scholarly journals Signal Transducer and Activator of Transcription 3 in Liver Diseases: A Novel Therapeutic Target

2011 ◽  
Vol 7 (5) ◽  
pp. 536-550 ◽  
Author(s):  
Hua Wang ◽  
Fouad Lafdil ◽  
Xiaoni Kong ◽  
Bin Gao
Keyword(s):  
Therapeutic Target ◽  
Liver Diseases ◽  
Signal Transducer ◽  
Transcription 3 ◽  
Novel Therapeutic

Expression of Activated and Latent Signal Transducer and Activator of Transcription 3 in 303 Non–Small Cell Lung Carcinomas and 44 Malignant Mesotheliomas: Possible Role for Chemotherapeutic Intervention

2007 ◽  
Vol 131 (9) ◽  
pp. 1350-1360 ◽  
Author(s):  
Rosanede Oliveira Duarte Achcar ◽  
Philip T. Cagle ◽  
Jaishree Jagirdar
Keyword(s):  
Therapeutic Target ◽  
Critical Role ◽  
Active Form ◽  
Small Cell ◽  
Tumor Type ◽  
Signal Transducer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Transcription 3 ◽  
Mib 1

Abstract Context.—Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse human cancers and plays a critical role in tumor cell survival, proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis. The phosphorylated active form of STAT3 (pSTAT3) mediates its effects via nuclear transcriptional activity. However, it was recently observed that the nonphosphorylated, cytoplasmic, inactive form of STAT3 is involved in cell motility and consequently tumor invasion. It appears that, although STAT3 is not absolutely required for tumor formation, tumors that develop in the presence of STAT3 become dependent on its expression for their survival, making it a potential therapeutic target. Objective.—To investigate the possible utility of STAT3 as a future therapeutic target in non–small cell lung carcinoma (NSCLC) and malignant mesothelioma (MM). Design.—Immunohistochemical expression of MIB-1, STAT3, and pSTAT3 was assessed in 303 NSCLC and 44 MM archival cases. Results.—A more conspicuous expression of inactive STAT3 (91.44% in NSCLC and 79.5% in MM cases) was present compared with the nuclear activated form pSTAT3 (60.53% in NSCLC and 61.4% in MM cases). MIB-1 did not correlate with the expression of STAT3 or pSTAT3. Conclusions.—The strong expression of cytoplasmic inactive STAT3 in NSCLC and MM cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway. We conclude that STAT3 and pSTAT3 are up-regulated in a high percentage of NSCLCs and MMs, regardless of tumor type, age, sex, smoking status, stage and grade of tumor, or survival, providing a basis for therapeutic intervention.

scholarly journals Intercellular Communication between Hepatic Cells in Liver Diseases

2019 ◽  
Vol 20 (9) ◽  
pp. 2180 ◽  
Author(s):  
Keisaku Sato ◽  
Lindsey Kennedy ◽  
Suthat Liangpunsakul ◽  
Praveen Kusumanchi ◽  
Zhihong Yang ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Therapeutic Target ◽  
Liver Diseases ◽  
Cell Communication ◽  
Liver Cells ◽  
Small Particles ◽  
Hepatic Cells ◽  
Donor Cells ◽  
Parenchymal Cells ◽  
Novel Therapeutic

Liver diseases are perpetuated by the orchestration of hepatocytes and other hepatic non-parenchymal cells. These cells communicate and regulate with each other by secreting mediators such as peptides, hormones, and cytokines. Extracellular vesicles (EVs), small particles secreted from cells, contain proteins, DNAs, and RNAs as cargos. EVs have attracted recent research interests since they can communicate information from donor cells to recipient cells thereby regulating physiological events via delivering of specific cargo mediators. Previous studies have demonstrated that liver cells secrete elevated numbers of EVs during diseased conditions, and those EVs are internalized into other liver cells inducing disease-related reactions such as inflammation, angiogenesis, and fibrogenesis. Reactions in recipient cells are caused by proteins and RNAs carried in disease-derived EVs. This review summarizes cell-to-cell communication especially via EVs in the pathogenesis of liver diseases and their potential as a novel therapeutic target.

scholarly journals Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

2021 ◽  
Vol 27 (2) ◽  
pp. 201-209
Author(s):  
Sijia Li ◽  
Kai Hu ◽  
Longjiang Li ◽  
Yi Shen ◽  
Jiayi Huang ◽  
...  
Keyword(s):  
Hepatic Damage ◽  
Protective Effects ◽  
Signal Transducer ◽  
Hepatocyte Apoptosis ◽  
Tnf Α ◽  
Caspase Cascade ◽  
Novel Target ◽  
Apoptotic Effects ◽  
Transcription 3 ◽  
Novel Therapeutic

Increasing evidence indicates that signal transducer and activator of transcription 3 (STAT3), a vital transcription factor, plays crucial roles in the regulation of inflammation. STAT3 has become a novel therapeutic target for intervention in inflammation-related disorders. However, it remains unclear whether STAT3 plays a part in acute hepatic damage. To investigate the effects of STAT3 here, LPS/d-GalN-induced hepatic damage was induced in mice, the STAT3 inhibitor Stattic was administered, and the degree of liver injury, inflammation, and hepatocyte apoptosis were investigated. The results showed that Stattic mitigated the hepatic morphologic abnormalities and decreased the level of aminotransferase in LPS/D-GalN-insulted mice. The results also indicated that Stattic decreased the levels of TNF-α and IL-6, prevented the activation of the caspase cascade, suppressed cleavage of PARP, and decreased the quantity of TUNEL-positive cells. These results suggest that Stattic provided protective benefits in LPS/d-GalN-induced hepatic damage, and the protective effects might be associated with its anti-inflammatory and anti-apoptotic effects. Therefore, STAT3 might become a novel target for intervening in inflammation-based and apoptosis-based hepatic disorders.

scholarly journals A Michael Acceptor Analogue, SKSI-0412, Down-Regulates Inflammation and Proliferation Factors through Suppressing Signal Transducer and Activator of Transcription 3 Signaling in IL-17A-Induced Human Keratinocyte

2021 ◽  
Vol 22 (16) ◽  
pp. 8813
Author(s):  
A-Ram Kim ◽  
Seungbeom Lee ◽  
Jung U Shin ◽  
Seung Hui Seok ◽  
Young-Ger Suh ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Strategy ◽  
Signal Transducer ◽  
Synthetic Compounds ◽  
Human Keratinocyte ◽  
Stat3 Phosphorylation ◽  
Michael Acceptor ◽  
Transcription 3 ◽  
Psoriatic Lesions ◽  
Novel Therapeutic

The activation of signal transducer and activator of transcription 3 (STAT3), as well as up-regulation of cytokines and growth factors to promote STAT3 activation, have been found in the epidermis of psoriatic lesions. Recently, a series of synthetic compounds possessing the Michael acceptor have been reported as STAT3 inhibitors by covalently binding to cysteine of STAT3. We synthesized a Michael acceptor analog, SKSI-0412, and confirmed the binding affinity between STAT3 and SKSI-0412. We hypothesized that the SKSI-0412 can inhibit interleukin (IL)-17A-induced inflammation in keratinocytes. The introduction of IL-17A increased the phosphorylation of STAT3 in keratinocytes, whereas the inactivation of STAT3 by SKSI-0412 reduced IL-17A-induced STAT3 phosphorylation and IκBζ expression. In addition, human β defensin-2 and S100A7, which are regulated by IκBζ, were significantly decreased with SKSI-0412 administration. We also confirmed that SKSI-0412 regulates cell proliferation, which is the major phenotype of psoriasis. Based on these results, we suggest targeting STAT3 with SKSI-0412 as a novel therapeutic strategy to regulate IL-17A-induced psoriatic inflammation in keratinocytes.

Could Signal Transducer and Activator of Transcription 3 be a Therapeutic Target in Obesity-Related Gastrointestinal Malignancy?

2013 ◽  
Vol 45 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Katie E. O’Sullivan ◽  
John V. Reynolds ◽  
Ciara O’Hanlon ◽  
Jacintha N. O’Sullivan ◽  
Joanne Lysaght
Keyword(s):  
Therapeutic Target ◽  
Signal Transducer ◽  
Gastrointestinal Malignancy ◽  
Transcription 3
Sign in / Sign up

Export Citation Format

Share Document