Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1038/s41388-018-0247-7 http://scihub22266oqcxt.onion/10.1038/s41388-018-0247-7 C6062502!6062502!29695835     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       Oncogene 2018 ; 37 (30): 4058-72 Nephropedia Template TP {{tp|p=29695835|t=2018. Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma |pdf=|usr=}}{{29695835}} gab.com Text Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma JO: Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=29695835 #FOAvip Targeting RAS is one of the greatest challenges in cancer therapy. Oncogenic mutations in NRAS are present in over 25% of melanomas and patients whose tumors harbor NRAS mutations have limited therapeutic options and poor prognosis. Thus far, there are no clinical agents available to effectively target NRAS or any other RAS oncogene. An alternative approach is to identify and target critical tumor vulnerabilities or non-oncogene addictions that are essential for tumor survival. We investigated the consequences of NRAS blockade in NRAS-mutant melanoma and show that decreased expression of the telomerase catalytic subunit, TERT, is a major consequence. TERT silencing or treatment of NRAS-mutant melanoma with the telomerase-dependent telomere uncapping agent, 6-thio-2?-deoxyguanosine (6-thio-dG), led to rapid cell death, along with evidence of both telomeric and non-telomeric DNA damage, increased ROS levels, and upregulation of a mitochondrial antioxidant adaptive response. Combining 6-thio-dG with the mitochondrial inhibitor Gamitrinib attenuated this adaptive response and more effectively suppressed NRAS-mutant melanoma. Our study uncovers a robust dependency of NRAS-mutant melanoma on TERT, and provides proof-of-principle for a new combination strategy to combat this class of tumors, which could be expanded to other tumor types. Twit Text FOAVip Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma ????Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=29695835 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29695835 #FOAvip English Wikipedia <ref>{{Cite pmid|29695835}}</ref> Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma #MMPMID29695835 Reyes-Uribe P; Adrianzen-Ruesta MP; Deng Z; Echevarria-Vargas I; Mender I; Saheb S; Liu Q; Altieri DC; Murphy ME; Shay JW; Lieberman PM; Villanueva J Oncogene 2018[]; 37 (30): 4058-72 PMID29695835show ga Targeting RAS is one of the greatest challenges in cancer therapy. Oncogenic mutations in NRAS are present in over 25% of melanomas and patients whose tumors harbor NRAS mutations have limited therapeutic options and poor prognosis. Thus far, there are no clinical agents available to effectively target NRAS or any other RAS oncogene. An alternative approach is to identify and target critical tumor vulnerabilities or non-oncogene addictions that are essential for tumor survival. We investigated the consequences of NRAS blockade in NRAS-mutant melanoma and show that decreased expression of the telomerase catalytic subunit, TERT, is a major consequence. TERT silencing or treatment of NRAS-mutant melanoma with the telomerase-dependent telomere uncapping agent, 6-thio-2?-deoxyguanosine (6-thio-dG), led to rapid cell death, along with evidence of both telomeric and non-telomeric DNA damage, increased ROS levels, and upregulation of a mitochondrial antioxidant adaptive response. Combining 6-thio-dG with the mitochondrial inhibitor Gamitrinib attenuated this adaptive response and more effectively suppressed NRAS-mutant melanoma. Our study uncovers a robust dependency of NRAS-mutant melanoma on TERT, and provides proof-of-principle for a new combination strategy to combat this class of tumors, which could be expanded to other tumor types. äExploiting TERT dependency as a therapeutic strategy for NRAS-mutant m(epmc).pdf DeepDyve Pubget Overpricing