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Yongfang Ma Ruyue Xu Xueke Liu Yinci Zhang Li Song Shuyu Cai Shuping Zhou Yinghai Xie Amin Li Weiya Cao Xiaolong Tang 《International journal of medical sciences》2021,18(6):1456
Background: Sorafenib, an oral multi-kinase inhibitor of rapidly accelerated fibrosarcoma; vascular endothelial growth factor receptor-2/3, platelet-derived growth factor receptor, c-Kit, and Flt-3 signaling, is approved for treatment of advanced hepatocellular carcinoma (HCC). However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. In this work, we investigated whether adding LY3214996, a selective ERK1/2 inhibitor, to sorafenib would increase the anti-tumor effectiveness of sorafenib to HCC cells.Methods: The Huh7 cell line was used as a cell model for treatment with sorafenib, LY3214996, and their combination. Phosphorylation of the key kinases in the Ras/Raf/MAPK and PI3K/Akt pathways, protein expression of the cell cycle, and apoptosis migration were assessed with western blot. MTT and colony-formation assays were used to evaluate cell proliferation. Wound-healing assay was used to assess cell migration. Cell cycle and apoptosis analyses were conducted with flow cytometry.Results: LY3214996 decreased phosphorylation of the Ras/Raf/MAPK and PI3K/Akt pathways, including p-c-Raf, p-P90RSK, p-S6K and p-eIF4EBP1 activated by sorafenib, despite increased p-ERK1/2 levels. LY3214996 increased the anti-proliferation, anti-migration, cell-cycle progression, and pro-apoptotic effects of sorafenib on Huh7R cells.Conclusions: Reactivation of ERK1/2 appears to be a molecular mechanism of acquired resistance of HCC to sorafenib. LY3214996 combined with sorafenib enhanced the anti-tumor effects of sorafenib in HCC. These findings form a theoretical basis for trial of LY3214996 combined with sorafenib as second-line treatment of sorafenib-resistant in advanced HCC. 相似文献
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Jennifer E. Amengual Jennifer K. Lue Helen Ma Renee Lichtenstein Bijal Shah Serge Cremers Simon Jones Ahmed Sawas 《The oncologist》2021,26(3):184-e366
Lessons Learned
- Oral selective HDAC6 inhibitors could allow for decreased toxicity compared to pan‐class inhibitors, and increased ease of use.
- ACY‐1215 is well tolerated and led to disease stabilization in 50% of patients treated on a twice‐daily dosing schedule.
- Rational drug combinations with ACY‐1215 improve efficacy in patients with lymphoma.
- Biomarkers such as XBP‐1 level or HDAC6‐score may improve patient selection.
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The effects of concurrent chemoradiation therapy to the base of tongue in a preclinical model
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Maternal and Child Health Journal - Low birth weight (LBW) is associated with significant mortality and morbidity and remains a significant preventable problem. Risk factors include socioeconomic,... 相似文献
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Farzaneh Pirmadah Nahid Ramezani-Jolfaie Mohammad Mohammadi Nasir Talenezhad Cain C. T. Clark Amin Salehi-Abargouei 《European journal of nutrition》2020,59(5):1767-1783
l-carnitine supplementation is proposed to reduce liver enzymes levels; however, previous findings were equivocal. The current systematic review and meta-a 相似文献