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31.
Dong-Xin Hu Qi-Feng Sun Lin Xu Hong-Da Lu Fan Zhang Zhen-Miao Li Ming-Yan Zhang 《World journal of gastroenterology : WJG》2022,28(4):464-478
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC. 相似文献
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Qiangsheng He Chongfei Huang Xiwen Qin Yuanyuan Yu Di Tang Junjie Huang Zi Chong Kuo Yuyao Ling Deli Mao Bin Xia Wenjing Li Kuiqing Lu Man Yang Yulong He Wenbo Meng Jinqiu Yuan Yihang Pan 《International journal of cancer. Journal international du cancer》2023,153(5):942-949
Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes. 相似文献
34.
目的 观察未破裂颅内动脉瘤(UIA)直径与其血流动力学、形态学及瘤壁强化(AWE)的关系。方法 对前瞻性纳入的85例UIA患者行数字减影血管造影(DSA)、高分辨率MR管壁成像(HRMR-VWI)及四维血流MRI (4D flow MRI),观察其100枚UIA的血流动力学、形态学及AWE,计算UIA纵横比(AR)、大小比(SR)、顶颈比(DNR)、高宽比(HWR)、强化率(ER)及壁面切应力(WSS);比较直径<7 mm (n=78)及≥ 7 mm (n=22) UIA各参数的差异。结果 直径<7 mm与≥ 7 mm UIA患者既往蛛网膜下腔出血(SAH)史、动脉瘤相关症状、SR、DNR、形态、AWE、ER及WSS差异均有统计学意义(P均<0.05)。多因素logistic回归分析显示,既往SAH史、UIA的SR、形态及ER为其直径≥ 7 mm的独立危险因素。WSS与UIA直径、SR及ER均呈负相关(r=-0.70、-0.67、-0.63,P均<0.001)。观察者间判断AWE的一致性极高(Kappa=0.87),测量ER及WSS的一致性均好(ICC=0.946、0.871,P均<0.001)。结论 既往SAH史,UIA的SR、形态及ER均为其直径≥ 7 mm的独立危险因素。 相似文献
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首都医科大学通过60年辛勤耕耘、精益求精,秉承“顶天立地”的人才培养理念,为社会培养了大批高水平的学术型与应用型医药卫生人才。回顾学校60年来本专科教育、全科医学教育、国际教育、研究生教育的人才培养成果,以总结经验并鼓舞全体首医人进一步求真务实、凝心聚力、积极进取、追求卓越,努力将学校建设成为国际一流的研究型医科大学。 相似文献
38.
ChiaChi Lin TsaiSheng Yang ChiaJui Yen Rebecca Cheng Junjun Liu Chiun Hsu 《The oncologist》2020,25(12)
Lessons Learned
- The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first‐line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated.
- Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC.
- Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC.
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Shiyu Jiang Yan Qin Hongxin Jiang Biao Liu Jianming Shi Fanlu Meng Peng Liu Jianliang Yang Sheng Yang Xiaohui He Shengyu Zhou Lin Gui Hao Liu Jing Lin Han Han-Zhang Yuankai Shi 《International journal of cancer. Journal international du cancer》2020,147(9):2611-2620
Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients. 相似文献