1. health and fitness
2. disease

FORORD
Kjære konferansedeltaker,
VELKOMMEN TIL FRAMPEIK 2015 I TROMSØ!
Frampeik er for de nysgjerrige. Konferansen er en årlig samling hvor studenter med
interesse for forskning kan utveksle ideer, resultater og erfaringer. Terskelen er lav, men
kvaliteten høy!
Årets konferanse er den ellevte i rekken, og det er tredje gang Tromsø er vertsby.
Fredag vil det være foredrag og paneldebatt, før kvelden avsluttes på et villmarkssenter utenfor byen. Lørdag er det fokus på studentpresentasjoner, avbrutt av et foredrag
midt på dagen som avveksling. På kvelden blir det tradisjonen tro gallamiddag med
påfølgende etterfest. Søndag avsluttes konferansen med et årsmøte.
I år har det faglige programmet fokus på evidens. Vi har tatt utgangspunkt i pillebruken
innen psykiatrien, hvor kritiske røster stiller spørsmål ved evidensgrunnlaget for dagens
behandlingsstrategier. I den anledning har vi invitert representanter fra akademia, politikken, myndighetene og klinikken. Vi tror myter både vil bekreftes og avkreftes innen
et område hvor motsetningene er steile.
Vi ser frem til en minneverdig helg sammen i Tromsø, og ønsker deg hjertelig velkommen til Frampeik 2015!
På vegne av styret,
Marcus Roalsø
Leder av Frampeikstyret 2015
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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STYREMEDLEMMER
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Marcus Roalsø
Leder
Morten S. Næss
Faglig ansvarlig
Lars Rødland
Økonomi
Tryge S. Ellingsen
Sponsor
Johanna Öberg
Sosialt ansvarlig
Kristine Andreassen
Sosialt ansvarlig
Marit K. Busund
PR
Lisa G. Hansen
PR
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
INNHOLDSFORTEGNELSE
FORORD
2
STYREMEDLEMMER
3
INNHOLDSFORTEGNELSE
4
SPONSORER
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FOREDRAGSGHOLDERE
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SOSIALT PROGRAM
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KORTPROGRAM
8
KART OVER CAMPUS
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ABSTRACTS
10
POSTERS
39
EGNE NOTATER
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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SPONSORER
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
FOREDRAGSHOLDERE
Peter C. Gøtzsche
Professor dr. med. Peter C. Gøtzsche er leder av det Nordiske Cochrane-senteret i København, spesialist i
indremedisin og professor i klinisk forskningsdesign og analyse ved Københavns Universitet. Han tok sin M.Sc.
i biologi og kjemi i 1974 og jobbet siden i legemiddelindustrien i perioden 1975-1983. I 1984 avla han medisinsk embetseksamen, og arbeidet ved sykehuset i København fra 1984 til 1995. Sammen med omlag 80
andre bidro Professor Gøtzsche til dannelsen av the Cochrane Collaboration i 1993, og han var sentral da
Nordisk Cochrane-senter ble opprettet senere samme år.
Professor Gøtzsche har publisert mer enn 70 vitenskapelige artikler i kjente tidsskrift som BMJ, Lancet, JAMA,
Annals of Internal Medicine og New England Journal of Medicine. Foreløpig har han blitt sitert over 15 000
ganger. Han er også forfatter av flere sakprosabøker om evidensbasert klinisk beslutningstaking, mammografiscreening og ikke minst - om legemidler.
Peter C. Gøtzsche har blitt kalt upresis, rabiat og endog uetisk korsfarer mot legemiddelindustrien av enkelte,
men han høster også lovord som høyst respektert og erfaren forsker. I 2014 vant hans oppsiktsvekkende bok
om legemiddelindustrien «Dødelig medisin og organisert kriminalitet» den britiske legeforenings (BMA) pris
i klassen «Basis of medicine». Oppfordringen fra BMAs litteraturkritiker var klar; “I would say that this book
should be compulsory reading for medical students and junior doctors to make them aware of these issues…”
Steinar Madsen
Steinar Madsen tok sin legeutdanning ved Universitetet i Oslo og ble uteksaminert i 1981. I dag er han privatpraktiserende spesialist i indremedisin og hjertesykdommer, samt medisinsk fagdirektør ved Statens legemiddelverk (LMV). Sistnevnte har flere oppgaver. Blant annet godkjenner LMV legemidler for bruk i Norge,
overvåker deres bivirkninger samt fastsetter pris på reseptbelagte legemidler. Deres overordnete mål er at
legemidler som markedsføres i Norge er sikre og effektive, samtidig som legemidler har lavest mulig pris.
I løpet av årene har Steinar Madsen gjort seg bemerket i den offentlige debatten i Norge rundt bruken, nytten
og sikkerheten vedrørende legemidler. Han brukes ofte som faglig kilde, men havner gjerne i kryssilden når
temaer som vaksiner og prioritering kommer på dagsordenen.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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SOSIALT PROGRAM
UTFLUKT FREDAG 30. OKTOBER
Fredag kveld etter avsluttet faglig program drar vi med buss ut til Kvaløya og Tromsø Villmarkssenter. Der
venter mat og kos i gamme. Er vi heldig er det nordlys og snø ute. Gammen er oppvarmet, men det anbefales
likevel å ha på seg godt med klær og gode sko. Det går buss tilbake til byen kl 23 og kl 01. Dersom deltakerne
har mulighet å sjekke inn på konferansehotellet The Edge før programmet på fredag er dette er fordel. Dersom
dette ikke er mulig har vi anledning til å oppbevare bagasjen.
Som en del av arrangementet på Villmarkssenteret spiller søstrene Gaup en liten konsert. Sara Marielle Gaup
Beaska, Risten Anine Kvernmo Gaup og gitarist Viktor Bomstad er tre velkjente og kjære lokale musikere, opprinnelig fra Kautokeino og Storfjord. De spiller et sammensurium av sjangre med tekster på samisk og engelsk
med joik og innslag av spoken words, og er kjente for å skape magisk stemning.
GALLAMIDDAG LØRDAG 31. OKTOBER
Vi feirer på hotell The Edge midt i Tromsø sentrum. Her blir det treretters middag fra det fantastiske og økologiske kjøkkenet til The Edge. Utsendinger fra Gratis Øl, lokale humoryndlinger og Norgesmestre i improteater
er konferansierer – for å geleide oss gjennom mat og taler.
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
PROGRAM
FREDAG 30. OKTOBER
KLOKKESLETT
HENDELSE
STED
15.00 - 16.30
Registrering
Store auditorium, Teorifagbygget hus 1
16.30 - 17.00
Åpning av konferansen ved rektor Anne Husebekk.
Store auditorium, Teorifagbygget hus 1
17.00 - 17.50
“Legemidler - i kryssild mellom industri, politikk og
pasienter“. Foredrag ved Steinar Madsen.
Store auditorium, Teorifagbygget hus 1
17.50 - 18.00
Pause
Store auditorium, Teorifagbygget hus 1
18.00 - 19.00
“Dødelig medisin og organisert kriminalitet”
Foredrag ved Peter C. Gøtzsche.
Store auditorium, Teorifagbygget hus 1
19.00 - 19.50
Paneldebatt. Spørsmål til foredragsholderne og
diskusjon. Åpent for innspill fra salen.
Store auditorium, Teorifagbygget hus 1
20.15
Busstransport til Tromsø Villmarksenter.
Utenfor Teorifagbygget hus 1
01.00
Busstransport tilbake til Tromsø og konferansehotellet
Tromsø Villmarkssenter
The Edge.
LØRDAG 31. OKTOBER
KLOKKESLETT
HENDELSE
STED
09.30 - 10.00
Registrering og kaffeservering
Store auditorium, MH-bygget
10.00 - 12.00
Parallelle symposier med studentpresentasjoner.
Diverse auditorium, MH-bygget
12.00 - 13.00
Lunsj
Farmasikantinen, MH-bygget
13.00 - 14.00
“Dødelig psykiatri og organisert fornektelse”
Foredrag ved Peter C. Gøtzsche.
Store auditorium, Teorifagbygget hus 1
14.00 - 14.20
Spørsmål og innspill fra salen.
Store auditorium, Teorifagbygget hus 1
14.20 - 14.30
Pause
Store auditorium, Teorifagbygget hus 1
14.30 - 15.15
Poster-presentasjoner.
Lysgården, MH-bygget.
15.15 - 15.30
Pause
Lysgården, MH-bygget
15.30 - 17.00
Parallelle symposier med studentpresentasjoner.
Diverse auditorium, MH-bygget
17.00 - 19.00
Fri!
19.00 - ?
Gallamiddag på The Edge, etterfest på Løkta.
Clarion Hotel The Edge, Tromsø sentrum
NB! Ikke glem Frampeiks årsmøte kl. 1100-1200 på The Edge søndag morgen!
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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KART OVER CAMPUS
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Nr. 20: MH-bygget.
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
Abstracts
I. Klinisk forskning
s. 11
II. Epidemiologisk forskning
s. 21
III.Grunnforskning
s. 28
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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ABSTRACTS
KLINISK FORSKNING
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
ABSTRACT
NO TITLE
AAREBROT AK1
Department of Dermatology, Haukeland University Hospital, Norway.
1
Background
Psoriasis is a chronic, inflammatory disease of the skin driven by a dysregulated cutaneous immune
response. Several comorbidities have been identified, indicating wider immunological derangements.
Psoriasis patients are often treated with systemic immunosuppressive drugs. If conventional treatment is insufficient or contraindicated, treatment with biopharmaceuticals may be warranted. Biopharmaceuticals are effective, but very expensive. Furthermore, patients on biopharmaceuticals may
lose effect or experience adverse events. Recently, assays for monitoring drug level in the blood and
antibodies against the biopharmaceuticals have been developed and may aid in optimizing and guiding treatment of individuals patients. However, these assays have several limitations.
Aim
In this project, we want to develop new, functional, cell-based assays for monitoring the efficacy of
biopharmaceuticals. Our hypothesis is that assays that evaluate medication closer to the target, the
intracellular pathways of immune cells, may offer more accurate parameters for clinician to tailor
treatment specific for individual patients.
Methods
At the Department of Dermatology, Haukeland University Hospital is a large quality register and
biobank for psoriasis patients treated with biopharmaceuticals. We plan to evaluate our assays in
patients and correlate results to those of other assays of biopharmaceutical efficacy, gaining insights
to the development of anti-drug antibodies. Moreover, with our functional assays, we plan to compare the efficacy of current biopharmaceuticals and new biosimilars. In a more high-risk endeavor, we
will prospective evaluate new psoriasis patients. In order to identify biomarkers, clinical, genetic, and
immunological factors will be correlated to therapy and development of anti-drug antibodies.
Results
We have started collecting blood samples from psoriasis patients treated with biopharmaceuticals. At
this point we have collected samples from 53 patients.
Conclusion: Our goal is to develop predictive tools for more “personalized immunotherapy”, providing
safer and more cost-efficient treatments.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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ABSTRACT
I. KLINISK FORSKNING
RAPPING OUR REALITY: VOICES ON DISTRESS, RESILIENCE
AND PROSPECTS FOR CHANGE FROM A YOUTH CLUB WITH
AT-RISK YOUTHS IN PORT AU PRINCE, HAITI
ANDREASSEN K1, KIRKENGEN AL1, JOHANSEN ML1
University of Tromsø, Norway.
1
Background
Young people inhabiting the poor areas of Port au Prince, stand an obvious risk of harmful, even
lethal exposures of diverse character. The participants of this study, whom are all members of Etap
Jenes, a youth club for at-risk youths, come from a background of severe poverty. Nonetheless they
are seen as experts on how to “grow up well” in their area through still being in school and with
hopes for leaving poverty, while they have seen many friends from similar backgrounds succumbing
to the drugs and violence of the streets.
Aim
The study seek to investigate the phenomenon of distress and resiliency in the context of the youths,
to understand more about the possibilities to balance out distress and foster resiliency and “growing
up well”. The study also seek to act facilitative for these young people by means of offering them new
and improving already established club activities, seeking to enable them to voice their own issues.
Methods
This qualitative study is a Critical Ethnography, using a diversity of participatory methods and a variety of Creative Methods to facilitate empowering and voice of the participants.
Material
5 fieldworks of a total of 25 weeks is conducted between 2012-2015. The material consists of field
notes from these stays, 8 focus groups, 10 semi-structured interviews, 6 YPAR-meetings and a variety of creative products.
Results
Results show that understanding distress and resiliency is context specific. Voicing the youths on
these fields applies new perspectives on “growing up well” than what is already presented by international aid organizations. Further suggesting that change is needed to facilitate youth voice on discussions concerning their own well-being – especially when considering development work in a country
with such heavy burdens of poverty, inequality and violent structures.
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
ABSTRACT
CHARACTERIZATION OF INFLAMMATORY CELL INFILTRATE IN
KIDNEY BIOPSIES OF PATIENTS WITH SJÖGREN’S SYNDROME
BORGE H1
Department of Clinical Medicine, University of Bergen, Norway.
1
Background
Sjögren’s syndrome (SS) is either primary or secondary in the context of a systemic disease, such as
systemic lupus erythematosus (SLE). Renal manifestations of primary SS are heterogeneous. Little is
known about the pathogenesis and characteristic features of the inflammatory cell infiltrate in kidney
biopsies from SS patients. Renal involvement can lead to severe kidney failure due to tubulointerstitial nephritis (TIN). The inflammatory cell infiltrate represents a characteristic feature of TIN.
Aims
The overall objective of this study is to determine, if there exists long-lived plasma cells in the kidney
lesions of patients with SS.
Methods
An important part of the project is looking into the Norwegian Kidney Biopsy Registry (NKBR) where
we identify SS patients with renal manifestations.
Immunohistochemistry (IHC) will then be used to characterize the mononuclear infiltrating cells and
inflammatory mediators in the kidney lesions. We will perform a single-, double and triple- staining on
formalin fixed paraffin-embedded sections from kidney biopsies. As controls we will use biopsies from
patients with 1) unspecific TIN and 2) TIN lesions affecting non-SS patients with other autoimmune
diseases, such as SLE.
Results
Ongoing research in the database will provide us with kidney biopsies from SS patients which will
enable us to characterize the microenvironment and identify if there exist long-lived plasma cells in
these autoimmune kidney lesions. This is also an important identification process where we survey for
the first time the amount of SS patients in the western part of Norway with diagnosed kidney lesions.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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ABSTRACT/POSTER
I. KLINISK FORSKNING
DOES ELECTROCONVULSIVE THERAPY HAVE AN ACUTE
EFFECT ON METABOLITES IN THE BRAIN?
ERCHINGER V1, ERSLAND L4, ØDEGAARD KJ1,3, KESSLER U1,3, OLTEDAL L1,2
Department of Clinical Medicine, University of Bergen, Bergen, Norway, 2Department of Radiology, Haukeland University
Hospital, Bergen, Norway, 3Division of Psychiatry, Haukeland University Hospital, Bergen, Norway, 4Department of Clinical
Engineering, Haukeland University Hospital, Bergen, Norway.
1
Introduction
Major depression (MD) reduces quality of life and can at its worst lead to suicide. Electroconvulsive
therapy (ECT) is the best acute treatment for major depression where other treatments have shown
no effect. Until today the exact mechanisms of action of ECT are unknown, and it is not known how
and if the anesthetic used affects metabolite concentrations in the brain. To correct for the potential
effect of the anesthetic we compare two patient groups that receive a similar anesthesia: 1) patients
with MD receiving ECT and 2) atrial fibrillation patients that receive electrical cardioversion.
Aim
Investigate acute effects of electroconvulsive therapy on metabolites in the brain.
Design
Both patient groups will be MR-scanned immediately before and after treatment.
Methods
Magnetic Resonance Spectroscopy (MRS)
Conclusion
This is the first study that will investigate ECT by comparing patients suffering from depression with
atrial fibrillation patients.
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
ABSTRACT
EFFECTS OF SYMPATHETIC ACTIVITY ON BLOOD FLOW AND
ENDOTHELIAL FUNCTION MEASURED BY FLOW MEDIATED
DILATATION
GUNDERSEN KM1, NYBORG C1,2, SUNDBY ØH2, HISDAL J1,2
The Medical Student Research Program, University of Oslo, Norway, 2Aker University Hospital, Department of Circulatory
Research, Norway.
1
Introduction
Cardiovascular diseases are estimated to cause 31 % of all global deaths (WHO), and it is the number
one cause of death on the planet. Endothelial dysfunction is one of the initial events of atherosclerosis and can be measured non-invasively by the flow-mediated dilatation (FMD) technique. It is so
far believed that major surgery, and in particular use of the heart-lung-machine, facilitates endothelial dysfunction. This is due to an observed decrease in FMD-response post operatively. The aim of
the present study is to elucidate the effect of blood flow on the FMD-response. Deeper knowledge
of the FMD-response, and the factors that affect this response, could in the future form a basis for
giving patients a more accurate cardiovascular status, regarding endothelial function. Our hypothesis
is that decreased flow results in a decreased FMD-response independent of endothelial function.
Methods
In this study we aim to investigate the FMD-response both during normal resting condition and
during a situation with increased sympathetic activity induced by exposure of one foot to cold water.
We plan to include 40 healthy test subjects. Monitored physiological variables includes: Blood flow
and FMD in the right brachial artery (ultrasound Doppler), blood flow in the left brachial artery (ultrasound Doppler), continuous blood pressure (Finometer), acral blood flow on both index-fingers (laser
Doppler), and heart rate (ECG).
Results
This study is scheduled to start collecting data in November 2015. Pilot tests have so far showed that
our test setup is feasible. Exposure to cold water induces an increase in sympathetic activity leading
to a marked reduction in blood flow in the brachial artery. Preliminary results will be presented at
Frampeik 2015.
Discussion
Increased sympathetic activity affects peripheral circulation, and may influence the FMD-response
independently of endothelial function. Adjustment of flow should therefore be considered if the
FMD-response is tested under different conditions, i.e before- and after an operation.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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I. KLINISK FORSKNING
ABSTRACT
OPTIMIZING DETECTION OF CANCER BIOMARKERS IN ORAL
SQUAMOUS CELL CARCINOMA
JACOBSEN MR1
University of Bergen, Norway.
1
Background
To date, there are no reliable method for prognosis and stratification for individualized treatment of
oral squamous cell carcinoma (OSCC). Biomarkers are increasingly recognized to provide earlier and
more precise diagnosis of cancer, but we also know that tumours are intricate and heterogeneous
systems. Therefore, in order to use biomarkers as a diagnostic and prognostic tool in oral cancer, it is
crucial to optimize the detection of cancer biomarkers in OSCC-tumours.
Aim
To optimize the use of immunohistochemistry for robust detection and quantification of the expression of various cancer biomarkers, selected from different tumour compartments in oral squamous
cell carcinoma.
Methods
Immunohistochemistry was performed using antibodies for selected markers on formalin fixed paraffin embedded tissues, which were collected from patients at Haukeland University Hospital. Diverse
methods of quantification was tested using the program ImageJ.
Results
Several markers carefully selected based on a literature study were optimized for use on OSCC using
various IHC-protocols. Various ways of quantification of their expression (as visualized by IHC) were
tested and the most robust method was chosen for further study.
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
ABSTRACT
HEART RATE VARIABILITY IN CHILDREN WITH ADHD AND
ANXIETY
KVADSHEIM ET1
Department of Biological and Medical Psychology (IBMP), Faculty of Psychology, University of Bergen, Norway.
1
Background
Heart rate variability (HRV), the variance in consecutive heart beats, is an index of autonomic flexibility. HRV is the result of interactions between the two sub-branches of the autonomic nervous system
(ANS) on the sinoatrial node: the excitatory sympathetic nervous system (SNS) and the inhibitory
parasympathetic nervous system (PNS). Studies show that the balance between SNS and PNS is altered in several psychiatric disorders. Children with anxiety disorders show increased SNS activation,
whereas children with ADHD tend to have increased PNS activation. To the best of our knowledge,
studies of HRV in children with both ADHD and anxiety have not yet been reported.
Aim
To investigate the ANS activity indexed by HRV in children with both ADHD and anxiety, compared
to healthy controls.
Methods
The study is part of the longitudinal research project Stoppventgå, investigating children between
8-12 (first wave) and 11-16 (second wave) years old. Children participated in a diagnostic interview to
identify ADHD and anxiety disorders, as well as completing questionnaires on self- reported anxiety
levels. In the second wave we measured resting EKG for six minutes. This will be used to calculate
HRV (RMSSD, the root mean square of interbeat intervals).
Results
Preliminary results on a subgroup of the children will be presented.
Conclusion
Based on previous findings, it is likely that the ANS in children with ADHD and anxiety differs from
control children. This study will investigate the nature of these alterations.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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I. KLINISK FORSKNING
ABSTRACT
THE PROGNOSTIC ROLE OF PROGESTERONE RECEPTOR
EXPRESSION IN NON-SMALL CELL LUNG CANCER PATIENTS:
GENDER-RELATED IMPACTS AND CORRELATION WITH
DISEASE-SPECIFIC SURVIVAL
SKJEFSTAD K1
University of Tromsø, Norway.
1
Introduction/background
Progesterone has been shown to impact the development of hormone- sensitive cancers, such as
breast and ovarian cancers. Emerging evidence has revealed a possible role of progesterone in the
tumorigenesis of other cancers, including lung cancer.
Objectives/aims: Herein, we aimed to elucidate the prevalence and prognostic significance of progesterone receptor (PR) expression in non-small cell lung cancer (NSCLC) tissue.
Methods: Tumor tissue samples were collected from our patient cohort consisting of 335 NSCLC patients with stage I–IIIA disease. Tissue microarrays (TMAs) were constructed, and immunohistochemical (IHC) analyses were performed to evaluate the PR expression in the tumor epithelial and stromal
compartments.
Results
In a univariate analysis, positive PR expression in the stromal tumor compartment (P=0.005) was
significantly and independently associated with a favorable outcome for both genders. Furthermore,
positive PR expression in tumor epithelial cells (P=0.003) correlated with a poor prognosis for female
patients. In a multivariate analysis, positive PR expression in the tumor stroma (P=0.007) was an
independent prognostic factor for improved disease-specific survival (DSS). Positive PR expression in
tumor epithelial cells emerged as an independent prognostic factor in female patients (P=0.001) for
poor DSS.
Conclusions
We show that PR expression in tumor-surrounding stromal cells is associated with improved DSS for
both male and female patients. Additionally, we reveal that positive PR expression in tumor epithelial
cells is an independent, unfavorable prognosticator for DSS in female patients, making PR expression
a potential marker for prognostic stratification in NSCLC.
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
ABSTRACT
EARLY CHANGES IN SIGNALLING NETWORKS OF ACUTE
MYELOID LEUKAEMIA IN RESPONSE TO CHEMOTHERAPY
TISLEVOLL BS1, PIECHACZYK LI2, DURAN MDPA2, ENSERINK J2, FLØISAND Y3, GJERTSEN BT1,4
Department of Clinical Science, University of Bergen, Bergen, Norway, 2Department of diagnostics and intervention, Oslo
university hospital, Oslo, Norway, 3Department of haematology, Oslo university hospital, Rikshospitalet, Oslo, Norway,
4
Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway.
1
Background
Acute myeloid leukaemia is an aggressive blood cancer of the myeloid origin of haematopoietic stem
cells. It is characterized by an abundance of poorly differentiated myeloid cells called blasts. The disruption of the myeloid differentiation leads to a disordered developmental hierarchy where leukemic
stem cells (LSC) are able to re- initiate the disease, even after initial remission.
AML is a heterogeneous disease, with a low overall survival. The genetics and epigenetics of the
disease have been studied extensively the latest decades, resulting in a myriad of potential targetable
mutations. But how these mutations influence the functional behaviour of the cells needs further
investigation. This can be evaluated by investigating the intracellular phosphorylation of the cells. A
profile of the cancer cells signalling system in response to environmental stimuli can reveal the underlying mechanisms of their survival and resistance to therapy.
Material and methods
To investigate the intracellular signalling in a clinical setting we have collected blood samples from
newly diagnosed AML patients, at the time of diagnosis and a few hours after the start of chemotherapy. The chemotherapy will then act as an external stimulus that will initiate the signalling networks of the cancer cells. For characterizing the functional aspect of the signalling we will employ a
mass-cytometry based approach. This provides the opportunity to investigate the intracellular signalling properties of the leukemic cells at the single cell level. At the same time the cells can be categorized based on their phenotypical caracteristics, using cluster of differentiation (CD) markers. Cells will
be stained with epitope-specific antibodies, conjugated to transition isotope reporters that each has a
different mass.
Results and conclusion
Previous results demonstrate that pre-apoptotic signalling systems are activated within hours after
the start of chemotherapy. This may be important for early patient prognostics and to find novel therapeutic targets in AML. This project is a continuation of the earlier discoveries of Øyan et al. BMC
Cancer 2009.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
20
ABSTRACTS
EPIDEMIOLOGISK
FORSKNING
21
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
II. EPIDEMIOLOGISK FORSKNING
ABSTRACT
THE PROGNOSTIC SIGNIFICANCE OF NEURO-EPITHELIAL
INTERACTIONS IN PROSTATE CANCER
BOGAARD M1, HAUGSTEN EM2, SÆTER T3, WAALER G3, NESLAND JM4 ,1, AXCRONA K5,
WIEDLOCHA A2, AXCRONA U4
The Medical Faculty, University of Oslo, Norway, 2Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway, 3Department of Urology, The Hospital of Southern Norway,
Arendal, Norway, 4Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Norway,
5
Department of Urology, Akershus university hospital, Lørenskog, Norway.
1
Background
Prostate cancer (PCa) is the most commonly diagnosed malignancy amongst men in Norway, approximately 5000 new cases were diagnosed in 2011, an increase from 4200 the previous year. PCa has
a heterogeneous clinical course ranging from indolent cancer to metastasizing cancer. It is therefore
important to find new prognostic markers in order to improve the diagnosis and patient treatment.
Both sympathetic and parasympathetic nerves constitute an important part of the prostate microenvironment, and have shown to be of great importance in the development and dissemination of PCa.
For instance, PCa patients using beta-blockers have an improved overall survival rate. Growth of cancer cells along nerves, perineural invasion (PNI), is correlated with a worsened prognosis as demonstrated in radical prostatectomy (RP) specimens. Objectives/aims: The aim of this study is to determine the role of PNI in diagnostic prostate needle biopsies (pNbx) with regard to clinical outcome, i.e.
PCa specific mortality (PCSM) and to further examine the interaction between nerves and epithelial
tumor cells.
Material and Methods
A retrospective population-based cohort study consisting of 281 patients with clinically-localized/
locally-advanced PCa diagnosed by prostate needle biopsy between the years 1991-1999 at The
Hospital of Southern Norway, Arendal is used. The study was limited to patients who were diagnosed
by trans-rectal pNbx and without evidence of systemic metastasis at the time of diagnosis (negative
bone scan M0 or Mx and a prostate-specific antigen (PSA) level <100 ng/mL). Patients were referred
from their general practitioner based on PSA-levels, urinary tract symptoms or generalized disease.
The primary treatment modalities are radical retro-pubic prostatectomy (RRP), external beam radiotherapy (EBRT), hormonal treatment (HT), i.e. anti-androgens, luteinizing hormone-releasing hormone
(LHRH)-agonists or surgical castration, or watchful waiting (WW).
Histo-pathological assessment of tissue samples was completed by two uro-pathologists without
prior knowledge of clinical data. The number of biopsies per patient varied from 2-10 biopsies. The
prostatic adenocarcinoma was graded according to the 2005 International Society of Urological
Pathology Consensus Conference on Gleason Grading of Prostate Carcinoma. PNI was defined as
adenocarcinoma within the perineural space adjacent to the nerve.
Different in vitro models were used to study the interplay between autonomic innervation and prostatic epithelial cells. The interaction of carbachol (cholinergic agonist) and norepinephrine (adrenergic
agonist), as well as nerve cells MC-IXC (cholinergic) and PC-12 (adrenergic)) co- cultured with either
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II. EPIDEMIOLOGISK FORSKNING
ABSTRACT
prostate cells (PNT2) or PCa cells (LnCap, 22Rv1 and PC-3) were examined with regard to differences
in migration, proliferation and expression of different signaling pathways.
Results
PNI in pNbx is significantly correlated with an advanced Gleason score and clinical T- stage. It is
shown that PNI was associated with PCSM in univariate analysis, but is not significant in multivariate
analysis when adjusting for Gleason score, PSA, clinical T-stage and treatment modality.
In vitro studies show that stimulation of PC-3 cells (from metastatic site) with carbachol lead to an
activation of AKT signaling as well as an increase in cell migration. Stimulation of PC-3 cells with norepinephrine did not lead to activation of AKT signaling or increase in cell migration. No differences in
activation of ERK signaling in PC-3 cells with either carbachol or norepinephrine were observed.
Preliminary results show that stimulation of 22rv1 cells (from primary tumor) with norepinephrine,
carbachol and media from PC-12 cells lead to activation of ERK signaling while no differences in AKT
signaling or cell migration were observed.
Conclusions
It was found that PNI in pNbx is associated with a worsened prognosis. In vitro findings indicate that
autonomic nerve cells signal directly to prostate cancer cells. The signaling pathways involved are
being further characterized to determine the role of autonomic nerves on the different stages of PCa
development and metastasis.
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II. EPIDEMIOLOGISK FORSKNING
ABSTRACT
RED CELL DISTRIBUTION WIDTH IS ASSOCIATED WITH
FUTURE RISK OF CANCER AND ALL-CAUSE MORTALITY
AMONG CANCER PATIENTS – THE TROMSØ STUDY
ELLINGSEN TS1,2, LAPPEGÅRD J1,2, SKJELBAKKEN T1,2,3, BRÆKKAN SK1,2,3, HANSEN JB1,2,3
K.G. Jebsen Thrombosis Research and Expertise Center, Department of Clinical Medicine, University of Tromsø, Norway,
Hematological Research Group, Department of Clinical Medicine, University of Tromsø, Norway, 3Division of Internal
Medicine, University Hospital of North Norway, Tromsø, Norway.
1
2
Background
Recent studies suggest an association between red cell distribution width (RDW) and several malignancies, but the association has never been investigated in a prospective study.
Objectives/aims
We aimed to investigate the impact of RDW on risk of incident cancer, cancer site, cancer stage and
mortality among cancer patients in a general population.
Methods
RDW was measured in 25383 participants in the Tromsø Study in 1994-95. Incident cancer diagnosis and mortality during follow-up were registered until December 31, 2010. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence
intervals (CI).
Results
In total, 1 191 men and 1 114 women were diagnosed with cancer during a median of 15.7 years of
follow-up. Men with RDW in the highest quartile (RDW≥13.2%) had 30% higher risk of cancer than
men in the lowest quartile (RDW≤12.3%). Women aged 55 years or older with RDW≥13.3% had
22% higher risk of cancer than those with RDW≤13.2% (HR 1.22, 95% CI 1.02-1.45). High RDW was
associated with increased all-cause mortality in cancer patients.
Conclusion
Our findings suggest that high RDW is a risk factor of incident cancer in males and postmenopausal
women, and that high RDW is associated with poor prognosis in cancer patients.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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II. EPIDEMIOLOGISK FORSKNING
ABSTRACT
EARLY-ONSET SEPSIS AND ANTIBIOTIC EXPOSURE IN TERM
INFANTS: A NATIONWIDE POPULATION-BASED STUDY IN
NORWAY
FJALSTAD J1
University of Tromsø, Norway.
1
Bakground
Sepsis is a leading cause of neonatal morbidity and mortality. Clinical suspicion may lead to overuse
of antibiotics.
Objective
To assess the epidemiology of early-onset sepsis (EOS) and antibiotic exposure during the first week
of life in Norwegian term infants.
Methods
Nationwide population-based study from the Norwegian Neonatal Network. During the 3-year study
period (2009-2011) 20 of Norway’s 21 neonatal units prospectively collected data. Among 168 877
live-born (LB) term infants born during the study period, 10 175 (6.0%) infants were hospitalized in
the first week of life and included in the study.
Results
There were 91 cases of culture-confirmed EOS (0.54 per 1000 LB) and 1447 cases classified as culture-negative EOS (8.57 per 1000 LB). The majority of culture-confirmed EOS cases were caused by
Gram-positives (83/91; 91%); most commonly group B streptococci (0.31 per 1000 LB). Intravenous
antibiotics were administered to 3964 infants; 39% of all admissions and 2.3% of all LB term infants.
Empiric therapy consisted of an aminoglycoside and either benzylpenicillin or ampicillin in 95% of the
cases. The median (IQR) treatment duration was 8 (7-10) days for culture-confirmed EOS and 6 (5-7)
days for culture-negative EOS. There was one EOS- attributable death (group B streptococcal EOS)
during the study period.
Conclusions
In this registry-based study the incidence of culture-confirmed EOS was in line with previous international reports and the mortality was very low. A large proportion of infants without infection were
treated with antibiotics. Measures should be taken to spare neonates unnecessary antibiotic treatment.
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II. EPIDEMIOLOGISK FORSKNING
ABSTRACT
RED CELL DISTRIBUTION WIDTH IS ASSOCIATED WITH
FUTURE RISK OF INCIDENT STROKE - THE TROMSØ STUDY
LAPPEGÅRD J1,2, ELLINGSEN TS1,2, SKJELBAKKEN T1,2,3, MATHIESEN EB1,4,5, NJØLSTAD I1,6,
WILSGAARD T6, BROX J1,2,7, BRÆKKAN SK1,2,3, HANSEN JB1,2,3
K.G.Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway, 2Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway, 3Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway, 4Brain and
Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Norway, 5Department
of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø, Norway, 6Department of Community
Medicine, UiT The Arctic University of Norway, Norway, 7Department of Clinical Chemistry, University Hospital of North
Norway.
1
Background
Red cell distribution width (RDW), an easy accessible measure of the variability in size of the circulating erythrocytes, is associated with cardiovascular morbidity and mortality.
Aim - We aimed to investigate whether RDW was associated with incident stroke and case fatality in
subjects recruited from the general population.
Methods
Baseline characteristics, including RDW, were obtained from 25992 subjects participating in the
fourth survey of the Tromsø Study, conducted in 1994/95. Incident stroke was registered from inclusion until December 31st 2010. Cox regression models were used to calculate hazard ratios (HR) with
95% Confidence Intervals (95% CI) for stroke, adjusted for age, sex, body mass index, smoking, hemoglobin level, white blood cell count, thrombocyte count, hypertension, total cholesterol, triglycerides,
self-reported diabetes, and red blood cell count.
Results
During a median follow-up of 15.8 years, 1152 participants experienced a first-ever stroke. A 1%
increment in RDW yielded a 13% higher risk of stroke (multivariable HR: 1.13, 95% CI: 1.07-1.20).
Subjects with RDW in the highest quintile compared to the lowest had a 37% higher risk of stroke in
multivariable analysis (HR: 1.37, 95% CI: 1.11-1.69). Subjects with RDW above the 95-percentile had
55% higher risk of stroke compared to those in the lowest quintile (HR: 1.55, 95% CI: 1.16-2.06). All
risk estimates remained unchanged after exclusion of subjects with anemia (n=1102). RDW was not
associated with increased risk of death within one year or during the entire follow-up after an incident stroke.
Conclusions
RDW is associated with incident stroke in a general population, independent of anemia and
traditional atherosclerotic risk factors.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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II. EPIDEMIOLOGISK FORSKNING
ABSTRACT
UNDIAGNOSED MALIGNANCY IN ISCHEMIC STROKE
PATIENTS: THE BERGEN NORSTROKE STUDY
SELVIK HA1
University of Bergen, Norway.
1
Background
We assessed the occurrence of cancer in patients with prior ischemic stroke to investigate whether
the ischemic stroke patients may have had an underlying malignancy at the time of the index stroke.
We hypothesized that the stroke patients with an underlying malignancy at ictus could have been in a
prothrombotic state that contributed to the stroke.
Methods
All ischemic stroke patients admitted to the Department of Neurology, Haukeland University Hospital were included. Patients were prospectively registered in the Norwegian Stroke Research Registry
(NORSTROKE). Cancer data was obtained from the The Cancer Registry of Norway. Patients with a
history of cancer were excluded form the study.
Results
From a total of 1282 ischemic stroke patients with no history of cancer, 55 (4.3%) patients was diagnosed with one or more cancer diagnoses after the stroke. Seventeen patients (30.9%) were diagnosed with cancer within 6 months of stroke onset, and 11 (20.0%) of these patients were diagnosed
within 2.5 months of ictus. The most common cancer type was lung cancer (19.0%), and these patients had a significant increase in D-dimer on admittance (p≤0.05).
Conclusion
The stroke patients diagnosed with cancer shortly after ictus may have suffered a cancer-associated
stroke as their cancer was undiagnosed, but potentially present, at the time of ictus. However, it is to
be taken into consideration that cancer- associated strokes are rare.
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ABSTRACTS
GRUNNFORSKNING
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ABSTRACT
III. GRUNNFORSKNING
HISTONE DEACETYLASE INHIBITORS IN COMBINED-MODALITY CANCER TREATMENT – EXPERIMENTAL STUDIES OF
NORMAL TISSUE EFFECTS
BARUA IS1,2, KALANXHI E2, REE AH1,2, REDALEN KR2
Institute of Clinical Medicine, Campus AHUS, University of Oslo, Norway, 2Department of Oncology, Akershus University
Hospital, Norway.
1
Background
In combined-modality cancer treatment, molecularly targeted agents may be combined with radiotherapy to increase therapeutic efficacy. One example is histone deacetylase (HDAC) inhibitors, and
in our Pelvic Radiation and Vorinostat (PRAVO) study we investigated the combination of radiation
with the HDAC inhibitor vorinostat ((suberoylanilide hydroxamic acid (SAHA)) in gastrointestinal carcinoma. Although such a combination treatment may result in improved therapeutic efficacy, it may
also increase treatment toxicity, such as diarrhea, and lead to undesired treatment interruptions or
dose limitations. HDAC inhibitors have been regarded as tumor specific, however, their influence on
relevant normal tissues remain poorly investigated.
Aim
To investigate potential treatment toxicity in experimental normal tissue models treated with the
HDAC inhibitor SAHA.
Methods: Two normal tissue models (rat IEC-6 intestinal epithelial cells and human BJ fibroblasts)
and two colorectal cancer cell lines (HCT116 and HT29) were exposed to SAHA for 24 hours before
mechanisms of cell death were analyzed with flow cytometry, western blot analysis and immunofluorescent imaging.
Results
By flow cytometry (annexin V and propidium iodide) and western blot analysis we found that SAHA
induced cell death in HCT116 and HT29 cells, but not in the BJ fibroblasts, and that induction of apoptosis was a main mechanism of cell death. Intriguingly, the intestinal epithelial IEC- 6 cells responded similarly as the cancer cells to SAHA. In addition to apoptosis we also found that SAHA induced
autophagy, both in the cancer cell lines and the IEC-6 cells, as reflected by increased expression of
autophagy proteins (LC3-II and p62) on western blot and as visualized by immunofluorescent imaging
of SAHA-treated cells.
Conclusion
Treatment with the HDAC inhibitor SAHA resulted in cell death through induction of apoptosis and
autophagy in a patient-relevant experimental normal tissue model. The results may contribute to
explain normal tissue adverse events, such as intestinal toxicity, in patients treated with HDAC inhibitors as part of combined-modality cancer treatment.
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III. GRUNNFORSKNING
ABSTRACT
CD4+ T-CELL BASED IMMUNOTHERAPY AGAINST MULTIPLE
MYELOMA
HENNIG K1, HAABETH OA1, FAUSKANGER M1, HOFGAARD P2, BOGEN B1,2, TVEITA A1
Centre for Immune Regulation and 2KG Jebsen Centre for Influenza Vaccine Research, Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Norway.
1
Background
Immunotherapy using tumor antigen-specific T cells is emerging as a promising approach towards
several malignant diseases. It has been shown that CD4+ T cells can induce therapeutic immune
responses in subcutaneous tumor models in mice and mounting evidence suggest that such cells may
be of relevance to immunotherapy in humans. We have previously shown that CD4+ T cells recognizing a V region idiotope (Id) on the M315 myeloma protein secreted by the MOPC315 multiple
myeloma (MM) cell line can protect against tumor development upon s.c. tumor challenge. The disseminated distribution of myeloma cells and its predilection for the bone marrow niche pose potential
challenges to adoptive T cell therapy (ACT). T cell responses occurring within the bone marrow are
poorly understood and until recently there were no reports on ACT in myeloma. We have now shown
that ACT using idiotype-specific CD4+ T cells can mediate complete eradication of disseminated myeloma following lymphodepletion of the mice. Here the lymphodepletion was achieved using sublethal,
whole-body irradiation. The use of irradiation in multiple myeloma is rare and more commonly highdose melphalan with autologous stem cell support (HMAS) is used. Melphalan has been shown to
cause lymphodepletion as well as immunogenic cell death.
Objective/Aims
The present project aims at elucidating the effect of ACT after low-dose melphalan treatment-induced lymphodepletion, as well as the effect of checkpoint inhibitors in combination with ACT.
Method
In order to evaluate the efficacy of ACT after low-dose melphalan treatment-induced lymphodepletion, we utilize a newly developed cell line, MOPC315.BM, that, upon i.v. injection causes MM-like
disease with osteolytic lesions within the bone marrow.
Results
Preliminary results show that low-dose melphalan treatment does in fact cause lymphodepletion
and that the following ACT has a curative effect. However, contrary to when irradiation is used for
lymphodepletion, several treated mice eventually suffer relapses; hence we are elucidating different
combinations of treatment to optimize the therapeutic effect, for example with the use of checkpoint
inhibitors.
Conclusion
Adoptive T cell therapy using Id.specific CD4+ T cells can mediate eradication of late- stage,
disseminated disease in a murine model of multiple myeloma
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ABSTRACT/POSTER
HYPO-OSMOTIC STRESS ELICITS UNIQUE CA2+ RESPONSES IN
ASTROCYTIC ENDFEET
EILERT-OLSEN M1, HJUKSE JB1, JENSEN V1, ENGER R2, P. HELM J1, TANG W3, THOREN AE1,
NAGELHUS EA1,2,3
GliaLab and Letten Centre, Dept. of Molecular Medicine, Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway, 2Department of Neurology, Oslo University Hospital, Rikshospitalet, Norway, 3Centre for Molecular Medicine Norway, University of Oslo, Norway.
1
Background
Astrocytes are crucial for maintaining brain ion and volume homeostasis, in part by Ca2+ dependent
mechanisms. It has previously been shown that hypo-osmotic stress induces Ca2+ fluctuation in astrocytes. However, the Ca2+ responses in subpial and perivascular endfeet, two specialized astrocytic
compartments, are still poorly characterized.
Aim
We wanted to characterize the Ca2+ response in astrocytes subjected to hypo-osmotic stress and
to compare the response between different astrocytic compartments. Further, by use of genetically
modified mice, we investigated the molecular mechanism behind this swelling-induced increase in
Ca2+ fluctuation.
Methods
We used the ultrasensitive genetically encoded Ca2+ indicator GCaMP6f to study Ca2+ signaling in
cortical astrocytes in response to hypo-osmotic stress. GCaMP6f was cloned into a recombinant
adeno-associated virus (rAAV) vector and driven by the glial fibrillary acidic protein (Gfap) promoter.
Acute cortical slices from rAAV-Gfap-GCaMP6f-transduced mice were subjected to artificial cerebrospinal fluid (aCSF) with 20% reduction in osmolality, and GCaMP6f fluorescence was imaged by
two- photon microscopy. Frequency, duration and amplitude of the astrocytic Ca2+ transients were
measured before and during hypo-osmotic stress in astrocytic somata, fine processes, perivascular
endfeet and subpial endfeet.
Results
In wild-type mice hypo-osmotic stress elicited a 4-5 fold increase in the frequency of Ca2+ signals in
astrocytic endfeet bordering pia mater and ensheathing cortical blood vessels, whereas Ca2+ signaling in fine astrocytic processes within the neuropil was only moderately elevated. In contrast, the
frequency of Ca2+ signals in astrocytic somata remained
unchanged. In mice deficient in dystrophin, a crucial component of the aquaporin-4 anchoring complex in endfoot membranes, the Ca2+ response to hypo-osmotic stress was significantly reduced only
in subpial endfeet. In mice devoid of the inositol triphosphate type 2 receptors (IP3R2) the Ca2+ response was decreased in both subpial and perivascular endfeet. We conclude that astrocytic endfeet
show a unique hypo-osmotic Ca2+ response that depend on dystrophin and IP3R2.
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III. GRUNNFORSKNING
ABSTRACT
DELIVERY OF AGENTS ACROSS THE BLOOD BRAIN BARRIER
FOR THERAPEUTIC PURPOSES
HORN SA1
University of Bergen, Norway.
1
Introduction
The presence and function of the blood-­brain barrier (BBB) presents a severe challenge to the treatment of several CNS disorders, prohibiting an estimated 98 % of small-­molecule drugs to exert their
effects in the brain. The synthetic peptide transporter K16ApoE is a 36 residue peptide transporter
consisting of a polylysine chain and the LDL receptor binding sequence from apolipoprotein E. It has
been shown to successfully deliver several molecules across an intact blood-­brain barrier in mice.
Objectives
By using dynamic contrast-­enhanced magnetic resonance imaging (DCE-MRI), we wanted to establish
a quantifiable method for investigating the permeability of the BBB upon injection with K16ApoE.
The results from this pilot study will be used as background for further studies with therapeutics
against brain tumors.
Methods
Three subject animals were injected with 200 ug K16ApoE in the tail vein ten minutes before injection of the MRI contrast agent gadodiamide. Images of the mouse brains were then obtained with a
small animal MRI scanner. Five control animals were injected with the same amount of gadodiamide
before scanning. The transfer rate constant and AUC from DCE-­MRI analysis can be used to detect
the influx and presence of contrast agent before, during and after injection. Resulting data was analyzed with DCE analysis software, measuring the change in relaxation rate in the brain and vessels
over time. The differences were tested for significance with a two-tailed t-test.
Results
Analysis shows the transfer rate constant and AUC values are significantly higher in the subject group
than in the control group. This is indicative of an influx of contrast agent into the brain of the subject
animals, which is absent in the control animals.
Conclusion
We have been able to demonstrate a transient opening of the blood-‑brain barrier, making it permeable to a 590 Da MRI contrast agent that normally does not cross an intact BBB. Several chemotherapeutics have limited use against brain tumors and metastases because they fail to reach their target
across the BBB, such as the BRAF inhibitor Vemurafenib against malignant melanoma. We will now
investigate if integrating K16ApoE into a Vemurafenib treatment protocol can improve survival in
mice with melanoma brain metastases.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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III. GRUNNFORSKNING
ABSTRACT/POSTER
ADREPAIR: ON THE IMPACT OF DNA REPAIR IN THE HUMAN
BRAIN IN ALZHEIMER’S DISEASE
JENSEN HLB1, LILLENES MS1,2, MISHAGIAN D1,2, GÜNTHER CC3, TØNJUM T1,2
Department of Microbiology, Division of Diagnostics and Intervention, Institute of Clinical Medicine, University of Oslo,
Norway, 2Department of Microbiology, Oslo University Hospital, Oslo, Norway, 3Norwegian Computing Center, Oslo,
Norway.
1
Introduction
Defects in the nucleotide excision repair (NER) pathway are known to be associated with neurodegenerative disorders like the Cockayne syndrome and some subtypes of Xeroderma pigmentosum,
and may play a role in the early stages of Alzheimer’s disease (AD).
Aim
To investigate the role of the NER pathway in the development of AD.
Material and methods: Analysis of the gene expression of selected members of the NER pathway in
four different brain parts from 43 post-mortem AD patients and 9 healthy controls (HC), as well as
blood samples from 51 AD patients, 24 patients with mild cognitive impairment (MCI) and 62 HC,
was performed. RNA was isolated from brain specimens and blood, and RNA levels were quantified
by quantitative real-time PCR (qRT-PCR), using TaqMan Gene Expression Assays.
Results
RNA levels for all NER genes were significantly higher in brain compared to blood. When comparing
brain regions in AD patients and HC, we found significantly higher expression of LIG3 in the frontal
cortex, and significantly lower expression of RPA1 in cerebellum and MPG in entorhinal cortex in AD.
Conclusion
NER components are more highly expressed in the brain than in blood, suggesting an important role
of NER in the brain. Alterations in NER gene expression in brain parts affected in AD patients connects DNA repair to AD pathogenesis.
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III. GRUNNFORSKNING
ABSTRACT/POSTER
MICROVASCULAR PROLIFERATION IN BREAST CANCER
KRABY MR1, KRÜGER K2, OPDAHL S3,4, VATTEN LJ4, AKSLEN LA2,5, BOFIN AM1
Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway, 2Department of Clinical Medicine, Centre for Cancer Biomarkers, University of Bergen, Norway,
3
Central Norway Regional Health Authority, Trondheim, Norway, 4Department of Public Health and General Practice,
Norwegian University of Science and Technology, Trondheim, Norway, 5Department of Pathology, Haukeland University
Hospital, Bergen, Norway.
1
Background
Angiogenesis is essential for tumour growth and metastasis, but how to best quantify angiogenesis in
histopathology is controversial. Microvessel Density (MVD), Proliferating Microvessel Density (pMVD)
and Vascular Proliferation Index (VPI) are established methods for quantification of tumour vascularity
Aims
This study examined MVD, pMVD and VPI and their association with prognosis in molecular subtypes
of breast cancer from a well-described cohort of breast cancer patients with long-term follow-up.
Materials and methods
Using immunohistochemistry (IHC), von Willebrand Factor and Ki67 were studied done in tissue
sections from 62 Luminal A and 62 basal-like Phenotype (BP) breast cancers, matched for grade.
Sections were selected from a population of 909 breast cancers previously reclassified into molecular
subtypes using IHC and in situ hybridization as surrogates for gene expression analysis. Linear regression and survival analyses were used to study associations between MVD, pMVD and VPI, molecular
subtypes and breast cancer prognosis..
Results
While no clear difference was found between subtypes for MVD, both pMVD and VPI were higher in
BP compared with luminal A (difference 1.9 microvessels/mm2 (p=0.003) and 1.7 percentage points
(p=0.014), respectively). Nevertheless, MVD was associated with prognosis. HR for breast cancer
death in all cases was 1.10 (95 % CI 1.02-1.18) per 10 vessels increase. However, HR was 1.22 per
10 vessels increase among Luminal A tumours (p<0.001) and 1.04 among BP tumours (p=0.37).
Conclusions
Vascular proliferation was higher in BP cancers, implying a more active angiogenesis pattern in this
subtype than in Luminal A. MVD was only associated with poor prognosis in Luminal A. However, the
Luminal A cancers in this study were mostly grade 3, and further studies are needed to clarify whether MVD provides additional prognostic information in Luminal A cancers regardless of grade.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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III. GRUNNFORSKNING
ABSTRACT
ROLE OF DECORIN IN ADIPOSE TISSUE AND METABOLIC
HOMEOSTASIS
NERGÅRD CE1,2, SVÄRD J1,2,3, RØST TH1,3, HAUGEN C1,3, GUDBRANDSEN OA4, FERNØ J1,2,3,
DANKEL SN1,2,3, MELLGREN AE4,5, RØDAHL E4,5, SAGEN JV1,2,3, MELLGREN G1,2,3
Department of Clinical Science, University of Bergen, Norway, 2Hormone Laboratory, Haukeland University Hospital,
Norway, 3KG Jebsen Center for Diabetes Research, Bergen, Norway, 4Department of Clinical Medicine, University of
Bergen, Norway, 5Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway.
1
Background
In a microarray analysis the gene encoding decorin (Dcn) was found to be significantly upregulated in
subcutaneous adipose tissue samples from obese patients after profound weight loss due to bariatric
surgery (n=16). The decorin (variant C) mRNA level in adipocytes from fractionated adipose tissue
from obese patients and lean controls was positively correlated with markers of insulin resistance
(serum TG/HDL ratio (r=0.62, P=0.001) and HOMA-IR (r=0.53, P=0.015)). Earlier studies imply that
decorin is a secreted protein associated with obesity and type 2 diabetes.
Objectives
The aim is to investigate the role of decorin in development of obesity and insulin resistance in Dcn
knock-out (KO) mice.
Materials and methods
We studied the effect of 11 weeks of high fat diet (HFD, 45% energy from fat) on 10 male C57Bl/6J
BomTac wild type (WT) mice and 10 male Dcn knock-out mice. A corresponding number of mice
were on a control diet. During 11 weeks of diet, the body weight was measured once a week. By the
end of the feeding period an oral glucose tolerance tests was performed, and the mice were placed
in metabolic cages to register food and water intake as well as excretion of urine and faeces. The
amount of adipose tissue was determined by MRI. After euthanasia, blood samples and tissue samples were isolated for biochemistry and gene expression, respectively.
Results
There was no significant difference in weight gain or fat accumulation between the different genotypes, but Dcn knock-out mice had impaired glucose homeostasis on HFD compared to WT mice,
with an area under the curve for plasma glucose during a glucose tolerance test differing significantly
in KO mice compared to WT littermates (p=0,0043). This difference was not found during a low-fat
diet.
Conclusion
Dcn KO mice on HFD have an impaired glucose homeostasis showing significantly higher glucose
levels after glucose tolerance test.
35
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
III. GRUNNFORSKNING
ABSTRACT
MAPPING OF NUCLEAR LOCATION SIGNALS AND NUCLEAR
EXPORT SIGNALS IN NBR1
NÆSS MS1, LAMARK T1, JOHANSEN T1
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, Norway.
1
Background
Nuclear location signals (NLS) and nuclear export signals (NES) are vitally important for shuttling
larger proteins between the nucleus and the cytoplasm, as proteins larger than 60 kilo Daltons (kD) or
9 nanometers do not pass freely through the nuclear pore complex (NPC). The protein NBR1, named
after its gene, neighboring gene of BRCA1 (NBR1), plays an important role as an autophagy receptor
connecting ubiquitinated cargo to the developing phagophore for subsequent lysosomal breakdown
and recycling in the cytoplasm of the cell. The autophagy process occurs in the cytoplasm, but NBR1
is also observed in the cell nucleus. We know very little about NBR1s role inside the nucleus. Due to
its 107 kD size, NBR1 requires NES and NLS to shuttle between the nucleus and the cytoplasm.
Aims/methods
Our primary aim is to map the different NES and NLS sequences in NBR1. To do so recombinant
DNA technology was first used to make various cDNA expression constructs of NBR1 carrying deletions and point mutations. All plasmid constructs have an N-terminal tag of enhanced green fluorescent protein (EGFP) to enable visualization of the whereabouts of the expressed proteins in human
cells by fluorescence microscopy. The EGFP-tagged plasmids, some of which may have defect NLS or
NES, were subsequently transfected into HeLa cells and analyzed by confocal fluorescence microscopy. In some experiments the nuclear export inhibitor Leptomycin B was included.
Results
Preliminary results suggest NBR1 has at least one pair of N-terminal NES and NLS in the 1-332 amino acid (aa) region, whilst a C-terminal NES is located in the 496-582 aa segment, and the C-terminal
NLS amid aa 574-684.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
36
ABSTRACT
III. GRUNNFORSKNING
FABRY NEPHROPATHY – DOES YOUR THERAPY WORK AND
HOW LONG WILL MY KIDNEYS LAST?
STRAUSS P1, EIKREM ØS, LANDOLT L, MARTI HP
University of Bergen, Norway.
1
Background
Fabry disease is an X-linked disorder caused by α-galactosidase A enzyme deficiency leading to globotriaosylceramide (GL3) deposits in several organs including the kidneys, impairing their functions.
Specific enzyme replacement therapy (ERT) as represented by Replagal® or Fabrazyme® is available
but it should be initiated prior to overt kidney failure. Therefore, very early diagnosis of nephropathy
is still paramount due to the otherwise progressive and irreversible nature of Fabry disease. Unfortunately, there are no early biomarkers that reliably predict disease outcome. Furthermore, long-term
effects of ERT are poorly understood and the treatment is extremely expensive. Biomarkers permitting individualized therapy could markedly increase treatment effectiveness while cutting financial
costs.
Aims
i) To perform next generation sequencing (NGS) of mRNA from isolated glomeruli and tubuli of archival kidney biopsies from patients with with Fabry nephropathy prior and during ERT for the identification of potential early biomarkers predicting outcome. ii) to map the transcriptome of isolated tubuli
and glomeruli in ERT treated Fabry patients for the definition of novel drug combinations to supplement ERT.
Methods
First, NGS of mRNA from archival, formalin-fixed and paraffin embedded (FFPE) is established by
the use of specimens from renal cell carcinoma (n=64). Second, the best RNA extraction kits for
micro-dissected renal glomeruli and tubuli from FFPE kidney biopsies need to be defined. Third, we
will use archival renal biopsy tissues to compare the mRNA profiles of i) ERT exposed Fabry patients
(n=12) at baseline as well as after 5 years and 10 years of therapy, ii) untreated Fabry patients (n=6)
and iii) patients displaying normal renal tissue as controls (n=6). RNA will be extracted using RNA
extraction kits. RNA concentration and quality will be assessed with NanoDrop spectrophotometer
(Nanodrop Technologies, Wilmington, USA) and Agilent RNA 6000 Nano Kit on a 2100 Bioanalyzer instrument (Agilent Technologies, Santa Clara, CA, USA). NGS will be performed at a Hiseq 2500
apparatus with the TruSeq RNA Access library kit (Illumina, Inc., San Diego, CA, USA).
Results
The analysis of the FFPE and the RNAlater® datasets from renal biopsies of renal cell carcinoma to
establish NGS yielded similar numbers of detected RNA species, differentially expressed transcripts
37
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
III. GRUNNFORSKNING
ABSTRACT
and significantly affected pathways. The average expression of detected transcripts in both datasets
correlated very well (R2=0.97), and the log2 fold changes of the transcripts which were significantly
altered in both datasets (n=997) correlated with R2=0.96. Among transcripts with the
highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 and
uromodulin that were confirmed by immunohistochemistry. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression
data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively.
Thereafter, we successfully microdissected glomerular cross-sections from FFPE renal carcinoma
biopsies to do low output RNA extraction. Having evaluated seven RNA extraction kits, we found
that total RNA can be obtained in sufficient quantity and quality for NGS from around 100 glomerular
cross-sections using the High Pure kit (Roche) or the ExpressArt kit (Amsbio).
Conclusion
NGS of mRNA from FFPE kidney biopsy samples, including microdissected glomerular cross-sections,
is feasible. Thus, we are about to initiate RNA extractions with subsequent NGS of Fabry nephropathy specimens.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
38
Posters
39
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
POSTER
NO TITLE
GRINDSTAD T1
University of Tromsø, Norway.
1
Background
Androgens are considered important in prostate physiology and prostate cancer (PCa) pathogenesis.
However, lack of efficient prostate cancer treatment targeting androgens indicates additional mediators contributing to cancer development. It is likely that other sex steroid hormones are involved in
the process. In this study we wanted to further investigate the prognostic significance of estrogen
receptors, ERα and ERβ, and the aromatase enzyme in prostate cancer.
Methods
Tissue microarrays were created from 535 prostate cancer patients treated with radical prostatectomy at 3 different hospitals between 1995 and 2005. The tissue expression of estrogen ERα, ERβ and
aromatase were evaluated using immunohistochemistry. Representative tumor epithelial- (TE) and
tumor stromal (TS) areas were investigated separately. Survival analyzes were used to evaluate the
markers correlation to PCa outcome.
Results
In univariate analyzes, ERβ expression in TS was associated with reduced time to biochemical failure
(BF). ERα in TS on the other hand was associated with both increased time to clinical failure (CF) and
PCa death (PCD). Aromatase in both TS and TE was associated with increased time to BF and CF
respectively. The same observations were further supported by multivariate analyzes indicating independent prognostic impact for all markers.
Conclusion
We found a difference between the role of ERα and ERβ in TS of PCa. While a high expression of
ERα was beneficial, high expression of ERβ was associated with worse outcome. In addition, a high
expression of aromatase in both TS and TE was favorable.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
40
POSTER
I. KLINISK FORSKNING
SERUM FREE AND BIO-AVAILABLE 25-HYDROXYVITAMIN D
CORRELATE BETTER WITH BONE DENSITY THAN SERUM
TOTAL 25-HYDROXYVITAMIN D
JOHNSEN MS1, GRIMNES G, FIGENSCHAU Y, TORJESEN PA, ALMÅS B, JORDE R
University of Tromsø, Norway.
1
Introduction/background
In the circulation 25-hydroxyvitamin D (25(OH)D) is bound to vitamin D- binding protein (DBP) and
albumin. Only a small fraction is in the unbound, free form. According to the ‘free-hormone-hypothesis’ only the free form is biologically active. Genetic differences in DBP may affect the binding to
25(OH)D and thereby the amount of free 25(OH)D.
Objectives/aims
In this study we aimed to explore the potential differences between the total 25(OH)D, bioavailable
25(OH)D and the calculated free fraction of 25(OH)D in correlation to biological outcomes. We also
want to examine the effects adjusting for individual genetic variations has on the correlation.
Methods
In the present study sera were obtained from 265 postmenopausal women with low bone mass density (BMD). Serum 25(OH)D, DBP and albumin were measured and the free and bio-available (free +
albumin-bound) 25(OH)D calculated. Based on genotyping of the polymorphisms rs7041 and rs4588,
the six common DBP phenotypes were identified and the free and bio-available 25(OH)D calculated
according to the corresponding binding coefficients. Relations between measures of 25(OH)D and
PTH and BMD were evaluated with linear regression adjusted for age and BMI.
Results
The calculated amount of free and bio-available 25(OH)D was 0.03% and 13.1%, respectively, of
the measured total serum 25(OH)D. Adjusting for DBP phenotype affected the calculated free and
bio-available 25(OH)D levels up to 37.5%. All measures of 25(OH)D correlated significantly with PTH,
whereas a significant association with BMD was only seen for the free and bio-available 25(OH)D
measures. Adjusting for the DBP phenotypes improved the associations. These relations were almost
exclusively seen in subjects not using vitamin D and/or calcium supplements.
Conclusion
The free and bio-available forms of 25(OH)D may be a more informative measure of vitamin D status
than total 25(OH)D. Adjustment for DBP phenotype may improve this further.
41
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
III. GRUNNFORSKNING
POSTER
THE POTENTIAL EFFECT OF ANDROGEN DEPRIVATION
THERAPY AND ANDROGEN TARGETED THERAPY ON ANTI
PD-1 TREATMENT IN PROSTATE CANCER CELLS
MARVYIN K1, OLSEN JR1, HUA Y1, AZEEM W1,2, HELLEM MR1, QU Y1,3, KE X1, ØYAN AM1,
KALLAND KH1,2,3
Department of Clinical Science, University of Bergen, Bergen, Norway, 2Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway, 3Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
1
Prostate cancer (PCa) is the most prevalent cancer among men in the developed world with around
5000 new cases of PCa diagnosed each year and around 1000 deaths in Norway alone. Today, standard treatment for invasive PCa consists of androgen deprivation therapy (ADT) and newer generation
androgen targeted therapy (ATT). The latter target the androgen receptor pathway, which is vital for
PCa progression. Both ADT and ATT give good initial response, but fail to hinder metastasis and the
fatal outcome for the patient. Currently, there is great interest in immunotherapy against prostate and
other cancers. In particular, the checkpoint inhibitors anti CTLA-4 and anti-PD-1 have long lasting
objective response and complete remission in a subset of patients. Previous reports have indicated
that ADT does potentiate the immune system in combating PCa. Nevertheless, it is still uncertain
how androgen and ADT can effect immunotherapy in PCa. We thus examined the changes of gene
expression, of immune related genes including the checkpoint inhibitor PD-L1, in both benign and
malignant prostate cell lines by genome-wide RNA-seq and microarray gene expression analyses.
EP156T cells are benign, transit amplifying prostate epithelial cells with suppressed AR expression
and not responsive to androgen. These cells were compared with progeny malignant EPT3-M1 cells
with low-level AR expression, androgen-responsive LNCaP and VCaP prostate cancer cells, and
22Rv1 cells which are considered an in vitro correlate of CRPC.
We found that the availability of androgen had limited effect on gene expression of several immune
related genes, but had profound effect on PD-L1 in androgen sensitive LNCaP cells, indicating a potential synergy between anti PD-1 therapy and ADT in PCa. The clinical relevance should be further
explored in prostate cancer cells obtained from solid and liquid patient biopsies.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
42
III. GRUNNFORSKNING
POSTER
AXL SIGNALING IS ESSENTIAL IN TUMOR PROGRESSION AND
MAINTAINING EMT
RANAWEERA R1
University of Bergen, Norway.
1
Background
Axl is a receptor tyrosine kinase that is associated with poor prognosis in many different types of cancer. It is activated by a ligand Gas-6, a vitamin K dependent protein, and is involved in growth, survival and avoiding apoptosis, as well as the maintaining of EMT (epithelial-to-mesenchymal transition),
which is important for migration. Thus, Axl plays an essential role in tumor progression.
Aim
We wanted to show that Axl plays an essential role in tumor progression, and that inhibition of Axl
using warfarin or other tumor-specific Axl targeting agents had anti-cancer effects.
Methods
Pancreatic cancer cells, Panc-1, were treated with warfarin, which indirectly inhibits Axl through its
ligand Gas-6, being a vitamin K “antagonist”. An in vivo experiment was done to look at the level of
tumor progression. We also looked at cervical HeLa cells and activated Axl receptor to establish that
Gas-6 activation was significant to create a downstream signal. We did a Western Blot analysis to
determine the level of activation.
Results
Inhibiting Gas-6 dependent Axl activation with low dose warfarin or with other tumor-specific
Axl-targeting agents blocked the progression and spread of pancreatic cancer, as well as inhibiting the
Axl dependent tumor cell migration, invasiveness and proliferation. We also found that Axl signaling
through the PI3K-Akt pathway increased significantly when activated by Gas-6.
Conclusion
Axl activation by its ligand Gas-6 results in a activation of downstream pathways, including PI3K-Akt
pathway, which in turn is associated with maintaining EMT and tumor invasiveness. Axl signaling is a
critical driver of pancreatic cancer progression, and its inhibition with low dose warfarin or Axl selective targeting agents may improve outcome in patients with Axl expressing tumors.
43
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
POSTER
LOW-DOSE OXYTOCIN DELIVERED INTRANASALLY WITH
BREATH POWERED DEVICE AFFECTS SOCIAL-COGNITIVE
BEHAVIOR: A RANDOMIZED FOUR-WAY CROSSOVER TRIAL
WITH NASAL CAVITY DIMENSION ASSESSMENT.
QUINTANA DS1, WESTLYE LT2, RUSTAN ØG1, TESLI N1, POPPY CL2, SMEVIK H2, TESLI M1, RØINE
M3, MAHMOUD RA4, SMERUD KT3, DJUPESLAND PG5, ANDREASSEN OA1
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo
University Hospital, University of Oslo, Oslo, Norway, 2NORMENT, KG Jebsen Centre for Psychosis
Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo,
Norway [2] Department of Psychology, University of Oslo, Oslo, Norway. 3Smerud Medical Research
International AS, Oslo, Norway, 4OptiNose US Inc, Yardley, PA, USA, 5OptiNose AS, Oslo, Norway.
1
Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has
provided mixed results. This may relate to suboptimal drug deposition achieved with conventional
nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered’ nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport,
we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV)
administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a
randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing
four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo).
The primary outcome was social cognition measured by emotional ratings of facial images. Secondary
outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association
between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on
anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after
8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship
between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These
findings provide support for a direct nose-to-brain effect, independent of blood absorption, of lowdose OT delivered from a Breath Powered device.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
44
III. GRUNNFORSKNING
POSTER
BETA-ADRENOCEPTOR STIMULATION REVEALS CA2+ OVERLOAD PARADOX IN LEFT VENTRICULAR CARDIOMYOCYTES
FROM POST-INFARCTION RATS WITH AND WITHOUT HEART
FAILURE
SADREDINI M1,2, DANIELSEN TK1,2, ARONSEN JM1,3, MANOTHEEPAN R1,2, HOUGEN K1,2,
SJAASTAD I1,2, STOKKE MK1,2,4
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway, 2KG Jebsen
Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway, 3Bjørknes College, Oslo,
Norway, 4Clinic for Internal Medicine, Lovisenberg Diakonale Hospital, Oslo, Norway.
1
Background
Abnormal cellular Ca2+ handling contributes to both contractile dysfunction and arrhythmias in heart
failure. Reduced Ca2+ transient amplitude due to decreased sarcoplasmic reticulum Ca2+ content is a
common finding in heart failure models. However, heart failure models also show increased propensity for sarcoplasmic reticulum Ca2+ release events associated with arrhythmias which usually depend
on increased sarcoplasmic reticulum Ca2+ content. These seemingly incompatible findings have been
termed the “Ca2+ overload paradox”.
Aim and methods
In this study we aimed to investigate the presence of the Ca2+ overload paradox in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction
compared to sham-operated controls. Video edge-detection, whole-cell Ca2+ imaging and confocal
line-scan imaging were used to investigate cardiomyocyte contractile properties, Ca2+ transients and
Ca2+ waves.
Results
At baseline conditions, i.e. without beta-adrenoceptor stimulation, cardiomyocytes from rats with
large myocardial infarction, but without heart failure, did not differ from sham-operated animals in
any of the investigated aspects of cellular function. However, when exposed to beta-adrenoceptor
stimulation, cardiomyocytes from both non-failing and failing rat hearts showed decreased sarcoplasmic reticulum Ca2+ content, decreased Ca2+ transient amplitude, and increased frequency of Ca2+
waves. Possibly contributing to this, was increased phosphorylation of Ca2+/calmodulin-dependent
protein kinase II at THR286 and increased protein phosphatase 1 abundance found in both non-failing and failing rat hearts.
Conclusion
These findings confirm the presence of the Ca2+ overload paradox, and suggest that the threshold for
diastolic Ca2+ release from the sarcoplasmic reticulum is decreased in cardiomyocytes from both nonfailing and failing rat hearts after myocardial infarction under beta-adrenoceptor stimulation.
45
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
I. KLINISK FORSKNING
POSTER
EFFECT OF MARGIN DESIGN ON FRACTURE LOAD IN DENTAL
ZIRCONIA CROWNS
SKJOLD A1, ØILO M2
Department of Clinical Dentistry – Biomaterials, Faculty of Medicine and Dentistry, University of Bergen, Norway, 2Department of Clinical Dentistry – Biomaterials, Faculty of Medicine and Dentistry, University of Bergen, Norway.
1
Background
A dental crown is a tooth-shaped “cap” placed over a damaged or decayed tooth. It improves several
properties of the tooth, such as shape, strength and appearance. Dental crowns can be produced as
all-metal (gold, cobalt chromium), all-ceramic (zirconia, alumina, leucite) or as a combination. Materials
may exert different mechanical properties, which further affects the clinical lifetime of the crown.
One type of all-ceramic crowns, zirconia crowns, tolerate well pressure load, but has low tolerance for
tensile stress. Therefore, the rate of failure of zirconia crowns is higher than that of the metal crowns.
One of the factors that can affect the crown strength is the crown margin design.
Aim of the study
The aim was to compare the load at fracture of zirconia crowns with different margin designs.
The H0 hypothesis was that fracture strength of zirconia crowns would not be significantly affected
by margin design.
Materials and methods
Three groups of zirconia crowns with different margin designs were loaded in a servo- hydraulic
system until fracture. The crowns in the control group had a circumferential champher design. In the
second and the third groups, the zirconia crowns had a circumferential slice design. In addition, the
crowns in the third group had an outer collar right above the crown margin. In total, 30 crowns were
used, 10 in each group.
Results
The results indicate significant differences in strength between the different margin designs.
Conclusion
Different margin designs affect crown fracture strength. Traditional champher design had the highest
load tolerance. All test groups fractured at loads well above clinically relevant values.
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
46
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
NOTATER
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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NOTATER
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
NOTATER
Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015
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NOTATER
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Medisinstudentens forskningskonferanse Frampeik, Tromsø, 30. oktober - 1. november, 2015