Brisbane Prostate Cancer Research Network

Chief Investigators

Prof Judith Clements, Head ¹

Prof Adrian Herington, Ghrelin Group ¹

Prof Beth Newman, Research Director ¹

Dr Lisa Chopin, Head, Ghrelin Group ¹

Dr Dimitri Odorico, Head, ADAMs Group ¹

Dr John Hooper, Head, Protease Group ¹

Dr Jon Harris, Head, Protein Biochemistry ¹

Dr Terry Walsh, Head, Proteomics ¹

Dr Mary-Anne Kedda, Head, Molecular Epidemiology ¹

Prof Martin Lavin, Radiation Biology and Oncology ^{2, 3}

Dr Chris Schmidt, Cancer Immunotherapy ³

Dr Kay Ellem, Cancer Immunotherapy ³

Dr Michelle Burger, Research Fellow ^{2, 3}

Dr Amanda Spurdle, Head, Molecular Cancer Epidemiology ³

Dr Ray Wilkinson, Research Fellow ⁴

Dr Rebecca Prue, Research Fellow ⁴

Ms Beth Morrison, Research Officer ^{1, 5}

Prof Derek Hart, Director ⁴

Prof RA (“Frank”) Gardiner, Urologist  ^{1, 2, 3, 5, 6}

A/Prof David Nicol, Urologist  ^{1, 2, 5, 6, 7}

Dr John Yaxley, Urologist ^{5, 7}

Dr Peter Swindle, Urologist ^{4, 5}

Dr Glen Wood, Urologist ⁵

Dr Peter Heathcote, Urologist ⁵

Dr Ross Cartmill, Urologist ⁵

Dr Graham Holmes, Urologist ⁵

Dr Greg Malone, Urologist ⁵

Dr John Preston, Urologist ⁵

Dr Hema Samaratunga, Pathologist ⁸

Dr Ian LeFerve, Pathologist ⁹

Dr. Angus Collins, Pathologist ¹⁰

Dr Suzanne Steginga, Director, Psycho-oncology Research Unit ¹¹

Ms Megan Ferguson, Project Manager ¹¹

Ms Pamela Saunders, QLD Coordinator ^{1, 12}

Ms Trish van den Bergh, Research Nurse ^{1, 12}

Affiliations

1. Cancer Program, Schools of Life Sciences & Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology

2. University of Queensland

3. Queensland Institute of Medical Research

4. Mater Medical Research Institute

5. Urology Units at Princess Alexandra, Royal Brisbane, Greenslopes, Brisbane Private & Mater Hospitals

6. Northern Section of the Urological Society of Australasia

7. Wesley Research Institute

8. Sullivan and Nicolaides Pathology

9. Queensland Medical Laboratories

10. IQP

11. Queensland Cancer Fund

12. APCC BioResource

Research Activity

The Brisbane Prostate Cancer Research Network is investigating aspects of prostate tumour cell biology and its association with cancer progression. From these studies, we are attempting to identify more discriminating tumour bio-markers (than the current PSA test/TRUS biopsy approach) for early cancer detection in ejaculate, urine and blood and more discriminating prognostic indicators, particularly for the more aggressive spectrum of disease. We are also using cDNA microarray and proteomic approaches to disease profiling as a potential source of new biomarkers. These tumour-associated antigens, along with cell-based and whole vaccine approaches, are also being used for targeted immuno-therapeutic strategies. These latter basic and pre-clinical studies are focussed on understanding the specific nature of prostate cancer immuno-biology and generating new prostate cancer cell lines that more typically reflect the broad spectrum of disease that is seen clinically. Other aspects of our research include generating in vitro and in vivo models of prostate cancer bone metastasis in order to understand why prostate cancer cells preferentially spread to the bone. We are also assessing the identified candidate genes for their potential as genotypic markers for prostate cancer risk and disease progression.

Clinicians in the group have initiated vaccine trials and have been centrally involved in pharmaceutical industry-sponsored studies examining the role of new drugs in both early prostate cancer and those with hormone escape disease. The three major clinical institutions (RBWH, PAH and Mater) and research institutes (QIMR and MMRI) have established infrastructure to support clinical trials. In addition, the impact on men with prostate cancer of new and established treatment regimens is being examined with respect to psychosocial and decision-related adjustment and cognitive effects.

Research Areas of Expertise:

Molecular and cell biology, bioinformatics and protein chemistry, particularly in prostate cancer cell biology, with a particular focus on proteases (PSA & the related kallikreins, transmembrane serine proteases, ADAMs), growth factors (ghrelin and the IGF axis) and transmembrane signalling proteins (such as the protease-activated receptors, PARs). Structure-function analysis of these factors and nuclear receptor (AR) co-factor interactions. Genetic and proteomic approaches for predictive and early cancer bio-markers, as well as markers of disease progression. Ejaculate as a tool for diagnostic and prognostic bio-markers. Dendritic cell biology; in vitro and in vivo bone metastasis models; xenograft tumour models. Immunotherapy and pharmaceutical clinical trials; psychological and cognitive aspects of prostate cancer treatment.

Major Prostate Cancer Related Grants (last 5 years):

• Characterisation of the roles of PSA and related genes in the progression of prostate cancer and their potential as a targeted therapeutic agent. 1999-2002, $115,000, Wesley Research Institute; J Clements, D Nicol.

• Prostate cancer: an internal solid-malignancy model for vaccine therapy. 2000-2002, $240,000. Queensland Cancer Fund; RA Gardiner, KAO Ellem, C Schmidt, D Hart, GJ Seymour, J Yaxley.

• Diagnosis and prediction of the natural history of Prostate Cancer; use of ejaculate for molecular profiling. 2002-2003, $136,000. Queensland Cancer Fund; RA Gardiner, J Clements, V Hyland, M Lavin.

• Characterisation of a novel prostate-expressed kallikrein-like protease and its target proteins. 2000-2004, $709,000, NHMRC; J Clements.

• The role of growth hormone releasing hormones in the autocrine/paracrine regulation of prostate cell growth. 2002-2004, $240,000, NHMRC; AC Herington & LK Chopin.

• Phase I trial of autologous dendritic cell vaccine for hormonal-refractory prostate cancer with novel tissue and immunologic monitoring techniques. 2003-2004, $130,000, QIMR Cell-Based Therapies Grants Committee; RA Gardiner, C Schmidt, KAO Ellem.

• Cell based vaccine therapies. 2003-2004, $1.17 million, Onyvax Ltd (United Kingdom); J Clements, D Nicol.

• PSA testing: a population-based longitudinal study of decision making, psychological effects and patterns of care. 2004. $572,601, NHMRC; D O’Connell, D Smith, M Gattellar, J Ward, SK Steginga, C Pinnock.

• A Phase I Clinical Trial of Novel Blood Dendritic Cell Preparation for the Immunotherapy of Prostate Cancer. 2004-2005, US$100,000, US Army Prostate Cancer Program; D Hart.

• Proteomic approaches to the early detection of prostate cancer. 2004-2005, $140,000, Queensland Cancer Fund; RA Gardiner, JA Clements, T Walsh, J Bartley, J Gorman, A Pettitt, J Yaxley, D Nicol.

• Characterisation of prostatic kallikrein gene expression during crosstalk between osteoblasts and prostate cancer cells. 2004-2005, $140,000, Queensland Cancer Fund; JA Clements, J Gao, D Nicol, & AC Herington.

• A novel one-step approach in the early diagnosis of prostate cancer. 2004-2005, $102,510, NHMRC; RA Gardiner, MF Lavin

• Regulation and functional roles of ADAM 10 in prostate cancer. 2004-2006, $456,000, NHMRC; AC Herington, JA Clements, D Odorico.

• Development of a novel, non-invasive diagnostic test for prostate cancer. 2004-2007, US$516,360, US Department of Defence; RA Gardiner, MF Lavin.

• Selection of prostate-derived kallikreins for dendritic cell immunotherapy. 2005-2006, $143,400, Queensland Cancer Fund; K Radford, R Wilkinson, P Swindle.

• A Phase I Clinical Trial of cmrf-56+ blood dendritic cell preparation for the immunotherapy of metastatic hormone refractory prostate cancer. 2005-2006, US$1million, US Army Prostate Cancer Program; D Hart.

• Ghrelin receptor isoforms in prostate cancer proliferation;roles of heterodimerisation and signalling cross-talk. 2005-2006, $140,000, Queensland Cancer Fund; LK Chopin & AC Herington.

• Multiple molecular markers for prostate cancer diagnosis from enriched prostatic cells from ejaculate. 2005-2006. $71,700, Queensland Cancer Fund; RA Gardiner, M Burger, J Yaxley, H Samaratunga, MF Lavin. 

• PSA testing: a population-based longitudinal study of decision making, psychological effects and patterns of care. 2005-2007, $572,601, NHMRC; O’Connell D, Smith D, Gattellari M, Ward J, Steginga SK, Pinnock C. 

• Kallikrein Gene Variants in Prostate Cancer: Analysis of Gene Regulation and Diagnostic/Prognostic Use. 2006-2008, $479,125, NHMRC, Kedda MA, Spurdle AB, Clements JA.

Selected Prostate Cancer Related Publications (last 5 years):

• Burger MJ, Mould M, Samaratunga HM, Clements J, Lavin MF, Gardiner RA.  Expression analysis of δ-catenin and Prostate Specific Membrane Antigen; their potential as diagnostic markers for Prostate Cancer. Int J Cancer 100: 228-37, 2002.

• Jeffery PL, Chopin LK & Herington AC. The expression and action of ghrelin and the growth hormone secretagogue receptor in prostate cancer cell lines. J Endocrinol 172: R7-R11, 2002.

• Chopin LK, Veveris-Lowe T, Philipps AF & Herington AC. Co-expression of growth hormone (GH) and GH receptor isoforms in prostate cancer cell lines. GH & IGF Res 12: 126-136, 2002.

• Gardiner RA, Burger M, Clements JA and Lavin MF. Realising the potential of Ejaculate/Seminal fluid in detecting and predicting natural history. In Methods Mol Med: Prostate Cancer 81:199-21, 2003.

• Swindle P, McCredie S, Russell P, Himmelreich U, Khadra M, Lean C, Mountford C. Pathologic characterization of human prostate tissue with proton MR spectroscopy. Radiology 228:144-51, 2003.

• Swindle PW, Kattan MW, Scardino PT. Markers and meaning of primary treatment failure. Urol Clin North Am 30: 377-401, 2003.

• Gardiner RA, Burger MJ, Steginga S, Walsh T, Schmidt C, Nicol DL, Lavin MF, Clements JA. Integrating molecular, proteomic and vaccine development, quality of life and psychometric evaluations in a comprehensive research program. In: Horizons in Cancer Research. Ed: Colombo F; Prostate Cancer Ed: Lucas JN. Nova Medical Books, New York. pp189-216, 2004.

• Landers KA, Burger MJ, Tebay MA, Purdie DM, Scells B, Samaratunga H, Lavin MF, Gardiner RA. Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int J Cancer, 114: 950-956, 2004.

• McCulloch D, Akl P, Samaratunga H, Herington AC & Odorico DM. Expression of ADAM-10 in prostate cancer and its regulation by dihydrotestosterone, insulin-like growth factor-I and epidermal growth factor in the prostate cancer cell model LNCaP. Clin Cancer Res 10:314-23, 2004.

• Steginga, S.K., Occhipinti, S., Gardiner, R. A., Heathcote, P. & Yaxley, J. A Prospective Study of Men’s Use of Alternative Therapies after Localised Prostate Cancer. Patient Education and Counseling, 55: 70-77, 2004.

• Swindle PW, Tepes S, Clements J. DC therapy for prostate cancer. Cytotherapy. 6:164-71, 2004.

• Han G, Buchanan G, Ittmann M, Harris JM, Yu X, Demayo FJ, Tilley W, Greenberg NM. “Mutation of the androgen receptor causes oncogenic transformation of the prostate” Proc Natl Acad Sci U S A. 102:1151-6, 2005.

• Wilson S, Greer B, Hooper JD, Zijlstra A, Quigley JP and Hawthorne S (2005) The membrane anchored serine protease, TMPRSS2, activates PAR2 on prostate cancer cells. Biochem J 388: 967-72, 2005.

• Steginga SK, Pinnock C, Baade P, Jackson C, Green A, Preston J, Heathcote P, McAvoy B. An educational workshop on the early detection of prostate cancer: a before-after evaluation.  Aust Fam Physician. 34: 889-891, 2005.

• Steginga SK, Pinnock C, Gardner M, Dunn J, Gardiner RA. Evaluating peer support for prostate cancer: the prostate cancer peer support inventory. Br J Urol. 95: 46-50, 2005.

• Baade P, Steginga SK, Pinnock C, Aitken J.  Communicating prostate cancer risk: what should we be telling our patients? Med J Aust. 182: 472-475, 2005.

• Yeh A, Jeffery PL, Herington AC & Chopin LK.  The role of ghrelin in prostate cancer cell proliferation: ghrelin activates mitogen-activated protein kinase (MAPK) pathways in LNCaP and PC3 prostate cancer cells and a novel preproghrelin isoform is highly Expressed In Prostate Cancer. Clin Cancer Research 11: 8295-303, 2005.

• Veveris-Lowe, T.L.*, Lawrence, M.G.*, Collard, R.L*, Bui, L., Herington, A.C., Nicol, D.L. And Clements, J.A. Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like Effect in Prostate Cancer Cells. Endocrine Related Cancer 12(3):631-43, 2005 (* equal first authors).

• Dong, Y., Bui, L.T., Odorico, D.M., Tan, O.L., Myers, S.A., Samaratunga, H., Gardiner, R.A. And Clements, J.A. Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. Endocrine Related Cancer 12(4):875-89, 2005.

• Wilkinson R, Kassianos AJ, Swindle P, Hart DNJ, Radford KJ. Numerical and functional assessment of blood dendritic cells in prostate cancer patients. Prostate, 66; 180-192, 2006.
   

International Patents:

• PCT/AU02/00582 Multiple Countries, 2002. Chopin LK, Jeffery PL & Herington AC. “Reproductive cancer diagnosis and therapy”  

• PCT/AU02/00378 Australia, 2002. Clements JA. “Polynucleotides and poly-peptides linked to cancer and/or benign tumours”

• PCT/AU03/00454 Australia, 2003. Clements JA. Australian Provisional Patent application (PS1870/02)- “Condition-specific molecules and uses therefore”