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10.1158/0008-5472.CAN-14-2397 http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-14-2397 C4452412!4452412!25840985     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25840985&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 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cancer+Res 2015 ; 75 (11): 2292-304 Nephropedia Template TP {{tp|p=25840985|t=2015. Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer |pdf=|usr=}}{{25840985}} gab.com Text Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer JO: Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25840985 #FOAvip The management of pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to lack of an efficient therapy and development of chemoresistance to the current standard therapy, gemcitabine (GEM). Recent studies implicate the intimate reciprocal interactions between epithelia and underlying stroma due to paracrine Sonic hedgehog (SHH) signaling in producing desmoplasia and chemoresistance in PDAC. Herein, we report for the first time that a nonsteroidal drug, ormeloxifene (ORM), has potent anti-cancer properties and depletes tumor-associated stromal tissue by inhibiting the SHH signaling pathway in PDAC. We found that ORM inhibited cell proliferation and induced death in PDAC cells, which provoked us to investigate the combinatorial effects of ORM with GEM at the molecular level. ORM caused potent inhibition of the SHH signaling pathway via downregulation of SHH and its related important downstream targets such as Gli-1, SMO, PTCH1/2, NF?B, p-AKT and Cyclin D1. ORM potentiated the anti-tumorigenic effect of GEM by 75% in PDAC xenograft mice. Further, ORM depleted tumor-associated stroma in xenograft tumor tissues by inhibiting the SHH cellular signaling pathway and mouse/human collagen I expression. Xenograft tumors treated with ORM in combination with GEM restored the tumor suppressor miR-132, and inhibited stromal cell infiltration into the tumor tissues. Additionally, invasiveness of tumor cells co-cultivated with TGF?-stimulated human pancreatic stromal cells was effectively inhibited by ORM treatment alone or in combination with GEM. We propose that ORM has high therapeutic index and in a combination therapy with GEM it possesses great promise as a treatment of choice for PDAC/pancreatic cancer. Twit Text FOAVip Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer ????Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25840985 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25840985 #FOAvip English Wikipedia <ref>{{Cite pmid|25840985}}</ref> Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer #MMPMID25840985 Khan S; Ebeling MC; Chauhan N; Thompson PA; Gara RK; Ganju A; Yallapu MM; Behrman SW; Zhao H; Zafar N; Singh MM; Jaggi M; Chauhan SC Cancer Res 2015[Jun]; 75 (11): 2292-304 PMID25840985show ga The management of pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to lack of an efficient therapy and development of chemoresistance to the current standard therapy, gemcitabine (GEM). Recent studies implicate the intimate reciprocal interactions between epithelia and underlying stroma due to paracrine Sonic hedgehog (SHH) signaling in producing desmoplasia and chemoresistance in PDAC. Herein, we report for the first time that a nonsteroidal drug, ormeloxifene (ORM), has potent anti-cancer properties and depletes tumor-associated stromal tissue by inhibiting the SHH signaling pathway in PDAC. We found that ORM inhibited cell proliferation and induced death in PDAC cells, which provoked us to investigate the combinatorial effects of ORM with GEM at the molecular level. ORM caused potent inhibition of the SHH signaling pathway via downregulation of SHH and its related important downstream targets such as Gli-1, SMO, PTCH1/2, NF?B, p-AKT and Cyclin D1. ORM potentiated the anti-tumorigenic effect of GEM by 75% in PDAC xenograft mice. Further, ORM depleted tumor-associated stroma in xenograft tumor tissues by inhibiting the SHH cellular signaling pathway and mouse/human collagen I expression. Xenograft tumors treated with ORM in combination with GEM restored the tumor suppressor miR-132, and inhibited stromal cell infiltration into the tumor tissues. Additionally, invasiveness of tumor cells co-cultivated with TGF?-stimulated human pancreatic stromal cells was effectively inhibited by ORM treatment alone or in combination with GEM. We propose that ORM has high therapeutic index and in a combination therapy with GEM it possesses great promise as a treatment of choice for PDAC/pancreatic cancer. äOrmeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcit(epmc).pdf DeepDyve Pubget Overpricing