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10.1016/j.juro.2012.10.018 http://scihub22266oqcxt.onion/10.1016/j.juro.2012.10.018 C4593314!4593314!23079374     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=23079374&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Urol 2013 ; 189 (6): 2317-26 Nephropedia Template TP {{tp|p=23079374|t=2013. CRM1 Blockade by Selective Inhibitors of Nuclear Export (SINE) attenuates Kidney Cancer Growth |pdf=|usr=}}{{23079374}} gab.com Text CRM1 Blockade by Selective Inhibitors of Nuclear Export (SINE) attenuates Kidney Cancer Growth JO: J Urol http://www.kidney.de/pget.php?&tw=1&pmid=23079374 #FOAvip Since renal cell carcinoma (RCC) often presents asymptomatically, patients are commonly diagnosed at the metastatic stage when treatment options are limited and survival is poor. Given that progression-free survival with current therapies for metastatic RCC is only one to two years and existing drugs are associated with a high rate of resistance, new pharmacological targets are desperately needed. We identified and evaluated the nuclear exporter protein, chromosome region maintenance protein 1 (CRM1), as a novel potential therapeutic for RCC.Purpose: To evaluate novel, selective inhibitors of nuclear export as potential RCC therapeutics. Materials and Methods: Efficacy of the CRM1 inhibitors, KPT-185 and -251, was tested in several RCC cell lines and in a RCC xenograft model. Apoptosis and cell cycle arrest were quantified, and localization of p53 family proteins was assessed using standard techniques. Results: KPT-185 attenuated CRM1 and showed increased cytotoxicity in RCC cells in vitro, with evidence of increased apoptosis as well as cell cycle arrest. KPT-185 caused both p53 and p21 to remain primarily in the nucleus in all RCC cell lines, suggesting a mechanism of action of these compounds dependent upon tumor-suppressor protein localization. Furthermore, when administered orally in a high-grade RCC xenograft model, the bioavailable CRM1 inhibitor KPT-251 significantly inhibited tumor growth in vivo with the expected on-target effects and with no obvious toxicity. Conclusions: The CRM1 inhibitor family of proteins are novel therapeutic targets RCC and deserve further intensive investigation in this and other urologic malignancies. Twit Text FOAVip CRM1 Blockade by Selective Inhibitors of Nuclear Export (SINE) attenuates Kidney Cancer Growth ????J Urol http://www.kidney.de/pget.php?&tw=1&pmid=23079374 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23079374 #FOAvip English Wikipedia <ref>{{Cite pmid|23079374}}</ref> CRM1 Blockade by Selective Inhibitors of Nuclear Export (SINE) attenuates Kidney Cancer Growth #MMPMID23079374 Inoue H; Kauffman M; Shacham S; Landesman Y; Yang J; Evans CP; Weiss RH J Urol 2013[Jun]; 189 (6): 2317-26 PMID23079374show ga Since renal cell carcinoma (RCC) often presents asymptomatically, patients are commonly diagnosed at the metastatic stage when treatment options are limited and survival is poor. Given that progression-free survival with current therapies for metastatic RCC is only one to two years and existing drugs are associated with a high rate of resistance, new pharmacological targets are desperately needed. We identified and evaluated the nuclear exporter protein, chromosome region maintenance protein 1 (CRM1), as a novel potential therapeutic for RCC.Purpose: To evaluate novel, selective inhibitors of nuclear export as potential RCC therapeutics. Materials and Methods: Efficacy of the CRM1 inhibitors, KPT-185 and -251, was tested in several RCC cell lines and in a RCC xenograft model. Apoptosis and cell cycle arrest were quantified, and localization of p53 family proteins was assessed using standard techniques. Results: KPT-185 attenuated CRM1 and showed increased cytotoxicity in RCC cells in vitro, with evidence of increased apoptosis as well as cell cycle arrest. KPT-185 caused both p53 and p21 to remain primarily in the nucleus in all RCC cell lines, suggesting a mechanism of action of these compounds dependent upon tumor-suppressor protein localization. Furthermore, when administered orally in a high-grade RCC xenograft model, the bioavailable CRM1 inhibitor KPT-251 significantly inhibited tumor growth in vivo with the expected on-target effects and with no obvious toxicity. Conclusions: The CRM1 inhibitor family of proteins are novel therapeutic targets RCC and deserve further intensive investigation in this and other urologic malignancies. äCRM1 Blockade by Selective Inhibitors of Nuclear Export (SINE) attenua(epmc).pdf DeepDyve Pubget Overpricing