Collaboration in prostate cancer translational research in Europe is not only vital to sustain the progress achieved in recent years but also to streamline current efforts between researchers and clinicians and avoid duplication or overlaps. This was amongst the goals of the two-day Prostate Cancer Translational Research in Europe (PCTRE) Meeting which opened recently in Amsterdam, The Netherlands.

“It is important that people with research background can communicate with clinicians and vice versa. By doing so we maximise the interaction amongst specialists. It is essential that we show our results to each other,” said Prof. Peter Mulders (Nijmegen, The Netherlands), chairman of the European Association of Urology Research Foundation (EAU-RF), organiser of the PCTRE meeting.

With more than 170 participants, the conference opened with lectures and updates on the work of prostate cancer consortia based in Europe. Within the European Community based framework programme these consortia received around €40 million in funding covering scientific topics such as the search for diagnostic and prognostic markers for prostate cancer.

Dr. Thorunn Rafnar (Reykjavic, IS) spoke on the current work regarding the identification of common genetic variants that affect the risk of prostate cancer. 42% of prostate cancer has a genetic cause. The lifetime risk of a man in the European Union to acquire prostate cancer is 10% and it is the third leading cause of death from cancer in men.

“First risk models including low risk variants are appearing,” Rafnar said as she added that “the search for genetic determinants of disease severity is ongoing.”

Polygene, one of the participating consortia, uses Genome-wide Association studies (see http://www.genome.gov) to analyse genomes responsible for cancers of the prostate and breast. However, current genetic risk models do not predict who will get progressive disease. Promark, another consortium, searches for genetic variants that do associate with aggressive cancer forms.

She also noted that the information on PSA genetics may improve utility in screening. Rafnar also pointed out that although “…much work remains…. finding causative variants at known loci define functions.”

The lecture by Prof. Freddie Hamdy (Oxford, UK), ‘What is the best practice in bio-banking?’ focussed on the dilemmas in prostate cancer (how to identify the population at risk, how to prevent overtreatment and treatment failure). “We can treat, we can cure, but who should we treat and cure?”, he said. Collection and cohorts of prostate cancer samples are important in order to look for new biomarkers. But the search for prognostic markers needs a multi-targeted approach. “The focus should be on the benefit to the patient; it should result in e.g. a reduction in mortality or of side effects”, says Hamdy.

Dr Schenk-Braat (Rotterdam, NL) says: “The incidence of prostate cancer will increase and PSA is not a sensitive enough tool to identify men at risk”. The P-Mark project evaluates promising biomarkers and has selected 3: osteoprotegerin (a bone turnover protein discovered by the group of Prof Hamdy), PCA3 (Jacques Schalkens (Nijmegen, NL) group) and multikallikreins (project of Profs Lilja (New York, US) and Petterson). An across marker validation study is ongoing. “We can name the European prostate biobank, increased support of the validation of biomakers and the prostate risk indicator as a few results from the P-Mark project”, says Schenk-Braat.

In another update lecture, Dr. O. Kallioniemi (Helsinki, Finland) discussed the integration of high-throughput technologies to identify drug targets and new therapeutic options for prostate cancer. Amongst his conclusions are:

* Majority of anti-cancer drugs are equally effective in cancer and control cells.

* TSA, thiram, disalfiram and monensin (are) identified as cancer selective compounds inhibiting VCaP cell growth at nanomolar concentrations.

* In vivo studies using VCaP cell xenografts showed reduced tumour growth in response to disulfiram exposure; disulfiram was not able to block tumour growth indicating the need for combined approaches.

* Disulfiram induced metallothionein expression, knockdown of MTI increased efficiency by five-fold.

Source:
Lindy Brouwer
European Association of Urology

New exercise guidelines are being developed that will give cancer survivors a comprehensive plan on how to safely start or maintain a physical activity program - and, in turn, enjoy a higher quality of life after battling the disease.

The guidelines are being spearheaded by the American College of Sports Medicine (ACSM), the organizer of the two-day scientific conference. Siteman Cancer Center at the Washington University School of Medicine in St. Louis is hosting the session. Leading experts in cancer and exercise from around the world will present scientific evidence on exercise considerations, risks and effects, and will produce a roundtable consensus statement within the next year.

“This consensus statement will be the most comprehensive exercise plan for cancer survivors ever developed,” said Kathryn Schmitz, Ph.D., FACSM, one of the lead presenters at the conference. “Often, cancer survivors are afraid to exercise or aren’t sure of the best ways to get active; the evidence-based paper we’re producing will give them the right information and the right tools they need.”

Physicians and health and fitness professionals will also be able to disseminate the information to their clients and patients, enabling them to give science-based advice to the cancer survivor population. In 2008, ACSM launched a specialty health and fitness certification specifically for trainers and fitness professionals working with cancer patients and survivors.

With more than 10 million cancer survivors currently living in the United States, Schmitz, a researcher at the University of Pennsylvania, says the new exercise guidelines will come at the perfect time. According to a study from Arizona State University, fewer than 21 percent of doctors tell their cancer-survivor patients about exercise, for lack of knowing how to guide them through a physical activity program.

“More than a million new cases of cancer are diagnosed each year - and more than two-thirds of these patients will become survivors,” Schmitz said. “They need guidance, largely through knowledgeable practitioners, on how to be active during remissions. Cancer survivorship should be about strength, fitness and prevention of recurrence.”

In addition to Siteman Cancer Center, the roundtable conference is supported by HUR USA.

Source
American College of Sports Medicine

Prostasin, a relatively unknown protease enzyme expressed in most epithelial cells, may play a role in the genesis of colorectal cancer. Researchers writing in the open access journal BMC Cancer have associated a reduction in the expression of inhibitors of the enzyme with malignant cellular behavior.

Lotte Vogel, from the University of Copenhagen, worked with a team of Danish and Norwegian researchers to investigate levels of prostasin and its inhibitors in colorectal tissue samples from 222 patients and 23 controls. They found that the mRNA levels of the inhibitor of prostasin, PN-1, increased at both the transition between normal tissue and mild/moderate dysplasia and again at the transition between severe dysplasia and colorectal cancer. According to Vogel, “It has previously been shown that overexpression of prostasin in mammary and prostate cancer cells reduces the invasive properties of cancer cells and that high prostasin expression in gastric tumours is associated with longer survival. In what may be support for this trend, our data shows that elevated mRNA levels for prostasin’s inhibitor, PN-1, coincides with the acquisition of malignant properties in colorectal tissue”.

The enzymatic activity of prostasin is almost certainly influenced by levels of inhibitors other than PN1, and PN1 itself is known to inhibit many other enzymes. This complex web of interactions between relevant proteases and their inhibitors makes firm conclusions difficult to draw. As Vogel writes, “Future studies are required to clarify whether down-regulation of prostasin activity via up regulation of PN-1 is causing the malignant progression or if it is a consequence of it”.

Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
Joanna Selzer-Plon, Jette Bornholdt, Stine Friis, Hanne C Bisgaard, Inger M. B. Lothe, Kjell M. Tveit, Elin H Kure, Ulla Vogel and Lotte K. Vogel
BMC Cancer (in press)

Article. All articles are available free of charge, according to BioMed Central’s open access policy.

Source:
Graeme Baldwin
BioMed Central