Research Grants 2002

Clinical and biological relevance of neuroendocrine cell differentiation in prostate cancer progression on androgen ablation therapy
Dr. Armen G. Aprikian, Urologic Oncologist, McGill University

Advanced prostate cancer can initially be controlled by removal of the male hormone (androgen) stimulus. However, eventually this form of therapy is unable to prevent the cancer from growing. The cause of this phenomenon is not well understood. This study will explore that issue by looking at a subtype of cancer cells called neuroendocrine cells. Specifically, Dr. Aprikian will determine whether hormone treatment alters the types of proteins that are produced by neuroendocrine cells. Changes in the types of proteins may help cells become resistant to the effects of hormone treatment.

A Phase II study of continuous low dose cyclophosphamide and celecoxib for hormone refractory prostate cancer
Dr. Scott R. Berry, Medical Oncologist, Sunnybrook Regional Cancer Centre

Although advanced prostate cancer is initially controlled by removal of the male hormones, eventually this stops working and the cancer becomes resistant to hormone treatment. Once this occurs, there are no other good treatments available. One potential strategy for controlling cancer growth in this situation is preventing production of new blood vessels that aid tumour growth. In this study, Dr. Berry will examine the ability of two drugs that block blood vessel growth to control cancer in patients with hormone resistant tumours. Side effects and safety of this drug combination will also be studied.

Engineering a prostate cancer-specific toxin
Dr. J. Thomas Buckley, Professor of Biochemistry, University of Victoria 

Dr. Buckley has created a toxin that is activated by PSA (or Prostate Specific Antigen), a molecule specific to prostate cells. This toxin can kill prostate cancer cells. However, it also has some activity against normal tissues. In the current study, Dr. Buckley will refine the toxin so that it is more specific for prostate cancer and less toxic to normal cells.

A randomized phase II trial of Strontium-89 with or without cisplatin for the palliation of bone pain secondary to hormone refractory prostate cancer
Dr. Kim Nguyen Chi, Medical Oncologist, British Columbia Cancer Agency 

Advanced prostate cancer often spreads to the bones. Initially, this can be controlled with hormone treatment that removes the effect of male hormones. Eventually, however, the cancer stops responding to this therapy. In this study, a radioactive product called Strontium-89 and the chemotherapy drug cisplatinum are being examined as possible treatments for painful cancer in the bones. The effectiveness of these treatments in alleviating bone pain and the potential side effects they cause will be determined.

Lycopene as a treatment of prostate cancer
Dr. Emma S. Guns, Research Scientist, University of British Columbia 
Many studies have suggested that the antioxidant lycopene, found in foods such as tomatoes, may prevent prostate cancer. Some newer studies have suggested that lycopene may even be beneficial for treating existing prostate tumors. This project will explore the ability of lycopene to slow the growth of advanced prostate cancers. Specific molecules responsible for growth of tumor cells will also be examined to see if their activity can be altered by lycopene.

A transgenic model of antioxidant prostate cancer prevention
Dr. Laurence H. Klotz, Chief, Division of Urology, Sunnybrook & Women's College Health Sciences Centre 

A number of studies have indicated that the antioxidants Vitamin E and selenium may have the ability to prevent prostate cancer. This study will determine whether giving these compounds as food supplements can prevent prostate cancer from developing in a mouse model. In addition, it will examine the specific molecular mechanisms by which vitamin E and selenium have an effect on prostate cancer prevention.

Development of a mouse knockout model to explore the role of AIbZIP in prostate cancer
Dr. Claude Labrie, Professeur agrégé de recherché, Laval University

AIbZIP is a molecule whose function is to help read DNA, particularly in prostate cells. Dr. Labrie has recently found that levels of this protein are higher in prostate cancer cells than in normal prostate. The purpose of this project is to further study the function of this molecule. The study will examine the effect produced by selectively deleting AIbZIP in mice and the mechanisms controlling its function. In addition, the human and mouse versions of this molecule will be compared.

An in vivo demonstration of the IGF-dependent and IGF-independent effects of IGFBP-3 on progression of prostate cancer
Dr. Liam J. Murphy, Professor, University of Manitoba 

IGF, or Insulin-like Growth Factor, stimulates the growth of cells, including prostate cancer cells. IGFBP-3 is a protein found in the blood that binds IGF. In this project, Dr. Murphy will determine whether IGFBP-3 can inhibit growth of prostate cancer cells. Mouse models that develop prostate cancer will be studied to see if high levels of this molecule can slow prostate cancer growth.

The MSR1 gene and screen-detected prostate cancer
Dr. Steven A. Narod, Professor, Department of Public Health Sciences, University of Toronto  

A recent found that the risk of developing prostate cancer may be five times higher than normal in men with a certain variant of the MSR1 gene. This variant could be a cause of hereditary prostate cancer. In this study, Dr. Narod will examine how frequently certain variants of the MSR1 gene occur, and whether any of the variants are associated with an increased risk of having prostate cancer.

The role of bone-related factors in modulating androgen receptor activity and in the progression of prostate cancer
Dr. Paul S. Rennie, Director of Laboratory Research, University of British Columbia 

Advanced prostate cancer often spreads to the bones. Treatment for this usually involves removing the effect of the male hormones, androgens, in order to slow the growth of prostate tumours. However, prostate cancer cells eventually start to grow despite the lack of androgens. This study will examine the interaction between bone and prostate cancer cells. It will determine whether bone contains factors that stimulate the growth of prostate cancer cells even in the absence of androgens.

SAGE analysis of androgen-independent prostate cancer
Dr. Marianne D. Sadar, Senior scientist, British Columbia Cancer Agency 

Prostate cancer initially responds to removal of the male hormones, androgens, and this treatment strategy is used to control advanced prostate cancer. However, eventually prostate cancer cells atop responding to this therapy and start to grow even without androgens. The objective of this study is to better understand how prostate cancer cells are eventually able to grow in the absence of androgens. Changes in the way that genes function will be examined using SAGE (Serial Analysis of Gene Expression).

Fluorescence-guided radical prostatectomy
Dr. John Trachtenberg, Fleck Tanenbaum Chair of Prostatic Disease, Princess Margaret Hospital 

During prostate cancer surgery, it is difficult to determine the presence and extent of disease beyond the prostate. This can result in inadvertently leaving cancer behind or in a more extensive surgery than necessary, which increases the risk of side effects. This study will examine whether giving a fluorescing compound just before surgery can help highlight where exactly the cancer is located.

A study of the value of plasma osteopontin as a tumor marker in men with hormone-refractory prostate cancer
Dr. Eric W. Winquist, Medical Oncologist, London Regional Cancer Center 

Osteopontin is a compound found in body fluids that is important for the growth, invasion, and spread of prostate cancer. It may be associated with prognosis in patients with prostate cancer. This study will measure the levels of osteopontin in the blood of patients with very advanced prostate cancer. The ability of osteopontin levels to predict response to therapy and survival will be determined.

Establishment and characterization of a knock out (in) mouse prostate cancer model
Dr. Jim W. Xuan, Associate Professor, University of Western Ontario 

Dr. Xuan's prior work has involved development of a mouse prostate cancer model. For this study, the objective is to study the tumors of this mouse model further, and for a longer period of time. Changes in genes that result in spread of prostate cancer will be examined.





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