Prostate cancer and prostatic diseases
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Prostate Cancer Prostatic Dis. · Mar 2012
Cyclin-dependent kinase inhibitor, P276-00, inhibits HIF-1α and induces G2/M arrest under hypoxia in prostate cancer cells.
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation and controls genes involved in glycolysis, angiogenesis, migration and invasion. Overexpression of HIF-1α has been demonstrated in many common human cancers. ⋯ Given its low toxicity profile, its demonstrated antitumor activity and its potential to inhibit the HIF-1 pathway, P276-00 should be considered as antiangiogenic chemotherapy for prostate cancer.
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Prostate Cancer Prostatic Dis. · Dec 2011
Randomized Controlled TrialThe effects of combination therapy with dutasteride plus tamsulosin on clinical outcomes in men with symptomatic BPH: 4-year post hoc analysis of European men in the CombAT study.
CombAT (Combination of Avodart and Tamsulosin) was a randomised, double-blind study in men (n=4844) aged ≥ 50 years with a clinical diagnosis of BPH. Patients were randomised to daily tamsulosin 0.4 mg, dutasteride 0.5 mg or both for 4 years. The primary endpoint was time to acute urinary retention (AUR) or BPH-related surgery. ⋯ Safety and tolerability of dutasteride plus tamsulosin was consistent with previous experience of this combination and with the monotherapies. These data provide further evidence to support the use of long-term combination therapy (dutasteride plus tamsulosin) in men with moderate-to-severe lower urinary tract symptoms because of BPH and prostatic enlargement. The results in the European subgroup are generally consistent with those in the overall study population.
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Prostate Cancer Prostatic Dis. · Sep 2011
Budget impact analysis of a new prostate cancer risk index for prostate cancer detection.
The objective of this study was to evaluate the budget impact of a new prostate cancer risk index for detecting prostate cancer. The index is calculated as the combination of serum prostate-specific antigen (PSA), free PSA and a precursor form p2PSA. We constructed two budget impact models using PSA cutoff values of ≥2 ng ml(-1) (model #1) and ≥4 ng ml(-1) (model #2) for recommending a prostate biopsy in a hypothetical health plan with 100 000 male members aged 50-75 years old. ⋯ Adding the index to the current PSA prostate cancer testing strategies including the total PSA and percent free PSA, the number of detected cancer cases decreased by 20 and 5, in models #1 and #2, respectively. The savings on expected 1-year cost for prostate cancer detection were $356 647 (or $0.30 per-member-per-month (PMPM)) in model #1 and $94 219 ($0.08 PMPM) in model #2. The index produced higher cost savings in the model #1 with PSA cutoff ≥2 ng ml(-1) than the model #2 with cutoff ≥4 ng ml(-1) with a small short-term reduction in the number of positive tests.
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Prostate Cancer Prostatic Dis. · Jun 2011
Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran.
We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). ⋯ The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.
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Prostate Cancer Prostatic Dis. · Jan 2009
Randomized Controlled Trial Multicenter StudyEfficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH.
Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this double-blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. ⋯ The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy.