[Show abstract][Hide abstract] ABSTRACT: The involvement of circulating microRNAs (miRNAs) in cancer and their potential as diagnostic and prognostic biomarkers are becoming increasingly known. However, the significance of circulating miRNAs in upper tract urothelial carcinoma (UTUC) has remained to be investigated. The present study performed a genome‑wide serum miRNA analysis using a deep sequencing platform for initial screening. Subsequently, serum samples of 46 UTUC patients and 30 cancer‑free individuals with hematuria were subjected to a quantitative reverse‑transcription polymerase chain reaction analysis. The expression of thirteen miRNAs (miR‑664a‑3p, miR‑423‑5p, miR‑431‑5p, miR‑191‑5p, miR‑92a‑3p, miR‑22‑3p, miR‑26a‑5p, miR‑33b‑3p, miR‑16‑5p, let‑7a‑5p, let‑7b‑5p, let‑7f‑5p and let‑7c) was significantly different in serum from UTUC patients compared with that in control samples. Receiver operator characteristic analysis showed that 10 miRNAs (miR‑664a‑3p, miR‑431‑5p, miR‑423‑5p, miR‑191‑5p, miR‑33b‑3p, miR‑26a‑5p, miR‑22‑3p, miR‑16‑5p, let‑7b‑5p and let‑7c) had the potential to distinguish individuals with UTUC from the controls (areas under the curve >0.8). The present study provided the first evidence for the potential use of circulating miRNAs as biomarkers for UTUC diagnosis, which remains to be verified by further studies.
Molecular Medicine Reports 08/2015; 12(5). DOI:10.3892/mmr.2015.4257 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aberrant microRNAs (miRNAs) are reported to contribute to the pathogenesis of most human malignancies. The miRNA, miR-134, has been found to be downregulated in renal cell carcinoma (RCC), but its function in the disease is unknown. The aims of this study were to detect the expression of miR-134 in human RCC samples and explore its function in RCC cell lines. Real-time qualitative polymerase chain reaction (qPCR) was used to quantify miR-134 in human RCC samples. Assays for cell cycle, viability, migration, and invasion were performed to assess the phenotypic changes in RCC cells. A luciferase reporter assay was carried out to confirm whether KRAS (Kirsten rat sarcoma viral oncogene homolog) is a direct target of miR-134. Western blot was used to identify the potential signaling pathways that had an impact on RCC cell growth and alterations of markers for epithelial-mesenchymal transition (EMT), which affected metastasis by miR-134. miR-134 was found to be downregulated in RCC samples (p<0.05), while overexpression of miR-134 suppressed proliferation (p<0.05) by triggering G1/G0 cell cycle arrest (p<0.05). Forced expression of miR-134 could also inhibit migration (p<0.05) and invasion (p<0.05) by blocking EMT in RCC cell lines. KRAS was identified as a target of miR-134, and miR-134 may act as a tumor suppressor through the KRAS-related MAPK/ERK pathway other than PI3K/AKT signaling. Thus, miR-134 may function as a tumor suppressor in cell proliferation and EMT by targeting KRAS in RCC cells.
DNA and cell biology 03/2015; 34(6). DOI:10.1089/dna.2014.2629 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Over the past two decades, the clinical presentation of renal masses has evolved, where the rising incidence of small renal masses (SRMs) and concomitant minimal invasive treatments have led to noteworthy changes in paradigm of kidney cancer. This study was to perform a proportional meta-analysis of observational studies on perioperative complications and oncological outcomes of partial nephrectomy (PN) and radiofrequency ablation (RFA).
The US National Library of Medicine's life science database (Medline) and the Web of Science were exhaustly searched before August 1, 2013. Clinical stage 1 SRMs that were treated with PN or RFA were included, and perioperative complications and oncological outcomes of a total of 9 565 patients were analyzed.
Patients who underwent RFA were significantly older (P < 0.001). In the subanalysis of stage T1 tumors, the major complication rate of PN was greater than that of RFA (laparoscopic partial nephrectomy (LPN)/robotic partial nephrectomy (RPN): 7.2%, open partial nephrectomy (OPN): 7.9%, RFA: 3.1%, both P < 0.001). Minor complications occurred more frequently after RFA (RFA: 13.8%, LPN/RPN: 7.5%, OPN: 9.5%, both P < 0.001). By multivariate analysis, the relative risks for minor complications of RFA, compared with LPN and OPN, were 1.7-fold and 1.5-fold greater (both P < 0.01), respectively. Patients treated with RFA had a greater local progression rate than those treated by PN (RFA: 4.6%, LPN/RPN: 1.2%, OPN: 1.9%, both P < 0.001). By multivariate analysis, the local tumor progression for RFA versus LPN/RPN and OPN were 4.5-fold and 3.1-fold greater, respectively (both P < 0.001).
The current data illustrate that both PN and RFA are viable strategies for the treatment of SRMs. Compared with PN, RFA showed a greater risk of local tumor progression but a lower major complication rate, which is considered better for poor candidates. PN is with no doubt the golden treatment for SRMs, and LPN has been widely accepted as the first option for nephron-sparing surgery by experienced urologists. RFA may be the best option for select patients with significant comorbidity.
Chinese medical journal 07/2014; 127(13):2497-503. DOI:10.3760/cma.j.issn.0366-6999.20132779 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Recent large-scale transcriptome analyses have found large numbers of transcripts, including that of long non-coding RNAs (lncRNAs), which are aberrant in various diseases, especially cancers. However, it is not clear whether lncRNAs are involved specifically in renal cell carcinoma (RCC). We investigated the expression patterns of lncRNAs in five RCC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via microarray.
A microarray with 33,045 lncRNA probes and 30,215 mRNA probes was used to identify deregulated lncRNAs in five RCC patients. Furthermore, we confirmed the relative expression levels of AK096725 and ENST00000453068 in 70 paired samples by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
The lncRNA microarray revealed 27,279 lncRNAs in RCC samples, of which 480 were significantly upregulated (P<0.05; T/N>1.5) and 417 were significantly downregulated (P<0.05; N/T>1.5) compared with the matched non-tumor samples. In addition, 19,995 mRNAs were detected, of which 458 were significantly upregulated (P<0.05; T/N>1.5) and 413 were significantly downregulated (P<0.05; N/T>1.5). The expression level changes of AK096725 (P = 0.043) and ENST00000453068 (P<0.001) in 70 paired samples were in accord with the microarray data.
The study uncovered expression patterns of lncRNAs in 5 RCC patients, as well as a number of aberrant lncRNAs and mRNAs in tumor samples compared with the non-tumor tissues. The revelation of an association between AK096725 expression and RCC is especially noteworthy. These findings may help to find new biomarkers in RCC.
PLoS ONE 06/2014; 9(6):e99372. DOI:10.1371/journal.pone.0099372 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: UGT2B17 is a vital member of the UGT2 family and functions as a detoxification enzyme which catalyzes the glucuronidation of lipophilic compounds. Accumulating evidences implicates that it may contribute to the susceptibility of tumor risk. Identification of a UGT2B17 deletion polymorphism has attracted studies to evaluate the association between the UGT2B17 deletion polymorphism and tumor risk in diverse populations. However, the available results are conflicting.
A meta-analysis based on 14 studies from 10 publications including 5,732 cases and 5,112 controls was performed. Published literature from PubMed, EMBASE and Web of Science was pooled and the crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the associations.
Conclusively, our results indicate that individuals with a UGT2B17 deletion polymorphism were associated with tumor risks (OR = 1.29, 95% CI = 1.03-1.63, P<0.001) in a recessive model. However, after excluding two studies for their heterogeneity, the result then demonstrated that the UGT2B17 deletion polymorphism was not associated with tumor risks (OR = 1.118, 95%CI = 0.938-1.332, P>0.1). A subgroup analysis based on tumor type, sex or race did not show significant results.
These results suggest that the UGT2B17 deletion polymorphism is not associated with tumor risks.
PLoS ONE 05/2014; 9(5):e96812. DOI:10.1371/journal.pone.0096812 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to evaluate the feasibility and clinical significance of using a modified liver-mobilization technique to treat renal cell carcinoma (RCC) combined with intrahepatic inferior vena cava (IVC) thrombosis.
A total of 11 level III thrombus patients underwent radical nephrectomy with resection of the tumor thrombus from intrahepatic IVC. A father clamp was used in combination with hepatic portal blocking to control the IVC.
The intraoperative mortality and postoperative complications were reduced in 11 cases of RCC with intrahepatic IVC thrombosis. The mean blood loss was 800 mL, and mean patient hospital stay was 13 days. Follow-up was conducted for one to four months, with only two cases of recurrence recorded.
The proposed modified liver-mobilization technique could safely and effectively treat RCC and reduce intrahepatic IVC thrombosis.
World Journal of Surgical Oncology 04/2014; 12(1):131. DOI:10.1186/1477-7819-12-131 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To report our initial experience in treating renal nutcracker syndrome by retroperitoneal laparoscopic extravascular stenting.
Patients and methods:
Two male patients, aged 13 and 16 years, were diagnosed with nutcracker syndrome and received retroperitoneal laparoscopic extravascular stent placement. The perioperative data were collected and evaluated. The follow-up was 10 and 18 months.
Both procedures were successful without obvious complications. Total operative time was 65 and 50 min, estimated blood loss was 110 and 70 ml, and postoperative hospital stay was 4 and 6 days. The symptom of gross hematuria ceased 3 and 6 days after surgery. Both patients had normal findings during follow-up.
Treatment of nutcracker syndrome by retroperitoneal laparoscopic extravascular stent placement is a safe and feasible procedure, especially for youngsters in the period of physical development. Longer follow-up and further experience are needed to evaluate the efficacy of this procedure.
Urologia Internationalis 02/2014; 92(4). DOI:10.1159/000353349 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are members of the insulin-like growth factor (IGF) family that play important roles in carcinogenesis. We hypothesized that the functional polymorphisms in IGF-I and IGFBP-3 may be associated with the risk of prostate cancer (PCa) in the Chinese population. This hospital-based case-control study included 664 PCa patients and 702 cancer-free controls. Nine SNPs in IGF-I and IGFBP-3 were genotyped using the TaqMan assay. The genetic associations between the pathogenesis and progression of PCa were assessed by logistic regression. We found that the genotype and allele frequency distribution of rs6218, rs35767 and rs5742612 were significantly different when comparing PCa cases to controls (P = 0.005, 0.005 and 0.020, respectively). In the combined analysis, individuals with 2-6 risk alleles had an elevated risk of PCa compared to those with 0-1 risk alleles. We also found that the association between the combined risk alleles and the risk of PCa appeared stronger in the following subgroups: individuals older than 71 years of age (OR = 1.41, 95%CI = 1.05-1.91, P = 0.020), nonsmokers (OR = 1.68, 95%CI = 1.21-2.32, P = 0.002), nondrinkers (OR = 1.32, 95%CI = 1.02-1.61, P = 0.002), and those with a negative family history of PCa (OR = 1.28, 95%CI = 1.02-1.71, P = 0.022). Our results indicate that the three SNPs (rs6218, rs35767 and rs5742612) and the joint genotypes with 2-6 risk alleles, may contribute to the susceptibility to PCa, but not the progression, in the Chinese population.
PLoS ONE 02/2014; 9(2):e85609. DOI:10.1371/journal.pone.0085609 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.
[Show abstract][Hide abstract] ABSTRACT: In most hospitals, several options for the management of renal stones are available: shockwave lithotripsy, endourologic treatment, or surgery. Choice of treatment is based on the anatomic characteristics of the patient, and the location and size of the stones. In this study we assessed a retroperitoneal laparoscopic technique for treatment of complex renal stones.
Seventy-five patients, including 53 men and 22 women with a mean age of 47.8 years (range 18-74 y), underwent retroperitoneal laparoscopy for the treatment of complex renal stones between July 2006 and November 2012 in our hospital.
The retroperitoneal laparoscopic procedures for treatment of complex renal stones were completely successful in 73 cases, while 2 cases converted to open surgery. The operative time was 85-190 min with a mean of 96 min. The estimated blood lost was 20-400 mL with a mean of 80 mL. After the operation 7 patients experienced urinary leakage. Ultrasonography, x-ray of the kidney, ureter and bladder, and intravenous urography were reviewed at post-procedural follow-up at 6-82 months. No hydronephrosis aggravation was found, and there was no calculus recurrence.
The merits of retroperitoneal laparoscopy for the treatment of complex renal stones include sparing the nephron, less bleeding, short hospitalization, quick postoperative recovery, and controllable procedure after training Success depends on the experience of surgeons and judicious selection of cases.
[Show abstract][Hide abstract] ABSTRACT: One-carbon metabolism is the basement of nucleotide synthesis and the methylation of DNA linked to cancer risk. Variations in one-carbon metabolism genes are reported to affect the risk of many cancers, including renal cancer, but little knowledge about this mechanism is known in Chinese population.
Each subject donated 5 mL venous blood after signing the agreement. The study was approved by the Institutional Review Board of the Nanjing Medical University, Nanjing, China. 18 SNPs in six one-carbon metabolism-related genes (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) were genotyped in 859 clear cell renal cell carcinoma (ccRCC) patients and 1005 cancer-free controls by the Snapshot.
Strong associations with ccRCC risk were observed for rs706209 (P = 0.006) in CBS and rs9332 (P = 0.027) in MTRR. Compared with those carrying none variant allele, individuals carrying one or more variant alleles in these two genes had a statistically significantly decreased risk of ccRCC [P = 0.001, adjusted odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.06-0.90]. In addition, patients carrying one or more variant alleles were more likely to develop localized stage disease (P = 0.002, adjusted OR = 1.37, 95%CI = 1.11-1.69) and well-differentiated ccRCC (P<0.001, adjusted OR = 1.42, 95%CI = 0.87-1.68). In the subgroup analysis, individuals carrying none variant allele in older group (P = 0.007, adjusted OR = 0.67, 95%CI = 0.49-0.91), male group (P = 0.007, adjusted OR = 0.71, 95%CI = 0.55-0.92), never smoking group (P = 0.002, adjusted OR = 0.68, 95%CI = 0.53-0.88) and never drinking group (P<0.001, adjusted OR = 0.68, 95%CI = 0.53-0.88) had an increased ccRCC risk.
Our results suggest that the polymorphisms of the one-carbon metabolism-related genes are associated with ccRCC risk in Chinese population. Future population-based prospective studies are required to confirm the results.
PLoS ONE 11/2013; 8(11):e81129. DOI:10.1371/journal.pone.0081129 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abnormal expression of Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of apoptosis protein (IAP) family, has implications in many types of cancer and is considered as a new therapeutic target. We suppose that genetic variant rs9904341 in the 5[prime] UTR region of survivin gene may be associated with the development and progression of prostate cancer (PCa) in Chinese population.
TaqMan assay method was used to genotype the polymorphism in the hospital-based case--control analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The genetic associations with the occurrence and progression of PCa were calculated by logistic regression.
Our results indicated that compared with GG genotypes, there was a statistically significant increased risk of PCa associated with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that the association was more pronounced in subgroups of nondrinkers, nonsmokers and those without a family history of cancer (all P < 0.05). In addition, we observed that PSA >= 20 was more frequent in patients carrying GC/CC genotypes than in those with a wild type genotype.
The functional survivin rs9904341 genetic variant may have a substantial influence on the PCa susceptibility and evolution.
BMC Cancer 07/2013; 13(1):356. DOI:10.1186/1471-2407-13-356 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152.
The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR.
TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152.
Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.
The Prostate 07/2013; 73(10). DOI:10.1002/pros.22656 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the expression pattern of Sprouty2 (Spry2) and its clinicopathologic significance among patients with renal cell carcinoma (RCC) and to detect its role in proliferation and invasion of RCC in vitro.
Materials and methods:
The expression profile of Spry2 in RCC and matched adjacent noncancerous tissues were detected by immunohistochemistry and Western blot analysis. The expression of Spry2 was depleted by stably transfecting with small, interfering ribonucleic acid and the effects of Spry2 were assessed using the cell proliferation and transwell assay.
We found Spry2 protein expressed at lower levels and modestly downregulated in cancerous RCC tissues compared with adjacent normal tissue (P <.001). We also measured the expression level of Spry2 in 103 archived RCC tissues by immunohistochemical staining and found its correlation with clinicopathologic findings such as tumor size (P = .002), pathologic TNM stage (P <.001), tumor grade (P <.001), lymph node metastasis (P = .001), distant metastasis (P <.001), and poor survival (P = .001). In addition, small interfering ribonucleic acid-induced depletion of Spry2 expression promoted proliferation and invasion in RCC cell lines.
Collectively, our results have demonstrated for the first time, to our knowledge, that Spry2 might offer an attractive new target for prognostic and therapeutic intervention in RCC.
[Show abstract][Hide abstract] ABSTRACT: Epithelial-mesenchymal transition (EMT) is a crucial process that plays an important role in the invasion and metastasis of human cancers. High-mobility group AT-hook 2 (HMGA2) has been found to be involved in the EMT program, with its aberrant expression having been observed in a variety of malignant tumors. However, the mechanisms regulating HMGA2 expression remain incompletely understood. The objective of this study was to investigate whether mir-154 plays a critical role in EMT by regulating HMGA2. The expression levels of HMGA2 were examined in four samples of prostate cancer (PCa) tissue and adjacent non-tumorous tissue by Western blot analysis. The effects of forced expression of miR-154 or HMGA2 knockdown on PCa cells were evaluated by cell migration and invasion assays and Western blot analysis. HMGA2 was upregulated in the PCa tissue samples compared with the adjacent normal ones. Forced expression of miR-154 or HMGA2 knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro and inhibited EMT gene expression, increased the levels of E-cadherin, an epithelial marker, and decreased the levels of vimentin, a mesenchymal marker. HMGA2 is a direct target gene of miR-154 by dual-luciferase reporter assay. Our findings suggest that miR-154 plays a role in regulating EMT by targeting HMGA2. Understanding the targets and regulating pathways of miR-154 may provide new insights into the underlying pathogenesis of PCa.
[Show abstract][Hide abstract] ABSTRACT: Background:
Research has shown reduced expression levels of miR-154 in prostate cancer (CaP). However, the function and molecular mechanisms of miR-154 in this cancer type remains unknown.
The aims of this study were to examine the functional significance of miR-154 in CaP cells and to identify the novel molecular targets regulated by miR-154.
Materials and methods:
miR-154 expression significantly decreased in primary CaP samples compared with nonmalignant samples measured by quantitative reverse transcription polymerase chain reaction. Restoration of miR-154 lowered the potential of CaP cell lines to grow and proliferate in vitro evaluated by CCK-8 assay, colony formation assay, and flow cytometry. miR-154 down-regulated the expression of CCND2 by binding to its 3'-untranslated region by luciferase reporter assay.
miR-154 plays a prominent role in CaP proliferation by suppressing CCND2, and it may provide a new approach to the treatment of CaP.
[Show abstract][Hide abstract] ABSTRACT: Fenofibrate, a peroxisome proliferator-androgen receptor-alpha agonist, is widely used in treating different forms of hyperlipidemia and hypercholesterolemia. Recent reports have indicated that fenofibrate exerts anti-proliferative and pro-apoptotic properties. This study aims to investigate the effects of fenofibrate on the prostate cancer (PCa) cell line LNCaP. The effects of fenofibrate on LNCaP cells were evaluated by flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, Western blot analysis, and dual-luciferase reporter assay. Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells, reduces the expressions of androgen receptor (AR) and AR target genes (prostate-specific antigen and TMPRSS2), and inhibits Akt phosphorylation. Fenofibrate can induce the accumulation of intracellular reactive oxygen species and malondialdehyde, and decrease the activities of total anti-oxidant and superoxide dismutase in LNCaP cells. Fenofibrate exerts an anti-proliferative property by inhibiting the expression of AR and induces apoptosis by causing oxidative stress. Therefore, our data suggest fenofibrate may have beneficial effects in fenofibrate users by preventing prostate cancer growth through inhibition of androgen activation and expression.
Biochemical and Biophysical Research Communications 02/2013; 432(2). DOI:10.1016/j.bbrc.2013.01.105 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mTOR signaling pathway plays a crucial role in the carcinogenesis of renal cell cancer (RCC). We sought to investigate the influence of genetic variations in the mTOR pathway-related genes on the risk of RCC.
We genotyped 8 potentially functional polymorphisms in AKT1, AKT2, PTEN and MTOR genes using the TaqMan method in a case-control study of 710 RCC patients and 760 cancer-free subjects. Unconditional logistic regression, adjusted for potential confounding factors, was used to assess the risk associations. We then examined the functionality of the important polymorphisms.
Of the 8 polymorphisms, after adjusting for multiple comparisons, we found a significant association between one variant (rs2295080) in the promoter of MTOR and reduced RCC risk (P = 0.005, OR = 0.74, 95%CI = 0.59-0.91, TG/GG vs. TT). Another variant (rs701848) in the 3'UTR region of PTEN was associated with increased RCC risk (P = 0.014, OR = 1.45, 95%CI = 1.08-1.96, CC vs. TT); however, the association was not significant after adjusting for multiple comparisons. Furthermore, we observed lower MTOR mRNA levels in the presence of the rs2295080G allele in normal renal tissues. The luciferase reporter assay showed that the rs2295080G allele significantly decreased luciferase activity. No other significant association between the selected polymorphisms and RCC risk was observed.
Our results suggest that the functional MTOR promoter rs2295080 variant affects RCC susceptibility by modulating the endogenous MTOR expression level. The risk effects and the functional impact of the MTOR rs2295080 variant need further validation.
PLoS ONE 11/2012; 7(11):e50302. DOI:10.1371/journal.pone.0050302 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Clamping the segmental renal artery instead of the main renal artery during nephron-sparing surgery is a promising technique to decrease warm ischemia injury. Understanding vasculature characteristics and adopting an appropriate hilar approach to segmental arteries are essential to the technique. OBJECTIVE: To study the role of the vasculature model and to standardize the renal hilar approach in segmental renal artery dissection during laparoscopic partial nephrectomy (LPN). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a consecutive series of 82 patients who underwent LPN with a precise clamping technique from December 2009 to June 2011 with a mean follow-up of 20 mo. SURGICAL PROCEDURE: Three-dimensional dynamic renal vascular models were established based on dual-source computed tomographic angiography. Clamping number, clamping position, and a different hilar approach accessing target segmental arteries were determined preoperatively. Target arteries were dissected and clamped based on the model. Tumor excision and renorrhaphy were performed under regional parenchymal ischemia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Renal vascular characteristics and surgical outcomes were analyzed. The outcomes among different surgical approaches were compared using one-way analysis of variance test or Fisher exact test. RESULTS AND LIMITATIONS: All surgeries were performed successfully without converting to main renal artery clamping or radical nephrectomy. The median operative time was 90min, and the mean clamping time was 24min. The median estimated blood loss (EBL) was 200ml, and six patients received blood transfusions. Five patients had hematuria without any intervention. One patient had a postoperative hemorrhage and received selective embolization intervention. Statistical analysis showed that appropriate surgical approaches chosen from the models led to comparable operative times, EBL, and complication rates. The limitation of the study lies on its retrospective feature. CONCLUSIONS: A renal vasculature model provides effective orientation for a precise clamping technique. A standardized hilar approach based on the model optimizes the surgical procedure and leads to satisfactory surgical outcomes.
European Urology 10/2012; 63(6). DOI:10.1016/j.eururo.2012.10.017 · 13.94 Impact Factor