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10.1080/15384047.2017.1373230 http://scihub22266oqcxt.onion/10.1080/15384047.2017.1373230 C5678691!5678691 !29099264     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29099264 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cancer+Biol+Ther 2017 ; 18 (10 ): 816-826 Nephropedia Template TP {{tp|p=29099264 |t=2017. Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma |pdf=|usr=}}{{29099264 }} gab.com Text Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma JO: Cancer Biol Ther http://www.kidney.de/pget.php?&tw=1&pmid=29099264 #FOAvip Undifferentiated pleomorphic sarcomas (UPSs) are aggressive mesenchymal malignancies with no definitive cell of origin or specific recurrent genetic hallmarks. These tumors are largely chemoresistant; thus, identification of potential therapeutic targets is necessary to improve patient outcome. Previous studies demonstrated that high expression of activated protein kinase B (AKT) in patients with UPS corresponds to poor disease-specific survival. Here, we demonstrate that inhibiting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling using a small molecule inhibitor reduced UPS cell proliferation and motility and xenograft growth; however, increased phosphorylation of insulin-like growth factor 1 receptor (IGF1R) indicated the potential for adaptive resistance following treatment through compensatory receptor activation. Co-treatment with a dual PI3K/mTOR inhibitor and an anti-IGF1R kinase inhibitor reduced in vivo tumor growth rates despite a lack of antiproliferative effects in vitro. Moreover, this combination treatment significantly decreased UPS cell migration and invasion, which is linked to changes in p27 subcellular localization. Our results demonstrate that targeted inhibition of multiple components of the IGF1R/PI3K/mTOR pathway was more efficacious than single-agent therapy and suggest that co-targeting this pathway could be a beneficial therapeutic strategy for patients with UPS. Twit Text FOAVip Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma ????Cancer Biol Ther http://www.kidney.de/pget.php?&tw=1&pmid=29099264 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29099264 #FOAvip English Wikipedia <ref>{{Cite pmid|29099264 }}</ref> Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma #MMPMID29099264 May CD ; Landers SM ; Bolshakov S ; Ma X ; Ingram DR ; Kivlin CM ; Watson KL ; Sannaa GAA ; Bhalla AD ; Wang WL ; Lazar AJ ; Torres KE Cancer Biol Ther 2017[Oct]; 18 (10 ): 816-826 PMID29099264 show ga Undifferentiated pleomorphic sarcomas (UPSs) are aggressive mesenchymal malignancies with no definitive cell of origin or specific recurrent genetic hallmarks. These tumors are largely chemoresistant; thus, identification of potential therapeutic targets is necessary to improve patient outcome. Previous studies demonstrated that high expression of activated protein kinase B (AKT) in patients with UPS corresponds to poor disease-specific survival. Here, we demonstrate that inhibiting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling using a small molecule inhibitor reduced UPS cell proliferation and motility and xenograft growth; however, increased phosphorylation of insulin-like growth factor 1 receptor (IGF1R) indicated the potential for adaptive resistance following treatment through compensatory receptor activation. Co-treatment with a dual PI3K/mTOR inhibitor and an anti-IGF1R kinase inhibitor reduced in vivo tumor growth rates despite a lack of antiproliferative effects in vitro. Moreover, this combination treatment significantly decreased UPS cell migration and invasion, which is linked to changes in p27 subcellular localization. Our results demonstrate that targeted inhibition of multiple components of the IGF1R/PI3K/mTOR pathway was more efficacious than single-agent therapy and suggest that co-targeting this pathway could be a beneficial therapeutic strategy for patients with UPS. |*Phosphoinositide-3 Kinase Inhibitors [MESH] |Animals [MESH] |Cell Line, Tumor [MESH] |Cell Movement/drug effects [MESH] |Cell Proliferation/drug effects [MESH] |Cyclin-Dependent Kinase Inhibitor p27/metabolism [MESH] |Enzyme Inhibitors/*pharmacology/therapeutic use [MESH] |Female [MESH] |Humans [MESH] |Imidazoles/pharmacology/therapeutic use [MESH] |Mice [MESH] |Mice, Hairless [MESH] |Mice, SCID [MESH] |Molecular Targeted Therapy/methods [MESH] |Phosphatidylinositol 3-Kinase/metabolism [MESH] |Phosphorylation [MESH] |Proto-Oncogene Proteins c-akt/metabolism [MESH] |Pyrimidines/pharmacology/therapeutic use [MESH] |Pyrroles/pharmacology/therapeutic use [MESH] |Quinolines/pharmacology/therapeutic use [MESH] |Receptor, IGF Type 1 [MESH] |Receptors, Somatomedin/*antagonists & inhibitors/metabolism [MESH] |Sarcoma/*drug therapy/pathology [MESH] |Signal Transduction/*drug effects [MESH] |TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism [MESH]Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for (epmc).pdf DeepDyve Pubget Overpricing