Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence shows that aldosterone plays an important role in the pathogenesis of renal fibrosis but its mechanism has not been completely defined. Recently, exogenous administration of aldosterone significantly alleviated ischemic states in a model of femoral artery ligated rats, accompanied by an obvious enhancement of VEGF upregulation. We hypothesized that aldosterone may also regulate the expression of VEGF in the kidney. To confirm this, cultured cortical collecting duct epithelial cells (M-1 cell line) were incubated with aldosterone and control media, respectively. The pathway by which aldosterone regulates VEGF expression was tested by the administration of spironolactone, a specific mineralocorticoid receptor (MR) antagonist. VEGF expression was detected by immunofluorescence staining, ELISA, Western blot and RT-PCR. Aldosterone induced an elevation of VEGF excretion in a time- and dose-dependent manner. Western blotting showed a 1.4-fold elevation in cytosolic VEGF expression following aldosterone (10(-8) M) incubation for 48 h (p<0.01). After aldosterone (10(-7) M) incubation for 48 h, the mRNA level of VEGF164 and VEGF120 showed 1.8- and 1.7-fold increases, respectively (p<0.01). This upregulation was almost completely blocked by spironolactone as shown both by mRNA levels and cytosolic protein levels. In addition, the mRNA of aldosterone receptor was detected in M-1 cells. We demonstrated for the first time that aldosterone induced VEGF expression in M-1 cells, an effect mediated by classic mineralocorticoid receptor. This finding provides experimental evidence for the local non-hemodynamic action of aldosterone.
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PMID:Aldosterone upregulates vascular endothelial growth factor expression in mouse cortical collecting duct epithelial cells through classic mineralocorticoid receptor. 1765 77

The advent of targeted systemic therapies has significantly improved treatment options for patients with metastatic renal cell carcinoma (RCC). Multiple agents that inhibit angiogenesis cell growth and proliferation via the VEGF and mTOR (TORC1) pathways have been USFDA-approved for locally advanced or metastatic renal cell carcinoma in recent years although the majority of clinical trials have focused only on clear cell RCC. While clear cell RCC is the most common histologic subtype nearly 25% of RCC cases are histologic variants representing a diverse group of diseases with different prognoses underlying biology and molecular targets and therapies. This review will focus on the incidence clinical and pathologic features pathogenesis and treatment strategies of non-clear cell RCC in both the adjuvant and metastatic setting. These non-clear cell subtypes include papillary type 1 and type 2 chromophobe translocation carcinoma and collecting duct RCC. Controlled studies in these relatively rare subgroups are needed to inform upon clinical practice which is currently based on small series of uncontrolled studies. Ongoing clinical trials and areas of future research will be discussed.
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PMID:Therapy for non-clear cell histologies in renal cancer. 2186 1

Endothelial markers platelet and endothelial cell adhesion molecule (PECAM-1), cluster of differentiation (CD31) and endoglin (CD105) may be used to identify endothelium and activated endothelium, respectively, with the CD105/CD31 ratio used to measure neovascularity. This study investigated the hypothesis that neovascularity in renal cell carcinoma (RCC) is associated with more aggressive RCC tumors and can be used to predict oncological outcomes. Multiplexed immunohistochemistry using antibodies to detect endoglin and PECAM-1 was performed on tissue microarray of benign kidney samples and RCC tumors including clear cell, papillary, chromophobe, and collecting duct and unclassified tumors (combined for statistics), and multispectral imaging was used for analysis. The CD105/CD31 ratio was compared with clinical and pathologic features of RCC as well as clinical outcomes after surgery using Cox proportional hazards regression and Kaplan-Meier analysis. A total of 502 tumor samples and 122 normal kidney samples from 251 RCC patients were analyzed. The average CD105/CD31 expression ratio, an indicator of neovascularization, was increased in higher pathologic stage tumors (P< .0001). Among RCC morphotypes, the ratio was lower in papillary RCC morphotype tumors (P= .001) and higher in collecting duct/unclassified tumors (P= .0001) compared with clear cell RCC. Among nuclear grades, grade 4 RCC displayed a significantly elevated CD105/CD31 ratio (P< .0001). In multivariable analysis, increased neovascularity was associated with decreased overall survival (hazard ratio, 1.54 [95% confidence interval, 1.06-2.23]; P= .02). In patients receiving anti-vascular endothelial growth factor therapy (VEGF, n = 13) for metastatic RCC, a low CD105/CD31 ratio was associated with increased survival (P= .02). We conclude that higher neovascularity is associated with worse outcomes after surgery for RCC. The ratio of CD105/CD31 expression is a potential indicator of response to anti-VEGF therapy.
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PMID:Neovascularity as a prognostic marker in renal cell carcinoma. 2743 27

Non-clear cell renal cell carcinomas (RCCs) account for up to 25% of kidney cancers and encompass distinct diseases with distinct pathologic features, different molecular alterations, and various patterns of response to systemic therapies. Recent advances in molecular biology and large collaborative efforts helped to better define the oncogenic mechanisms at play in papillary, chromophobe, collecting duct, medullary, translocation, and sarcomatoid RCCs. Papillary RCCs are divided into several subsets of tumors characterized by distinct gene expression profiles, chromatin remodeling genes, cell cycle changes, and alterations of the MET pathway. Chromophobe RCC genomic analysis revealed mostly metabolic pathway alterations with mitochondrial dysfunctions. Translocation RCCs are characterized by MITF fusions and wide genomic reprogramming. Collecting duct carcinomas are distinct entities from upper tract urothelial carcinomas associated with high T-cell infiltration and metabolic alterations. Medullary RCCs present alterations of the INI1 gene and rhabdoid features at pathologic analysis. Finally, sarcomatoid RCCs represent sarcomatoid differentiation for any subsets of RCCs with specific alterations associated with mesenchymal dedifferentiation. From the standpoint of systemic therapy, more than a decade of using VEGF and mTOR inhibitors showed that they generally had limited efficacy in non-clear cell RCCs compared with clear cell RCCs. MET inhibitors are actively being developed for papillary RCC with a specific focus on MET-driven tumors. Other strategies under investigation include CDK4/6 inhibitors in tumors with cell cycle alterations and EZH2 inhibitors in RCCs with INI1 loss. The emergence of immune checkpoint inhibitors and combination strategies enlarges the spectrum of investigational treatments. Better understanding of driver and passenger alterations and better patient stratification along with dedicated clinical networks will be key to improving the management of these rare tumors.
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PMID:Non-Clear Cell Renal Cell Carcinomas: From Shadow to Light. 3037 89