Molecular Determinants of Radio Resistance in Prostate Cancer
Abstract
We are studying the radiation response of prostate tissues in relation to the sensing and repair of DNA breaks. Specific aims relate to determining the interaction of DNA repair proteins in vitro using immunoflorescent confocal microscopy and biochemical DNA rejoining assays under both hypoxic and oxic conditions (given in vivo tumor cell populations). An in vivo program of prostate xenograft radioresponse and patient biopsy studies will determine the level of DNA repair in situ using immunohistochemistry and immunoflorescent markers. Our studies show that DNA repair protein expression is abnormal in malignant% versus normal prostate epithelial cultures, and that particularly the Rad51 protein is defective in localizing to the nucleus following DNA damage. We have accrued 13 patients onto a pre-operative radiotherapy trial and all patients' tumors are p53 wild type based on direct DNA sequencing. Post irradiation immunohistochemistry supports an induction of p53-pathway signaling following 25Gy in 5 fractions of clinical radiotherapy. Current experiments are designed to determine whether DNA protein focal interactions using 2- phtoon microscopy can predict the radioresponse of prostate xenografts and human tumors, in vivo. Our studies support the use of novel molecular based therapies that target NDA repair for prostate cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA419374
Entities
People
- Robert G. Bristow
Organizations
- University Health Network