignancy induced by trichloroacetic acid (TCA). Design: Eight groups of rats were assigned as follows: First, untreated normal control. Second, treated with 5-fluorouracil (5-FU), (75 mg/kg), intraperitoneally (IP) once weekly for 3 weeks. Third, treated with oral AOLE (500 mg/kg) once daily for 28 days. The 4th group co-treated with AOLE and 5-FU as mentioned above. The 5th group treated with oral daily doses of TCA (500mg/kg) for five days. The 6th group treated with TCA for 5 days, from the sixth day with 5-FU for 3 weeks. Group 7 given TCA then, with AOLE. Group 8 received TCA, 5-FU and AOLE. Blood samples were collected by decapitation after 28 days. Liver tissues were histologically studied. Results: TCA showed neoplastic tissue features, greatly improved by treatment with AOLE and 5-FU combination. TCA significantly increased blood ALT, AST, alkaline phosphatase (ALP) and acetyl CoA synthase (fatty acid synthase, FAS) activities, total bilirubin (T Bil), triglycerides (TG), total glycosaminoglycans (TGAGs), alpha-fetoprotein (AFP), reduced serum total lipoprotein lipase (TLPL) activity. AOLE, combined with 5-FU produced a pronounced improvement in most of studied parameters. Conclusion: AOLE showed promising hepatoprotective and adjuvant anticancer properties if combined with 5-FU. Key word: HCC, 5-FU, Olive Leaves, Acyl Co Synthase, Lipase, Adjuvant Herbal. 91 P 3.9 Medicinal Plants Immunohistochemical changes in mouse liver infected with Schistosoma mansoni and the protective role of milk thistle extract Doha M. Beltagy1 and Ehab Tousson2 1 Biochemistry, Department of Chemistry, Faculty of Science, Damanhour University (e-mail: [email protected]); 2Department of Zoology, Faculty of Science, Tanta University (e-mail: [email protected]), Egypt. Correspondence: Dr. Doha M Beltagy: [email protected] Abstract Schistosomiasis is one of the major human parasitic diseases in many developing countries and is one of the causes of morbidity and mortality in the human population. The present work has been planned to study the histopathological and immunohistochemical expression of P53 and CD68 in mouse liver tissues experimentally infected with Schistosoma mansoni, in addition to the ameliorating role of milk thistle extract (silymarin). Fifty adult male mice were divided into five groups (10 animals each). First and second groups were the control and silymarin groups respectively while the third group was the infected group in which mice were infected with Schistosoma mansoni live cercariae for 6 weeks. The fourth and fifth groups were the co- and post treated groups in which mice were infected with Schistosoma mansoni cercariae and treated with silymarin during and after Schistosoma infection respectively. The major histopathological lesions were variable numbers of perioval granulomas, diffuse infiltration of inflammatory cells, mainly eosinophils and small mononuclear cells, and fibrosis of portal areas and interlobular septa. Treatment with silymarin led to a significant reduction in granuloma area in all treated infected mice compared to nontreated infected mice. Immunohistochemical observations of the liver tissues showed a significant increase of the apoptotic protein P53 and CD68 after infection with the cercariae of schistosoma, comparing with the control one. The expression of the cytoplasmic P53 and CD68 were very low in the control liver sections. A significant decrease in the expression of the cytoplasmic P53 and CD68 were observed after silymarin treatment. Key words: P53; CD68; immunoreactivity; Schistosoma; Mice; Liver; silymarin 92 3. Epidemiology P 4.1 Epidemiology What do know Iranian women about breast cancer? Roghaiyeh Nourizadeh*1, Fatemeh Bakhtariagdam2, Leila Sahebi 2 1 PhD candidate in reproductive health, Shahid Beheshti University of Medical sciences; 2Academic member of Health and Nutritin Faculty, Tabriz University of Medical sciences, Iran Correspondence: Roghaiyeh Nourizadeh ([email protected]); mobile No. 09144131729 Abstract Background: Breast cancer is the most common cancer among women in Iran and the worldwide. It is the second cause of death due to women’s cancer after lung cancer. Early detection in improvement of outcomes and survival rates is very crucial. Aims: The purpose of this study was to determine women’s health knowledge, beliefs and population needs in order to design appropriate educational programs in promotion of breast cancer screening behaviors. Methods & Materials: The study design was a descriptive cross- sectional one, in which 219 women referring to Health Centers of Tabriz (one of the five biggest cities of the country) were selected through cluster random sampling. Data were collected by using a self-administered questionnaire consisted of 4 sections: demographic characteristics, knowledge of breast self examination, health beliefs and behaviors of breast cancer screening. Health beliefs questions derived from Champion’s Health Belief Model Scales. logistic regression, independent t-test, pearson correlation and Chi square test were used for statistical analysis using SPSS 17. Results: 5% of participants had adequate knowledge regarding breast cancer and breast self examination (BSE). The percentage of women who performed BSE was 41.6%, while regular performance was 8.2%. 16% and 8.5% of eligible people reported having had a clinical breast exam and mammogram respectively. Severity perceptions of women who had a screening mammogram was significantly higher than those who had not had (p=0.008). Conclusions: Low rates of knowledge and breast cancer screening behaviors of participants in this study show importance of continues education and focus on early detection. Educational programs should be designed in the ways that improve early detection performance in the population. Key words: Breast Cancer, Screening, Health Belief Model 93 O 4.2 Epidemiology The role of health belief model in promotion of beliefs and behaviors of breast cancer screening in women referring to health care centers of Tabriz, 2010 Fatemeh Bakhtariagdam1, Roghaiyeh Nourizadeh *2, Leila Sahebi3 1Academic member of Health and Nutrition Faculty, Tabriz University of Medical Sciences; 2Shaheed Beheshti University of Medical sciences; 3Academic member of Health and Nutrition Faculty, Tabriz Tabriz University of Medical Sciences, Iran Correspondence: Roghaiyeh Nourizadeh ; E-mail: [email protected]; Tel. 09144131729 Abstract Background: Breast cancer is the most common cancer among women in Iran and the worldwide. It is the second cause of death due to women’s cancer after lung cancer. Early detection in improvement of outcomes and survival rates is very crucial. Aim: The purpose of this study was to determine to what extent educational program based on HBM can change women’s health beliefs and behaviors of breast cancer screening. Methods & Materials: The study design was quasi experimental, in which 219 women referring to Health Care Centers of Tabriz selected through cluster random sampling divided into case and control groups. Data were collected by using a self-administered questionnaire consisted of 4 sections: demographic characteristics, knowledge of breast cancer and its screening methods, health beliefs and behaviors of screening. 3 months after the intervention, 2 groups sat for posttest. Logistic regression, Paired t test, Wilcoxon, t-test, Man-Whitney U, McNemar, Pearson Correlation and Chi-square test were used for statistical analysis using SPSS. Results: Post intervention, there was a remarkable increase within the experimental group in perceived seriousness (p=0.02), threat (p=0.01) and benefit (p<0.001), while within control group there was a meaningful decrease in perceived sensitivity (p=0.01) and an increase in perceived seriousness (p=0.01). Also it was seen an increase of 15.4% in frequency of BSE in experimental group. Overall, post intervention was found a significant difference in screening behaviors between groups (p=0.03). Conclusion: The culturally-sensitive educational intervention based on HBM was to some extent effective in change of health beliefs and screening behaviors. In future educational programs, it seems focus on inducing perceived sensitivity and also reducing perceived barriers would have an important effect on mammography practice in long time follow up. Key words: Breast cancer, Cancer screening, Health Belief Model 94 P 4.3 Epidemyology Women with breast cancer in North East of Iran are obese 3 1 Fatemeh Homaei-Shandiz, M.D., Associated professor of Radiation-Oncology, cancer Research Center, MUMS, Iran; 2Mohammad-Reza Ghavam-Nassiri, M.D, Associate Professor of Radiation-Oncology, 1,2 Department of Radiation-Oncology, Faculty of Medicine, Omid Hospital, Mashhad University of Medical Sciences, Iran; 3Mommamad Khaje-daloee, M.D, Associate Professor of Epidemiology,3Social Medical Center; 4Elham Esmaelee-Shandiz, MD, General Practitioner, Omid Hospital, Mashhad University of Medical Sciences, Iran; 5Marzyeh Razban, MD, General Practitioner, Omid Hospital, Mashhad University of Medical Sciences, Iran; 6Abdolreza Norouzy PhD, MRCP, Assistant Professor of Clinical Nutrition; 7 Mohsen Nematy *, MD, PhD, Assistant Professor of Clinical Nutrition ; 6,7 Department of Nutrition and Biochemistry, Faculty of Medicine, MUMS, IRAN Dr. Fatemeh Homaei Shandiz <[email protected]> Abstract Background: Breast cancer is the most frequent cancer among women worldwide. It has been the most common cancer (%32) and the second cause of cancer mortality (19%) among Iranian women in 2004, affecting women at least one decade younger than their counterparts in developed countries. Epidemiological studies have shown that obesity is a risk factor for post-menopausal breast cancer. Objectives: The aim of this study was to determine obesity prevalence in patients with pre and post menopausal breast cancer and controls. Methods: A case control study was performed to determine the body mass index (BMI) in 231 patients with either pre or post menopause documented breast cancer using excisional biopsy in both Omid and Ghaem teaching hospitals (Mashad, Iran) between June 2007 and June 2008. . Patients were compared with five hundred and sixteen healthy women. Results: Results showed that 27.7%, 37.7%, and 34.6% of patients regardless of being in pre or post menopause were obese or severely obese, overweight, and normal or underweight respectively. In control group this data was significantly different and only 19.4% of controls were obese or severely obese (p-value = 0.022). Considering menstruation status with BMI, overweight and obesity ratio was higher in cases in both premenopausal status than controls (25.7 kg/m 2 vs. 18.3 kg/m2 p = 0.17) and postmenopausal status than controls (30.8 kg/m 2 vs. 21.3 kg/m2 p = 0.11). Conclusion: Results from this study showed that overweight and obesity may predict risk of breast cancer in both pre and post menopausal north east Iranian women. Key words: Breast Cancer, Body mass index, Obesity, Pre menopause, Post menopause. Source of founding: Mashhad University of Medical Sciences 95 P 4.4 Epidemiology The relationship of diabetes, body shape and breast cancer Samira Ebrahimzadeh Zagami, M.Sc. 1, Nahid Golmakani, M.Sc. 1, Azadeh Saki, PhD2, Dr. Fatemeh Homaii Shandiz, MD.3 1 Lecturer and faculty of midwifery, School of nursing and midwifery, Mashhad University of Medical Science, Mashhad, Iran; 2Mashhad University of Medical Science, Mashhad, Iran; 3Omid Hospital, Mashhad University of Medical Science, Mashhad, Iran. Corresponding author: Samira Ebrahimzadeh Zagami; Email: [email protected] Abstract Background: Breast cancer is the most common malignancy among women in the world. So, it is important to identify high risk women. It is thought that the body size and shape may have a key role in increasing breast cancer. There are controversial studies about it. Aim: The purpose of this study was to determine the relationship between the size and shape of the body and breast cancer. Methods: In this case control study, 400 women participated (200 were diagnosis for breast cancer and 200 were healthy women). The study was done in Omid Hospital and Ghaem Hospital (Mashhad, Iran) in 20102011. After completing the interview form, it was measurement the weight, height, breast size and waist, hip, arm and chest circumference. Body shape questionnaire was used. The data were analyzed using t- test, correlation and Chi-square test. Results: The cases had higher weight, and waist, hip, and chest circumference compared to the controls (the difference was statistically significant in women aged ≥50 years) and significant lower height and arm circumference in total cases. Thyroid and android bodies were higher in case group and gynaeoid and lymphatic bodies were higher in healthy women. This difference was statistically significant (P <0.001). Conclusion: Our findings demonstrated that a few body size factors and body shape influence the risk of breast cancer. Age appears to affect the relationships. Key Words: Body circumferences, body shape, breast cancer P 4.5 Epidemiology The relationship of diabetes, body shape and breast cancer Samira Ebrahimzadeh Zagami, M.Sc. 1, Nahid Golmakani, M.Sc. 1, Azadeh Saki, PhD.2, Masoumeh Bagheri, B.Sc.3 1 Lecturer and faculty of midwifery, School of nursing and midwifery, Mashhad University of Medical Science, Mashhad; 2Mashhad University of Medical Science, Mashhad; 3Ghaem Hospital, Mashhad University of Medical Science, Mashhad, Iran.Correspondance: Nahid Golmakani; Email: [email protected] Abstract Introduction: Incidences of breast cancer and diabetes have increased over the past decades with the obesity. Insulin resistance is associated with breast cancer risk and is characteristic for type 2 diabetes. More than 16% of patients with breast cancer have 96 diabetes, and old age and obesity are two major risk factors for type 2 diabetes and also are associated with breast cancer. On the other hand, few studies have shown that there may be a correlation between breast cancer and body shape. Aim: So this study was performed to evaluate the relationship of diabetes, body shape and breast cancer. Methods: In this case control study, 400 women (200 were diagnosis for breast cancer and 200 were healthy women) participated. The study was done in Omid Hospital and Ghaem Hospital (Mashhad, Iran) in 2010-2011. The Samples filled a questionnaire included demographic characteristics, reproductive and body shape questionnaire. Data were analyzed using Chi-square and regression.Results: In this study, 17.7% of patients with breast cancer had diabetes. Women with diabetes had an increased incidence of breast cancer (2.64; 95% CI 1.41– 4.92) compared with women without diabetes. Body shapes were android in 30.6% and lymphatic in 29.4% of women with both diabetes and breast cancer. There was significant difference between diabetes, body shape and breast cancer (p=0.004). Conclusion: It seems that diabetes together with the body shape may be a predictive of breast cancer in women. More studies are needed to do with larger sample in this regard. Key Words: Diabetes mellitus, body shape, breast cancer. P 4.6 Epidemiology Are Asian breast cancer patients younger? An age-period-cohort analysis of data from International Agency for Research on Cancer (IARC). Alireza Mosavi-Jarrahi, Ph.D. Associate Prof. of Epidemiology Dept. Social Medicine, Medical School Shahid Beheshti University of Medical Sciences, The Cancer Institute Research Center, Tehran, Iran Correspondence: Alireza Mosavi-Jarrahi, Ph.D., Tel: +98-912-114-5572 Fax: +9821-66428655; E.Mail: [email protected] or; URL:http://sites.google.com/site/epiamosavi/ Abstract Introduction: Breast cancer is the most frequent cancer among females almost in all population of the world. There is a good volume of literature that patients of Middle East and Asia are in average one decade younger than their counterpart in developed and European countries. This study aimed to utilize the data from cancer in five continent volumes I through XIII to examine if a younger age is, in fact, a through phenomenon of breast cancer natural history in Asian populations. Material and methods: Data from cancer in five continent volume I through XIII were obtained from IARC data repository for 8 populations; four from Asia (Singapore, China-Honking, Japan-Ozaka, ChinaShanghai), and four from developed countries (Denmark, Australia, Germany, Norway). Under the assumption that age specific incidence is a function of age specific risk plus a risk acquired due to exposure to risk factors in a period and an underlying risk acquired due to a cohort effect, data were prepared to fit an age-cohort-period analysis. A Poisson regression model were fitted to the data for each population, the age specific incidence was obtained after taking into account the period and cohort effect. Result: The adjusted age specific cohort indicated no difference in terms of magnitude between countries of 97 Asia and Europe before age 50 years (premenopausal) however, significant difference was observed post menopausal age. In the European countries incidence increased as age increased but in Asian population incidence plateau after age 50-60. Conclusion: It was concluded that a younger age among Asian population is in fact an artifact of identification Bias. P 4.7 Epidemiology Cancer overview in Iran comparing Middle East global problem and regional solutions Ali Motlagh*, Payam Azadeh**, Abdolah Fazalizadeh, Mohamad Esmaeil Akbari, Rashid Ramezani, Fatemeh Nadali *Radiation Oncologist, MD, MPH, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Radiation Oncologist, MD, Jorjani Cancer Center, Imam Hossein Hospita, Shahid Beheshti University of Medical Sciences, Tehran, Iran President of Iranian Cancer Society, Tehran, Iran Professor of Surgery, Head of Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Cancer Office, Ministry of Health, Tehran, Iran Abstract Based on WHO estimation the incidence of cancer will rise from 10 million in 2000 to 20 million in 2020 and nearly 70% of this increase will occur in developing countries. The last report of pathology based cancer registery program show the age-standardized rate (ASR) is 148 and 135 in men and women respectively. The incident case are more than 80,000 each year that is estimated increase two to three fold in 10 to 15 years. The main cause of this raising is increasing life expectancy that has reached from 58.9 in 1979 to 71.7 in 2009. The most common incident cases are breast, stomach, colorectal and bladder cancer in both sexes. In Iranian men, stomach, bladder, prostate and colorectal are most common while breast, colorectal, stomach and esophagus are common in women. The five years survival is not available in national level but there are some institutional reports. For example, cancer research center of Shahid Beheshti Medical University organized some research project for estimation of survival of prevalent cancer in Iran using follow up of patients that were registered in national cancer regitery program before. Bsed on these studies the five years survival of breast cancer were 71% in Iran. Recently Iranian Cancer Society has planned to start a data rgistery for collection of clinical, pathologic characteristics and routine practices in seven main cancer centers around the country. The registration will do using web-based software named CRABCARE that prepared for this purpose. There are some similarities between Middle East country regarding population pyramid and most of them are categorized as low prevalent area for cancer in the world but seems with increasing the life expectancy the incidence of cancer more dramatically increase comparing developed countries. The ASR of cancer has some diversity in Middle East and differs from 76.6 in Syria and 177.8 in Lebanon for men and 69.3 in Syria and 162.1 in Lebanon for women. In contrast, of most 98 of the western countries, some countries in Middle East have more incident case in women than in men and majority of them are categorized as high and low income countries. Control of cancer need to a comprehensive program and each program cannot be planned without valid data. Such data including clinical, pathology, stage at presentation and routine practice. One of the opportunities of mutual program between Middle East countries can be registration of cancer data in cancer centers via a web based program like program that have be designed for this purpose in Iran. 5. Cancer Genetics P 5.1 Cancer Genetics Micronucleus frequency among Iraqi thyroid disorder patients AL-Ramahi I.J.1 , AL-Faisal A.H.M2, and Abudl-Hassan I.A. 1 1 Genetic Engineering and Biotechnology Institute (GEBI; [email protected]), Baghdad, Iraq. Ministry of Industry, Baghdad, Iraq Correspondence: Dr. Intesar Jawad Kadhm The A1-Razi Center for Research & Medical Diagnostic Kits Production Ministry of Industry & Minerals, Baghdad, Iraq. E-mail: [email protected] Mobile: 009647702731130 2 Abstract Background: Micronucleus assay has been extensively used in detection of DNA damage and instability in cancer and genetic disorders. Aim: This study was aimed to investigate the micronucleus frequency among Iraqi thyroid disorder patients.Materials and Methods: In the current study, Micronucleus, binucleated cells and nuclear division index (NDI) were investigated in Iraqi patients with thyroid disorders. Results: The results indicated that significantly (p<0.05) increased BN Micronucleus frequencies in thyroid cancer group (37.58±3.07) versus other thyroid disorder groups (6.60 ± 1.29, 14.90 ± 1.69, 15.56 ± 1.76). While the frequency of micronucleus per 1000 and the NDI were significantly (p<0.05) decreased in hypothyroidism (Micronucleus 1.55±0.36) (NDI 0.009±0.001) versus other thyroid disorder groups (MN: 6.05 ± 0.97, 6.09 ± 0.53, 5.34 ± 0.56) (NDI: 0.049±0.003, 0.032±0.002, 0.025±0.002), with no difference versus healthy group (0.0±0.0). The number of BN Micronucleus and micronucleus are parallel to the severity of thyroid disorders which were 6.60±1.29, 14.90±1.69, 15.56±1.76 and 37.58 ± 3.07 for hypothyroidism, thyroid toxic goiter, thyroid non toxic goiter and thyroid cancer, respectively. The number of BN Micronucleus and Micronucleus are parallel to the severity of thyroid disorders which were 6.60±1.29, 14.90±1.69, 15.56±1.76 and 37.58 ± 3.07 for hypothyroidism, thyroid toxic goiter, thyroid non toxic goiter and thyroid cancer, respectively. Conclusion: The results indicated that there were no significant differences among age and sex groups as related with BN Micronucleus formation within each thyroid disorder groups and healthy control group. Key words: Micronucleus; Thyroid; Cancer; DNA 99 P 5.2 Cancer Genetics Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma Imen MILADI-ABDENNADHER, Rania ABDELMAKSOUD-DAMAK, Lobna AYADI, Abdelmajid KHABIR, Foued FRIKHA, Lamia KALLEL, Mounir FRIKHA, Tahia SELLAMIBOUDAWARA, Ali GARGOURI and Raja MOKDAD-GARGOURI Centre de Biotechnologie de Sfax – Tunisia e-mail: "imen miladi" <[email protected]> Abstract Background: The methylation of CpG islands in the promoters is associated with loss of protein via repression of gene transcription. Several studies have demonstrated that tumour suppressor and DNA repair genes are often aberrantly hypermethylated in colorectal cancer. Aim: The present study was conducted to examine whether the methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was associated with clinical features and patients’survival in CRC (colorectal carcinoma). Results: Aberrant methylation of p16INK4a and hMLH1 promoters was found in 47.2 and 53.4% of tumours respectively. For adjacent non-tumoral mucosa, p16INK4a was fully unmethylated in 30% of the cases, whereas hMLH1 was predominantly unmethylated (76%). Methylation of p16INK4a correlated with gender and tumour size (P=0.005 and 0.035 respectively), whereas those of hMLH1 significantly correlated with overall survival (P log rank = 0.007). Concomitant methylation of p16INK4a and hMLH1 was associated with TNM (tumour, lymph node and metastases) stage and tumour size (P=0.024 and 0.021 respectively). Conclusion: Our data show that loss of hMLH1 expression through aberrant methylation could be used as a marker of poor prognosis in CRC. Keywords: Methylation; hMLH1; p16INK4a; Tunisian patients; sporadic colorectal adenocarcinoma P 5.3 Cancer Genetics Molecular analysis of the RET proto-oncogene in patients with medullary thyroid carcinoma El Annas Abdessamad1, Charaibi Abdelmjid2, Iraqi Hind2, El Mzibri Mohammed3, Hilal latifa1,4 1 Laboratoire de Génétique et de Physiologie Neuroendocrinienne – Bases Moléculaires de Maladies Génétiques, Faculté des Sciences, Université Ibn Tofail, Kénitra 14 000, Morocco, [email protected] 2 Service d’Endocrinologie Diabétologie et Nutrition, Ibn Sina Hospital, Rabat, Morocco 3 CNESTEN BP1382 RP10001, Rabat, Morocco 4 Laboratoire de Biochimie et Immunologie, Université Mohammed V – Agdal, Faculté des Sciences, Rabat, Morocco Abstract Objective: Germline mutations of RET proto-oncogene are the known cause of hereditary medullary thyroid carcinoma (MTC), which account for approximately 25% of 100 all MTC cases and occur as multiple endocrine neoplasia type 2 (MEN2) syndromes. Here, we present the contribution of RET proto-oncogene to MTC in Moroccan patients with different form of MTC. Patients and Methods: A total of 31 patients with MTC, from 31 separate families constitute the case study of this research. All patients were referred to the endocrine department for a post-operative management, 27 of them were clinically characterized as apparently sporadic cases, 3 patients with NEM2B and one with MEN2A. RET genetic screening was performed by direct sequencing RET exons 5, 8, 10, 11 and 13–16. Results: Sequence analysis revealed that 10 (37%) of the apparently sporadic cases carried an RET germline mutation who were reclassified as hereditary form. We have identified seven different mutations: 7 patients with MEN2A syndrome, all with mutation in codon 634, 4 patients with FMTC syndrome, 2 of them with mutation in codon 891 and 2 in codon 804, 3 patients with MEN2B syndrome all with mutation in codon 918. Conclusions: This is the first comprehensive genetic screening and analysis of MTC among Moroccan families. Our study confirm that C634R having the highest prevalence among the afflicted families . The results further confirm the necessity and advantages of DNA sequencing for identification of hereditary MTC cases. This will contribute to the definition of a national policy of this cancer control. Key words: Multiple endocrine neoplasia type 2, proto-oncogene RET, genetic screening. * This study has been supported by the CNRST Morocco (PROTARS/P12-20) P 5.4 Cancer Genetics Analyzing of new mutations in Iranian families with breast and ovarian cancer Sadr-Nabavi Ariane1&4, Dastpak Mahtab1, 2, 1, 4,*, Homaei-Shandiz Fatemeh 5, Bahrami Ahmad-Reza1, 2, 3,*, Bidkhori Hamid-Reza1, 2, Raeesolmohaddeseen Mahmood 1, 1 Cellular and Molecular Biology Research Department, ACECR- Mashhad Branch, Mashhad, Iran 2 Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran 3 Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran 4 Department of Medical Genetics, Mashhad University of Medical Sciences, Mashhad, Iran 5 Department of Radiation Oncology, Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Correspondence: Dr. Sadr-Nabavi Ariane1 (PhD); [email protected] Tel;00985118002226; 00989155570305 Abstract Background: The most common malignancy among females in the world, is Breast cancer. In Iran, Breast cancer is the first malignancies among women. Familial history and Age are the significant risk factors for the progress of this disease in Iran. The majority of hereditary breast cancers can be associated with inherited mutations in BRCA1 and BRCA2 genes. Some new studies demonstrated that BRCA1 mutations are seen in high-risk women with positive family history of breast cancer. Methods: Two patients were included in this study. The first one was a 41 years old woman who developed bilateral cancer in two different ages of 24 and 41. The second patient was one of the monozygotic twins at the age of 24. The pathological characteristics of the studied tumors were different. 10 families were also included in this study as control group, who 101 showed no cancer in three generations. BRCA1 gene was screened for all exons by PCR and sequencing methods. The data was analyzed with ABI Sequencing Analysis Seq Scap 2.5 software. The sequencing data was compared with the NCBI/GenBank data base using BLAST and with our data base using BioEdit and Mega software. Results: We found some polymorphisms and a novel mutation (Arg762Ser) in exon 11F for BRCA1 gene. DNA samples of 10 control families and one pair twin reanalyzed for new mutation on exon-11F by direct sequencing. The results confirmed that new mutation is not the case in the controls and twins. Conclusion: We conclude that this mutation is a missense mutation and unclassified variant (UV). This mutation could be used as a predictive factor in Iranian families with familiar breast and ovarian cancer. However, this needs to be further analyzed by functional tests. GenBank accession number: These sequence variant have already been submitted to GenBank: accession number BankIt1473921 JN686490 Key words: Breast cancer, BRCA1, unclassified variant, Iran P 5.5 Cancer Genetics Secondary chromosomal abnormalities of de novo acute meyloid leukemia: the first report from Middle East Abolfazl Movafagh 1*, Maryam HajiSeyed Javadi1, Abbas Hajifathali2 *1 For correspondence; Department of Medical Genetics,Shahid Beheshti University of Medical Sciences (SBMU) , Tehran Iran, Fax +98(21) 2240067- +98 -21 - 23872572, E mail: [email protected] 2-Department of Internal Medicine, Oncology, Hematology, Cancer research Centre,Shahid Beheshti University of Medical Sciences 3-Department of Paramedical and Proteomics, Shahid Beheshti University of Medical Sciences Abstract Background and Aims: The secondary chromosome aberration in de novo Acute Meyloid Leukemia (AML) is less specific and occur in addition to the primary chromosome abnormalities. Secondary chromosome aberration in acute nonlymphocytic leukemia has been recognized for many years as the most serious long – term complication malignant disease. Our aim of this study was one that focused on patients with ANLL associated with secondary chromosomal abnormalities in an Iranian populations following conventional and High Resolution Cell Synchronization technique. Methods: We analyzed 127 consecutive patients with AML using Methotrexate cell synchronization and 24h un-stimulated cultures of bone marrow cells to determine the incidence of chromosomal aberrations and association of specific primary and secondary chromosome anomalies according to French American British (FAB) morphological subtypes. Results: The distribution of the secondary changes was clearly nonrandom. The most frequent numerical changes were –X,- Y, -7, +8, -10 and +22 and the most common structural aberrations were i(17q), 9q-, dicentric and marker chromosome. Conclusion: We believe this report is the first of de novo ANLL patients showing secondary chromosomal abnormalities presented here. These findings could contribute to widen the knowledge of the related chromosomal abnormalities to ANLL patients being 102 reported here. The information provided in this study, demonstrated that the distribution of secondary chromosomal changes in our ANLL patients is quite nonrandom. Key Words: Abnormality, Chromosome, Iran, Leukemia, Secondary P 5.6 Cancer Genetics Genotoxicity of anticancer drug Azathioprine (Imuran): Role of omega-3 (ω-3) as protective agent Elelaimy I.A*; Elfiky, S.A.**; Hassan, A.M.**; Ibrahim, H.M.*Alsayad; R.I**. Faculty of Science Monoufia University* Shebin Elkom, Egypt& National Research Centre NRC**, Dokki, Egypt. Correspondence: Dr. Ibrahim Elaimy: [email protected] Abstract: Omega-3 (ω-3), is long-chain, polyunsaturated fatty acids (PUFAs) of plant and marine origin. The present study was conducted to evaluate the protective effect of omega-3 against cytotoxicity and genotoxicity of anticancer drug; Azathioprine (Imuran). Male levels; therapeutic (5mg|kg) and double therapeutic (10mg|kg) doses. Azathioprine was intraperitonealy injected with the previous doses in 0.1 ml of 0.9% NaCl for 3 times at 48 hour interval. Omega-3 was orally administered with 0.05 ml per head for ten consecutive days either before or after Azathioprine treatments. At the end of experimentation period, samples of bone marrow were collected from five mice within each group for micronucleus assay. The liver and testis tissue samples were removed and stored at – 80 C until use for DNA extraction, and determination of glutathione contents. Another animal group was treated at the same regimen and were used for the determination of sperm abnormalities and sacrificed after 35 days. Epididymis were removed for the sperm abnormality study. The results indicated that oral administration of omega-3 either before or after treatment of Azathioprine was effective in reduction of the frequencies of Mn-PCEs, decreased the DNA fragmentation, total sperm abnormalities and significantly increased sperm count, percentage of PCEs, enhanced the ratio of PCEs to NCEs. However, random amplified polymorphism of DNA (RAPD) showed distinct differences in animal groups intoxicated with Azathioprine before and after omega-3 treatment, which reflected DNA protective effect of omega-3. Depletion in glutathione content in testis was also observed in Azathioprine treated mice, which was improved by oral administration of Omega-3 either before or after treatment with Azathioprine. Keywords: Omega-3, micronucleus test, sperm abnormalities, RAPD, Genotoxicity. 103 P 5.7 Cancer Genetics Studies on a new novel detoxification-related gene Mohamed Nassef1, Yuji Oshima2 1 Labortory of Biotechnology and Immunity, Tanta University Egypt, Division of Bioscience and Biotechnology, Kyushu University, Japan Correspondence: Dr. M. Nassef; E-mail: [email protected] 2 Abstract Full-length cDNA sequence of tributyltin-binding protein type1 in Japanese medaka (Oryzias latipes) (Olat.TBT-bp1) was determined by means of rapid amplification of cDNA ends (3´/5´-RACE) of liver tissue. Genomic analysis of the structure of the gene encoding Olat.TBT-bp1 protein revealed that the exon–intron organization of this gene corresponded to that of the genes encoding lipocalin superfamily proteins, suggesting that Olat.TBT-bp1 can be categorized as a member of the lipocalin superfamily, which plays an important role as a detoxification-related gene for carcinogenic components. Additionally, intraperitoneal injection with tributyltin-d27 (TBT-d27) fish–1. Blood samples were then collected on day 7 after injection and BT-bp1 in the blood sera were purified and quantified by western blotting analysis. As a result, a positive relationship between the concentrations of TBT-bp and TBT was observed. We suggest that TBT-bp may play an important role in detoxification cycle of carcinogenic components. More studies are required to confirm this point. 6. Tumor Markers P 6.1 Tumor Markers Tumor safe margin ambiguity: different expression of CCND1 in normal adjacent and normal tissues in breast cancer Rezvan Esmaeili, Ph.D candidate; Keivan Majidzadeh-A, MD, MPH, Ph.D; Asieh Olfatbakhsh, MD; Leila Eini, MSc; Ali akbar Zare, MSc Cancer Genetics Research Group (CGRG), Iranian Center for Breast Cancer (ICBC), Academic Center for Culture, Education and Research (ACECR); Iran E-mail: Dr. Keivan Majidzadeh" <[email protected] Rezvan Esmaeili <[email protected]> Abstract Background: The safety of tumor margin in breast cancer surgery is one of the most important issues affecting prognosis and survival of the patients. Some observations have showed that pathologically confirmed tumor free tissues around the excised tumor may have some differences with normal tissue. Aim: To help to confirm possible differences between normal tissue adjacent to the tumor and normal tissue, we compared the gene expression in “normal tissue adjacent to the tumor”,” tumor tissue” and “absolute normal tissue obtained from non-affected women”. Method: mRNA was extracted from 195 104 breast tissues ( 90 tumors, 90 normal adjacent and 15 normal breast tissues from cosmetic reductive surgery) using RNXplus (cinagen, Iran), cDNA was prepared using 1ug of total RNA (Qiagen, GmbH ).mRNA expression of ki67, CDKN1B, CDKN1A, CCND1, CCNE was measured by Real- Time PCR (ABI7500) using ACTB and TFRC as endogenous control. Raw data was analyzed by Applied Bio Systems SDS software v.2. Gene expression analysis was done with REST 2009 software (Qiagen, GmbH). Results: Comparison of gene expression between tumor and normal adjacent reveal that KI67 is up-regulated in tumors by mean factor of 3.025 with P (H1) =0. Same analysis between tumor and normal breast tissue shows up-regulation in Ki67 and down-regulation in CDKN1B by mean factor of 6.192 and 0.131 and P (H1)= 0.001 and 0.014 respectively. At last CCND1 is up regulated in normal adjacent in comparison with normal breast tissue by mean factor of 4.687and P(H1)= 0.039. Conclusion: Although differences in gene expression profile of the tumor tissue vs. normal tissue are obvious, those of normal adjacent vs. normal breast tissue may spot to the fact that molecular analysis of surgical normal adjacent tissues can help to detect non-clear adjacent tissues which may change to tumor in the future. Obviously Excision of these tissues will reduce recurrence and improve prognosis and survival of the patients. P 6.2 Tumor Markers Survey efficacy of polymorphism LEPR (Lys109 Arg) in susceptibility to breast cancer Fatemeh Homaei Shandiz, M.D. 1;Jalil Tavakkol Afshari, PhD; *2; Parvaneh Sanglakh1; Azam Brook1; Rashin Ganjali1; Monavar Afzalaghaee, MD3; Mohsen Nematy, MD, PhD.4; Shadi Emami, M.D.3; Javad Aghamohammadian. 1 Associated professor of Radiation Oncology, Cancer Research Center of Mashhad University Medical of Sciences, Omid and Ghaem Hospitals, Iran; 2* Immunology research center, Buali Institute, Mashhad University of Medical Sciences; 3 Mashhad University of Medical Sciences; 4 Department of Nutrition and Biochemistry, Faculty of Medicine, MUMS, IRAN * Corresponding author: Dr. Jalil Tavakkol Afshari, Associated professor of Immunology, Immunology Research Center, Buali Institute, Mashhad University of Medical Sciences Abstract: Introduction: Breast cancer is one of the most frequent malignancies among Iranian women. The most obvious character of this cancer is young age susceptibility. The prevalence of this affliction in Iran has been reported 17.44 cases per100000in 2007 [1]. Having strongly confirmed the relation between Leptin receptor as a mediator in obesity and breast cancer, we evaluated the gene polymorphism of leptin receptor [2]. The aim of this study was to assess the gene polymorphism of leptin receptor (109 codon) in breast cancer patients and comparison with control group. Material and Methods: In this study we compared 89 patients of breast cancer with 94 cases as control group. Having extracted the DNA from blood leucocytes by salting out method, the gene polymorphism of leptin receptor in 109 codon was assessed by PCR-SSCP method. Results: The results 105 of our survey revealed no meaningful relation between breast cancer and gene polymorphism of LEPR109 (p=0.54). Also, there was not a meaningful relation between allele's frequency and induction of breast cancer among our patients. No significant relation between this gene polymorphism and BMI was also observed (p=0.722). Conclusions: The results of this study showed that LEPR (Arg 109 Lys) mutation did not have any role in our breast cancer patients. It was also proved that our cases did not have higher BMI compared to control group. Key Words: breast cancer –PCR-SSP- LEPR109 P 6.3 Tumor markers PIVKA II, cytokeratin 19, and glypican as biomarkers for Hepatitis C virus related hepatocellular carcinoma Rasha A. Alm El-Din, M.D. 1, Mohamed M. El-Bedewy, M.D. 2, Mohamed A. Alm El-Din, M.D.3 Department of Medical Microbiology and Immunology 1, Internal Medicine2, and Clinical Oncology3 , Tanta University Hospital, Tanta Faculty of Medicine, Tanta, Egypt Correspondence: Dr. Mohamed Alm El-Din [[email protected]] Background: PIVKA-II, cytokeratin and glypican-3 (GP3) have been investigated in several setting as new biomarkers for diagnosis of Hepatitis C virus (HCV) related hapatocellular carcinoma (HCC). Aim of work: To evaluate the serum level of PIVKAII, cytokeratin and GP3 as new biomarkers for diagnosis of HCV related HCC. Materials and Methods: Two groups of patients were studied; the first group consisted of 30 patients with radiologically-diagnosed or biopsy-confirmed HCC with underlying HCV cirrhosis and the second group included 30 patients with HCV cirrhosis Serum samples were assessed by specific ELISA assay for PIVKAII, cytokeratin and Glypican-3. Results were compared to that of the established biomarker, alpha-fetoprotein (AFP). Results: The mean serum level of AFP was significantly higher in patients with HCC complicating HCV cirrhosis as compared to those with HCV cirrhosis (91.62 ng/ml vs. 5.41 ng/ml, respectively, p value <0.0001). Similarly, the serum of patients with HCC showed significantly higher level for both PIVKA-II and cytokeratin (41.72 ng/ml and 167.38 ng/ml, respectively), when compared to patients with HCV (8.56 ng/ml and 94.97 U/L, respectively p value <0.0001). There was no significant difference in the serum level of GP3 between the study groups. Conclusion: PIVKAII and cytokeratin 19 are good biomarkers for diagnosis of HCC in HCV cirrhotic patients with comparable specificity and sensitivity to AFP. 106
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