Research Grants 2000

The peroxisome proliferator-activated receptor gamma in early progression
Dr. Janice Dodd, Associate Professor of Physiology, University of Manitoba

Dietary fat is thought to be important in prostate cancer progression. Specific receptor molecules which respond to fat-related factors are found in prostate cells, called PPAR g. This investigator will determine whether PPAR g is involved in the progression of prostate cancer, and whether drugs which target this receptor might prevent progression to invasive prostate cancer. A new transgenic mouse model will be used. This research could identify a new target for prevention of prostate cancer.

Novel pharmacological targets in the treatment of prostate cancer metastasis
Dr. Charles Graham, Associate Professor of Anatomy & Cell Biology, Queen's University

This scientist will study the relationship between spread of prostate cancer (metastasis) and decreased levels of oxygen in the tumour (hypoxia). His approach will provide fundamental knowledge in determining whether the effect of hypoxia is the result of reduced production of nitric oxide, a small gaseous molecule which is widely present. If so, this would provide the basis for a treatment based on drugs which act to mimic nitric oxide.

Dr. Graham is a graduate of the University of Western Ontario and considers hypoxia and drug resistance in cancer and the role of oxygen and nitric oxide in gene regulation as a few of his research interests.

Micronutrients and cell cycle effects in prostate cancer
Dr. Laurence Klotz, Chief of Urology, Sunnybrook & Women's College Health Science Centre

This uro-oncologist proposes to study the effect of Vitamin E and Selenium on the molecules which control the cell cycle. Both Vitamin E and Selenium have potential as prostate cancer prevention agents, and several studies have suggested that they indeed can prevent the disease. In preliminary studies, Dr. Klotz has shown that these micronutrients induce arrest of the cell cycle. He proposes to study the relationship between the activity of these molecules and male hormones, which will provide a clue as to their mechanism of action.

Angiopoientin gene expression and regulation in human prostate cancer angiogenesis
Dr. Robert Stewart, Principal Investigator Department of Surgery, St. Michael's Hospital

This investigator will study angiogenesis (or the growth of new blood vessels) in prostate cancer. He will study the regulation of a family of molecules which regulate angiogenesis, known as angiopoietins, in prostate cancer. The results of these studies will provide insights into the regulation of angiogenesis, and will be relevant to anti-angiogenic therapeutic strategies that may hinder the growth of new blood vessels that is a pre-requisite to cancer progression in most cases.

Establishment of PSP94 gene driven transgenic mice prostate cancer model
Dr. Jim Xuan, Assistant Professor of Surgery, University of Western Ontario

This scientist has discovered a gene which is very specific to the prostate called PSP94. He proposes to develop a transgenic mouse which will develop prostate cancer as a result of an increased expression of the gene which promotes (causes activation of) PSP94. This has the potential to identify a target, which would be useful in gene therapy, for imaging prostate cancer, and many other potential applications.

Dr. Xuan studied at the Shanghai Institute of Cell Biology where he received his Master of Science in 1982 and the Institut National Agronomique in France where he received his Ph.D. in 1988.

Dr. Armen Aprikian, Surgery Department, Urology Division,
McGill University


It is impossible to predict in which prostate cancer patients, when and how fast prostate cancer will spread. We have shown that an important protein called Focal Adesion kinase (FAK) was significantly increased in cases of advanced prostate cancer and associated with prostate cancer cell movement. We seek to better understand how FAK is related to prostate cancer progression and determine if alterations in FAK activation lead to changes in aggressiveness of the disease. We hope that these studies will lead to potential diagnostic markers of prostate cancer progression risks and new therapeutic strategies directed at this important protein.

Dr. Aprikian is a graduate from the Universite de Sherbrooke, Faculte de Medecine, Sherbrooke, Quebec (1985) and has lectured and taught at a steady pace for the past eight years.

Identification of a new tumour suppressor gene implicated in prostate cancer
Dr. Mario Chevrette, Assistant Professor of Surgery, McGill University

This scientist has identified a new tumour suppressor gene on chromosome 12 which can inhibit the cancerous potential of prostate cancer cells. He will characterize this new gene. A tumour suppressor gene linked to prostate cancer would be of tremendous importance. Studying it may permit an assessment of the risk of developing the disease, the prognosis, and it is potentially a target for therapy using drugs which mimic its effect.

Dr. Chevrette has a B.Sc. Biochemistry, M.Sc. Biology and a Ph.D. Molecular and Cellular Biology and has been honoured with a number of awards, the most recent being the T.H.P. Molson fellowship award at McGill University Health Centre, Montreal.

Osteoporosis in prostate cancer patients receiving adjuvant hormone therapy
Dr. Richard C. Choo, Radiation Oncologist, Toronto-Sunnybrook Regional Cancer Centre

Hormone therapy is used in conjunction with radiation therapy in many patients. However, this leads to osteoporosis. This investigator will study the effect of hormone therapy on bone mineral density in prostate cancer patients treated with this combination. This study would identify a subgroup of men at high risk of developing osteoporosis for whom early treatment could improve their outcome and quality of life.

A graduate of the University of Alberta, Dr. Choo is a longtime prostate cancer researcher who has a number of abstracts being presented at this year's Annual Scientific meeting of the Canadian Urology Association, Canadian Association of Radiation Oncologists and the American Society of Therapeutic Radiology and Oncology.

Detection of mutations and/or deletions in mitochondrial DNA in prostate cancer
Dr. John P.H. Th'ng, Career Scientist, Northwestern Ontario Regional Cancer Centre

This researcher will study mutations in the DNA contained in mitochondria, the internal power plant of the cell. Genetic changes in mitochondria may provide an early signal of cancerous changes in the nucleus. This research would provide biomarkers for early diagnosis and permit more accurate prognosis of prostate cancer.

Molecular Radiobiology of Prostate Cancer: Utility and Feasibility of DNA Microarray Technologies
Dr. Robert Bristow, Assistant Professor Radiation Oncology/Medical Biophysics, University of Toronto

The overall goal of the study is to evaluate markers of radiation sensitivity in prostate epithelium. The project will focus on markers of apoptosis, the P 53 pathway and DNA - DSB repair protein foci analysis. This work will provide insight into the cell cycle, cell death and DNA repair and will help to predict which patients will respond best to radiation therapy.

Dr. Bristow is an expert in the genetic factors of cancer treatment response and experimental radiotherapy. He is also a national Co-Administrator of the Canadian Prostate Biology Network. He is sits on European and North American scientific advisory boards and is the Chair of a CARO Task Force in Translational Radiation Biology.





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