Evaluation of de-escalation of anti-TNF-α therapy in inflammatory bowel disease

Sedaño, Rocío; Pino, Rodrigo Quera; Correa, Jaime Lubascher; Jofré, Gonzalo Pizarro; Marín, Daniela Simian

doi:10.1016/j.gastre.2019.02.013

Cited by 1 publication

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of Bax/Bak is mediated by BH3-only proteins, including BIM, tBID and PUMA, which directly interact with Bax/Bak to trigger conformational changes (30). Tumor necrosis factor α (TNF-α) is a major pro-inflammatory cytokine that participates in multiple inflammatory pathologies and is produced by macrophages, endothelial cells, fibroblasts and T lymphocytes (31). TNF-α binds with TNFR1, leading to conformational changes that activate TNF receptor type-1-associated death domain protein, the adaptor protein of TNF-α, resulting in activation of NF-κB, MAPK and apoptotic signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway

et al. 2019

View full text Add to dashboard Cite

Liver cancer is the fifth most commonly occurring cancer in men and the ninth most commonly occurring cancer in women, worldwide, and is associated with a high mortality rate. Sorafenib is a new inhibitor of multiple kinases, that is regarded as standard treatment for liver cancer. Human breast carcinoma metastasis-suppressor 1 (BRMS1) is a tumor-suppressor gene, that reduces the metastatic ability of tumor cells without affecting their tumorigenicity. In the present study, a model of BRMS1 overexpression and BRMS1 knockdown was established in HepG2 cells. The results revealed that the proliferation of HepG2 cells was inhibited in response to sorafenib treatment using MTT assay. Furthermore, BRMS1 overexpression enhanced the effect of sorafenib. In addition, expression of inflammatory response-related genes was increased, while secretion of angiogenesis-related molecules was decreased, and apoptosis was also activated after sorafenib treatment using qPCR method, and it was further demonstrated that this effect was mediated by inhibition of the PI3K/AKT/mTOR/ERK signaling pathway using western blot analysis. In conclusion, overexpression of BRMS1 potentiated the effect of sorafenib via PI3K/AKT/mTOR/ERK signaling, while knockdown of BRMS1 expression attenuated this effect. These findings may present a novel therapeutic strategy for liver cancer.

show abstract

Section: Discussionmentioning

confidence: 99%