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A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells 被引量:7
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作者 Zuo-fu PENG Lin-xiang LAN +4 位作者 Fang ZHAO Jing LI Qiang TAN Han-wei YIN hui-hui zeng 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第1期16-21,共6页
Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigat... Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors. 展开更多
关键词 硫氧还蛋白还原酶 细胞生长 细胞凋亡 HL-60细胞 K562细胞
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Detection of a novel panel of 24 genes with high frequencies of mutation in gastric cancer based on next-generation sequencing
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作者 hui-hui zeng Ze Yang +3 位作者 Ye-Bei Qiu Shoaib Bashir Yin Li Meng Xu 《World Journal of Clinical Cases》 SCIE 2022年第15期4761-4775,共15页
BACKGROUND Gastric cancer is a leading cause of cancer-related mortality worldwide.Many somatic mutations have been identified based on next-generation sequencing;they likely play a vital role in cancer treatment sele... BACKGROUND Gastric cancer is a leading cause of cancer-related mortality worldwide.Many somatic mutations have been identified based on next-generation sequencing;they likely play a vital role in cancer treatment selection.However,nextgeneration sequencing has not been widely used to diagnose and treat gastric cancer in the clinic.AIM To test the mutant gene frequency as a guide for molecular diagnosis and personalized therapy in gastric cancer by use of next-generation sequencing.METHODS We constructed a panel of 24 mutant genes to detect somatic nucleotide variations and copy number variations based on a next-generation sequencing technique.Our custom panel included high-mutation frequency cancer driver and tumour suppressor genes.Mutated genes were also analyzed using the cBioPortal database.The clinical annotation of important variant mutation sites was evaluated in the ClinVar database.We searched for candidate drugs for targeted therapy and immunotherapy from the OncoKB database.RESULTS In our study,the top 16 frequently mutated genes were TP53(58%),ERBB2(28%),BRCA2(23%),NF1(19%),PIK3CA(14%),ATR(14%),MSH2(12%),FBXW7(12%),BMPR1A(12%),ERBB3(11%),ATM(9%),FGFR2(8%),MET(8%),PTEN(6%),CHD4(6%),and KRAS(5%).TP53 is a commonly mutated gene in gastric cancer and has a similar frequency to that in the cBioPortal database.33 gastric cancer patients(51.6%)with microsatellite stability and eight patients(12.5%)with microsatellite instability-high were investigated.Enrichment analyses demonstrated that high-frequency mutated genes had transmembrane receptor protein kinase activity.We discovered that BRCA2,PIK3CA,and FGFR2 gene mutations represent promising biomarkers in gastric cancer.CONCLUSION We developed a powerful panel of 24 genes with high frequencies of mutation that could detect common somatic mutations.The observed mutations provide potential targets for the clinical treatment of gastric cancer. 展开更多
关键词 Gastric cancer Next-generation sequencing Mutated genes Target sites Microsatellite instability
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Early chronic obstructive pulmonary disease:A new perspective 被引量:8
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作者 Huan-Huan Lu hui-hui zeng Yan Chen 《Chronic Diseases and Translational Medicine》 CSCD 2021年第2期79-87,共9页
Chronic obstructive pulmonary disease(COPD)is a respiratory disease with a high incidence,mortality,and disability rate.Because there are few symptoms in the early stages of COPD,diagnosis and treatment are seriously ... Chronic obstructive pulmonary disease(COPD)is a respiratory disease with a high incidence,mortality,and disability rate.Because there are few symptoms in the early stages of COPD,diagnosis and treatment are seriously insufficient.It is necessary to find effective clues for early COPD diagnosis and provide appropriate interventions.Several studies suggest that small airway disease is the earliest stage of COPD because it is correlated with subsequent development of airflow obstruction.However,there are currently no globally accepted criteria for defining early COPD.This study mainly introduced risk factors,definition,diagnosis,and treatment of early COPD from a new perspective. 展开更多
关键词 Chronic obstructive pulmonary disease Early diagnosis Risk factors INTERVENTION Treatment
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硫氧还蛋白还原酶抑制剂乙烷硒啉逆转顺铂耐药及其机制研究(英文) 被引量:1
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作者 Suo-fu YE Yong YANG +2 位作者 Lin WU Wei-wei MA hui-hui zeng 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2017年第5期373-382,共10页
目的:研究凋亡调控相关蛋白来了解顺铂耐药成因,同时考察乙烷硒啉(Ethaselen)在K562耐药细胞中逆转顺铂耐药的作用,并初步探讨其作用机制。创新点:首次研究乙烷硒啉在逆转顺铂耐药中的作用,且此作用与乙烷硒啉诱导细胞凋亡相关。方法:... 目的:研究凋亡调控相关蛋白来了解顺铂耐药成因,同时考察乙烷硒啉(Ethaselen)在K562耐药细胞中逆转顺铂耐药的作用,并初步探讨其作用机制。创新点:首次研究乙烷硒啉在逆转顺铂耐药中的作用,且此作用与乙烷硒啉诱导细胞凋亡相关。方法:通过长时间脉冲诱导得到顺铂耐药K562细胞,并观察耐药细胞形态及倍增时间。采用MTT法考察乙烷硒啉、顺铂及其联用组在不同细胞株间的生长抑制作用。流式细胞术分析细胞凋亡情况以及细胞内活性氧(ROS)水平。最后,通过蛋白质免疫印迹(Western blot)考察凋亡调控相关蛋白水平的变化。结论:脉冲诱导得到的K562耐药细胞对顺铂的耐受性是原K562细胞的5.34倍。形态学观察发现,耐药细胞体积增大,粘附性进一步降低。乙烷硒啉与顺铂联用表现出协同效应。当加入少量的乙烷硒啉(顺铂与乙烷硒啉的摩尔比率为10:1),顺铂作用K562耐药细胞的半抑制浓度(IC50)值可以减少21倍。流式细胞术及Western blot表明,乙烷硒啉能够诱导耐药细胞凋亡。其逆转顺铂耐药主要是通过调控Bcl-2及Bax蛋白比例以及通过提高细胞内活性氧水平引起线粒体通透转运孔道(PTP)蛋白孔道的形成来促使释放细胞色素c,进而引起Caspase凋亡途径。 展开更多
关键词 乙烷硒啉 顺铂耐药 K562 凋亡 BCL-2
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新型硫氧还蛋白还原酶抑制剂丁烷硒啉通过下调PD-L1的表达来抑制肿瘤的发生(英文) 被引量:1
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作者 Qiao ZOU Yi-fan CHEN +4 位作者 Xiao-qing ZHENG Suo-fu YE Bin-yuan XU Yu-xi LIU hui-hui zeng 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2018年第9期689-698,共10页
目的:评估新型硫氧还蛋白还原酶抑制剂丁烷硒啉(BS)对小鼠免疫系统及肿瘤发生的影响,并初步探讨其作用机制。创新点:实验室自主设计的硫氧还蛋白还原酶抑制剂BS对免疫系统的调节作用及机制探究。方法:将24只体重为18~22g的正常雄性KM小... 目的:评估新型硫氧还蛋白还原酶抑制剂丁烷硒啉(BS)对小鼠免疫系统及肿瘤发生的影响,并初步探讨其作用机制。创新点:实验室自主设计的硫氧还蛋白还原酶抑制剂BS对免疫系统的调节作用及机制探究。方法:将24只体重为18~22g的正常雄性KM小鼠随机分为4组,分别为BS低、中、高剂量组和对照组,每组6只动物。于接种小鼠肝癌H22细胞(1×106个/只)后第2天开始给药,给药剂量分别为:空白对照组(5g/L羧甲基纤维素钠(CMC-Na),灌胃(i.g.),每日一次(q.d.));BS低剂量组(90mg/kg,i.g.,q.d.);BS中剂量组(180mg/kg,i.g.,q.d.);BS高剂量组(360 mg/kg,i.g.,q.d.)。每天观察小鼠状态,连续8天。结论:BS通过促进小鼠脾淋巴细胞的活化来抑制肿瘤增殖。BS能够通过下调体内肿瘤细胞表面的程序性死亡配体1(PD-L1)的表达,提高小鼠CD4^-CD8^+T淋巴细胞百分比和下游细胞因子的分泌。在HepG2和BEL-7402细胞中的进一步研究表明,通过抑制信号传导子及转录激活子3(STAT3)磷酸化,BS处理后PD-L1表达水平降低。综上所述,BS通过STAT3途径降低PD-L1表达,从而产生促进免疫应答的作用,抑制肿瘤发生。 展开更多
关键词 丁烷硒啉 信号传导子及转录激活子3(STAT3) 程序性死亡配体1(PD-L1) 免疫 硫氧还蛋白还原酶
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Potential metal-related strategies for prevention and treatment of COVID-19
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作者 Ya-Qiong Ni hui-hui zeng +4 位作者 Xian-Wen Song Jun Zheng Hui-Qiong Wu Chun-Tai Liu Yi Zhang 《Rare Metals》 SCIE EI CAS CSCD 2022年第4期1129-1141,共13页
The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has posed severe threats to human health,public safety,and the global economy.Metal nutrient elements can dir... The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has posed severe threats to human health,public safety,and the global economy.Metal nutrient elements can directly or indirectly take part in human immune responses,and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years,providing potential solutions to the prevention and treatment of COVID-19.Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bio activities,demonstrating irreplaceable advantages in pharmacology.This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology.The current and potential utilization of metal-based drugs is briefly introduced.Specifically,metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19. 展开更多
关键词 COVID-19 SARS-CoV-2 Metal-related drugs Metal nutrient elements Metallohydrogel
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