Search

Rapalogs (everolimus and temsirolimus) are allosteric mTORC1 inhibitors and approved agents for advanced clear cell renal cell carcinoma (ccRCC), although only a subset of patients derive clinical benefit. Progress in genomic characterization has made it possible to generate comprehensive profiles of genetic alterations in ccRCC; however, the correlations between recurrent somatic mutations and rapalog efficacy remain unclear. Here, we demonstrate by using multiple patient-derived ccRCC cell lines that compared to PTEN-proficient cells, PTEN-deficient cells exhibit hypersensitivity to rapalogs. Rapalogs inhibit cell proliferation by inducing G

Objective To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. Patients and methods We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. Results A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). Conclusion Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa.

To evaluate the correlation between the level of adipocytokines expression in periprostatic adipose tissue and the prostate cancer aggressiveness.The periprostatic adipose tissues were collected from 30 patients who underwent radical retropubic prostatectomy. The subcutaneous adipose, periprostatic adipose tissues and prostate cancer tissue from the same patient were collected from 10 patients for match research. The expression level of IL-6, Leptin and Adiponectin was detected by immunohistochemistry and by Real-time quantitative PCR in periprostatic adipose tissues.There were differences in the positive rates of IL-6, Leptin and Adiponectin expression in the periprostate adipose between prostate cancer and control (P0.001, P=0.032, 0.003). Nothing but the "IL-6 expression intensity" was seen in difference with the aggressiveness of prostate cancer (P=0.001), and was relevant with the prostate cancer aggressiveness (rs=0.668, P0.001); The mRNA expression of IL-6 in periprostatic adipose tissues of prostate cancer was higher than that of control (P=0.049), and the mRNA expression of Adiponectin was lower (P0.0001); IL-6 mRNA expression in periprostate adipose tissue and prostate cancer tissue were higher than that in subcutaneous adipose (P0.001, P=0.001); IL-6 mRNA expression in periprostate adipose was correlated with that in prostate cancer tissue (r=0.663, p=0.036); Adiponectin mRNA expression in prostate cancer tissue was lower than that in periprostate adipose (P=0.006), and Adiponectin mRNA expression in periprostate adipose was correlated with that in prostate cancer tissue (r=0.707, p=0.022).IL-6, Leptin and Adiponectin were expressed in the periprostatic adipose tissues, which constitute the microenvironment of prostate cancer aggressiveness. There might be intimate relationship between periprostate adipose and prostate cancer tissue.

The [-2]proPSA (p2PSA) and its derivatives, the p2PSA-to-free PSA ratio (%p2PSA), and the Prostate Health Index (PHI) have greatly improved discrimination between men with and without prostate cancer (PCa) in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen (tPSA), free PSA, and p2PSA. For each patient, the free-to-total PSA ratio (%fPSA), PSA density (PSAD), p2PSA-to-free PSA ratio (%p2PSA), and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml −1 . Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

To test the hypothesis that miR429 expression in renal cancer patients is increased and plays a role in the pathogenesis of the disease.Twenty-seven renal cancer patients admitted to our hospital from May 2014 to May 2015 were enrolled as the study group, and 28 non-cancer patients were selected during the same period as the control group. Renal biopsy and serum samples were used to detect miR429 expression levels, and the patient histories were obtained to make relevant associations to clinical outcomes. In addition, the renal cancer cell line SK458 was used for overexpressing or knocking out miR429 in in vitro experiments to observe changes in proliferation and apoptosis rates.The expression levels of miR429 in renal tissues and serum of renal cancer patients were significantly higher compared with control patients (p0.05). In addition, a correlation was found between the levels of miR429 in the serum of renal cell cancer patients and their clinical outcome after conventional treatment, with patients expressing lower miR429 levels showing better clinical outcomes. Finally, experiments with renal cancer cells revealed that the proliferation of cells overexpressing miR429 was increased and their apoptosis rate was significantly reduced, while the opposite was true in miR429-knockout cells.It seems that miR429 can inhibit normal apoptosis rates and lead to high proliferation rates. Accordingly, the higher serum miR429 level in renal cancer patients suggests that it plays a role in the pathogenesis of the disease, while the differential miR429 levels according to the patients' clinical outcomes after treatment suggest that miR429 may be useful as a marker for prognosis.

The neutrophil-to-lymphocyte ratio (NLR) is associated with clinical outcomes of various cancers. This study aimed to evaluate whether pretreatment NLR can be used as a prognostic factor in patients with metastatic renal cell carcinoma (mRCC) receiving targeted therapy. In this single-center retrospective study, the Kaplan–Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) of 373 mRCC patients receiving targeted therapy. The survival outcomes of patients with high (≥2.2) and low (

Although pretreatment neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), and platelet–lymphocyte ratio (PLR) are reportedly associated with clinical outcomes of many cancers, their roles in patients with bladder cancer (BCa) who undergo radical cystectomy (RC) have not been widely investigated. We analyzed relationships between preoperative NLR, LMR, PLR, and overall survival (OS) in 124 BCa patients undergoing RC. OS curves were drawn using the Kaplan–Meier method and evaluated using the log-rank test. Relationships between OS and potential confounding variables were determined using Cox’s proportional hazard regression model. Decreased LMR was associated with shorter OS (P = 0.012); OS in the low PLR group was significantly longer than that in the high PLR group (P = 0.029), and NLR was not significantly associated with oncological outcomes. However, after adjusting for confounding variables, patients in the high-LMR group indicated >30 % decreased mortality than the low-LMR group (hazard ratio 0.674; 95 % confidence interval 0.412–0.890; P = 0.003), and PLR was not an independent predictor of OS. Our results show that preoperative LMR is a better prognostic factor in BCa patients undergoing RC, compared with NLR and PLR.

// Gui-Ming Zhang 1, 2 , Fang-Ning Wan 1, 2 , Xiao-Jian Qin 1 , Da-Long Cao 1 , Hai-Liang Zhang 1 , Yao Zhu 1 , Bo Dai 1 , Guo-Hai Shi 1 , Ding-Wei Ye 1 1 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Correspondence to: Guo-Hai Shi, e-mail: guohaishi@126.com Ding-Wei Ye, e-mail: yedingwei1963@126.com Keywords: TREK-1, prostate cancer, biochemical recurrence, cell proliferation, cell cycle Received: March 05, 2015 Accepted: April 13, 2015 Published: April 21, 2015 ABSTRACT Background: TREK-1 channels belong to the two-pore domain potassium channel superfamily and play an important role in central nervous system diseases. However, few studies have examined their role in carcinogenesis. Methods: In this study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues using immunohistochemistry and further analyzed its clinicopathological significance. Next, cell proliferation and cell cycle analysis were carried out on human PCa PC-3 cell lines where TREK-1 was stably knockdown. Results: We found that compared with normal prostate tissues, PCa tissues showed overexpressed TREK-1 levels and TREK-1 levels were positively associated with Gleason score and T staging. High level of TREK-1 expression was related to shorter castration resistance free survival (CRFS). Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo , and induced a G1/S cell cycle arrest. Conclusion: Our results suggest that TREK-1 might be a biomarker in CRFS judgment of PCa, as well as a potential therapeutic target.

// Yi-Ping Zhu 1,2,* , Fang-Ning Wan 1,2,* , Yi-Jun Shen 1,2 , Hong-Kai Wang 1,2 , Gui-Ming Zhang 1,2 and Ding-Wei Ye 1,2 1 Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Ding-Wei Ye, email: // Keywords : castration-resistant prostate cancer, COL6A1, reactive stroma, tumorigenesis Received : January 12, 2015 Accepted : March 01, 2015 Published : March 30, 2015 Abstract Castration-resistant prostate cancer (CRPC) remains the most critical challenge in the clinical management of prostate cancer (PCa). Reactive stromal changes in PCa are likely involved in the emergence of CRPC. In the present study, we identified a novel oncogene termed COL6A1 which was upregulated in the reactive stroma of CRPC. We established an androgen-independent LNCaP (LNCaP-AI) cell line in steroid-reduced (SR) medium within 2 months. We examined COL6A1 expression with western blot during the LNCaP-AI induction, and studied the function of COL6A1 in vitro and in vivo . Immunohistochemical staining of COL6A1 was performed in ten pairs of androgen-sensitive PCa and CRPC samples. We demonstrated that COL6A1 expression was markedly increased in LNCaP-AI cells and CRPC tissues compared with LNCaP cells and paired androgen-sensitive PCa specimens. In vitro , COL6A1 knockdown resulted in G1-S cell cycle arrest and descended vitality. Overexpression of COL6A1 was associated with accelerated S phase entry and elevated vitality in prostate cancer cells. COL6A1 also promoted tumorigenesis of LNCaP cells in vivo . Taken together, these data suggest an important role of COL6A1 in the molecular etiology of castration-resistant prostate cancer, and support the potential use of COL6A1 in CRPC therapy.

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.

Purpose. To investigate the association between ABO blood types and clinicopathological characteristics in patients with prostate cancer (PC). Methods. A total of 237 pathologically diagnosed PC patients were enrolled. All patients were classified as low–middle or high-risk group. The correlation of ABO blood types with high-risk PC was determined by univariate and multivariate regression analysis. Results. Data indicated 144 (85.7%) patients were stratified as high risk in the non-O group, while 50 (72.5%) patients in the O group (p=0.025). However, there was no significant difference regarding PSA, Gleason score, stage, or metastasis between O and non-O group (p>0.05). Univariate logistic regression analyses revealed PSA, Gleason score, and blood type non-O were all correlated with high-risk PC (OR = 1.139, p<0.001; OR = 9.465, p<0.001; OR = 2.280, p=0.018, resp.). In the stepwise multivariate regression analysis, the association between blood type non-O and high-risk PC remained significant (OR = 33.066, 95% CI 2.391–457.323, and p=0.009) after adjusting for confounding factors as well as PSA and Gleason score. Conclusion. The present study firstly demonstrated that non-O blood type was at higher risk of aggressive PC compared with O type, suggesting that PC patients with non-O blood type should receive more attention in clinical practice.

Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b. Phosphorylations of extracellular signal–regulated kinase, p38, and c-Jun NH2-terminal kinase were stimulated by dihydrotestosterone or fibroblast growth factor 8b. Among these major downstream pathways for mitogen-activated protein kinase, c-Jun NH2-terminal kinase signaling was most significantly enhanced. Protein kinase C phosphorylation was higher than AKT by the combined stimulation of dihydrotestosterone and fibroblast growth factor 8b. The phosphorylation of CDC2 was significantly induced by dihydrotestosterone and fibroblast growth factor 8b synergetically, and Smad underwent the same induction as CDC2. So the promoting effect of fibroblast growth factor 8b on cell cycle might contribute to the G2/M transition. This study indicated that the functional interaction between fibroblast growth factor 8b and androgen was essential for the prostate cancer cell proliferation.

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03–1.11) and HGPCa (OR = 1.14 95%Cl 1.09–1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60–0.72) to 0.71 (95%Cl 0.65–0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection.

Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the messenger RNA (mRNA) function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects. Logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs). The association between genetic variants and levels of LDLR mRNA and protein was also evaluated. Compared with the CC genotype, multivariate logistic regression analysis showed that the LDLR rs2738464 variant GG genotype was associated with a significantly decreased ccRCC risk (P = 0.002, OR: 0.605, 95% CI: 0.439-0.833). Further functional experiments showed that the rs2738464 variant G allele affected miR-330 regulation of the LDLR 3'-untranslated region (UTR), increasing LDLR mRNA levels in patient kidney tissues. These findings suggest that LDLR rs2738464 may affect the affinity of miR-330 binding to the LDLR 3'-UTR, thus regulating LDLR expression and contributing to ccRCC risk.

Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down-regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC-3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets.

Supplemental Digital Content is available in the text, Clinically localized prostate cancer is curative. Nevertheless many patients suffered from biochemical recurrence (BCR) after radical prostatectomy (RP). Mounting evidence suggest that estrogen and xenobiotic carcinogens play an essential role in progression of prostate cancervia oxidative estrogen metabolism. CYP1B1 is an enzyme involved in the hydroxylation of estrogens, a reaction of key relevance in estrogen metabolism. Given the role of CYP1B1 in the oxidative metabolism of endogenous/exogenous estrogen and compounds, CYP1B1 polymorphisms have the potential to modify its expression and subsequently lead to progression. We hypothesize that genetic variants of the CYP1B1 gene may influence clinical outcome in clinically localized prostate cancer patients. In this cohort study, we genotyped 9 tagging single nucleotide polymorphisms (SNPs) from the CYP1B1 gene in 312 patients treated with RP. For replication, these SNPs were genotyped in an independent cohort of 426 patients. The expression level of CYP1B1 in the adjacent normal prostate tissues was quantified by reverse transcription and real-time polymerase chain reaction. Kaplan–Meier analysis and Cox proportional hazard models were utilized to identify SNPs that correlated with BCR. CYP1B1 rs1056836 was significantly associated with BCR (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.40–0.89, P = 0.002) and relative CYP1B1 mRNA expression. Our findings suggest inherited genetic variation in the CYP1B1 gene may contribute to variable clinical outcomes for patients with clinically localized prostate cancer.

To examine whether the predictive performance of prostate-specific antigen (PSA) and PSA-related markers for prostate cancer (PCa) is modified by body mass index (BMI). Patients with a PSA 2–10 ng/mL who underwent multicore prostate biopsies were recruited from three tertiary centers. Serum markers measured included total PSA (tPSA), free-to-total PSA (f/tPSA), p2PSA, percentage of p2PSA (%p2PSA) and prostate health index (PHI). The association between serum markers and PCa risk was assessed by logistic regression. Predictive performance for each marker was quantified using the area under the receiver operator curves (AUC). Among 516 men, 18.2% had PCa at biopsy. For all tested markers, their predictive value on PCa risk was lower in obese patients compared to normal weight patients. We found statistically significant interactions between BMI and tPSA (P = 0.0026) and p2PSA (P = 0.038). PHI achieved an AUC of 0.872 in normal weight patients and 0.745 in obese patients, which outperformed the other predictors regardless of BMI category. In conclusion, PHI achieved the best predictive performance for detecting PCa and was not influenced by BMI.

Herein, we aimed to examine whether the association of body mass index (BMI) with prostate cancer (PCa) at biopsy differs according to genetic susceptibility. In a multicenter prospective cohort including 1120 men undergoing diagnostic prostate biopsy in China, we evaluated the interaction between BMI and genetic risk score (GRS) comprising 24 PCa-associated single nucleotide polymorphisms (SNPs), as well as a GRS consisting of 7 SNPs derived from an East-Asian population. The genetic risk was defined as low, intermediate, or high when GRS fell in the first, second, and third tertiles, respectively. We observed a significant interaction between BMI and PCa GRS (Pinteraction = 0.047), suggesting that the predictive value of BMI on PCa was strongly modified by genetic susceptibility. In men with high genetic risk, BMI was an independent predictor of PCa (odds ratio [OR] = 1.167, P = 0.008) after adjusting for conventional risk factors. The relationship between BMI and PCa risk diminished (P = 0.990) in men with low genetic risk. The interaction was more pronounced with the East-Asian GRS (Pinteraction = 0.032), suggesting that the overall GRS interaction most likely occurs through genetic susceptibility in the East-Asian population. Our results suggest that the predictive effect of BMI on the PCa risk is strongly modified by individual genetic susceptibility. The association is more positive among men with high genetic risk for PCa.

To develop and externally validate a prostate health index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy in Chinese men with prostate-specific antigen 4–10 ng/mL and normal digital rectal examination (DRE). 347 men were recruited from two hospitals between 2012 and 2014 to develop a PHI-based nomogram to predict PCa. To validate these results, we used a separate cohort of 230 men recruited at another center between 2008 and 2013. Receiver operator curves (ROC) were used to assess the ability to predict PCa. A nomogram was derived from the multivariable logistic regression model and its accuracy was assessed by the area under the ROC (AUC). PHI achieved the highest AUC of 0.839 in the development cohort compared to the other predictors (p

MicroRNAs (miRNAs) are involved in cancer development and progression. Renal cell carcinoma (RCC) frequently undergoes metastasis and has a high mortality rate. The current study measured miRNA-126 (miR-126) expres- sion levels in 128 pairs of clear cell RCC and adjacent normal kidney tissue samples by reverse transcription-quantitative polymerase chain reaction, and analyzed the association between miR-126 and various clinicopathological param- eters. In addition, cell proliferation, wound healing and cell invasion assays were conducted using RCC cells over- expressing miR-126. Potential miR-126 target genes and the signaling pathways that may be regulated by miR-126 were then examined. miR‑126 expression was significantly reduced in patients with metastatic RCC compared with patients without metastasis. Consistently, overexpression of miR‑126 in RCC cells significantly inhibited cell prolifera - tion, migration and invasion in vitro compared with negative control miRNA. A luciferase reporter assay demonstrated that miR-126 targets Rho associated coiled-coil containing protein kinase 1 (ROCK1) by directly binding the 3'-untrans- lated region. Furthermore, western blotting identified miR-126 as an important regulator of the AKT and extracel- lular signal-regulated 1/2 signaling pathways. The results of the present study indicate that miR-126 inhibits RCC cell proliferation, migration and invasion by downregulating ROCK1. These findings suggest that miR‑126 may be valu - able as a potential target for therapeutic intervention in RCC.

Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa.

To examine the prevalence of dyslipidaemia in patients with renal cell carcinoma (RCC) in a Chinese population.In all, 550 histologically confirmed RCC cases and 570 controls, matched for age and sex were included. Total cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were assessed before treatment using standard techniques. The lipid profiles were defined as 'normal', 'borderline high', 'high' and 'low' according to Chinese Guidelines on Adult Dyslipidaemia. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression in both unadjusted and adjusted models.Abnormal LDL elevation was common in RCC cases compared with controls (P0.001). Results for total cholesterol, triglyceride and HDL levels between groups were insignificant. The OR for RCC for high levels of LDL (≥160 mg/dL) compared with those with a normal LDL profile was 4.675 (95% CI 1.900-11.500). After adjustment for age, gender, body mass index, smoking status, hypertension, diabetes, total cholesterol and triglyceride, the coexistence of high levels of LDL and RCC was large and statistically significant (OR 8.955, 95% CI 3.371-23.786). There was a significant coexistence of RCC for participants with high LDL levels when subgroups of cases with clear cell subtypes and advanced T stages were compared with controls.Abnormal LDL elevation was prevalent in Chinese patients with RCC. The results remain to be evaluated in prospective cohorts.

Supplemental Digital Content is available in the text, Determination of Fuhrman grade (FG) on biopsies of renal masses is relatively inaccurate, being prone to underestimating the true grade as ascertained from surgical specimens. This study evaluated whether anatomical features of tumors could predict tumor upgrading between core biopsies and surgical specimens. We prospectively enrolled 249 patients undergoing surgical resection of solid renal masses at our institution from 2012 to 2013. Tumor anatomical features were defined using RENAL nephrometry scores. Two peripheral and 1 central ex vivo core biopsies were taken from surgical specimens with an F18-gauge needle. Logistic regression was used to assess associations between covariates and FG upgrading. A comprehensive nomogram was constructed to quantitate the probability of tumor upgrading. The median tumor size was 4.75 cm and FG upgrading occurred in 43.6% of cases. In tumors of low, intermediate, and high complexity, the risk of FG upgrading was 22.0%, 47.6%, and 50.6%, respectively. According to multivariate analyses, anatomical features R (radius) and L (location) scores correlated significantly with FG upgrading. A combination of anatomical features and core biopsy findings predicted tumor upgrading with an accuracy of 0.884. With a threshold of 30%, our nomogram identified 92.4% of cases with upgrading; however, it overrated 26.8% of patients without upgrading. This ex vivo prospective study demonstrated that RENAL nephrometry score can aid prediction of FG upgrading between core biopsies and surgical specimens. Our nomogram uses anatomical features to predict true FG from renal biopsies.

Background: Desmoplastic small round cell tumor (DSRCT) is an uncommon and highly aggressive malignancy with undetermined histogenesis and poor prognosis. To date, no case of testicular DSRCT has been reported in the literature. Case: A 42-year-old Chinese man presented with painless swelling of his left testis and a painless palpable nodule in his left inguinal region. Computed tomography showed a solid mass in the left testis and multiple metastases in the body. Laboratory tests gave no abnormal results. Left radical orchiectomy was performed, and histopathological and molecular pathological examination showed typical features of DSRCT. Six cycles of chemotherapy were administrated after the operation, leading to partial remission. Postoperative 9-month follow-up indicated no progression.

Background Metabolic syndrome (MS) is a cluster of metabolic abnormalities, which has been regarded as a pivotal risk factor for cardiovascular diseases. Recent studies focusing on the relationship between MS and cancer have recognized the significant role of MS on carcinogenesis. Likewise, growing evidence suggests that MS has a strong association with increased renal cell carcinoma (RCC) risk. This review outlines the link between MS and RCC, and some underlying mechanisms responsible for MS-associated RCC. Materials and methods A National Center for Biotechnology Information PubMed search (http://www.pubmed.gov) was conducted using medical subject headings ‘metabolic syndrome’, ‘obesity’, ‘hypertension’, ‘diabetes’, ‘dyslipidemia’, and ‘renal cell carcinoma’. Results This revealed that a variety of molecular mechanisms secondary to MS are involved in RCC formation, progression, and metastasis. A deeper understanding of these molecular mechanisms may provide some strategies for the prevention and treatment of RCC. Conclusions In summary, there is a large body of evidence regarding the link between MS and RCC, within which each component of MS is considered to have a close causal association with RCC.