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 Chemother-apy 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 chemo-therapy 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 progres-sion, 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 chemothera-py. The p53 homologue p73 was studied in papers II and III. In paper II, a G4C14A4T14 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 re-sponse to oxaliplatin, and p53 and p73 influenced this rere-sponse.
Keywords: Colorectal cancer, Radiotherapy, Chemotherapy, p53, p73, PINCH, miRNAs.
Jasmine Evert, Department of Medical and Health Sciences,
