Sydney University/Royal Prince Alfred Hospital
Prostate Cancer Consortium
Chief Investigators
Dr Qihan Dong, Scientist1,2
Dr Manish Patel, Urologist3
Dr Paul Sved, Urologist4
Dr Duncan McLeod, Pathologist5
Assoc Prof Michael Boyer, Oncologist6
Dr Lisa
Horvath, Oncologist6
Affiliations
- Cancer
Genetics Group, Sydney Cancer Centre, Royal Prince Alfred
Hospital
- Division
of Medicine, Central Clinical School, the University of Sydney
- Department
of Surgery, the University of Sydney
- Department
of Urology, Sydney Cancer Centre, Royal Prince Alfred Hospital
- Department
of Anatomical Pathology, the Royal Prince Alfred Hospital
- 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:
-
Assays for measuring cell growth, proliferation and apoptosis of
prostate cancer cells and angiogenesis of endothelial cells in vitro
and in vivo;
-
In vitro systems for enriching prostate progenitor cells;
-
Gene expression knock-down protocols using siRNA in prostate cancer
cell lines (LNCaP, PC3 and DU-145);
-
Systems for selective expression of genes of interest in transgenic
mouse prostate;
-
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.
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