Commonwealth Bank Australian Prostate Cancer Bio-Resource
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National Project Manager      Assoc Professor David Horsfall
Dame Roma Mitchell Cancer Research Laboratories
Hanson Institute,
Adelaide Univ. and Institute of Medical and Veterinary Sciences.

Courier address:
Frome Rd, Adelaide

Postal address:
PO Box 14 Rundle Mall, Adelaide, SA 5000

Tel: 0421 098 384
Fax: 08-8222-3217

david.horsfall@imvs.sa.gov.au


 

About us

Mission Statement

To reduce mortality and morbidity and improve the quality of life of men with prostate cancer by facilitating translational research that will lead to improved prostate cancer management.

How It Came About
Scientific Basis for a National Prostate Cancer BioResource
The BioResource Management Committee
Working Model for the BioResource - Phase I Activities
Phase II Activities
Phase III Activities
Phase IV Activities 

 

How It Came About 

The Australian Prostate Cancer Collaboration (APCC) through the Translational Research Working Group determined that in order to enhance translational research endeavours nationally in prostate cancer, there was a need to establish a national prostate tumour BioResource and associated clinical database. The Prostate Cancer Foundation of Australia (PCFA) with the Commonwealth Bank of Australia and Andrology Australia provided the initial funds to establish the BioResource, which the APCC coordinated through a BioResource Management Committee. Our aim is that the BioResource tissue collections will be freely and equitably available to all Australian prostate cancer researchers.

The tissue collections are based at four Australian Capital City nodes and not centralised in one institution. The nodes are in Adelaide (Hanson Institute of Medical Research), Brisbane (Queensland University of Technology), Melbourne (Monash Institute of Medical Research), and Sydney (Garvan Institute of Medical Research). The 4 nodes will be linked via a web-based database, which can be interrogated for assembly of specific tissue cohorts, hence the "virtual face" will allow easy access nationally with the participation of multiple "real" tumour bank nodes Australia-wide. 

Scientific Basis for a National Prostate Cancer BioResource

Prostate cancer is the most common cancer (excluding non-melanoma skin cancers) in older males and the second most common cause of cancer deaths in males in Australia and the Western world. The aetiology of prostate cancer is still unknown. The dilemmas facing clinicians, patients and asymptomatic older men, with respect to the current choices available for prostate cancer detection and treatment, have been expounded in many a scientific and public forum. In spite of the wealth of published literature regarding the value of PSA testing and the various treatment options, there have been essentially no major advances in prostate cancer management in the past decade. Clearly, we still need more discriminating and specific tests that can detect localised prostate cancer early and determine the nature (slow growing or aggressive) of the disease. We also need more effective therapeutic approaches that are tailored to the disease type and stage, are less invasive and without the current associated high morbidity. These outcomes are the target of the current move worldwide to translational research and the need for a more intimate collaboration between basic and clinical researchers, also a goal of the APCC. 

The BioResource Management Committee 

Members of the Committee are drawn from the key stakeholders and people with expertise in tissue bank collections and/or clinical databases across Australia. This Committee decides the policy and procedures of the BioResource eg. the nature of the material and data to be collected, and guidelines for the standardised collection of tissue/data and for researcher access to the facility. Teleconferences are held quarterly, and full day workshops are held annually at the APCC Conference. 

Current members of the Management Committee are: 

  • Professor Judith Clements - (Chairman) Scientist, Queensland University of Technology, Qld

  • Professor Gail Risbridger - Scientist, Monash University, Vic

  • Professor Robert Sutherland, Scientist, Garvan Institute of Medical Research, NSW

  • Professor Wayne Tilley - Scientist, Hanson Institute of Medical Research, SA

  • Assoc Prof David Horsfall – (Project Manager) Scientist, Hanson Institute Medical Research, SA

  • Dr Jurgen Stahl, Pathologist, Adelaide Pathology Partners, SA

  • Assoc Prof RA (Frank) Gardiner, Urologist, Royal Brisbane Hospital & University of Queensland

  • Dr Lisa Horvath - Medical Oncologist, Garvan Institute of Medical Research, NSW

  • Dr Renea Taylor - Scientist, Monash Institute of Reproduction & Development, Vic

  • Dr Elizabeth Williams - Scientist, Monash Institute of Medical Research, Vic

  • Dr Mary-Anne Kedda - Scientist, Queensland University of Technology, Qld

  • Dr Tina Bianco-Miotto - Scientist, Hanson Institute of Medical Research, SA

  • Mr Spence Broughton - Consumer representative, Qld

Working Model for the BioResource 

Phase I Activities - Development of the BioResource Web Site 

The BioResource website acts as the repository for information about prostate research in Australia. It will also provide essential information on prospectively collected and archived prostate tissues available for Australian research. This has never been done before in Australia. The main objective of the website is to facilitate and encourage high quality research, as well as to foster collaboration. 

This is being achieved by: 

Identifying and profiling all groups in Australia undertaking prostate (cancer) research. The information for each group includes a summary of the key investigators, major prostate-related research grants last 5 years, 20 key prostate-related publications last 5 years, as well as patents or other outcomes from research undertaken in the field of prostate disease. Each of the research groups profiled on the BioResource web site has provided a short overview of their research activity. This includes a statement of their key areas of research, identifying areas of expertise and techniques or resources utilised in their research. The research summary indicates the nature of experimental systems used in the research program (e.g. human tissues, experimental models, cell culture systems). Ultimately, non laboratory-based projects will also be highlighted on the website, especially those that utilise clinical data sets. 

Developing such research group profiles showcases Australian prostate cancer research, and facilitates research collaborations. The profiles are an important resource for potential BioResource users, and for future applications to government bodies and other funding agencies for support of the BioResource. 

Until the BioResource prospective tissue and retrospective tissue microarray collections are fully posted on this website (see Phase II below), researchers can still obtain collaborative access to tissues held by the research groups profiled in this website. The project for which they require access to prostate tissue must be approved by an Institutional Ethics Committee. The procedure is that researchers will approach the National Project Manager of the BioResource with details of their project and tissue requirements. The National Project Manager will then circulate the enquiry to the research groups participating in the BioResource to determine who might hold the required tissues. The individual institutions would then have the opportunity to initiate collaboration with the applicant. This procedure has to date facilitated initiation of several research collaborations.

The initatives of Phase I have now been essentially completed. 

Phase II - Development of a Database of Archived Tissues Available to
 Other Researchers
 

A web-based central database will be established during 2007, which will contain minimum pathology and clinical datasets for both specific sets of retrospective tissue microarrays (TMAs) produced from existing pathology archives (see below) and the prospective frozen tissue collection. Currently, each tissue bank node has a database containing clinical and pathological information associated with the tissues being prospectively collected from prostate cancer patients. Until the central database is available for data mining and cohort building, the prospective tissue collection will be accessed for research via consultation with the Project Manager. Current policy is that 50% only of stored materials from any single patient tissue will be released over the first 5 years, with the remainder being retained until after 5 years of clinical follow up has been collected. When downloaded to the central site, the prospective tissue collection will not be identified in association with any specific institution. Ultimately, researchers who need access to large datasets of a particular tissue type, clinical spectrum or experimental model will be able to interrogate the central database to determine whether suitable tissues are available for their research project. For a synopsis of the tissue currently available, see Bio-Resource page. 

A Tissue Access Policy, Letter of Intent, Full Application Form and procedural guidelines are available. The Letter of Intent and Full Application will need to be submitted to the National Project Manager of the BioResource to gain access to both the retrospective TMA sets and the prospective tissue collection. A fee structure is in place to recover some of the costs associated with prospective tissue collection and in production of the microarrays. (See Bio-Resource page for more details) 

- Identify and Facilitate Development of Key Infrastructure Required to Enhance Research into Prostate Disease in Australia 

The second initiative in phase II has been the development of prostate cancer tissue microarrays (TMAs). Tissue microarrays provide high throughput expression profiling (immunohistochemistry, in situ hybridisation) of candidate genes identified by DNA microarrays, and facilitate characterisation of protein expression. TMAs can be used to evaluate predictive and prognostic markers, validate candidate diagnostic and therapeutic targets, and aid in the selection of patients with treatments based on expression of target genes. Making TMAs widely available to prostate cancer researchers in Australia will accelerate translational research in prostatic disease and facilitate rapid transfer of molecular discoveries to the clinic.

To facilitate implementation of a human and animal model TMA programme, workshops were held to define the nature of the TMAs required for research purposes and the implementation process. Completed arrays are:

·          Human disease progression array incorporating normal and cancer tissues with Gleason grading 4-10

·          A human pilot array for preliminary testing and reagent optimization

·          Development of hormone resistance in murine prostate cancer (TRAMP)

·          A murine pilot array for preliminary testing and reagent optimization

Later TMA sets will incorporate tissues with 5 year follow up of clinical outcome, premalignant histology such as high grade prostatic intraepithelial neoplasia (HGPIN) or normal prostate age-related histological change. In addition, microarrays of human prostate cancer cell line culture systems are planned for production.

Access to the completed arrays is now available to researchers, via application to the Project Manager.  

The individual institutions (nodes) are contributing the materials for generation of the TMAs. The process of generating the TMAs is being subcontracted to the Garvan and Hanson Institutes in the first instance. The BioResource is providing funding to support the provision of tissues and the generation of TMAs. Investigators utilising tissue resources from the BioResource will be required to provide the BioResource with the results obtained (e.g. expression of a particular gene/protein). This information will be securely stored in the BioResource database, and will be used only for future collaborative research undertaken by the BioResource (see below).

Phase II initiatives now are well under way. Sequential release of the TMA sets indicated above is expected through 2007. 

Phase III - Initiation of the Prospective Tissue Collection and the Development of Additional Essential Infrastructure for Prostate Research             

Phase III began with an identification of the tissue types that were required for the prospective collection, and negotiation with the individual contributing nodes to ensure that there will be a renewable supply of appropriate tissues for the different infrastructure initiatives sponsored by the BioResource. This aspect of Phase III has been completed, and prospective collection is being implemented at all four nodes, with funding provided by the NHMRC Enabling Grant. Current accrual rate at November 2006 is 50 patients per month.

Phase III also involves addressing on an ongoing collaborative basis between the BioResource Management Committee and the research community, the precise nature of the infrastructure initiatives that will be provided to the research community. One option that has created interest and which would be of immense value to researchers is to coordinate laser capture micro-dissection of prostate tissues and extraction of RNA/DNA from the pure cell populations. This would be performed by a core facility which would undertake to supply the laser captured micro-dissected cell populations, RNA extracts and cDNA preparations to investigators. Genomic DNA from peripheral blood buffy coat leukocytes will also be produced by the BioResource ultimately. 

Phase IV - Initiate Collaborative Research Proposals

Once the core infrastructure requirements have been defined and implemented the BioResource could undertake research activities of its own, such as utilisation of the collective data generated from the use of tissues and TMAs supplied by the BioResource. These meta-analyses will be conducted on a collaborative basis with the researchers who provided the information to the BioResource.

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