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1. chinaXiv:202007.00041 [pdf]

BRAF mutation predicts survival after immunotherapy across multiple cancer types

Ge, Weiting; Cai, Wen; Wu, Dehao; Hu, Wangxiong; Han, Weidong; Zheng, Shu; Hu, hanguang
Subjects: Medicine, Pharmacy >> Clinical Medicine

Recently studies in selected tumors suggested that BRAF mutation may associates with survival benefit from immune checkpoint inhibitor (ICI) therapy. To broadly investigate this association at a pan-cancer level, we analyzed two independent ICI treatment cohorts (MSKCC: n = 1630, and Dana-Farber: n = 249). BRAF-mutant patients exhibit better overall survival in the MSKCC cohort (Hazard ratio [HR] = 0.55, 95% confidence interval [CI]: 0.43-0.72; P <.001) and the result is validated by the Dana-Farber cohort (HR = 0.68, 95% CI: 0.46-0.99; P = .045). A multivariate analysis adjusting tumor mutational burden, mismatch repair status, cancer type, age and sex confirmed the results (adjusted HR = 0.58, 95% CI = 0.43-0.78; P < .001). Immunogenomic features analysis of TCGA dataset indicated that patients may respond to immunotherapy in various mechanisms. This finding substantially improve the therapeutic prospects for a sizeable fraction of patients who benefit from immunotherapy.

submitted time 2020-07-21 Hits15323Downloads1494 Comment 0

2. chinaXiv:201707.00654 [pdf]


代立婷; 吴忠南; 黄翔; 杨杰; 王国才; 蒋建伟
Subjects: Biology >> Bioengineering

目的:探讨卤地菊Wedelia prostrate( Arn.)Hemsl.的乙醇提取物W40单体对非小细胞肺癌GLC-82细胞的抗肿瘤作用分子机制。方法: 通过MTT和克隆形成抑制实验检测W40对非小细胞肺癌GLC-82细胞增殖的影响; 通过细胞划痕实验检测W40对细胞迁移的影响; 通过Annexin V-FITC /PI 双染法检测W40对细胞凋亡的诱导; 通过Western blotting分析细胞增殖和凋亡相关蛋白的水平。结果: MTT实验表明,W40对GLC-82细胞有较为明显的细胞毒作用;克隆形成抑制实验表明,W40可以显著抑制GLC-82细胞增殖, 且抑制程度呈现浓度依赖效应;细胞划痕实验表明,W40能够一定程度上抑制GLC-82细胞的迁移能力; Annexin V-FITC /PI 双染的结果显示,随着药物浓度的增加, 细胞凋亡率逐渐增加; Western blotting 结果表明,随着药物浓度的增加, p-Stat3蛋白的表达水平下降, Stat3下游蛋白Bcl-2、Mcl-1的表达减少。同时,促凋亡蛋白Bax的表达增多, 并伴随Caspase-9、Caspase-3 活化及多聚ADP- 核糖聚合酶PARP 酶切失活;p-BRAF蛋白的表达水平下降, p-BRAF下游蛋白p-MEK、p-ERK表达减少。结论: W40 通过抑制BRAF / MAPK / ERK 及Stat3信号通路来诱导细胞凋亡。

submitted time 2017-07-24 From cooperative journals:《中国生物工程杂志》 Hits1507Downloads919 Comment 0

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