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| 1 | IDO1 in cancer: a Gemini of immune checkpoints显示文摘Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。 | Lijie Zhai Erik Ladomersky Alicia Lenzen Brenda Nguyen Ricky Patel Kristen L Lauing Meijing Wu Derek A Wainwright | 2018 | Cellular & Molecular Immunology2018，15，5： | 17 |
| 2 | 新形势·新策略--中药新药及健康产品研发与国际化发展显示文摘'2017中国(连云港)国际医药技术大会'于2017年11月15-17日在江苏省连云港市召开。会议期间,中国药理学会中药与天然药物药理专业委员会与江苏康缘药业股份有限公司共同举办了'中药新药及健康产品研发与国际化发展论坛'。中国药理学会理事长兼中药与天然药物药理专业委员会主任委员、国际药理学联合会(IUPHAR)天然药物药理分会主席张永祥教授,中国药理学会前任理事长兼中药与天然药物药理专业委员会副主任委员杜冠华教授和江苏康缘药业股份有限公司董事长、中药与天然药物药理专业委员会副主任委员肖伟担任论坛共同主席。IUPHAR秘书长Michael SPEDDING教授、IUPHAR天然药物药理分会副主席Valérie SCHINI-KERTH教授、英国Robert Gordon大学天然产物研究中心主任Cherry WAINWRIGHT教授和韩国药理学会理事长金仁谦教授等外籍专家、中国药理学会中药与天然药物药理专业委员会委员以及江苏康缘药业股份有限公司主研人员70余人参加了本次论坛。国家卫生和计划生育委员会科技教育司重大专项处顾金辉处长应邀参会。论坛针对中药新药与健康产品研发与国际化发展等有关问题进行了综合讨论。为促进国内外学术交流,本文对部分专家的观点和意见进行了整理,以期为提高我国中药新药与健康产品研发水平及国际化发展起到积极的推动作用。 | 蒋宁 齐春会 曹亮 陈兰英 顾金辉 康永 Inkyeom KIM 连晓媛 陆茵 吕圭源 聂克 齐云 Valérie SCHINI-KERTH Michael SPEDDING Cherry WAINWRIGHT 王月华 肖伟 杨勇 余林中 张丹参 张永鹤 周文霞 杜冠华 张永祥 | 2018 | 中国药理学与毒理学杂志2018，32，1： | 16 |
| 3 | Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling显示文摘The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1neo/neo and K14cre:SmoM2YFP). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis. | Qipeng Fan Dongsheng Gu Miao He Hailan Liu Tao Sheng Guorui Xie Ching-xin Li Xiaoli Zhang Brandon Wainwright Arash Garrossian Massoud Garrossian Dale Gardner Jingwu Xie | 2011 | Chinese Journal of Cancer2011，30，7： | 3 |
| 4 | Prospective cohort study of hostility and the risk of cardiovascular disease mortality 显示文摘 | Surtees PG Wainwright NW Luben R | 2005 | Int J Cardiol2005，100，1： | 1 |
| 5 | The Janus face of glial-derived S100B :beneficial and detrimental functions in the brain 显示文摘 | Van Eldik LJ Wainwright MS | 2003 | Re- stor Neurol Neurosci2003，21，34： | 1 |
| 6 | Use of an acelluar allograft dermal matrix (AlloDerm) in the mangement of full-thickness bums显示文摘 | WAINWRIGHT D J | 1995 | Bums1995，21，： | 1 |
| 7 | Knowledge Management: Strategy or Software Management显示文摘 | Man J Beckett Charles E R Wainwright David Bance | | Decision0，38，： | 1 |
| 8 | Binding and neutralization of endotoxin by Limulus antilipopolysaccharide factor 显示文摘 | Warren H S Glennon M L Wainwright N | 1992 | Infect Immun1992，60，6： | 1 |
| 9 | Use of an acellular allograft matrix ( alloderm) in management of full - thickness burns 显示文摘 | Wainwright DJ | 1995 | Burns1995，21，4： | 1 |
| 10 | Local treatment of viral disease using photodynamic therapy显示文摘 | Wainwright M | 2003 | Int J Antimicrobial Agents2003，21，： | 1 |
| 11 | Image denoising using scale mixtures of gaussians in the wavelet domain显示文摘 | PORTILLA J STRELA V WAINWRIGHT M J | 2003 | IEEE Trans Image Processing2003，12，11： | 1 |
| 12 | Locally administered anfiproliferative drugs inhibit hypercontractility to serotonin in balloon-injured pig coronary artery显示文摘 | Kennedy S Wadsworth RM and Wainwright CL | 2006 | Vascul Pharmacol2006，44，5： | 1 |
| 13 | Use of an acellular allograft dermal matrix (Alloderm) in the management of full thickness bums显示文摘 | Wainwright DJ | 1995 | Burns1995，21，4： | 1 |
| 14 | HLA-F is a predominantly empty,intracellular,TAP-associated MHC class Ib protein with a restricted expression pattern显示文摘 | Wainwright SD Biro PA Holmes CH | 2000 | J Immunol2000，164，1： | 1 |
| 15 | Distributed dynamic modeling of interrill overland flow 显示文摘 | Parsons A J Wainwright J Abrahams A D | 1997 | Hydrological Processes1997，11，： | 1 |
| 16 | Clinical evaluation of an cellular allograft dermal matrix in full thickness burns显示文摘 | Wainwright DJ Madden M Luterman A | 1996 | J Bum Care Rehabil1996，17，1： | 1 |
| 17 | Photodynamic therapy: the development of new photosensitisers 显示文摘 | WAINWRIGHT M | 2008 | Anticancer Agents Med Chem2008，8，3： | 1 |
| 18 | Pathways to improving skin regeneration显示文摘 | Adolphe C Wainwright B | 2005 | Expert Rev Mol Med2005，7，： | 1 |
| 19 | The effect of porosity on the strength of foamed concrete显示文摘 | KEARSLEYA E P WAINWRIGHT P J | 2002 | CCR2002，32，2： | 1 |
| 20 | Hydrogenolysis of diethyl oxalate over copper-based catalysts显示文摘 | Thomas D J Wehrli J T Wainwright M S | | 0，，： | 1 |
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