Publications (24)46.17 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them. NLRP3 inflammasomes were detected by RT-PCR and immunofluoresence methods. The relationship between NLRP3 and clinical/pathologic indexes was analyzed. RT-PCR analyses demonstrated that the mRNA levels of NLRP3 and caspase-1 genes were elevated significantly in renal tissues of PGN patients compared to those from normal pericarcinoma tissues. Moreover, the increased level of NLRP3 mRNA was correlative with a decrease in nephrin mRNA level and an increase in desmin mRNA level, which indicates that NLRP3 participates in podocyte injury in PGN patients. Immunofluorescence analysis also showed the protein expressions of NLRP3 and caspase-1 were increased in the glomeruli of PGN patients. Neverthless, there was no obvious regularity was presented in further subgroup analysis according to pathological types. In addition, increased NLRP3 was associated with the deterioration of renal function and glomerulosclerosis. IL-1β, a product of NLRP3 inflammasome activation, had a significant correlation with proteinuria. The formation and activation of NLRP3 inflammasomes in podocytes has been importantly implicated in the development of PGN-associated glomerular injury. © 2015 S. Karger AG, Basel.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: Recently, novel endothelins like zibotentan and atrasentan and other novel taxanes have been introduced to treat prostate cancer. This study reviews zibotentan in the treatment of castration-resistant prostate cancer (CRPC) and derives a more precise estimate of their effect of treatment. Two reviewers searched and extracted data of the published trials and review articles on zibotentan for prostate cancer using the Medline, Embase and Cochrane Controlled Trials Register database. We used hazard ratios (HRs) to assess the effects on overall survival (OS), progression-free survival (PFS), or time to PSA progression (TTP), and relative risk (RR) for the different types of toxicity. Four randomized controlled trials were identified. The pooled HR showed that zibotentan did not improve OS and PFS (HR = 0.92, 95%CI = 0.82-1.03, p = 0.161, HR = 0.98, 95% CI = 0.89-1.08, p = 0.714). Zibotentan had modest benefits on TTP (HR = 0.94, 95% CI = 0.91-0.97, p = 0.001). In addition, zibotentan led to more peripheral edema, anemia, cardiac failure and pneumonia. Our study concludes that zibotentan is not an attractive option for CRPC patients. However, additional studies on other novel therapies are needed to improve patient outcomes.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: To investigate the clinical characteristics and surgical treatment of penile Paget's disease. We 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. All 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. When 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.
- [Show abstract] [Hide abstract] ABSTRACT: To explore the long-term survival and prognosis of prostate cancer patients after treated by androgen deprivation therapy. 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. 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). 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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. © 2013 Wiley Periodicals, Inc.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
Dataset: Supplementary material 1
Dataset: Supplementary material 2
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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. 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. 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. 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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. In this study, 222 male patients with PCa and 244 cancer-free controls were evaluated MKK4-1304T>G genotype. The transcriptional activity of MKK4 gene was measured by luciferase assay, and MKK4 serum expression was measured by ELISA. As a whole, we found that compared to the most common -1304TT genotype, carriers of -1304G variant genotypes had a decreased risk of PCa (OR = 0.670; 95 % CI = 0.452-0.993, P = 0.046 for TG, and OR = 0.647; 95 % CI = 0.441-0.948, P = 0.025 for TG + GG). We found that carriers of the -1304G variant genotypes had greater transcriptional activity and serum expression of MKK4 than carriers of the -1304T allele. Our meta-analysis also suggested that the -1304G variant contributes to decreased risk of various cancers. Our results suggest that the functional -1304G variant in the MKK4 promoter decreases the risk of PCa by increasing the promoter activity. In the future, prospective researches on patients from many parts of the world may validate our findings.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: Albumin, which is the most abundant component of urine proteins, exerts injurious effects on renal cells in chronic kidney diseases. However, the toxicity of albumin to podocytes is not well elucidated. Here, we show that a high concentration of albumin triggers intracellular calcium ([Ca(2+)](i)) increase through mechanisms involving the intracellular calcium store release and extracellular calcium influx in conditionally immortalized podocytes. The canonical transient receptor potential-6 (TRPC6) channel, which is associated with a subset of familial forms of focal segmental glomerulosclerosis (FSGS) and several acquired proteinuric kidney diseases, was shown to be one of the important Ca(2+) permeable ion channels in podocytes. Therefore we explored the role of TRPC6 on albumin-induced functional and structural changes in podocytes. It was found that albumin-induced increase in [Ca(2+)](i) was blocked by TRPC6 siRNA or SKF-96365, a blocker of TRP cation channels. Long-term albumin exposure caused an up-regulation of TRPC6 expression in podocytes, which was inhibited by TRPC6 siRNA. Additionally, the inhibition of TRPC6 prevented the F-actin cytoskeleton disruption that is induced by albumin overload. Moreover, albumin overload induced expression of the endoplasmic reticulum (ER) stress protein GRP78, led to caspase-12 activation and ultimately podocyte apoptosis, all of which were abolished by the knockdown of TRPC6 using TRPC6 siRNA. These results support the view that albumin overload may induce ER stress and the subsequent apoptosis in podocytes via TRPC6-mediated Ca(2+) entry.
- [Show abstract] [Hide abstract] ABSTRACT: Proteinuria is an exacerbating factor of chronic kidney diseases, leading to glomerulosclerosis. However, the molecular mechanisms mediating protein overload-induced podocyte injury are poorly understood. Recent studies have shown that apoptosis mediated by endoplasmic reticulum (ER) stress participated in the progression of a variety of kidney diseases. In the present study, we investigated the role of CD2-associated protein (CD2AP) in protein overload-induced ER stress and subsequent podocyte apoptosis. Conditionally immortalized mouse podocytes were cultured in vitro and treated with different concentrations of bovine serum albumin (BSA). In addition, CD2AP eukaryotic expression vector or siRNA was transfected into podocytes before exposed to BSA. Albumin endocytosis and podocyte apoptosis were visualized by confocal microscopy. The subcellular organelles were observed by transmission electron microscopy. The expressions of GRP78, caspase-12 and CD2AP were detected by RT-PCR or Western blot analysis. It was found that albumin was endocytosed by podocytes in a time-dependent manner. Accumulation of albumin in podocytes induced ER stress and apoptosis in a concentration-dependent manner as indicated by upregulation of GRP78 and caspase-12. Meanwhile, the subcellular organelles were disrupted and the expression of CD2AP was downregulated by high concentration of albumin. Transfection of CD2AP eukaryotic expression vector into podocytes increased CD2AP expression, depressed GRP78 and caspase-12 expressions, and inhibited podocyte apoptosis. In contrast, transfection of CD2AP siRNA deteriorated the above changes induced by BSA. It is concluded protein overload induces podocyte apoptosis via ER stress and CD2AP may play a crucial role in albumin overload-induced ER stress and apoptosis in podocytes.
Nanjing Medical UniversityNan-ching, Jiangsu Sheng, China
Huazhong University of Science and Technology
Wu-han-shih, Hubei, China
- Division of Nephrology