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Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor

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Cancer Communications 2020年第7期40卷 285-300页

作者： Yuqi Yang Ning Ji Chao-Yun Cai Jing-Quan Wang Zi-Ning Lei Qiu-Xu Teng Zhuo-Xun Wu Qingbin Cui Yihang Pan Zhe-Sheng Chen Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNew York 11439USA State Key laboratory of Experimental Hematology Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Hematology and Blood Diseases HospitalTianjin 300020P.R.China School of Public Health Guangzhou Medical UniversityGuangzhouGuangdong 511436P.R.China tomas lindahl nobel laureate laboratory the Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107P.R.China

Background:Overexpression of ATP-binding cassette(ABC)transporter is a major contributor to multidrug resistance(MDR),in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic *** this work,we evaluated the sensitizing effect of sitravatinib,a broad-spectrum tyrosine kinase inhibitor(TKI),on ATP-binding cassette subfamily B member 1(ABCB1)-and ATP-binding cassette subfamily C member 10(ABCC10)-mediated ***:MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non-toxic ***-labeled paclitaxel transportation,Western blotting,immunofluorescence analysis,and ATPase assay were carried out to elucidate the mechanism of sitravatinib-induced *** in vitro findings were translated into preclinical evaluation with the establishment of xenograft ***:Sitravatinib considerably reversed MDR mediated by ABCB1 and partially antagonized ABCC10-mediated *** in silico docking simulation analysis indicated that sitravatinib strongly and stably bound to the transmembrane domain of ABCB1 human-mouse chimeric ***,sitravatinib inhibited hydrolysis of ATP and synchronously decreased the efflux function of ***,sitravatinib could considerably enhance the intracellular concentration of anticancer ***,no significant alterations of both expression level and localization of ABCB1 were *** importantly,sitravatinib could remarkably restore the antitumor activity of vincristine in ABCB1-mediated xenograft model without observable toxic ***:The findings in this study suggest that the combination of sitrvatinib and substrate antineoplastic drugs of ABCB1 could attenuate the MDR mediated by the overexpression of ABCB1.

关键词： Sitravatinib

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Epitranscriptomics and epiproteomics in cancer drug resistance:therapeutic implications

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Signal Transduction and Targeted Therapy 2020年第1期5卷 865-880页

作者： Huibin Song Dongcheng Liu Shaowei Dong Leli Zeng Zhuoxun Wu Pan Zhao Litu Zhang Zhe-Sheng Chen Chang Zou Shenzhen People’s Hospital(The Second Clinical Medical College Jinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518001 GuangdongChina College of Pharmacy and Health Sciences St.John’s UniversityQueens11439 New YorkUSA tomas lindahl nobel laureate laboratory Research CentreThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107 GuangdongChina Department of Research Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021 GuangxiChina Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis Shenzhen 518001 GuangdongChina

Drug resistance is a major hurdle in cancer treatment and a key cause of poor *** and epiproteomics are crucial in cell proliferation,migration,invasion,and epithelial–mesenchymal *** recent years,epitranscriptomic and epiproteomic modification has been investigated on their roles in overcoming drug *** this review article,we summarized the recent progress in overcoming cancer drug resistance in three novel aspects:(i)mRNA modification,which includes alternative splicing,A-to-I modification and mRNA methylation;(ii)noncoding RNAs modification,which involves miRNAs,lncRNAs,and circRNAs;and(iii)posttranslational modification on molecules encompasses drug inactivation/efflux,drug target modifications,DNA damage repair,cell death resistance,EMT,and *** addition,we discussed the therapeutic implications of targeting some classical chemotherapeutic drugs such as cisplatin,5-fluorouridine,and gefitinib via these *** together,this review highlights the importance of epitranscriptomic and epiproteomic modification in cancer drug resistance and provides new insights on potential therapeutic targets to reverse cancer drug resistance.

关键词： therapeutic cancer drug

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Our Global Civilization

Our Global Civilization

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文明的和谐与共同繁荣：对人类文明方式的思考——北京论坛（2006）

作者： Amartya Kumar Sen Harvard University 1998 nobel laureate in Economics

1 I am very happy to have the opportunity of coming to this distinguished Forum and to be able to join and interact with *** my topic I have chosen the controversial subject of civilization,which has been something of a battleground in recent years. There are two ways approach the history of civilization in the world. One is to pursue the story in an inclusive form,paying attention to the

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Looking For the Equilibrium through the Game with Life

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中国金融家 2005年第7期 60-61页

作者： John F. Nash The laureate of 1994 nobel Memorial Prize in Economic Science Jr.

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Base-excision repair and beyond—A short summary attributed to scientific achievements of tomas lindahl, nobel Prize laureate in Chemistry 2015

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Science China(Life Sciences) 2016年第1期59卷 89-92页

作者： Shuangli Mi Arne Klungland Yun-Gui Yang Key laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development CAS Center for Excellence in Molecular Cell Science Beijing Institute of Genomics Chinese Academy of Sciences Department of Microbiology Division of Diagnostics and Intervention Institute of Clinical Medicine Oslo University HospitalRikshospitalet Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo

tomas lindahl contributed his scientific career to unveiling fundamental mechanisms of DNA decay and repair. He made several ground-breaking discoveries on genome in- stability, novel DNA repair activities and pathway... 详细信息

关键词：碱基切除修复诺贝尔奖得主托马斯科学成果归结化学科学生涯修复机制

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Endogenous DNA Damage and Repair Enzymes—A short summary of the scientific achievements of tomas lindahl,nobel laureate in Chemistry 2015

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 122-125页

作者： Arne Klungland Yun-Gui Yang Department of Microbiology Division of Diagnostics and InterventionInstitute of Clinical MedicineOslo University Hospital Department of Molecular Medicine Faculty of MedicineInstitute of Basic Medical SciencesUniversity of Oslo CAS Key laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of Sciences

tomas lindahl completed his medical studies at Karolinska Institute in ***,his work has always been dedicated to unraveling fundamental mechanisms of DNA decay and DNA *** research is characterized with groundbreaking discoveries on the instability of our genome,the identification of novel DNA repair activities,the characterization of DNA repair pathways,and the association to diseases,throughout his 40 years of scientific career.

关键词： DNA repair completed career instability decay dedicated summary Clare breaking

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Late-stage modification of bioactive compounds:Improving druggability through efficient molecular editing

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1030-1076页

作者： Tongyu Huo Xinyi Zhao Zengrui Cheng Jialiang Wei Minghui Zhu Xiaodong Dou Ning Jiao State Key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Changping laboratory Beijing 102206China Shanghai Key laboratory of Green Chemistry and Chemical Processes East China Normal UniversityShanghai 200062China

Synthetic chemistry plays an indispensable role in drug discovery,contributing to hit compounds identification,lead compounds optimization,candidate drugs preparation,and so *** nobel Prize laureate James Black emphasized,“the most fruitful basis for the discovery of a new drug is to start with an old drug”***-stage modification or functionalization of drugs,natural products and bioactive compounds have garnered significant interest due to its ability to introduce diverse elements into bioactive compounds *** modifications alter the chemical space and physiochemical properties of these compounds,ultimately influencing their potency and *** enrich a toolbox of chemical modification methods for drug discovery,this review focuses on the incorporation of halogen,oxygen,and nitrogen—the ubiquitous elements in pharmacophore components of the marketed drugs—through late-stage modification in recent two decades,and discusses the state and challenges faced in these *** also emphasize that increasing cooperation between chemists and pharmacists may be conducive to the rapid discovery of new activities of the functionalized ***,we hope this review would serve as a valuable resource,facilitating the application of late-stage modification in the construction of novel molecules and inspiring innovative concepts for designing and building new drugs.

关键词： Late-stage modification Drug space Halogenation Oxygenation Nitrogenation Synthetic chemistry

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In-situ oriented oxygen-defect-rich Mn-N-O via nitridation and electrochemical oxidation based on industrial-scale Mn_(2)O_(3) to achieve high-performance aqueous zinc ion battery

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Journal of Energy Chemistry 2023年第1期76卷 11-18,I0001页

作者： Yao Liu Shuailong Guo Wei Ling Mangwei Cui Hao Lei Jiaqi Wang Wenzheng Li Qingjiang Liu Lukuan Cheng Yan Huang Sauvage laboratory for Smart Materials School of Materials Science and EngineeringHarbin Institute of TechnologyShenzhen 518055GuangdongChina Shenzhen Key laboratory of Flexible Printed Electronics Technology Harbin Institute of TechnologyShenzhen 518055GuangdongChina State Key laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001HeilongjiangChina

As a general problem in the field of batteries,materials produced on a large industrial scale usually possess unsatisfactory electrochemical *** them,manganese-based aqueous rechargeable zinc-ion batteries(ARZBs)have been emerging as promising large-scale energy storage systems owing to their high energy densities,low manufacturing cost and intrinsic high ***,the direct application of industrial-scale Mn2O3(MO)cathode exhibits poor electrochemical performance especially at high current ***,a highly reversible Mn-based cathode is developed from the industrial-scale MO by nitridation and following electrochemical oxidation,which triples the ion diffusion rate and greatly promotes the charge ***,the cathode delivers a capacity of 161 m Ah g^(-1) at a high current density of 10 A g^(-1),nearly-three times the capacity of pristine MO(60 m Ah g^(-1)).Impressive specific capacity(243.4 m Ah g^(-1))is obtained without Mn^(2+) additive added in the electrolyte,much superior to the pristine MO(124.5 m Ah g^(-1)),suggesting its enhanced reaction kinetics and structural *** addition,it possesses an outstanding energy output of 368.4 Wh kg^(-1) at 387.8 W kg^(-1),which exceeds many of reported cathodes in ARZBs,providing new opportunities for the large-scale application of highperformance and low-cost ARZBs.

关键词： Aqueous rechargeable zinc-ion battery Mn-based cathode Oxygen defect Nitridation Electrochemical oxidation

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Quantum Dots Compete at the Acme of MXene Family for the Optimal Catalysis

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Nano-Micro Letters 2022年第10期14卷 36-82页

作者： Yuhua Liu Wei Zhang Weitao Zheng Key laboratory of Automobile Materials MOE and School of Materials Science and Engineeringand Jilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy Materialsand Electron Microscopy Centerand International Center of Future ScienceJilin UniversityChangchun 130012People’s Republic of China

It is well known that two-dimensional(2D)MXene-derived quan-tum dots(MQDs)inherit the excellent physicochemical properties of the parental MXenes,as a Chinese proverb says,“Indigo blue is extracted from the indigo plant,but is bluer than the plant it comes from.”Therefore,0D QDs harvest larger surface-to-volume ratio,outstanding optical properties,and vigorous quantum confinement ***,MQDs trigger enormous research enthusiasm as an emerging star of functional materials applied to physics,chemistry,biology,energy conversion,and *** the surface properties of small-sized MQDs include the type of surface functional groups,the functionalized surface directly determines their *** the nobel laureate Wolfgang Pauli says,“God made the bulk,but the surface was invented by the devil,”and it is just on the basis of the abundant surface functional groups,there is lots of space to be thereof excavated from *** are witnessing such excellence and even more promising to be ***,MQDs have been widely applied to catalysis,whereas the related reviews are rarely ***,we provide a state-of-the-art overview of MQDs in catalysis over the past five years,ranging from the origin and development of MQDs,synthetic routes of MQDs,and functionalized MQDs to advanced characterization *** explore the diversity of catalytic application and perspectives of MQDs,our review will stimulate more efforts toward the synthesis of optimal MQDs and thereof designing high-performance MQDs-based catalysts.

关键词： MXene Quantum dots Catalysis Surface groups Structure

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NF-κB,a hot topic in biochemical and medical studies in China

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Science China(Life Sciences) 2010年第12期53卷 1485-1487页

作者： WEI Yan State Key laboratory of Brain and Cognitive Sciences,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China State Key laboratory of Brain and Cognitive Sciences Institute of Biophysics Chinese Academy of Sciences Beijing China

In 1986, nuclear factor (NF)-κB was first discovered in the laboratory of nobel Prize laureate David Baltimore via its interaction with a sequence (5′-GGGACTTTCC-3′) in the immunoglobulin light-chain enhancer in B

关键词： NF-κB transcription factor signaling pathway upregulation downregulation

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