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Molecular Cancer, Vol. 5 (18 July 2006), 28.Partha Das, Kavitha Ramachandran, Jane Vanwert, Larry Ferdinand, Gopal Gopisetty, Isildinha Reis, Rakesh Singal, citeulike.org

N Engl J Med, Vol. 351, No. 15. (7 October 2004), pp. 1502-1512.BACKGROUND: Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease. METHODS: From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone. RESULTS: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P, citeulike.org

BMC Cancer, Vol. 6, No. 1. (2006)BACKGROUND:Prostate cancer that has recurred after local therapy or disseminated distantly is usually treated with androgen deprivation therapy; however, most men will eventually experience disease progression within 12 to 20 months. New data emerging from randomized controlled trials (RCTs) of chemotherapy provided the impetus for a systematic review addressing the following question: which non-hormonal systemic therapies are most beneficial for the treatment of men with hormone-refractory prostate cancer (HRPC) and clinical evidence of metastases?METHODS:A systematic review was performed to identify RCTs or meta-analyses examining first-line non-hormonal systemic (cytotoxic and non-cytotoxic) therapy in patients with HRPC and metastases that reported at least one of the following endpoints: overall survival, disease control, palliative response, quality of life, and toxicity. Excluded were RCTs of second-line hormonal therapies, bisphosphonates or radiopharmaceuticals, or randomized fewer than 50 patients per trial arm. MEDLINE, EMBASE, the Cochrane Library, and the conference proceedings of the American Society of Clinical Oncology were searched for relevant trials. Citations were screened for eligibility by four reviewers and discrepancies were handled by consensus.RESULTS:Of the 80 RCTs identified, 27 met the eligibility criteria. Two recent, large trials reported improved overall survival with docetaxel-based chemotherapy compared to mitoxantrone-prednisone. Improved progression-free survival and rates of palliative and objective response were also observed. Compared with mitoxantrone, docetaxel treatment was associated with more frequent mild toxicities, similar rates of serious toxicities, and better quality of life. More frequent serious toxicities were observed when docetaxel was combined with estramustine. Three trials reported improved time-to-disease progression, palliative response, and/or quality of life with mitoxatrone plus corticosteroid compared with corticosteroid alone. Single trials reported improved disease control with estramustine-vinblastine, vinorelbine-hydrocortisone, and suramin-hydrocortisone compared to controls. Trials of non-cytotoxic agents have reported equivocal results.CONCLUSION:Docetaxel-based chemotherapy modestly improves survival and provides palliation for men with HRPC and metastases. Other than androgen deprivation therapy, this is the only other therapy to have demonstrated improved overall survival in prostate cancer in RCTs. Further investigations to identify more effective therapies for HRPC including the use of systemic therapies earlier in the natural history of prostate cancer are warranted.Eric Winquist, Tricia Waldron, Scott Berry, Scott Ernst, Sebastien Hotte, Himu Lukka, citeulike.org

Eur Urol, Vol. 29 Suppl 2 (1996), pp. 69-74.Prostate cancer patients deemed unsuitable for curative therapy by means of radical prostatectomy or radiation are offered androgen ablation or suppression therapy, which normally results in an inhibition of prostate cellular growth for a period of 12-18 months. Death of patients from prostate cancer is directly related to the development of clones of cells capable of multiplying and metastasising without androgen stimulation, and to date efforts to suppress these cells have been singularly unsuccessful. There are a number of treatment options available, and these include secondary hormone therapy, growth factor inhibition, chemotherapy, combination therapies and interstitial radiotherapy. The merits and disadvantages of these management approaches are discussed.DW Newling, citeulike.org

Urology, Vol. 58, No. 2 Suppl 1. (August 2001), pp. 114-122.Stimulation of the signal transduction pathway of the epidermal growth-factor receptor (EGFR) tyrosine kinase family of receptors in tumor cells enhances cellular proliferation, prevents apoptosis, and promotes tumor-cell mobility, adhesion, and invasion. Therapeutic approaches used to target the EGFR and its signal transduction cascade include (1) monoclonal antibodies (eg, cetuximab ) directed against the extracellular binding domain of the receptor; and (2) trastuzumab, a monoclonal antibody binding to the HER2 receptor; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin. All are in clinical trials for a number of cancers, including prostate cancer. Antisense strategies are in preclinical development. Low-molecular-weight inhibitors of the EGFR tyrosine kinase also in clinical development include OSI-774, PD182905, PKI-166, CI-1033, and ZD1839. ZD1839 has shown encouraging results in patients with prostate cancer in phase 1 trials. mnJ Barton, G Blackledge, A Wakeling, citeulike.org

Cancer immunology, immunotherapy : CII, Vol. 56, No. 1. (January 2007), pp. 81-87.Numerous immunotherapy trials have been carried out in prostate cancer (PC) patients, with induction of antigen-specific T cells in some cases. Despite this capability, limited success is seen in terms of tumor regression or survival. In this review, we discuss the evidence for tumor escape strategies that may contribute to vaccine failure in the setting of PC. These include defects in antigen presentation, production of immunosuppressive substances, induction of T cell death, T cell receptor dysfunction, and the presence of tolerogenic dendritic cells and regulatory T cells inside prostate tumors. It is clear that novel strategies aimed at preventing tumor escape, such as small molecular weight inhibitors of immunosuppressive molecules, adoptive transfer of TCR transgenic T cells, removal of Tregs, combined with anti-androgen therapy and prostate-specific vaccines, need to be examined further in PC patients.AM Miller, P Pisa, citeulike.org

Medical Hypotheses, Vol. 70, No. 2. (2008), pp. 435-443.We propose and evaluate the hypothesis that the CAG repeat region of the androgen receptor represents a locus of antagonistic pleiotropy in the context of sexual selection and sexual conflict. Short repeats are associated with increased transactivation of the androgen receptor at the molecular level, and increased fertility at the phenotypic level. However, short repeats are also associated with increased risk of prostate cancer, and with more aggressive forms of the disease. The somatic evolution of cancer cell lineages also shows a repeated pattern of shortening of the CAG repeat in association with cancer progression, apparently as a result of positive selection among cell lineages. We further postulate that other genes associated with prostate cancer are likely to mediate antagonistic pleiotropy in the context of sexual selection and sexual conflict. A key prediction of this hypothesis is that the genes mediating antagonistic pleiotropy will show historical evidence of positive selection, particularly in the context of sexual conflict. Previous research on the molecular evolution of specific genes associated with prostate cancer supports this prediction, and we suggest further critical tests of the role for genomic conflicts and tradeoffs in the evolution of cancer risk.K Summers, B Crespi, citeulike.org

Journal of computer assisted tomography, Vol. 32, No. 4. (g 2008), pp. 523-528.OBJECTIVE: To analyze the enhancement of the prostate using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in patients with prostate cancer. METHODS: Sixty patients were enrolled. The signal-to-noise ratios (SNRs) of the central and peripheral zones (CZ and PZ, respectively) of the prostate were evaluated on T2- and T2*-weighted magnetic resonance imaging before and 24 hours after USPIO-enhanced MRI. The changes in SNR after USPIO-enhanced MRI were analyzed and correlated with serum prostate-specific antigen and histopathologic Gleason scoring based on surgically removed prostate gland. RESULTS: Decrease in SNR was noted in each zone of the prostate after USPIO-enhanced MRI (P < 0.001). Mean SNR decrease in the CZ was higher than that in the PZ (P < 0.05). High-grade prostate cancer was associated with a higher decrease in SNR (P < 0.05). The SNR change was negatively correlated with serum prostate-specific antigen at low or intermediate levels (P < 0.05). CONCLUSIONS: Enhancement of the prostate gland after USPIO administration may be associated with primary prostate cancer.CS Li, MG Harisinghani, WC Lin, M Braschi, PF Hahn, PR Mueller, citeulike.org

The Prostate, Vol. 9999, No. 9999. (2008), n/a.Prostate cancer continues to be a major cause of morbidity and mortality in men around the world. The field of prostate cancer research continues to be hindered by the lack of relevant preclinical models to study tumorigenesis and to further development of effective prevention and therapeutic strategies. The Prostate Cancer Foundation held a Prostate Cancer Models Working Group (PCMWG) Summit on August 6th and 7th, 2007 to address these issues. The PCMWG reviewed the state of prostate cancer preclinical models and identified the current limitations of cell line, xenograft and genetically engineered mouse models that have hampered the transition of scientific findings from these models to human clinical trials. In addition the PCMWG identified administrative issues that inhibit the exchange of models and impede greater interactions between academic centers and these centers with industry. The PCMWG identified potential solutions for discovery bottlenecks that include: (1) insufficient number of models with insufficient molecular and biologic diversity to reflect human cancer, (2) a lack of understanding of the molecular events that define tumorigenesis, (3) a lack of tools for studying tumor-host interactions, (4) difficulty in accessing model systems across institutions, and (5) addressing why preclinical studies appear not to be predictive of human clinical trials. It should be possible to apply the knowledge gained molecular and epigenetic studies to develop new cell lines and models that mimic progressive and fatal prostate cancer and ultimately improve interventions. Prostate © 2008 Wiley-Liss, Inc.Kenneth Pienta, Cory Abate-Shen, David Agus, Ricardo Attar, Leland Chung, Norman Greenberg, William Hahn, John Isaacs, Nora Navone, Donna Peehl, Jonathon Simons, David Solit, Howard Soule, Terry Vandyke, Michael Weber, Lily Wu, Robert Vessella, citeulike.org

European Urology Supplements, Vol. 6, No. 8. (March 2007), pp. 525-532.Objectives To assess the value of pelvic-phased array (PPA) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting intraprostatic tumour location and volume for clinically localised prostate cancers.Methods Suspicious areas on prospective prebiopsy MRI were located with respect to anatomic features, gland side, and transition zone (TZ) and peripheral zone (PZ) boundaries. These MRI findings were compared with histopathology findings for the radical prostatectomy specimens. Literature review of original studies correlating MRI and histologic results was performed.Results DCE-MRI with a PPA is superior to T2-weighted sequences for the detection and depiction of intraprostatic prostate cancer. In a series of 24 cases with 56 separate cancer foci, sensitivity, specificity, and positive and negative predictive values for cancer detection by MRI were, respectively, 77%, 91%, 86%, and 85% for foci >0.2 cc, and 90%, 88%, 77%, and 95% for foci >0.5 cc. Median focus volume was 1.37 cc (range: 0.338-6.32) for foci >0.2 cc detected by MRI in PZ, and 0.503 cc (range: 0.337-1.345) for those not detected by MRI (p < 0.05). The corresponding values for TZ foci were 2.54 (range: 0.75-16.87) and 0.435 (range: 0.26-0.58).Conclusions Prebiopsy PPA DCE-MRI is an accurate technique for detecting and quantifying intracapsular TZ or PZ tumour foci >0.2 cc. It has several applications, such as screening for prostate cancer and excluding cancer in patients with a raised PSA level, targeting of biopsies, estimating cancer volume and prognosis, and, in the future, monitoring of disease both during active surveillance and after focal therapy.Arnauld Villers, Philippe Puech, Xavier Leroy, Jacques Biserte, Jean-Christophe Fantoni, Laurent Lemaitre, citeulike.org