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Emerging roles of Aurora-A kinase in cancer therapy resistance

药学学报:英文版 2023年第7期13卷 2826-2843页

作者： Dayong Zheng Jun Li Han Yan Gang Zhang Wei Li edward chu Ning Wei School of Pharmacy North China University of Science and TechnologyTangshan 063210China Basic Medical Science College Liaoning University of Traditional Chinese MedicineShenyang 110032China Division of Biology and Biological Engineering California Institute of TechnologyPasadenaCA 91125USA Department of Oncology and Cancer Therapeutics Program Montefiore Einstein Cancer CenterAlbert Einstein College of MedicineBronxNY 10461USA

Aurora kinase A(Aurora-A),a serine/threonine kinase,plays a pivotal role in various cellular processes,including mitotic entry,centrosome maturation and spindle formation.Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer,including lung cancer,colorectal cancer,and breast cancer.Alteration of Aurora-A impacts multiple cancer hallmarks,especially,immortalization,energy metabolism,immune escape and cell death resistance which are involved in cancer progression and resistance.This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance,including chemoresistance(taxanes,cisplatin,cyclophosphamide),targeted therapy resistance(osimertinib,imatinib,sorafenib,etc.),endocrine therapy resistance(tamoxifen,fulvestrant) and radioresistance.Specifically,the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair,feedback activation bypass pathways,resistance to apoptosis,necroptosis and autophagy,metastasis,and stemness.Noticeably,our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1,ARID1A and MYC gene mutation tumors,and potential synergistic strategy for m TOR,PAK1,MDM2,MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase.In addition,we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.

关键词： Aurora-A Therapy resistance Chemoresistance Targeted therapy Radioresistance Synthetic lethality Alisertib PROTAC

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Herbal formula enhances 5-fluorouracil activity through suppression of thymidylate synthase

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中国药理学与毒理学杂志 2019年第9期33卷 644-645页

作者： LIU Hai-zhou LIU Hui ZHOU Zhi-yi Robert A.PARISE edward chu John C.SCHMITZ Cancer Therapeutics Program UPMC Hillman Cancer CenterUniversity of PittsburghPittsburghPennsylvaniaUSA Department of Oncology Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 200021China Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200000China

Traditional Chinese herbal medicine(TCM)has been shown to enhance the efficacy of standard anticancer agents.However,there are only a limited number of well-controlled preclinical and clinical studies documenting the potential benefit of TCM.OBJECTIVE To identify biologically active formulas that were effective against colorectal cancer(CRC)by screening TCM formulas in in vitro and in vivo animal models.METHODS Cell growth assays,cell cycle analysis,immunoblot analysis and qRT-PCR were performed to investigate the mechanism(s)of action of the formulason human CRC cells.In vivo animal models were used to evaluate the antitumor activity of formulasalone and in combination with 5-FU.RESULTS We identified Huangqin Gegen Tang(HQGGT)which suppressed the in vivo growth of human CRC HT-29 xenografts.HQGGT significantly inhibited the growth of CRC cell lines.HQGGT enhanced the cytotoxicity of 5-FU against human 5-FU-resistant cells(H630R1)and mouse colon cancer cells(MC38).This synergy was the result of suppression of thymidylate synthase expression by HQGGT.HQGGT significantly enhanced the antitumor effect of 5-FU in mice bearing MC38 xenografts.Ongoing studies have identified Huangqin as the herb responsible for TS inhibi⁃tion.CONCLUSION These findings provide support for the potential role of HQGGT as a novel modulator of fluoropyrim⁃idine chemotherapy for CRC treatment.

关键词： colorectal cancer thymidylate synthase 5-fluorouracil

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Soil respiration under three different land use types in a tropical mountain region of China

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Journal of Mountain Science 2016年第3期13卷 416-423页

作者： WU Jun-jie Stefanie Daniela GOLDBERG Peter edward MORTIMER XU Jian-chu Center for Mountain Ecosystem Studies Kunming Institute of BotanyChinese Academy of Sciences Key Laboratory of Tropical Forest Ecology Xishuangbanna Tropical Chinese Academy of Sciences World Agroforestry Centre East and Central Asia

Soil respiration (SR) Wis one of the largest contributors of terrestrial CO_2 to the atmosphere.Environmental as well as physicochemical parameters influence SR and thus, different land use practices impact the emissions of soil CO_2. In this study, we measured SR, bi-monthly, over a one-year period in a terrace tea plantation, a forest tea plantation and a secondary forest, in a subtropical mountain area in Xishuangbanna, China. Along with the measurement of SR rates, soil characteristics for each of the land use systems were investigated. Soil respiration rates in the different land use systems did not differ significantly during the dry season, ranging from2.7±0.2 μmol m^(-2) s^(-1) to 2.8±0.2 μmol m^(-2) s^(-1). During the wet season, however, SR rates were significantly larger in the terrace tea plantation(5.4±0.5 μmol m^(-2)s^(-1)) and secondary forest(4.9±0.4 μmol m^(-2)s^(-1)) than in the forest tea plantation(3.7±0.2 μmol m^(-2) s^(-1)).This resulted in significantly larger annual soil CO_2 emissions from the terrace tea and secondary forest,than from the forest tea plantation. It is likely that these differences in the SR rates are due to the 0.5times lower soil organic carbon concentrations in thetop mineral soil in the forest tea plantation, compared to the terrace tea plantation and secondary forest.Furthermore, we suggest that the lower sensitivity to temperature variation in the forest tea soil is a result of the lower soil organic carbon concentrations. The higher SR rates in the terrace tea plantation were partly due to weeding events, which caused CO_2 emission peaks that contributed almost 10% to the annual CO_2 flux. Our findings suggest that moving away from heavily managed tea plantations towards low-input forest tea can reduce the soil CO_2 emissions from these systems. However, our study is a casestudy and further investigations and upscaling are necessary to show if these findings hold true at a landscape level.

关键词：土壤呼吸作用土地利用类型热带山地中国土地利用系统土壤呼吸速率土地利用方式亚热带山区

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Trap catches of the sweetpotato whitefly （Homoptera： Aleyrodidae） in the Imperial Valley, California, from 1996 to 2002

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Insect Science 2007年第2期14卷 165-170页

作者： CHANG-CHI chu edward BARNES ERIC T. NATWICK TIAN-YECHEN DAVID RITTER THOMAS J. HENNEBERRY USDA ARS U.S. ALARC Maricopa Arizona E1 Centro California USA Agricultural Research Cotton Inc. Cary North Carolina E1 Centro California USA University of California Cooperative Extension DANR Holtville California E1 Centro California USA Imperial County Agricultural Commissioner' s Office E1 Centro California USA

An outbreak of the sweetpotato whitefly, Bemisia tabaci （Gennadius）, biotype B occurred in the Imperial Valley, California in 1991. The insects destroyed melon crops and seriously damaged other vegetables, ornamentals and row crops. As a result of the need for sampling technology, we developed a whitefly trap （named the CC trap） that could be left in the field for extended time periods. We used the traps to monitor populations ofB. tabaci adults during year-round samplings from 1996 to 2002 to study variations in the weekly trap catches of the insect. The greatest number ofB. tabaci adults was recorded in 1996, followed by a continuing annual decrease in trap catches each year through 2002. The overall decline of B. tabaci is attributed in part to the adoption of an integrated pest management （IPM） program initiated in 1992 and reduced melon hectares from 1996 to 2002. Other factors may also have contributed to the population reductions. Seasonally, B. tabaci trap catches decreased during the late summer and fall concurrent with decreasing minimum tempera- tares that are suggested to be a significant factor affecting seasonal activity and reproduction.

关键词： Bemisia tabaci biotype B CC trap cotton melons ornamentals

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The Number of Intestinal Bacteria Is Not Critical For the Enhancement of the Antitumor Activity and Reduction of Intestinal Toxicity of Irinotecan by Chinese Medicinal Formula PHY906（KD018）

The Number of Intestinal Bacteria Is Not Critical For the En...

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第十四届全国中药和天然药物学术研讨会

作者： Wing Lam Zaoli Jiang Fulan Guan Rong Hu Shwu-Huey Liu edward chu Yung-Chi Cheng Yale University School of Medicine University of Pittsburgh Cancer InstitutePittsburgh

＜正＞The four-herb Chinese Medicine PHY906（KD108）could enhance irinotecan’s antitumor activity on colon cancer and promote the recovery of irinotecan-damaged intestines.Here,we access whether intestinal bacteria play critical role for PHY906 to achieve the above activities in murine colon-38 tumor bearing mice.Intestinal bacteria was depleted using

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胸苷酸合成酶表达调控的分子机制

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细胞生物学杂志 2005年第2期27卷 105-108页

作者：阎松牛荣丽 chu edward 林秀坤中国科学院海洋研究所实验海洋生物学重点实验室耶鲁大学医学院医学与药理学系 newhavenct06520

胸苷酸合成酶(thymidylate synthase,TS)是生物体内催化胸苷酸合成所必需的酶,多年来一直作为肿瘤化疗的重要靶酶。对TS基因调控机制的研究表明:基因扩增、转录、翻译和翻译后过程都参与了TS表达的调控。先前的研究表明:TS可与自身的mRN... 详细信息

胸苷酸合成酶(thymidylate synthase,TS)是生物体内催化胸苷酸合成所必需的酶,多年来一直作为肿瘤化疗的重要靶酶。对TS基因调控机制的研究表明:基因扩增、转录、翻译和翻译后过程都参与了TS表达的调控。先前的研究表明:TS可与自身的mRNA结合形成TS-mRNA复合物,使mRNA翻译受阻,5-氟尿嘧啶(5-fluorouracil,5-FU)等抗代谢药物可与TS蛋白结合,结合后的复合物不能与TS mRNA作用,导致体内TS的表达升高,是肿瘤细胞产生抗药性的重要分子机制之一。现对TS基因表达调控研究进展、翻译调控与抗药性产生的分子机制进行综述。

关键词：胸苷酸合成酶分子机制基因调控抗药性抗肿瘤药物

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极区月壤和水冰形成演化机制及物理特性研究

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深空探测学报（中英文） 2022年第2期9卷 123-133页

作者：李雄耀魏广飞曾小家李阳唐红刘建忠姜生元邹猛马继楠王储贺怀宇郑万平 CLOUTICS edward 中国科学院地球化学研究所贵阳550081 哈尔滨工业大学机电学院哈尔滨150001 吉林大学长春130021 中国空间技术研究院北京100094 中国科学院地质与地球物理研究所北京100029 卢森堡航天技术有限公司卢森堡温尼伯格大学温尼伯格R3B 2E9

月球极区独特的光照条件和表面环境特征是水富集和保存的理想场所,探测永久阴影区内的水冰对科学研究和开发利用月球资源具有重要的意义。综合调研了国际上在月球极区开展的理论研究和遥感探测成果,阐述了极区地质、表面光照条件和热环... 详细信息

月球极区独特的光照条件和表面环境特征是水富集和保存的理想场所,探测永久阴影区内的水冰对科学研究和开发利用月球资源具有重要的意义。综合调研了国际上在月球极区开展的理论研究和遥感探测成果,阐述了极区地质、表面光照条件和热环境特征。介绍了极区月壤和水的形成演化机制及水冰可能的赋存状态。系统梳理了国际上关于极区水冰的探测历程和方法,综合各种探测结果后取得的关于水冰分布特征的认识。根据分析Apollo 16样品后得到的物性、化学、矿物组成和粒径分布基本特征,提出了极区月壤模拟样品制备标准。通过对月球极区探测结果梳理并建立了系统认识极区地质演化的框架,为将来的月球极区月壤和水冰探测提供较为全面的参考。

关键词：月球极区探测含冰月壤水冰赋存状态演化机制目标特性

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道娜·托尔与英国马克思主义史学

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史学理论研究 2020年第4期 109-116,160页

作者：初庆东华中师范大学历史文化学院 430079

道娜·托尔是英国马克思主义史学家群体中为数不多的女性史家之一,她在译介马列经典著作、书写英国工人运动史、投身政治活动等方面都做出了重要贡献。托尔虽是语言专业出身,但对历史抱有浓厚兴趣,用毕生精力为英国工人运动的领导者汤... 详细信息

道娜·托尔是英国马克思主义史学家群体中为数不多的女性史家之一,她在译介马列经典著作、书写英国工人运动史、投身政治活动等方面都做出了重要贡献。托尔虽是语言专业出身,但对历史抱有浓厚兴趣,用毕生精力为英国工人运动的领导者汤姆·曼作传。这部传记成为英国最早的一批马克思主义史学著作之一,生动地再现了汤姆·曼时代普通民众的创造性活动。托尔还积极推动建立英国共产党历史学家小组,深刻影响了克里斯托弗·希尔、爱德华·汤普森等年轻一代英国马克思主义史学家的史学研究,为英国马克思主义史学的发展奠定了基础。

关键词：道娜·托尔汤姆·曼马克思主义史学英国

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Zoon’s balanitis with mucinous metaplasia: A case report and review of literature

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Open Journal of Clinical Diagnostics 2013年第2期3卷 33-36页

作者： Jin-Ping Lai edward W. Cowen Jere B. Stern Leomar Y. Ballester Emily Y. chu Rodolfo E. Chirinos Richard W. Childs Chyi-Chia Richard Lee Department of Dermatology Georgetown University Hospital Washington DC USA Dermatology Branch National Cancer Institute National Institutes of Health Bethesda USA Hematology Branch National Hear Lung and Blood Institute National Institutes of Health Bethesda USA Laboratory of Pathology National Cancer Institute National Institutes of Health Bethesda USA

Mucinous metaplasia of the squamous epithelium of the glans penis is very rarely seen in the setting of Zoon’s balanitis. We report a case of 40 year old male with a past medical history of paroxysmal nocturnal hemoglobinuria, status-post allogeneic hematopoietic cell transplantation from an HLA-matched sibling 6 years prior to evaluation, complicated by oral and cutaneous chronic graft-versus-host disease. Mucinous metaplasia was confirmed by PAS and Mucin stains, and plasmacytosis was confirmed by immunohistochemistry for CD138 and MUM1 markers. Kappa and Lambda immunostains revealed a polyclonal pattern. The etiology of zoon’s balanitis as well as the significance of mucinous metaplasia in these setting are unclear and need to be further investigated.

关键词： Bone Marrow Transplant Squamous Cell Carcinoma Erythroplasia of Querat Graft versus Host Disease

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哺乳动物少突胶质细胞分化、成熟和功能化的研究进展

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中国细胞生物学学报 2020年第8期42卷 1443-1456页

作者：谢登峰邱小燕熊春霞李云鑫褚新月黄云李彤 OTIENO edward 姜江肖雄西南大学动物科技学院重庆400715

少突胶质细胞(oligodendrocytes,OLs)是中枢神经系统(central nervous system,CNS)中的一类神经胶质细胞,具有生成髓鞘、包裹轴突的功能,对神经信号传导至关重要。OLs的分化调控涉及微小RNA(microRNA,miRNA)、Y染色体性别决定区域相关... 详细信息

少突胶质细胞(oligodendrocytes,OLs)是中枢神经系统(central nervous system,CNS)中的一类神经胶质细胞,具有生成髓鞘、包裹轴突的功能,对神经信号传导至关重要。OLs的分化调控涉及微小RNA(microRNA,miRNA)、Y染色体性别决定区域相关高迁移率族盒(sex-determining region of Y chromosome related high-mobility-group box,Sox)基因家族和细胞周期蛋白依赖性激酶(cyclin dependent kinases,CDKs)家族成员等。音猬因子(sonic hedgehog,Shh)、Wnt、Notch和骨形态发生蛋白(bone morphogenetic protein,BMP)信号通路,以及Olig 1、Sox 5/6、Sox 10、Nkx 2.2、Zfp 24和Hes 5转录因子等参与了OLs成熟和功能化的调节。该文就上述相关调控机制进行了综述,为深入解析和人工干预OLs的发育进程、防治脱髓鞘疾病提供参考。

关键词：少突胶质细胞分化成熟功能化调控机制

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