Sydney University/Royal Prince Alfred Hospital Prostate Cancer Consortium

Chief Investigators

Dr Qihan Dong, Scientist^1,2  

Dr Manish Patel, Urologist³

Dr Paul Sved, Urologist⁴

Dr Duncan McLeod, Pathologist⁵

Assoc Prof Michael Boyer, Oncologist⁶

Dr Lisa Horvath, Oncologist⁶

Affiliations

1. Cancer Genetics Group, Sydney Cancer Centre, Royal Prince Alfred Hospital
2. Division of Medicine, Central Clinical School, the University of Sydney
3. Department of Surgery, the University of Sydney
4. Department of Urology, Sydney Cancer Centre, Royal Prince Alfred Hospital
5. Department of Anatomical Pathology, the Royal Prince Alfred Hospital
6. Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital

Research Activity

(1) Annexin and phospholipase A2 in prostate cancer. This group pioneered the application of first generation gene expression arrays and subtractive hybridization technology to normal and diseased human prostate tissues, leading to the discovery that annexin A2 a membrane phospholipids binding protein, is silenced in prostate cancer. Subsequently, a therapeutic target downstream of annexin A2 was identified for treatment of prostate cancer. Currently cocktail treatments comprising drugs in use for non-prostate cancer related disease and synthetic chemicals based on traditional Chinese Medicine are being developed.

(2) Using congenital androgen-deficient mice to understand androgen-independent prostate cancer growth. Affymetrix gene expression arrays have been used to profile the gene expression pattern of the rudimentary prostate of the congenital androgen-deficient mouse (hpg). Database searching permits identification of genes expressed in the absence of androgens in the rodent prostate, and whether they are responsive to androgen treatment. This knowledge will assist in understanding how human cancer cells survive in the absence of androgens, and identifying genes that are important in sustaining the prostate in the absence of androgens.

(3) Isolation of prostatic progenitor cells for understanding and treatment of androgen-independent prostate cancer. A characteristic trait of both prostatic progenitor cells and androgen-independent prostate cancer cells is the ability to survive at castrate levels of androgens. A process for enrichment and expansion of prostate progenitor cells in vitro without androgen supplement has been developed. This system will permit biochemical characterization of the progenitor cells and the effects of novel cocktail treatments.

 
Research Areas of Expertise:

1. Assays for measuring cell growth, proliferation and apoptosis of prostate cancer cells and angiogenesis of endothelial cells in vitro and in vivo;

2. In vitro systems for enriching prostate progenitor cells;

3. Gene expression knock-down protocols using siRNA in prostate cancer cell lines (LNCaP, PC3 and DU-145);

4. Systems for selective expression of genes of interest in transgenic mouse prostate;

5. Gene expression profiling of congenital androgen-deficient mice treated with androgens in vivo.

Prostate Cancer Related Grants (last 5 years)

• The Role of FHL1 & SPINK1 in Androgen independent Prostate Cancer. 2002-2004, $185,000, NSW Cancer Council; Dong Q, Singh J.

• Function and regulation of inhibitor of DNA binding-1 in prostate cancer. 2004, $60,000, Cure Cancer Foundation, Australia; Dong Q, McLeod D.

• Function and regulation of inhibitor of DNA binding-1 in prostate cancer. 2004, $60,000, Cure Cancer Foundation, Australia; Dong Q, McLeod D

• Oncogenic action and therapeutic potential of PLA2 in prostate cancer. 2004-2006, $490,500, NHMRC-DVA; Dong Q, Scott K, Graham G, Russell P.

• Career Development & Support Fellowship. 2005-2007, $592,800, Cancer Institute NSW, Dong Q.

• Isolation of adult prostate stem cells from prostate tissue. 2006-2007, $98,000, The University of Sydney Cancer Fund; Dong Q.

Prostate Cancer Related Publications (last 5 years)

• Singh J, Young L, Handelsman D and Dong Q. Prostate epithelial expression of a novel androgen target gene. Journal of Andrology 23: 652-660, 2002.

• Boyer MJ, Rosenthal MA, Eisinger D, Goad J, Webb D, Stockler MR. Adjuvant mitoxantrone chemotherapy for men at high risk of relapse following radical prostatectomy: a pilot study. UroOncology, 2: 15-17, 2002.

• Young L and Dong Q. TAMS technology for simple and efficient in vitro site-directed mutagenesis and mutant screening. Nucleic Acid Research 31: e11, 2003.

• Young L and Dong Q. Two step total gene synthesis method. Nucleic Acid Research 32: e59, 2004.

• Sved P, Scott K, McLeod D, King N, Singh J, Tsatralis T, Nikolov B, Bolus J, Nallan L, Gelb M, Sajinovic M, Russell P, and Dong Q. Oncogenic action of secreted phospholipase A2 in prostate cancer. Cancer Res 64: 6934-40, 2004.

• Patel MI, DeConcini D, Lopez-corona E, Ohori M, Scardino P. An analysis of men with clinically localized prostate cancer who defer therapy. J Urol 171: 1520-4, 2004.

• Patel MI, Subbaramaiah K, Du B, Chang M, Yang P, Newman RA, Cordon-Cardo C, Thaler HT, Dannenberg AJ. Celecoxib inhibits prostate cancer growth: evidence of a cyclooxygenase-2-independent mechanism. Clin Canc Res 11: 1999-2007, 2005.

• Singh J, Young L, Handelsman D and Dong Q. Molecular cloning and characterization of a novel androgen repressible gene expressed in the prostate epithelium. Gene 348: 55-63, 2005.

• Patel MI, Tuckerman R, and Dong Q. A pitfall of the MTS assay due to evaporation in wells on the edge of a 96 well plate. Biotechnology Letters (in press), 2005.
  Young L and Dong Q. Developing murine prostate specific 2-in-1 Tet-off overexpression system for ODC. Biotechnology Letters (in press), 2005.

• Young L and Dong Q. Developing murine prostate specific 2-in-1 Tet-off overexpression system for ODC. Biotechnology Letters 27:823-8, 2005.

• Singh J, Manickam P, Shmoish M, Natik S, Denyer G, Handelsman D, Gong DW and Dong Q. Functional annotation of genes differentially expressed in human prostate cancer based on Affymetrix analysis of mouse prostate. Cancer Letter, 237:298-304, 2006.

• Dong Q, Patel M, Scott K, G Graham and Russell P. Annexin and phospholipase A2 in prostate cancer. Cancer Letters, 240:9-16, 2006.

• Young L, Au W, Allan C, Russell P, and Dong Q. Overexpressed ODC in human prostatic cancer. J Histochem Cytochem 54:223-9, 2006.