Sydney University/Royal Prince Alfred Hospital Prostate Cancer Consortium

Chief Investigators

A/Prof. Qihan Dong, Scientist1,2
Dr Manish Patel, Urologist3
Dr. Paul Sved, Urologist4
Dr Duncan McLeod, Pathologist5
A/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, University of Sydney
3. Department of Surgery, University of Sydney
4. Department of Urology, Sydney Cancer Centre, Royal Prince Alfred Hospital
5. Department of Anatomical Pathology, Royal Prince Alfred Hospital
6. Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital

Research Activity

The team demonstrated a loss of annexin and gain of phospholipase A2 (PLA2) in prostate cancer. They provided evidence in animals to substantiate the therapeutic potential by targeting PLA2. They found a feed forward loop between cPLA2 and PI3K/Akt pathways in prostate cancer cells. As the activated Akt is associated with poor clinical outcome, identification of a novel regulator of Akt activity has a potential to impact on clinical practice.

The finding of a characteristic loss of Annexin and gain of PLA2 in prostate cancer has been adopted in clinical use by pathologists as a diagnostic test. The topic has been included in the 2nd Edition of the Encyclopaedia of Cancer. The team has characterised a blueberry-based phytochemical for anti-cancer effect. A recent presentation of the work (2007) was selected by AACR for Newswothy session. A randomised clinical trial will begin in 2008.

The team has developed a protocol for in vitro mutagenesis. A paper describing the protocol was awarded ‘the best methodology paper of the year’ by Nucleic Acids Res (2004). The team has received invitation to contribute to the third volume of In Vitro Mutagenesis Protocols (2009) from Springer.

 
Research Areas of Expertise:

• Assays for measuring cell growth, proliferation and apoptosis of prostate cancer cells and angiogenesis of endothelial cells in vitro and in vivo;
• Primary culture of human adult prostate epithelial cells;
• Gene expression knock-down protocols using siRNA or shRNA in prostate cancer cell lines (LNCaP, and PC3);
• Gene expression profiling of (i) normal and cancerous prostate tissues, and (ii) prostates from congenital androgen-deficient mice treated with androgens in vivo.

Prostate Cancer Related Grants (last 5 years)

Secreted Phospholipase A2 in Prostate Cancer. Scott K, Graham G, Dong Q, and Russell P. Cancer Council NSW, $420,000

Australian Urological Foundation Research Award Sved P, Q Dong, $30,000

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

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

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)

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 27:805-8, 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

Niknami M, Patel M, Witting P, Dong Q. Aberrant activation of arachidonic acid and eicosanoid pathways - targets for treating prostate cancer. Recent patents in Endocrine, Metabolic & Immune Drug Discovery 2:9-15, 2008

Patel M, Kurek C, and Dong Q. The arachidonic acid pathway and its role in prostate cancer development and progression. J Urol, 179(5):1668-75, 2008

Niknami M., Patel M., Witting P.K., and Dong Q. Molecules in Focus: Cytosolic Phospholipase A2-α. Int. J. Biochem. Cell. Biol. 2008 In press

Dong Q Phospholipase A2. In: The Cancer Encyclopedia, Ed. Manfred Schwab. Springer, UK 2008 (in press)

Patel M, Singh J, Niknami M, Kurek C, Yao M, Lu S, Maclean F, King N, Gelb MH, Scott KF, Russell PM, Boulas J, Dong Q. Cytosolic Phospholipase A2-α: A Potential Therapeutic Target for Prostate Cancer. Clin Cancer Res, in press, 2008