Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma

2015 ◽  
Vol 45 (13) ◽  
pp. 1283-1291 ◽  
Author(s):  
Takuji Okusaka ◽  
Hideki Ueno ◽  
Masafumi Ikeda ◽  
Shuichi Mitsunaga ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase 1 ◽  
Advanced Hepatocellular Carcinoma ◽  
Signal Transducer ◽  
Pharmacological Trial ◽  
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scholarly journals NT157 Inhibits HCC Migration via Downregulating the STAT3/Jab1 Signaling Pathway

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
SiZhe Yu ◽  
Yu Wang ◽  
KeJia Lv ◽  
Jia Hou ◽  
WenYuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Lung Metastasis ◽  
Carcinoma Cell ◽  
Binding Protein ◽  
Signal Transducer ◽  
Activation Domain ◽  
Carcinoma Cell Lines ◽  
Hepatocellular Carcinoma Cell ◽  
Transcription 3

Purpose: The high fatality-to-case ratio of hepatocellular carcinoma is directly related to metastasis. The signal transducer and activator of transcription-3 is a key mediator of the cytokine and growth factor signaling pathways and drives the transcription of genes responsible for cancer-associated phenotypes. However, so far, no specific inhibitor for signal transducer and activator of transcription-3 has been used in clinical practice. Therefore, targeting the signal transducer and activator of transcription-3 for cancer therapy is highly desired to improve outcomes in patients with hepatocellular carcinoma. Experimental Design: Using the small-molecule inhibitor NT157, the effect of signal transducer and activator of transcription-3 inhibition on cell migration was tested in hepatocellular carcinoma cell lines and a lung metastasis model of the disease. Results: NT157 significantly inhibited the migration of hepatocellular carcinoma cell lines in vitro and lung metastasis of hepatocellular carcinoma in vivo. Mechanistically, it inhibited the phospho-signal transducer and activator of transcription-3 in a dose- and time-dependent manner. Furthermore, NT157 treatment suppressed the c-Jun activation domain-binding protein-1 levels in the nucleus but no significant decrease was observed in its expression in the cytoplasm. Finally, high mRNA expression levels of signal transducer and activator of transcription-3 and c-Jun activation domain-binding protein-1 in hepatocellular carcinoma were associated with significantly low survival rates. Conclusion: NT157 inhibits hepatocellular carcinoma migration and metastasis by downregulating the signal transducer and activator of transcription-3/c-Jun activation domain-binding protein-1 signaling pathway and targeting it may serve as a novel therapeutic strategy for the clinical management of hepatocellular carcinoma in the future.

Phase 1 study of N 1,N 11-diethylnorspermine (DENSPM) in patients with advanced hepatocellular carcinoma

2013 ◽  
Vol 72 (6) ◽  
pp. 1305-1314 ◽  
Author(s):  
Lipika Goyal ◽  
Jeffrey G. Supko ◽  
Jordan Berlin ◽  
Lawrence S. Blaszkowsky ◽  
Amanda Carpenter ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase 1 ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 1 Study

scholarly journals Signal Transducer and Activator of Transcription 3 for the Differentiation of Hepatocellular Carcinoma from Cirrhosis

2017 ◽  
Vol 130 (22) ◽  
pp. 2686-2690 ◽  
Author(s):  
Yan-Ping Li ◽  
Wen-Ze Wang ◽  
Xue-Qi Chen ◽  
Ling-Bo Li ◽  
Zhi-Yong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signal Transducer ◽  
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scholarly journals Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial

The Lancet ◽  
2017 ◽  
Vol 389 (10088) ◽  
pp. 2492-2502 ◽  
Author(s):  
Anthony B El-Khoueiry ◽  
Bruno Sangro ◽  
Thomas Yau ◽  
Todd S Crocenzi ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dose Escalation ◽  
Phase 1 ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label

scholarly journals Nardilysin promotes hepatocellular carcinoma through activation of signal transducer and activator of transcription 3

2017 ◽  
Vol 108 (5) ◽  
pp. 910-917 ◽  
Author(s):  
Yosuke Kasai ◽  
Kan Toriguchi ◽  
Etsuro Hatano ◽  
Kiyoto Nishi ◽  
Mikiko Ohno ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signal Transducer ◽  
Transcription 3
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