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10.1158/1078-0432.CCR-16-1216 http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-16-1216 C5457806!5457806!27913567     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Cancer+Res 2017 ; 23 (11): 2880-90 Nephropedia Template TP {{tp|p=27913567|t=2017. Drug-repositioning screens identify Triamterene as a selective drug for the treatment of DNA Mismatch Repair deficient cells |pdf=|usr=}}{{27913567}} gab.com Text Drug-repositioning screens identify Triamterene as a selective drug for the treatment of DNA Mismatch Repair deficient cells JO: Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=27913567 #FOAvip Purpose: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. Experimental Design: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs. We have identified the potassium-sparing diuretic drug Triamterene, as a novel sensitizing agent in MMR-deficient tumor cells, in vitro and in vivo. Results: The selective tumor cell cytotoxicity of Triamterene occurs through its antifolate activity, and depends on the activity of the folate synthesis enzyme, thymidylate synthase. Triamterene leads to a thymidylate synthase-dependent differential increase in reactive oxygen species in MMR-deficient cells, ultimately resulting in an increase in DNA double strand breaks. Conclusion: Conclusively, our data reveal a new drug repurposing and novel therapeutic strategy that has potential for the treatment of MMR-deficiency in a range of different tumor types and could significantly improve patient survival. Twit Text FOAVip Drug-repositioning screens identify Triamterene as a selective drug for the treatment of DNA Mismatch Repair deficient cells ????Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=27913567 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27913567 #FOAvip English Wikipedia <ref>{{Cite pmid|27913567}}</ref> Drug-repositioning screens identify Triamterene as a selective drug for the treatment of DNA Mismatch Repair deficient cells #MMPMID27913567 Guillotin D; Austin P; Begum R; Freitas MO; Merve A; Brend T; Short S; Marino S; Martin SA Clin Cancer Res 2017[Jun]; 23 (11): 2880-90 PMID27913567show ga Purpose: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. Experimental Design: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs. We have identified the potassium-sparing diuretic drug Triamterene, as a novel sensitizing agent in MMR-deficient tumor cells, in vitro and in vivo. Results: The selective tumor cell cytotoxicity of Triamterene occurs through its antifolate activity, and depends on the activity of the folate synthesis enzyme, thymidylate synthase. Triamterene leads to a thymidylate synthase-dependent differential increase in reactive oxygen species in MMR-deficient cells, ultimately resulting in an increase in DNA double strand breaks. Conclusion: Conclusively, our data reveal a new drug repurposing and novel therapeutic strategy that has potential for the treatment of MMR-deficiency in a range of different tumor types and could significantly improve patient survival. äDrug-repositioning screens identify Triamterene as a selective drug fo(epmc).pdf DeepDyve Pubget Overpricing