MicroRNAs (miRNAs) are short, conserved segments of non-coding RNA which play a significant role in prostate cancer development and progression. To identify miRNAs associated with castration resistance, we performed miRNA microarray analysis comparing castration resistant prostate cancer (CRPC) with androgen dependent prostate cancer (ADPC). We identified common underexpression of miR-4638-5p in CRPC compared to ADPC samples, which were further confirmed by quantitative PCR analysis. The role of miR-4638-5p in prostate cancer androgen-independent growth has been demonstrated both in vitro and in vivo. We also identified Kidins220 as a target gene directly regulated by miR-4638-5p and shRNA-mediated knockdown of Kidins220 phenocopied miR-4638-5p restoration. Subsequently, we revealed that Kidins220 activates PI3K/AKT pathway, which plays a key role in CRPC. Loss of miR- 4638-5p may lead to CRPC through the activity of Kidins220 and PI3K/AKT pathway. Furthermore, we found that miR-4638-5p, through regulating Kidins220 and the downstream activity of VEGF and PI3K/AKT pathway, influences prostate cancer progression via angiogenesis. The identification of miR-4638-5p down-regulation in CRPC and the understanding of the functional role of miR-4638-5p and its downstream genes/pathways have the potential to develop biomarkers for CRPC onset and to identify novel targets for novel forms of treatments of this lethal form of PCa.

Objective To investigate the expression of miR-363-3p in human prostate cancer cells and normal prostate epithelial cells, and explore its impact on the biological behaviors of prostate cancer cells. Methods Total RNA in human prostate cancer cells DU145, PC3 and normal prostate epithelial cells RWPE-1 were extracted respectively. The expressions of miR-363-3p in prostate cancer cells and normal prostate epithelial cells were detected by SYBR Green real-time PCR(RT-PCR). DU145 cells and PC3 cells were infected with the synthesized PCDH, miR-363-3p and miR-363-3p sponge, respectively. CCK 8 and Colony assay were utilized to evaluate cell proliferation, transwell assay was applied to detect migration ability, and microtubule assay to measure tube formation ability. Results The expressions of miR-363-3p in the DU-145 and PC3 cells were all significantly lower than that in the RWPE-1 cells (P<0.05). Compared with the control, overexpression of miR-363-3p can significantly enhance cell proliferation, migration and invasion, and microtubule formation of DU-145 and PC3 cells (P<0.05). In contrast, knockdown of miR-363-3p significantly reversed these changes in biological phenotypes mentioned above (P<0.05). Conclusion miR-363-3p was upregulated in prostate cancer cells. Overexpression of miR-363-3p can promote cell proliferation, invasion and migration and microtubule formation. miR-363-3p may play an important role in the development of prostate cancer, which may become a new target for treatment of prostate cancer.

Extramammary Paget's disease (EMPD) is a special type of cancers. The etiology of the disease is still unclear. We aimed to study the expression differences of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in EMPD tissues and corresponding adjacent normal tissues. The mRNA expression was detected by RT-PCR and the protein expression was explored by immunohistochemistry. Higher immunostaining signal scores of bFGF and VEGF in EMPD tissues had been found (z=-3.827, P<0.001, z=-3.729, P<0.001, respectively). In addition, the mRNA expression of bFGF and VEGF was higher in EMPD tissues, which had been validated by RT-PCR (t=5.771, P<0.001, t=3.304, P=0.004, respectively). The VEGF and bFGF might be the key signaling proteins in angiogenesis of EMPD. How to block the VEGF and bFGF in EMPD and to destroy the blood supply of the tumor cells becomes the focus of our future research.

Peyronie’s disease (PD) is marked by severe penile curved deformity and/or abnormal sexual function. The study aim was to determine the clinical efficacy of a new surgical procedure for PD, aimed at restoration of normal erection and improvement of the coital function. For this purpose, 5 cases of PD with erectile pain and curved deformity, aged 26–49 (median: 37.2) years, who previously underwent penile induration resection and autologous testicular tunica vaginalis patch grafting were retrospectively analyzed to determine the clinical efficacy of the treatment and impact on the postoperative sexual function. After follow-up for more than 12 months, all patients experienced normal penile erection without the erectile pain, and they were all fully satisfied with their sexual performance. No testicular atrophy, torsion, or necrosis of the operative side was observed. The curved deformity while penile erection was satisfactorily corrected, and the 4 out of 5 (80 %) cases displayed completely normal appearance of the penile erection. However, the remaining one case experienced local slake and bulging of the repair site while penile erection. We, therefore, concluded that the testicular tunica vaginalis patch grafting was a safe, convenient, economical, and effective procedure for the treatment of PD.

Acute aortic dissection (AAD) is a life threatening cardiovascular medical emergency with a poor prognosis. To explore the utility of D-dimers (DD) in the diagnosis of AAD, we performed a prospective study and conducted a meta-analysis of previous studies. 368 suspected patients were enrolled, including AAD n = 89, PE n = 12, AMI n = 167, normal controls n = 100. All patients had a DD test immediately after admission. We then performed a comprehensive computer search to identify studies investigating using DD as a screening tool for AAD. Finally, we pooled these data to estimate sensitivity, specificity, positive and negative likelihood ratios (LRs) by using DerSimonian-Laird random-effects models. The DD concentrations in the AAD group were significantly higher than those in the AMI and normal control groups. However, the DD level of 500 ng/ml had a poor sensitivity of 51.7 % and specificity of 89.2 % in the diagnosis of AAD. Subgroup analyses found that DD only showed a well discriminative ability of distinguishing AAD patients from normal controls (specificity and positive LR was 97 % and 17.2, respectively). The pooled sensitivity, specificity, positive and negative LR in our meta-analysis was 89, 68 %, 2.71, 0.07, respectively. In conclusion, our results suggest that plasma DD levels cannot add to the certainty of AAD diagnosis and it is not a good biomarker for AAD. In the future, prospective research on patients from many parts of the world is warranted to validate our findings. In addition, different controls, methods of plasma DD assays and other factors should be considered.

OBJECTIVETo investigate the clinical characteristics and surgical treatment of penile Paget's disease.METHODSWe retrospectively analyzed the treatment and follow-up data of 10 cases of penile Paget's disease surgically treated in Jiangsu Provincial Government Hospital and Jiangsu Provincial People's Hospital from 2008 to 2012.RESULTSAll the 10 patients received expanded local resection of the lesion with reconstruction of the defects with scrotal skin flaps or free skin flaps from the thigh. All surgeries were successful and the postoperative course was uneventful with complete graft survival and no lymph node metastasis. IIEF scores obtained before and 1 -2 months after surgery showed no statistically significant differences in the penile erectile function (P = 0.229), sexual orgasm (P = 0.761), and sexual satisfaction (P = 0.801) of the patients.CONCLUSIONWhen penile skin lesions suggest the possibility of Paget's disease, biopsy should be performed and surgery should follow as soon as possible. The ideal surgical option is expanded local resection of the lesion with reconstruction of the defects with scrotal skin flaps or free flaps according to the patient's specific conditions.

Several genes encoding DNA repair molecules have been proposed as cancer-susceptibility genes. Many studies have suggested that SNPs in XRCC4 could be implicated in altering the risk of prostate cancer (PCa). We examined the role of the functional variant (−652T>G) in the XRCC4 promoter in PCa. The transcriptional activity of XRCC4 gene was measured by luciferase assay. We performed real-time PCR/immunohistochemical assay to verify the association between expression level of XRCC4 mRNA/protein and XRCC4 −652T>G polymorphism. In addition, electrophoretic mobility shift assay (EMSA) was used to confirm whether this polymorphism has an effect on binding ability of the transcription factor. We found that the G variant significantly increased the transcription activity of the XRCC4 gene and the binding ability of transcriptional factor GATA-1 to the XRCC4 promoter. Furthermore, the results suggested that the XRCC4 protein and mRNA were overexpressed in individuals who carried the −652G allele compared to carriers of the −652T allele. In addition, the expression of XRCC4 in PCa tissues was lower than in adjacent normal tissues. Our data suggest that the XRCC4 promoter −652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. Case–control studies are required to validate our findings in the future.

Recently, novel therapies of prostate cancer, such as immunotherapy, endothelin receptor antagonists, novel androgen receptor antagonist and novel taxanes, and others have been introduced into clinical practice. This study was performed to summarize these results of immunotherapy and endothelin receptor antagonists in the treatment of castration‐resistant prostate cancer (CRPC) and derive a more precise estimation of their effect on future treatment. The PubMed database, references of published trials, and review articles were searched. Two reviewers independently extracted data of these trials. We used hazard ratios (HRs) to assess the effects on overall survival (OS), progression‐free survival (PFS), or time to disease progression (TTP), and relative risk (RR) for the different types of toxicity. In addition, 95% confidence intervals (CIs) give a sense of the precision of the estimate. Nine randomized controlled trials were ultimately identified. The pooled HR showed that immunotherapy could prolong OS significantly in patients with CRPC compared to placebo (HR = 0.70, 95% CI: 0.58–0.83, p < 0.001). Endothelin receptor antagonists also had modest benefits (HR = 0.90, 95% CI: 0.82–1.00, p = 0.046). Nevertheless, there were no significant benefits from both therapies on PFS or TTP. In addition, immunotherapy led to more fatigue, pyrexia, chills, and endothelin receptor antagonists led to more peripheral edema, anemia, and dyspnea. Our article suggested that the very acceptable toxicity and improving OS in patients with CRPC made immunotherapy an attractive option for such patients. However, future studies with thoughtful clinical trial designs are warranted.

OBJECTIVE:To explore the long-term survival and prognosis of prostate cancer patients after treated by androgen deprivation therapy.METHODS:We conducted a follow-up study of 124 patients with prostate cancer treated by androgen deprivation therapy, and compared the survival times of the patients with different pathological grades and clinical characteristics using Kaplan-Meiers survival curves.RESULTS:The mean survival time of the 124 patients after androgen deprivation therapy was 5. 912 years, with the median survival time of 7.81 years. The patients with bone metastases showed a shorter survival time than those with non-bone metastasis (P = 0.04). Pathological grades and PSA levels were not prognostic factors. No significant differences were found in the mean survival time between those died of prostate cancer (n = 35) and those from other factors (n = 23) (P = 0.50).CONCLUSION:Bone metastasis is an important prognostic factor in advanced prostate cancer following androgen deprivation therapy, which is more significantly correlated with the survival time of the patients than tumor grades and clinical classification.

BACKGROUND:Extramammary Paget's disease (EMPD) is considered an intraepithelial adenocarcinoma. Paget's disease of the penis is the most common disease of EMPD in male patients.OBJECTIVE:The objective of this study was to investigate and improve our knowledge of the clinical features, diagnosis, therapeutic methods and outcome of penile Paget's disease.MATERIALS AND METHODS:Eleven patients from 2007 to 2012 with Paget's disease of the penis were analyzed retrospectively based on diagnosis, treatment and the results on follow-up. All patients received local expanding resection with intraoperative frozen sections and reconstruction of defects with split-thickness skin graft from autologous thigh tissue.RESULTS:All surgeries were successful, and the postoperative course was uneventful with complete wound healing and graft survival. No lymph node metastasis was obtained. Both the morphology of the penis and its function were well maintained.CONCLUSIONS:Chronic skin lesions of the penis should be biopsied as soon as possible, if they are suspected to be due to Paget's disease. Paget's disease of the penis should be treated with wide local excision and intraoperative frozen section examination. In addition, reconstruction of defects with split-thickness skin graft from the patient's thigh is an ideal choice for treatment.

目的:探讨手术治疗阴茎Paget病对患者性生活质量的影响.方法:回顾性分析南京医科大学第一附属医院及江苏省省级机关医院自2008年至今手术治疗10例阴茎Paget病患者的临床资料.结果:10例均行局部扩大切除术及自身皮瓣修补术.术前3例无性生活,7例在术后2个月左右恢复性生活.总体患者术后3及6个月时的性生活质量比术前明显好转.结论:手术是治疗阴茎Paget病的一种有效的方法,可以改善患者的性生活质量,并且这种改善效果在术后3个月时最明显.

目的 研究CD14基因-260A/G位点多态性与前列腺癌易感性的关系.方法 提取168例前列腺癌患者和208例对照组的外周血DNA标本,应用聚合酶链反应-连接酶特异检测技术(polymerase chain reaction-ligase detection reaction,PCR-LDR)分析前列腺癌患者CD14 -260A/G位点多态性,比较不同基因型和前列腺癌易感性的关系,并探讨不同基因型与前列腺癌患者年龄、体重指数(body mass index,BMI)、吸烟、饮酒及肿瘤家族史的关系.结果 总体来说CD14基因-260A/G多态性与前列腺癌易感性之间无显著相关性(P=0.284,OR=1.27,95% CI=0.82~1.94);饮酒(P=0.003)和肿瘤家族史(P＜0.001)与前列腺癌的发生密切相关;在分层分析中,年龄＜70岁的男性携带CD14-260G(AG+GG)等位基因者能增加前列腺癌的易感性(P=0.011,OR=2.93,95%CI=1.28~6.70).结论 CD14基因-260A/G位点多态性在总体上与前列腺癌易感性无显著相关性,但在年龄小于70岁男性中,携带有CD14-260G等位基因者患前列腺癌的危险性却明显增高.

To the Editor: The cornerstone of therapy for extensive-stage small cell lung cancer (E-SCLC) has been etoposide combined with platinum (EP) over the past two decades. Irinotecan plus platinum (IP) has also been demonstrated effective, while the superiority of IP over EP as first-line therapy for E-SCLC remains controversial. In the issue of May 2010, Jiang et al.1Jiang J Liang X Zhou X et al.A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer.J Thorac Oncol. 2010; 5: 867-873Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar reported a meta-analysis which demonstrated the superiority of IP versus EP in the first-line treatment of patients with E-SCLC. We have updated the data by two new studies published after the literature search completion date of the above meta-analysis. Among them, one was a randomized phase III study2Zatloukal P Cardenal F Szczesna A et al.A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease.Ann Oncol. 2010; 21: 1810-1816Crossref PubMed Scopus (113) Google Scholar published in March 2010 and the other was a German phase III trial3Schmittel A Sebastian M Fischer von Weikersthal L et al.A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer.Ann Oncol. 2011; 22: 1798-1804Crossref PubMed Scopus (83) Google Scholar published in January 2011. In fact, the German phase III trial3Schmittel A Sebastian M Fischer von Weikersthal L et al.A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer.Ann Oncol. 2011; 22: 1798-1804Crossref PubMed Scopus (83) Google Scholar was just the final outcome of a phase II trial4Schmittel A Fischer von Weikersthal L Sebastian M et al.A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer.Ann Oncol. 2006; 17: 663-667Crossref PubMed Scopus (73) Google Scholar published in 2006 which was analyzed in the meta-analysis by Jiang et al.1Jiang J Liang X Zhou X et al.A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer.J Thorac Oncol. 2010; 5: 867-873Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Using the same method as Jiang et al.1Jiang J Liang X Zhou X et al.A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer.J Thorac Oncol. 2010; 5: 867-873Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar did for meta-analysis, we complemented it including the latest data. At last, data of seven trials were analyzed. The baseline characteristics of each trial are presented in Table 1. A total of 2027 patients with E-SCLC were available for the meta-analysis. Statistical analyses were calculated using STATA 10.1 package (StataCorp, College Station, TX).TABLE 1Characteristics of the Seven Trials Included in the Meta-AnalysisAuthorQuality (Scores)RegimensEnrolled PatientsMedian AgePS 0–1 (%)Noda2I: 60 mg/m2 d1, 8, 15 + DDP: 60 mg/m2 d1, 28 d/cycle776392(2002)E: 100 mg/m2 d1–3 + DDP: 80 mg/m2 d1, 21 d/cycle776387Hanna2I: 65 mg/m2 d1, 8 + DDP: 30 mg/m2 d1, 8, 21 d/cycle2216392(2006)E: 120 mg/m2 d1–3 + DDP: 60 mg/m2 d1, 21 d/cycle1106288Pan4I: 80 mg/m2 d1, 8, 15 + DDP: 27 mg/m2 d1–3, 28 d/cycle3054100(2006)E: 120 mg/m2 d1–3 + DDP: 27 mg/m2 d1–3, 21 d/cycle3151100Hermes2I: 65 mg/m2 d1, 8 + CBP: AUC = 4 d1, 21 d/cycle1056753(2008)E*: 120 mg/m2 d1–5 + CBP: AUC = 4 d1, 21 d/cycle1046852Lara2I: 60 mg/m2 d1, 8, 15 + DDP: 60 mg/m2 d1, 28 d/cycle32462100(2009)E: 100 mg/m2 d1–3 + DDP: 80 mg/m2 d1, 21 d/cycle32763100Zatloukal2I: 65 mg/m2 d1, 8 + DDP: 80 mg/m2 d1, 21 d/cycle2026099(2010)E: 100 mg/m2 d1–3 + DDP: 80 mg/m2 d1, 21 d/cycle20361100Schmittel3I: 50 mg/m2 d1, 8, 15 + CBP: AUC = 5 d1, 28 d/cycle1066080(2011)E: 140 mg/m2 d1–3 + CBP: AUC = 5 d1, 21 d/cycle1106380I, irinotecan; E, etoposide; E*, oral etoposide; DDP, cisplatin; CBP, carboplatin; AUC, area under (the plasma concentration time) curve; PS, performance status by Zubrod-ECOG-WHO; ECOG, Eastern Cooperative Oncology Group; WHO, World Health Organization. Open table in a new tab I, irinotecan; E, etoposide; E*, oral etoposide; DDP, cisplatin; CBP, carboplatin; AUC, area under (the plasma concentration time) curve; PS, performance status by Zubrod-ECOG-WHO; ECOG, Eastern Cooperative Oncology Group; WHO, World Health Organization. The pooled relative risk (RR) for overall response rate (ORR) showed that there was no significant difference between two regimens (RR = 1.04, 95% confidence interval [CI]: 0.95–1.13, p = 0.378). The heterogeneity test did not yield a significant result (p = 0.190), and the pooled RR for ORR was calculated using fixed-effects model. The subgroup meta-analysis and sensitivity analysis of the trials using cisplatin also showed no significant difference between two regimens (Figure 1). The pooled hazard ratio (HR) for overall survival (OS) showed that IP was superior to EP (HR = 0.81, 95% CI: 0.71–0.93, p = 0.003). There was no significant heterogeneity (p = 0.081), and the pooled HR for OS was calculated using fixed-effects model. The subgroup meta-analysis and sensitivity analysis of the trials using cisplatin also showed an advantage of IP (Figure 1). The pooled HR for progression-free survival failed to display a difference between two regimens (HR = 0.90, 95% CI: 0.76–1.07, p = 0.227). There was significant heterogeneity (p = 0.012), and the pooled HR for progression-free survival was calculated using random-effects model. The subgroup meta-analysis and sensitivity analysis of the trials using cisplatin also showed no significant difference between two regimens (Figure 1). Compared with EP, IP led to less grade 3 to 4 neutropenia (odds ratio [OR] = 0.18, 95% CI: 0.10–0.34, p < 0.00001), anemia (OR = 0.58, 95%CI: 0.44–0.78, p = 0.0003), and thrombocytopenia (OR = 0.31, 95% CI: 0.19–0.53, p < 0.0001) while more grade 3 to 4 vomiting (OR = 1.78, 95% CI: 1.26–2.51, p = 0.001) and diarrhea (OR = 9.81, 95% CI: 4.37–22.02, p < 0.00001) (Table 2).TABLE 2Grade 3 to 4 Toxicities of Irinotecan/Platinum vs. Etoposide/Platinum in E-SCLCGrade 3 to 4 ToxicitiesNo. of PatientsOR95% CIpI2 (%)Leukopenia16960.420.26–0.680.000468.6Neutropenia16020.180.10–0.34<0.0000181.0Anemia20270.580.44–0.780.00030Thrombocytopenia20270.310.19–0.53<0.000165.9Vomiting18181.781.26–2.510.00111.5Diarrhea20279.814.37–2.02<0.0000146.9An OR <1 favors irinotecan/platinum regimen, whereas an OR >1 favors etoposide/platinum regimen. E-SCLC, extensive-stage small cell lung cancer; OR, odds ratio; CI, confidence interval. Open table in a new tab An OR <1 favors irinotecan/platinum regimen, whereas an OR >1 favors etoposide/platinum regimen. E-SCLC, extensive-stage small cell lung cancer; OR, odds ratio; CI, confidence interval. The present meta-analysis failed to display a difference in ORR between two regimens, which was different from results of Jiang et al.1Jiang J Liang X Zhou X et al.A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer.J Thorac Oncol. 2010; 5: 867-873Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Nevertheless, our results demonstrated a significant superiority in OS for IP compared with EP, which was in line with the meta-analysis by Jiang et al.1Jiang J Liang X Zhou X et al.A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer.J Thorac Oncol. 2010; 5: 867-873Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar and another one by Lima et al.5Lima JP dos Santos LV Sasse EC et al.Camptothecins compared with etoposide in combination with platinum analog in extensive stage small cell lung cancer: systematic review with meta-analysis.J Thorac Oncol. 2010; 5: 1986-1993Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar In conclusion, these results demonstrated significant OS benefit of IP over EP with a different toxicity profile. Consequently, IP regimen should be strongly considered as a standard first-line treatment for patients with E-SCLC. At the same time, we recognized that significant heterogeneity was found between the enrolled studies. The reasons for heterogeneity may be the pharmacogenomic differences between study populations and race, as well as differences in the studied treatment regimens and their pharmacokinetics. In the future, an analysis of individual patient data is awaited to confirm our findings.

Objective:To examine the clinical value of risk scoring system to improve the positive rate of prostate repeat biopsies. Method:From 1999 to 2010,129 patients underwent transrectal ultrasound(TRUS)-guided repeat biopsies were included in present study.Potential predictors as age,body mass index(BMI),digital rectal examination(DRE),total PSA(tPSA),free PSA(fPSA),free-to-total PSA ratio(f/tPSA),prostate volume(PV),PSA density(PSAD),PSA velocity(PSAV),PSA doubling time(PSADT)and volume/biopsy ratio(VBR)were subjected to univariate analysis and multivariate stepwise logistic regression.Based on this model,a scoring system was constructed as a tool predictive of prostate cancer in repeat biopsies. Result:Thirty-four patients(26.36%)were diagnosed with prostate cancer.On a series of analysis,DRE,tPSA,f/tPSA and VBR were independently significant predictors.Moreover,based on the scoring system we know that patients with 3-5 risk scores had higher prostate cancer detection rate than those with 0-2 scores. Conclusion:Based on our findings,key predictors do exist that help formulate a scoring system enabling urologists to identify old men in need of repeat biopsies of their prostate glands.

MKK4 has been suggested as a tumor suppressor. The functional variant (−1304T>G) in the MKK4 promoter has been implicated as a risk factor for many types of cancer. However, its role in prostate cancer (PCa) is unclear. To determine whether this SNP constitutes a risk factor for PCa susceptibility and to derive a more precise estimation of the associations between this SNP and cancer risk, we performed a case–control study and then a meta-analysis covering previous case–control studies.

Objective To investigate the associations between-1304T ＞ G polymorphism in the promoter of mitogen-activated protein kinase kinase 4 (MKK4) gene and prostate cancer (PCa) susceptibility in the Han population in Jiangsu and Anhui.Methods A case control experiment was performed,consisting of 174 cases of newly diagnosed PCa and 252 cancer-free healthy controls.The peripheral blood genome DNA was extracted.The polymorphism of MKK4-1304 locus was analyzed by polymerase chain reaction-ligase detection reaction (PCR-LDR) technique.The associations between the susceptibility to PCa and different genotypes were compared.Results TT,TG,and GG genotypes were identified in the promoter of MKK4 gene (-1304T/G).Logistic regression analysis revealed there was no significant difference at MKK4-1304 site between TG,GG,and TG + GG genotypes and TT genotype ( OR =0.775,95％ CI =0.516-1.164; OR=0.650,95％ CI =0.216-1.956; OR =0.763,95％CI =0.514-1.135,respectively).However,in the stratification analysis,the decreased risk of PCa was associated with the-1304G variant genotypes (-1304TG/GG),particularly in the subgroups of subjects older than 70 years ( OR =0.575,95％ CI=0.348-0.951) and no-smokers (OR=0.477,95％ CI=0.252-0.906).Conclusion The MKK4-1304 polymorphism is not related directly to the susceptibility to PCa in the Han population in Jiangsu and Anhui.

Objective: Evidence is accumulating that several genes encoding DNA repair molecules may be cancer-susceptibility genes. Recently, SNPs in XRCC4, a member of DNA repair genes, have been implicated in altering the risk of various cancers. However, the results of these studies are inconclusive or controversial. To derive a more precise estimation, we performed an updated meta-analysis. Methods: A comprehensive search was conducted to examine all the eligible studies about XRCC4 polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We included 31 studies investigated 8 SNPs in XRCC4. Overall, our paper showed significant associations between the rs28360071, rs2075686 polymorphisms and cancer risk. In addition, significant association was maintained in prostate cancer (rs28360071), lung cancer (rs6869366) and bladder cancer (rs1805377) subgroups analysis. Conclusions: We conducted a systematic search and combined the available results in this meta-analysis, which provided evidence of the associations between SNPs in XRCC4 and cancer risk. The results suggested that rs28360071 polymorphisms were significantly associated with cancer risk. However, future studies are needed to investigate molecular mechanisms underlying the biological functions of XRCC4 SNPs in cancer development.

Evidence is accumulating that cyclooxygenase-2 (COX-2) may play an important role in prostate cancer (PCa). Recently, gene polymorphisms in COX-2 have been implicated to alter the risk of PCa and overexpression of COX-2 may be associated with clinical and prognostic significance in PCa. However, the results of these studies are inconclusive or controversial. To derive a more precise estimation of the relationships, we performed an updated meta-analysis. A comprehensive search was conducted to examine all the eligible studies of COX-2 polymorphism and expression in PCa. We used odds ratios (ORs) to assess the strength of the association and the 95 % confidence intervals (CIs) give a sense of the precision of the estimate. Overall, no significant associations between COX-2 polymorphism and PCa risk were found. However, high expression of COX-2 was significantly higher in T3-T4 stages of PCa than in T1-T2 stages of PCa (OR = 2.33, 95 %CI: 1.54-3.53, P < 0.0001). COX-2 might play an important role in the progress of PCa, overexpression of COX-2 correlates with T3-T4 stages of PCa. COX-2 might be a potential therapy target for PCa and work as a prognostic factor for PCa patients.

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios （RR） with 95% confidence intervals （CIs） were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found （Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, P heterogeneity = 0.016, I 2 = 55.8%; Pro/Pro+Pro/Arg vs Arg/ Arg, RR = 1.05, 95%CI=1.00-1.11, P heterogeneity = 0.077, I 2 = 51.1%）. In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model （RR = 0.31, 95%CI=0.10-0.91, P heterogeneity = 0.110, I 2 =60.8%）. This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.

BACKGROUND:Castration-resistant prostate cancer (CRPC) is a leading cause of cancer-related deaths in elder men. This disease has limited therapeutic options and poor prognosis as the underlying molecular mechanisms are not clearly understood. Given the emerging roles of microRNA (miRNA) as a key regulator, we postulated that miRNA may play a significant role in CRPC formation. METHODS:miR-146a levels in 15 androgen-dependent prostate cancer (ADPC) tissues and 5 CRPC tissues were measured by qRT-PCR. Effects of miR-146a in cell proliferation and migration in vitro and in vivo were evaluated by MTT assay, colony formation assay, transwell migratory assay, and tumor formation assay, respectively. RESULTS:we found that miR-146a expression was significantly decreased in CRPC tissues compared to ADPC tissues. Functional analyses showed that ectopic overexpression of miR-146a in androgen-independent cell lines not only inhibited cell growth, colony formation, and migration in vitro, but also reduced tumorigenicity and angiogenesis in vivo. Mechanistic studies revealed that miR-146a repressed the expression of EGFR through binding to its 3'-untranslated region. Also, miR-146a inhibited the expression of MMP2, one of the most important genes in tumor progression. Moreover, downregulation of p-ERK expression significantly abrogated miR-146a-induced prostate cancer cell proliferation. CONCLUSIONS:Our findings suggest that ubiquitous loss of miR-146a is a critical mechanism for overexpression of EGFR in CRPC, which is crucial to better understanding the pathogenesis of CRPC.