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10.1186/1471-2407-14-431 http://scihub22266oqcxt.onion/10.1186/1471-2407-14-431 C4072609!4072609 !24927938     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 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\24927938 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       BMC+Cancer 2014 ; 14 (ä): 431 Nephropedia Template TP {{tp|p=24927938 |t=2014. Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim |pdf=|usr=}}{{24927938 }} gab.com Text Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim JO: BMC Cancer http://www.kidney.de/pget.php?&tw=1&pmid=24927938 #FOAvip BACKGROUND: A common approach to cancer therapy in clinical practice is the combination of several drugs to boost the anticancer activity of available drugs while suppressing their unwanted side effects. In this regard, we examined the efficacy of combination treatment with the widely-used genotoxic drug doxorubicin and the mitochondriotoxic Hsp90 inhibitor gamitrinib to exploit disparate stress signaling pathways for cancer therapy. METHODS: The cytotoxicity of the drugs as single agents or in combination against several cancer cell types was analyzed by MTT assay and the synergism of the drug combination was evaluated by calculating the combination index. To understand the molecular mechanism of the drug synergism, stress signaling pathways were analyzed after drug combination. Two xenograft models with breast and prostate cancer cells were used to evaluate anticancer activity of the drug combination in vivo. Cardiotoxicity was assessed by tissue histology and serum creatine phosphokinase concentration. RESULTS: Gamitrinib sensitized various human cancer cells to doxorubicin treatment, and combination treatment with the two drugs synergistically increased apoptosis. The cytotoxicity of the drug combination involved activation and mitochondrial accumulation of the proapoptotic Bcl-2 family member Bim. Activation of Bim was associated with increased expression of the proapoptotic transcription factor C/EBP-homologous protein and enhanced activation of the stress kinase c-Jun N-terminal kinase. Combined drug treatment with doxorubicin and gamitrinib dramatically reduced in vivo tumor growth in prostate and breast xenograft models without increasing cardiotoxicity. CONCLUSIONS: The drug combination showed synergistic anticancer activities toward various cancer cells without aggravating the cardiotoxic side effects of doxorubicin, suggesting that the full therapeutic potential of doxorubicin can be unleashed through combination with gamitrinib. Twit Text FOAVip Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim ????BMC Cancer http://www.kidney.de/pget.php?&tw=1&pmid=24927938 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24927938 #FOAvip English Wikipedia <ref>{{Cite pmid|24927938 }}</ref> Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim #MMPMID24927938 Park HK ; Lee JE ; Lim J ; Jo DE ; Park SA ; Suh PG ; Kang BH BMC Cancer 2014[Jun]; 14 (ä): 431 PMID24927938 show ga BACKGROUND: A common approach to cancer therapy in clinical practice is the combination of several drugs to boost the anticancer activity of available drugs while suppressing their unwanted side effects. In this regard, we examined the efficacy of combination treatment with the widely-used genotoxic drug doxorubicin and the mitochondriotoxic Hsp90 inhibitor gamitrinib to exploit disparate stress signaling pathways for cancer therapy. METHODS: The cytotoxicity of the drugs as single agents or in combination against several cancer cell types was analyzed by MTT assay and the synergism of the drug combination was evaluated by calculating the combination index. To understand the molecular mechanism of the drug synergism, stress signaling pathways were analyzed after drug combination. Two xenograft models with breast and prostate cancer cells were used to evaluate anticancer activity of the drug combination in vivo. Cardiotoxicity was assessed by tissue histology and serum creatine phosphokinase concentration. RESULTS: Gamitrinib sensitized various human cancer cells to doxorubicin treatment, and combination treatment with the two drugs synergistically increased apoptosis. The cytotoxicity of the drug combination involved activation and mitochondrial accumulation of the proapoptotic Bcl-2 family member Bim. Activation of Bim was associated with increased expression of the proapoptotic transcription factor C/EBP-homologous protein and enhanced activation of the stress kinase c-Jun N-terminal kinase. Combined drug treatment with doxorubicin and gamitrinib dramatically reduced in vivo tumor growth in prostate and breast xenograft models without increasing cardiotoxicity. CONCLUSIONS: The drug combination showed synergistic anticancer activities toward various cancer cells without aggravating the cardiotoxic side effects of doxorubicin, suggesting that the full therapeutic potential of doxorubicin can be unleashed through combination with gamitrinib. |Animals [MESH] |Antineoplastic Agents/administration & dosage/*pharmacology [MESH] |Apoptosis Regulatory Proteins/*agonists/metabolism [MESH] |Apoptosis/drug effects [MESH] |Bcl-2-Like Protein 11 [MESH] |Cell Line, Tumor [MESH] |Cell Survival/drug effects [MESH] |Disease Models, Animal [MESH] |Doxorubicin/administration & dosage/*pharmacology [MESH] |Drug Synergism [MESH] |Humans [MESH] |Membrane Proteins/*agonists/metabolism [MESH] |Mice [MESH] |Mitochondria/drug effects/metabolism [MESH] |Neoplasms/drug therapy/metabolism/pathology [MESH] |Proto-Oncogene Proteins/*agonists/metabolism [MESH] |Transcription Factor CHOP/agonists/metabolism [MESH] |Tumor Burden/drug effects [MESH]Combination treatment with doxorubicin and gamitrinib synergistically (epmc).pdf DeepDyve Pubget Overpricing