German Cancer Research Center, Heidelberg, Germany.
To review and summarize evidence from longitudinal studies on the association between serum 25-hydroxyvitamin D (25(OH)D) and the risk of prostate cancer (PC).
Relevant prospective cohort studies and nested case-control studies published until July 2009 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, PC incidence/PC mortality according to serum vitamin D status and the respective risk ratios, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase in serum 25(OH)D by 10ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods.
Overall, eleven original articles were included, ten of which reported on the association between serum vitamin D levels and PC incidence and one article reported on the association with PC mortality. Meta-analysis of studies on PC incidence resulted in a summary OR (95% confidence interval, CI) of 1.03 (0.96-1.11) associated with an increase of 25(OH)D by 10ng/ml (P=0.362). No indication for heterogeneity and publication bias was found.
According to available evidence from longitudinal studies, serum 25(OH)D is not associated with PC incidence.
UroToday.com Prostate Cancer Section
Inhibiting TNF-receptor associated protein-1 (TRAP-1) may prevent cancer cell death, according to investigators at the University of Massachusetts Medical School. They also note that TRAP-1 is a marker of localized and metastatic prostate cancer and is required for prostate cancer cell viability.
The report will appear in the January 2010 issue of the American Journal of Pathology in a paper titled “Cytoprotective Mitochondrial Chaperone TRAP-1 as a Novel Molecular Target in Localized and Metastatic Prostate Cancer.”
Since TRAP-1 is known to regulate cell death, the researchers decided to study its role in prostate cancer. They found that the protein was highly expressed in both high-grade human prostate cancer lesions and mouse models of prostate cancer but not in benign or normal prostate tissue.
In addition, TRAP-1 overexpression in noncancer prostate cells inhibited cell death, whereas TRAP-1-deficient prostate cancer cells had enhanced levels of cell death. Moreover, treatment with gamitrinibs, a class of small molecules that inhibit TRAP-1, resulted in prostate cancer cell death but not death of noncancerous prostate cells.
Dario C. Altieri, M.D., who led this research, reported in February on the synthesis and properties of gamitrinib as a treatment for prostate cancer in The Journal of Clinical Investigation. He designed gamitrinibs to selectively target Hsp90 in human tumor mitochondria. TRAP-1 is a mitochondria-localized Hsp90 chaperone. Therefore, Dr. Altieri believes that based on his research, targeting TRAP-1 via gamitrinib may be a viable therapeutic strategy for patients with advanced prostate cancer.
Dr. Altieri’s experiments also found that TRAP-1 was differentially expressed in localized and metastatic prostate cancer compared with normal prostate.
A similar approach may be also suitable for other types of cancer, as TRAP-1 is broadly expressed in disparate human malignancies, Dr. Altieri continues. He plans to “further dissect the biology of TRAP-1 cytoprotection in cancer cells and test whether disabling its function may overcome drug resistance, the most common reason of treatment failure and dismal outcome in patients with advanced prostate cancer.”
GEN News Highlights
