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Molecular Studies of Radiotherapy and Chemotherapy in
Colorectal Cancer
av
Jasmine Evert
Akademisk avhandling
Avhandling för medicine doktorsexamen i medicinsk vetenskap,
som kommer att försvaras offentligt
fredag den 29 maj 2015 kl. 13:00,
Hörsal P2, Prismahuset, Örebro universitet
Opponent: Professor Karin Jirström
Lunds universitet
Lund
Örebro universitet
Institutionen för hälsovetenskap och medicin
701 82 ÖREBRO
Abstract
Jasmine Evert (2015): Molecular Studies of Radiotherapy and Chemotherapy in Colorectal Cancer. Örebro Studies in Medicine 122.
Colorectal cancer is a common malignancy, with more than 6000 new
cases diagnosed each year in Sweden. The primary treatment is surgery,
which is often combined with radiotherapy and/or chemotherapy in
order to decrease the risk of recurrence. Both radiotherapy and chemotherapy are associated with side effects and there is significant variation
in treatment response among patients. The aim of this thesis was to
study molecular factors influencing the response to radiotherapy and
chemotherapy.
The adaptor protein PINCH, thought to promote tumour progression, was studied in paper I. PINCH was expressed in stromal cells in
and around tumours, and expression in normal mucosa was related to
survival. PINCH expression was also related to outcome of chemotherapy. The p53 homologue p73 was studied in papers II and III. In paper II,
a G4C14A4T14 polymorphism of the p73 gene was investigated in
rectal cancer patients with or without radiotherapy. It was found that
the polymorphism could influence the outcome of radiotherapy. When
combining the GC/GC genotype with wild-type p53 and low expression
of survivin, the results were significant. In paper III, the p73 isoform
ΔNp73β was found to increase cellular viability in colon cancer cells. In
paper IV, the effects of the chemotherapeutic drug oxaliplatin, p53 and
p73 status on the expression profile of miRNAs in colon cancer cells
were studied. A number of miRNAs were up-or down-regulated in response to oxaliplatin, and p53 and p73 influenced this response.
Keywords: Colorectal cancer, Radiotherapy, Chemotherapy, p53, p73,
PINCH, miRNAs.
Jasmine Evert, Department of Medical and Health Sciences,
Örebro University, SE-701 82 Örebro, Sweden, [email protected]