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10.18632/oncotarget.15206 http://scihub22266oqcxt.onion/10.18632/oncotarget.15206 C5410264!5410264 !28423558     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28423558 &cmd=llinks): Failed to open stream: HTTP request failed! 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Biological basis and clinical study of glycogen synthase kinase- 3?-targeted therapy by drug repositioning for glioblastoma |pdf=|usr=}}{{28423558 }} gab.com Text Biological basis and clinical study of glycogen synthase kinase- 3 -targeted therapy by drug repositioning for glioblastoma JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28423558 #FOAvip BACKGROUND: Glycogen synthase kinase (GSK)-3? has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3? activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3? in the primary tumor. GBM cells and a mouse model were examined for the effects of GSK3?-inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ were tested in the mouse model and in a clinical study for recurrent GBM patients. RESULTS: Activation of GSK3? in the tumor inversely correlated with patient survival as an independent prognostic factor. CLOVA cocktail significantly inhibited cell invasion and proliferation. The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone. CONCLUSIONS: Repositioning of the GSK3?-inhibitory drugs improved the prognosis of refractory GBM patients with active GSK3? in tumors. Combination of CLOVA cocktail and TMZ is a promising approach for recurrent GBM. Twit Text FOAVip Biological basis and clinical study of glycogen synthase kinase- 3 -targeted therapy by drug repositioning for glioblastoma ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28423558 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28423558 #FOAvip English Wikipedia <ref>{{Cite pmid|28423558 }}</ref> Biological basis and clinical study of glycogen synthase kinase- 3?-targeted therapy by drug repositioning for glioblastoma #MMPMID28423558 Furuta T ; Sabit H ; Dong Y ; Miyashita K ; Kinoshita M ; Uchiyama N ; Hayashi Y ; Hayashi Y ; Minamoto T ; Nakada M Oncotarget 2017[Apr]; 8 (14 ): 22811-22824 PMID28423558 show ga BACKGROUND: Glycogen synthase kinase (GSK)-3? has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3? activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3? in the primary tumor. GBM cells and a mouse model were examined for the effects of GSK3?-inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ were tested in the mouse model and in a clinical study for recurrent GBM patients. RESULTS: Activation of GSK3? in the tumor inversely correlated with patient survival as an independent prognostic factor. CLOVA cocktail significantly inhibited cell invasion and proliferation. The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone. CONCLUSIONS: Repositioning of the GSK3?-inhibitory drugs improved the prognosis of refractory GBM patients with active GSK3? in tumors. Combination of CLOVA cocktail and TMZ is a promising approach for recurrent GBM. |*Drug Repositioning [MESH] |Aged [MESH] |Animals [MESH] |Antineoplastic Agents, Alkylating/pharmacology [MESH] |Apoptosis/drug effects [MESH] |Biomarkers, Tumor/metabolism [MESH] |Brain Neoplasms/*drug therapy/metabolism/pathology [MESH] |Cell Proliferation/drug effects [MESH] |Dacarbazine/*analogs & derivatives/pharmacology [MESH] |Drug Resistance, Neoplasm/drug effects [MESH] |Drug Therapy, Combination [MESH] |Enzyme Inhibitors/*pharmacology [MESH] |Female [MESH] |Follow-Up Studies [MESH] |Gene Expression Regulation, Neoplastic/*drug effects [MESH] |Glioblastoma/*drug therapy/metabolism/pathology [MESH] |Glycogen Synthase Kinase 3 beta/*antagonists & inhibitors [MESH] |Humans [MESH] |Male [MESH] |Mice [MESH] |Middle Aged [MESH] |Neoplasm Staging [MESH] |Prognosis [MESH] |Temozolomide [MESH] |Tumor Cells, Cultured [MESH]Biological basis and clinical study of glycogen synthase kinase- 3?-ta(epmc).pdf DeepDyve Pubget Overpricing