The Role of Adiponectin in Breast Cancer: A Meta-Analysis

Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.     

Prostatitis,Sexually Transmitted Diseases,and Prostate Cancer: The California Men's Health Study

Background

Prostatitis and sexually transmitted diseases (STDs) have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive.

Methodogy/Principal Findings

We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men''s Health Study. Our analysis included 68,675 men, who completed a detailed baseline questionnaire in 2002–2003. We identified 1,658 incident prostate cancer cases during the follow-up period to June 30, 2006. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Overall, men having a history of prostatitis had an increased risk of prostate cancer than men with no history (RR = 1.30; 95% CI: 1.10–1.54). Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer (P trend = 0.003). In addition, among men screened for prostate cancer (1 or 2 PSA tests), a non-significant positive association was observed between prostatitis and prostate cancer (RR = 1.10; 95% CI: 0.75–1.63). STDs were not associated with overall prostate cancer risk. In racial/ethnic stratified analysis, Latinos reporting any STDs had an increased risk of disease than those with no STDs (RR = 1.43; 95% CI: 1.07–1.91). Interestingly, foreign-born Latinos displayed a larger risk associated with STDs (RR = 1.87; 95% CI: 1.16–3.02) than U.S. born Latinos (RR = 1.15; 95% CI: 0.76–3.02).

Conclusion

In summary, results from this prospective study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility. While we cannot rule out the possible influence of incidental detection, future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development.     

Obesity Affects the Biopsy-Mediated Detection of Prostate Cancer,Particularly High-Grade Prostate Cancer: A Dose-Response Meta-Analysis of 29,464 Patients

Background and Objectives

In previous studies, obesity (measured according to the body mass index) has correlated inconsistently with the risk of biopsy-measured prostate cancer, and specifically high-grade prostate cancer. This meta-analysis aimed to clarify these correlations.

Methods

A comprehensive literature search of the MEDLINE and EMBASE databases was conducted for relevant studies published through January 2014. The pooled estimates of odds ratios (OR) and confidence intervals (CI) were computed, and the meta-analysis was performed with the STATA software according to a random effects approach.

Results

A total of 11 studies that included 29,464 individuals were identified. A 5-kg/m² increase in body mass index was associated with a 15% (OR, 1.15; 95% CI, 0.98–1.34) higher risk of prostate cancer detection and a 37% (OR, 1.37; 95% CI, 1.19–1.57) higher risk of high-grade prostate cancer detection at biopsy. There were no differences among the results of studies conducted in the USA, Europe or Asia. We also found that studies that had adjusted for prostate-specific antigen levels, digital rectal examination results, and prostate volumes obtained positive significant outcomes (OR, 1.27; 95% CI, 1.12–1.44), whereas studies that did not adjust for the above-mentioned confounding variables obtained negative results (OR, 0.92; 95% CI, 0.68–1.25). Moreover, the positive correlation between body mass index and the detection of both prostate cancer and high-grade diseases tended to be stronger as the number of biopsy cores increased.

Conclusion

The present meta-analysis demonstrated that a high body mass index correlated positively with prostate cancer detection, especially high-grade prostate cancer detection. The adoption of a modified and possibly more aggressive biopsy strategy was suggested for obese populations.     

The Role of Androgen Receptor Mutations in Prostate Cancer Progression

Prostate tumour growth is almost always dependent upon the androgen receptor pathway and hence therapies aimed at blocking this signalling axis are useful tools in the management of this disease. Unfortunately such therapies invariably fail; and the tumour progresses to an “androgen-independent” stage. In such cases androgen receptor expression is almost always maintained and much evidence exists to suggest that it may still be driving growth. One mechanism by which the receptor is thought to remain active is mutation. This review summarises the present data on androgen receptor mutations in prostate cancer, and how such substitutions offer a growth advantage by affecting cofactor interactions or by reducing ligand specificity. Such alterations appear to have a subsequent effect upon gene expression suggesting that tumours may “behave” differently dependent upon the ligand promoting growth and if a mutation is present.     

Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis

Zinc is an essential dietary element that has been implicated in the pathogenesis of prostate cancer, a cancer that disproportionately affects men of African descent. Studies assessing the association of zinc intake and prostate cancer have yielded inconsistent results. Furthermore, very little is known about the relationship between zinc intake and prostate cancer among African Americans. We examined the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study of African Americans. We then compared our results with previous studies by performing a meta-analysis to summarize the evidence regarding the association between zinc and prostate cancer. Newly diagnosed African American men with histologically confirmed prostate cancer (n = 127) and controls (n = 81) were recruited from an urban academic urology clinic in Washington, DC. Controls had higher zinc intake, with a mean of 14 mg/day versus 11 mg/day for cases. We observed a non-significant, non-linear increase in prostate cancer when comparing tertiles of zinc intake (OR _{<6.5 vs 6.5–12.5mg/day} 1.8, 95% CI: 0.6,5.6; OR _{<6.5 vs >12.5mg/day} 1.3, 95% CI: 0.2,6.5). The pooled estimate from 17 studies (including 3 cohorts, 2 nested case-control, 11 case-control studies, and 1 randomized clinical trial, with a total of 111,199 participants and 11,689 cases of prostate cancer) was 1.07_{hi vs lo} 95% CI: 0.98–1.16. Using a dose-response meta-analysis, we observed a non-linear trend in the relationship between zinc intake and prostate cancer (p for nonlinearity = 0.0022). This is the first study to examine the relationship between zinc intake in black men and risk of prostate cancer and systematically evaluate available epidemiologic evidence about the magnitude of the relationship between zinc intake and prostate cancer. Despite of the lower intake of zinc by prostate cancer patients, our meta-analysis indicated that there is no evidence for an association between zinc intake and prostate cancer.     

Prognostic Role of microRNA-21 in Colorectal Cancer: a Meta-Analysis

Background

To date, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. The present meta-analysis summarizes the recent advances in the use of microRNA-21 (miR-21) in the assessment of colorectal cancer and analyzes the prognostic role of miR-21 for survival outcome.

Methodology/Principal Findings

The present meta-analysis was performed by searching PubMed through multiple search strategies. Data were extracted from studies comparing overall survival (OS) in patients with colorectal cancer who showed higher expression of miR-21 than similar patients. Pooled hazard ratios (HRs) of miR-21 for survival and 95% confidence intervals (CI) were calculated. Seven studies with a total of 1174 patients were included this meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in colorectal cancer was 1.76 (95% CI: 1.34–2.32, P=0.000). After elimination of heterogeneity, the pooled HR was 2.32 (95% CI: 1.82–2.97, P=0.000), which was found to significantly predict poorer survival. The subgroup analysis suggested that elevated miR-21 level and patients’ survival correlated with III/IV stage (HR=5.35, 95% CI: 3.73–7.66).

Conclusions/Significance

The present findings suggest that high expression of miR-21 might predict poor prognosis in patients with colorectal cancer.     

Statin Use and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies

Background

Emerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on prostate cancer (PCa) is conflicting. We therefore examined the association between statin use and risk of PCa by conducting a detailed meta-analysis of all observational studies published regarding this subject.

Methods

Literature search in PubMed database was undertaken through February 2012 looking for observational studies evaluating the association between statin use and risk of PCa. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed.

Results

A total of 27 (15 cohort and 12 case-control) studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Statin use significantly reduced the risk of both total PCa by 7% (RR 0.93, 95% CI 0.87–0.99, p = 0.03) and clinically important advanced PCa by 20% (RR 0.80, 95% CI 0.70–0.90, p<0.001). Long-term statin use did not significantly affect the risk of total PCa (RR 0.94, 95% CI 0.84–1.05, p = 0.31). Stratification by study design did not substantially influence the RR. Furthermore, sensitivity analysis confirmed the stability of results. Cumulative meta-analysis showed a change in trend of reporting risk from positive to negative in statin users between 1993 and 2011.

Conclusions

Our meta-analysis provides evidence supporting the hypothesis that statins reduce the risk of both total PCa and clinically important advanced PCa. Further research is needed to confirm these findings and to identify the underlying biological mechanisms.     

CYP1B1 Polymorphisms and Susceptibility to Prostate Cancer: A Meta-Analysis

Background

Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) and prostate cancer (PCa) risk report conflicting results. To derive a more precise estimation of the relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was performed.

Methodology/Principal Findings

A comprehensive literature search was conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk. A total of 14 independent studies, including 6380 cases and 5807 controls, were identified. We investigated by meta-analysis the effects of 5 polymorphisms in CYP1B1 L432V (12 studies, 5999 cases, 5438 controls), R48G (6 studies, 1647 cases, 1846 controls), N453S (4 studies, 1407 cases, 1499 controls), −13C/T (4 studies, 1116 cases, 1114 controls), and A119S (4 studies, 1057 cases, 1018 controls). There was no evidence that L432V had significant association with PCa in overall population. After subgroup analyses by ethnicity, we found that L432V was significantly associated with PCa risk in Asians (additive: OR = 2.38, 95%CI = 1.31-4.33, P = 0.004; recessive: OR = 2.11, 95%CI = 1.17–3.79, P = 0.01; dominant: OR = 1.52, 95%CI = 1.14–2.01, P = 0.004; allelic: OR = 1.52, 95%CI = 1.20–1.92, P = 0.0006). When stratified by source of controls, significantly elevated PCa risk was found in all genetic models in population based studies (additive: OR = 1.34, 95%CI = 1.14–1.57, P = 0.0003; recessive: OR = 1.25, 95%CI = 1.09–1.43, P = 0.002; dominant: OR = 1.25, 95%CI = 1.11–1.41, P = 0.0002; allelic: OR = 1.18, 95%CI = 1.09–1.28, P<0.0001). For N453S, there was a significant association between N453S polymorphism and PCa risk in both overall population (dominant: OR = 1.18, 95%CI = 1.00–1.38, P = 0.04) and mixed population (domiant: OR = 1.31, 95%CI = 1.06–1.63, P = 0.01; allelic: OR = 1.27, 95%CI = 1.05–1.54, P = 0.01). For A119S, our analysis suggested that A119S was associated with PCa risk under recessive model in overall population (OR = 1.37, 95%CI = 1.04–1.80, P = 0.03).

Conclusions

The results suggest that L432V, N453S, and A119S polymorphisms of CYP1B1 might be associated with the susceptibility of PCa. Further larger and well-designed multicenter studies are warranted to validate these findings.     

斑点型痘病毒蛋白对前列腺癌分层治疗的探讨

前列腺癌（prostate cancer,PCa）已经成为男性第二大常见癌症，并且随着人口老龄化的不断发展，PCa的发病率和死亡率也呈现上升的趋势，其发生发展的机制也较为复杂。雄激素受体（androgen receptor,AR）信号通路的过度激活不仅促进去势抵抗性前列腺癌（castration-resistance PCa,CRPC）的发生，还对耐药性的产生起了关键作用。目前的治疗手段较为有限且伴随较多的不良反应，因此随着精准靶向治疗的不断发展，需要寻找新的治疗方案来提高疗效。已有大量研究证明，E3泛素连接酶斑点型痘病毒蛋白（speckle-type POZ protein,SPOP）与AR存在密切的相互作用关系，从而对PCa的发生发展起重要作用。因此本文将结合近年的研究论文，阐述SPOP的基本结构与功能，总结SPOP突变对PCa的影响，并从SPOP出发探讨对PCa进行分层治疗的可能性。SPOP发生突变后，可显著影响AR信号相关的通路、DNA损伤应答、免疫应答等的正常生理功能，产生不同的病理状况；而在SPOP野生型的状况下，也会发生其他基因融合事件，致应激反应蛋白失衡等病理状况，进而...     

ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis

Background

Many published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of this relationship.

Methods

A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association.

Results

Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T) and XbaI (A>G) polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T) polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C), codon 325 (C>G), codon 594 (G>A) and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed.

Conclusion

Results from the current meta-analysis indicate that ESR1 PvuII (C>T) polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may increase the risk of prostate cancer among American population.     

Effect of Metformin on Cancer Risk and Treatment Outcome of Prostate Cancer: A Meta-Analysis of Epidemiological Observational Studies

Background

Laboratory studies have shown the anti-tumor effect of metformin on prostate cancer. However, recent epidemiological studies have yielded inconclusive results.

Methods

We searched PubMed database from the inception to May 30 2014 for studies which assessed the effect of metformin use on cancer risk of prostate cancer, biochemical recurrence (BCR) and all-cause mortality of patients with prostate cancer. The pooled results and 95% confidence intervals (CIs) were estimated by random-effect model.

Results

Twenty-one studies were eligible according to the inclusion criteria. Based on the pooled results of available observational studies, metformin use was significantly associated with a decreased cancer risk (14 datasets, 963991 male subjects, odds ratio: 0.91, 95% CI: 0.85–0.97) and BCR (6 datasets, 2953 patients, hazard ratio: 0.81, 95% CI: 0.68–0.98) of prostate cancer. However, the association of metformin use with all-cause mortality of patients with prostate cancer was not significant (5 datasets, 9241 patients, hazard ratio: 0.86, 95% CI: 0.64–1.14).

Conclusion

Results suggest that metformin use appears to be associated with a significant reduction in the cancer risk and BCR of prostate cancer, but not in all-cause mortality of patients with prostate cancer.     

Prognostic Role of Survivin in Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose

The objective of the present study was to conduct a systematic review and meta-analysis of published literature investigating the survivin expression and its effects on bladder cancer prognosis.

Materials and Methods

We carefully searched online Pubmed, Cochrane Library and SCOPUS database from August 1997 to May 2013.

Results

A total of 14 articles met the eligibility criteria for this systematic review. The eligible studies included a total of 2,165 patients with a median number of 155 patients per study (range: 17–726). Of the 14 studies, nine evaluated immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. In non-muscle invasive bladder tumor, the pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.81; 95% confidence interval [CI], 1.30–2.52), progression-free survival (pooled HR, 2.12; 95% CI, 1.60–2.82), cancer-specific survival (pooled HR, 2.01; 95% CI, 1.32–3.06), and overall survival (pooled HR, 1.53; 95% CI, 1.02–2.29). The overall HRs by survivin status were robust across advanced stages. When only adjusted survival data were included, statistically significant differences were identified for all survival subgroup analyses. There was no between-study heterogeneity in the effect of survivin status on the majority of meta-analyses. There was no clear evidence of publication bias in this meta-analysis.

Conclusions

Survivin expression indicates worse prognosis in patients with bladder cancer but the results should be interpreted with caution. It is necessary that better-designed studies with standardized assays need to provide a better conclusion about the relationship between survivin expression and the outcome of patients with bladder cancer.     

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Localized and Advanced Prostate Cancer: A Systematic Review and Meta-Analysis

MethodsWe performed a meta-analysis to determine the predictive value of NLR for overall survival (OS), recurrence-free survival (RFS), and clinical features in patients with PCa. We systematically searched PubMed, ISI Web of Science, and Embase for relevant studies published up to October 2015.ResultsA total of 9418 patients from 18 studies were included in the meta-analysis. Elevated pretreatment NLR predicted poor OS (HR 1.628, 95% CI 1.410–1.879) and RFS (HR 1.357, 95% CI 1.126–1.636) in all patients with PCa. However, NLR was insignificantly associated with OS in the subgroup of patients with localized PCa (HR 1.439, 95% CI 0.753–2.75). Increased NLR was also significantly correlated with lymph node involvement (OR 1.616, 95% CI 1.167–2.239) but not with pathological stage (OR 0.827, 95% CI 0.637–1.074) or Gleason score (OR 0.761, 95% CI 0.555–1.044).ConclusionsThe present meta-analysis indicated that NLR could predict the prognosis for patients with locally advanced or castration-resistant PCa. Patients with higher NLR are more likely to have poorer prognosis than those with lower NLR.     

The Prognostic Role of BRAF Mutation in Metastatic Colorectal Cancer Receiving Anti-EGFR Monoclonal Antibodies: A Meta-Analysis

Background

BRAF mutation has been investigated as a prognostic factor in metastatic colorectal cancer (mCRC) undergoing anti-EGFR monoclonal antibodies (moAbs), but current results are still inconclusive. The aim of this meta-analysis was to evaluate the relationship between BRAF mutation status and the prognosis of mCRC patients treated with moAbs.

Methods

Eligible studies were identified by systematically searching Pubmed, the Cochrane Library, Web of Knowledge, and OVID. Risk ratio (RR) for overall response rate (ORR), Hazard ratios (HRs) for Progression free survival (PFS) and Overall survival (OS) were extracted or calculated. Prespecified subgroup analyses were conducted in KRAS wild-type and in different study types. The source of between-trial variation was explored by sensitivity analyses. Quality assessment was conducted by the Hayden’s criteria.

Results

A total of twenty one trials including 5229 patients were identified for the meta-analysis. 343 patients displayed BRAF mutations of 4616 (7.4%) patients with known BRAF status. Patients with BRAF wild-type (WT) showed decreased risks of progression and death with an improved PFS(HR 0.38, 95% confidence intervals 0.29–0.51) and an improved OS (HR 0.35 [0.29–0.42]), compared to BRAF mutant. In KRAS WT population, there were even larger PFS benefit (HR 0.29[0.19,0.43]) and larger OS benefit (HR 0.26 [0.20,0.35]) in BRAF WT. A response benefit for BRAF WT was observed (RR 0.31[0.18,0.53]) in KRAS WT patients, but not observed in unselected patients (RR 0.76 [0.43–1.33]). The results were consistent in the subgroup analysis of different study types. Heterogeneity between trials decreased in the subgroup and explained by sensitivity analysis. No publication bias of ORR, PFS and OS were detected.

Conclusions

The results indicate that BRAF mutant is a predictive biomarker for poor prognosis in mCRC patients undergoing anti-EGFR MoAbs therapy, especially in KRAS WT patients. Additional large prospective trials are required to confirm the predictive role of BRAF status.     

GSTP1 Ile105Val Polymorphism and Prostate Cancer Risk: Evidence from a Meta-Analysis

Background

Glutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed.

Methodology/Principal Findings

A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90–1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91–1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73–4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38–3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk.

Conclusions

This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.     

Nutraceuticals in Prostate Disease: The Urologist's Role

Interest in and use of complementary and alternative therapies, especially nutraceuticals, is high in prostate disease. These therapies have shown potential in benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. Some have produced results equal to or better than pharmaceuticals currently prescribed for BPH. In category III prostatitis, some nutraceuticals may offer relief to patients who get little from standard therapy. Because it is becoming apparent that inflammation may play a role in the progression of BPH and development of prostate cancer, nutraceuticals, which commonly have anti-inflammatory properties, may play a role. These therapies have also shown potential in prostate cancer treatment and prevention, especially those that also reduce cardiovascular events or risk. Nevertheless, uses of some nutraceuticals in prostate disease have had less desirable consequences, showing lack of efficacy, adulteration, and/or severe side effects or drug interactions. By ensuring that these therapies undergo careful study for effectiveness, quality, and safety, urologists can look forward to adding them to their evidence-based armamentarium for prostate disease.     

Insulin Therapy and Risk of Prostate Cancer: a Systematic Review and Meta-Analysis of Observational Studies

Background

Previous observational studies have shown that insulin therapy may modify the risk of prostate cancer (PCa). However, these studies yielded controversial results. Thus, we performed this meta-analysis to determine whether insulin use was associated with PCa risk in patients with diabetes mellitus (DM).

Method

A literature search was carried out in PubMed, EMBASE, and Cochrane Library Central database between January 1966 and January 2013. Fixed-effect and random-effect models were used to estimate pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were also performed.

Result

A total of 11 (10 cohorts, and one case–control) studies published between 2007 and 2013 were included in the meta-analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There were five studies investigating the influence of insulin and other glucose-lowering agents on the risk of PCa , and six studies investigating the influence of glargine and non-glargine insulin. Insulin use was not associated with PCa risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72-1.09). Use of insulin glargine did not contribute to susceptibility to PCa as compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84). Sensitivity analysis confirmed the stability of present results, since no individual study affected the pooled result significantly.

Conclusions

Our results suggest that, there may be no significant association between insulin use and risk of PCa as compared with other glucose-lowering agents in patients with DM, and there was no substantial evidence for increase risk of PCa among insulin glargine users as compared to non-glargine insulin users. Further studies are warranted to validate these conclusions.     

Prognostic Significance and Functional Role of CEP57 in Prostate Cancer

We have recently shown that centrosomal protein 57 (CEP57) is overexpressed in a subset of human prostate cancers. CEP57 is involved in intracellular transport processes, and its overexpression causes mitotic defects as well as abnormal microtubule nucleation and bundling. In the present study, we further characterized the prognostic and functional role of CEP57 in prostate cancer. Unexpectedly, we found that high CEP57 expression is an independent prognostic factor for a more favorable biochemical recurrence-free survival in two large patient cohorts. To reconcile this finding with the ability of CEP57 to cause cell division errors and thus potentially promote malignant progression, we hypothesized that alterations of microtubule-associated transport processes, in particular nuclear translocation of the androgen receptor (AR), may play a role in our finding. However, CEP57 overexpression and microtubule bundling had, surprisingly, no effect on the nuclear translocation of the AR. Instead, we found a significant increase of cells with disarranged microtubules and a cellular morphology suggestive of a cytokinesis defect. Because mitotic dysfunction leads to a reduced daughter cell formation, it can explain the survival benefit of patients with increased CEP57 expression. In contrast, we show that a reduced expression of CEP57 is associated with malignant growth and metastasis. Taken together, our findings underscore that high CEP57 expression is associated with mitotic impairment and less aggressive tumor behavior. Because the CEP57-induced microtubule stabilization had no detectable effect on AR nuclear translocation, our results furthermore suggest that microtubule-targeting therapeutics used in advanced prostate cancer such as docetaxel may have modes of action that are at least in part independent of AR transport inhibition.     

The Role of Adhesion Molecules as Biomarkers for the Aggressive Prostate Cancer Phenotype

Background

Currently available methods for diagnosis and staging of prostate cancer lack the sensitivity to distinguish between patients with indolent prostate cancer and those requiring radical treatment. Alterations in key adherens (AJ) and tight junction (TJ) components have been hailed as potential biomarkers for prostate cancer progression but the majority of research has been carried out on individual molecules.

Objective

To elucidate a panel of biomarkers that may help distinguish dormant prostate cancer from aggressive metastatic disease.

Methods

We analysed the expression of 7 well known AJ and TJ components in cell lines derived from normal prostate epithelial tissue (PNT2), non-invasive (CAHPV-10) and invasive prostate cancer (LNCaP, DU145, PC-3) using gene expression, western blotting and immunofluorescence techniques.

Results

Claudin 7, α –catenin and β-catenin protein expression were not significantly different between CAHPV-10 cells and PNT2 cells. However, in PC-3 cells, protein levels for claudin 7, α –catenin were significantly down regulated (−1.5 fold, p = <.001) or undetectable respectively. Immunofluoresence showed β-catenin localisation in PC-3 cells to be cytoplasmic as opposed to membraneous.

Conclusion

These results suggest aberrant Claudin 7, α – and β-catenin expression and/or localisation patterns may be putative markers for distinguishing localised prostate cancer from aggressive metastatic disease when used collectively.