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Immune checkpoint inhibitors in cancer therapy

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The Journal of Biomedical Research 2018年第5期32卷 317-326页

作者： Eika S.Webb Peng Liu Renato Baleeiro Nicholas R.lemoine Ming Yuan Yaohe Wang Center for Molecular Oncology Barts Cancer Institute Queen Mary University of London EC1M 6BQ UK Sino-British Research Centre for Molecular Oncology National Center for International Research in Cell and Gene Therapy Zhengzhou University School of Basic Medical Sciences Academy of Medical Sciences Zhengzhou UniversityZhengzhou Henan 450002 China

In recent years immune checkpoint inhibitors have garnered attention as being one of the most promising types of immunotherapy on the horizon. There has been particular focus on the immune checkpoint molecules, cytotoxic Tlymphocyte antigen-4（CTLA-4） and programmed cell death protein 1（PD-1） which have been shown to have potent immunomodulatory effects through their function as negative regulators of T cell activation. CTLA-4, through engagement with its ligands B7-1（CD80） and B7-2（CD86）, plays a pivotal role in attenuating the activation of naive and memory T cells. In contrast, PD-1 is primarily involved in modulating T cell activity in peripheral tissues via its interaction with PD-L1 and PD-L2. The discovery of these negative regulators of the immune response was crucial in the development of checkpoint inhibitors. This shifted the focus from developing therapies that targeted activation of the host immune system against cancer to checkpoint inhibitors, which aimed to mediate tumor cell destruction through the removal of coinhibitory signals blocking anti-tumor T cell responses.

关键词： checkpoint inhibitor CTLA-4 PD-1 immunotherapy cancer

Sperm concentration measurement with a disposable counting chamber

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Asian Journal of Andrology 2018年第5期20卷 525-526页

作者： Mathilde lemoine Xavier Ferraretto Marie-Astrid Llabador-de Royer Achraf Benammar Jacques Darolles Sylvie Epelboin Florence Eustache Catherine Patrat Biology of Reproduction Department Bichat Hospital Paris Nord Val de Seine University Hospitals Public Hospitals of Paris (APHP) Paris 75018 France UFR of Medicine Paris Diderot University PRES Sorbonne Paris Cite Paris 75010 France Espacebio Laboratory of Medical Biology France-Senart-Conseil Montgeron Society Metz 57000 France Gynecology and Obstetrics Department Bichat Hospital Hopitaux Universitaires Paris Nord Val de Seine Public Hospitals of Paris (APHP) Paris 75018 France Biology of Reproduction Department - CECOS Jean Verdier Hospital Paris Seine Saint Denis University Hospital Public Hospitals of Paris (APHP) Bondy 93140 France U1016 INSERM- UMR 8104 CNRS Cochin Institute Paris Descartes University PRES Sorbonne Paris Cite Paris 75014 France Biology of Reproduction Department - CECOS Cochin Hospital Paris Centre University Hospitals Public Hospitals of Paris (APHP) Paris 75014 France

Dear Editor, In its latest edition, the World Health Organization （WHO） provides guidelines regarding the standardization of techniques for the measurement of sperm concentrationI and recommends use of a 100 μm-deep hemocytometer. However, these instructions are not always followed correctly.2 Furthermore, although hemocytometers provide more accurate and consistent results, they present several drawbacks： the chamber must be properly assembled prior to its use so as to ensure that the counts are correct and it needs to be cleaned thoroughly to remove all traces of sperm, which risks breaking the glass coverslip.

关键词： QUALITY-CONTROL VARIABILITY MOTILITY

Two-level uncapacitated lot-sizing problem considering the financing cost of working capital requirement

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Frontiers of Engineering Management 2020年第2期7卷 248-258页

作者： Yuan BIAN David lemoine Thomas G.YEUNG Nathalie BOSTEL School of Economics and Management University of Chinese Academy of SciencesBeijing 100049China LS2N UMR CNRS 6004 IMT AtlantiqueNantes 44300France LS2N UMR CNRS 6004 University of NantesSaint-Nazaire 44606France

During financial crisis,companies constantly need free cash flows to efficiently react to any uncertainty,thus ensuring *** capital requirement(WCR)has been recognized as a key factor for releasing tied up cash in ***,in literatures related to lot-sizing problem,WCR has only been studied in the single-level supply chain *** this paper,we initially adopt WCR model for a multi-level case.A two-level(supplier–customer)model is established on the basis of the classic multi-level lot-sizing model integrated with WCR financing *** tackle this problem,we propose sequential and centralized approaches to solve the two-level case with a serial chain *** ZIO(Zero Inventory Ordering)property is further confirmed valid in both *** property allows us to establish a dynamic programming-based algorithm,which solves the problem in O(T).Finally,numerical tests show differences in optimal plans obtained by both approaches and the influence of varying delays in payment on the WCR of both actors.

关键词： two-level ULS problem lot-sizing working capital requirement ZIO property infinite production capacity

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

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World Journal of Gastroenterology 2016年第34期22卷 7692-7707页

作者： lieselotte lemoine Paul Sugarbaker Kurt Van der Speeten Department of Medicine and Life Sciences Hasselt University3500 Hasselt Belglum Department of Surgical Oncology Ziekenhuis Oost-Limburg 3600 Genk Belgium Washington Cancer Institute Washington Hospital Center Washington DC 20010 United States

Colorectal cancer(CRC) is the third most common cancer and the fourth most common cause of cancerrelated death worldwide. Besides the lymphatic and haematogenous routes of dissemination,CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity,which ultimately leads to peritoneal carcinomatosis(PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However,this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements,involving several well-defined steps,together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor,gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum,subsequently invade the subperitoneal space,where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript,we review current data regarding the molecular mechanisms underlying the development of colorectal PC,with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread.

关键词： Peritoneal carcinomatosis Pathophysiology Peritoneal metastatic cascade Cytoreductive surgery Peritoneum Hyperthermic intraperitoneal peroperative chemotherapy

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反义治疗技术作为治癌新方法能否实现

国际肿瘤学杂志 1993年第6期20卷 347-351页

作者： Carter G lemoine NR 曲显俊崔淑香

通过抑制DNA复制与翻译过程为主的反义治疗技术其特点在于能特异性地与DNA核苷酸链结合并调节或降低其表达水平。这个方法可能比以蛋白质为靶点的治疗手段容易实现,原因就在于前者分子结构相对简单,进一步说就是如何将癌细胞阻滞在癌基... 详细信息

通过抑制DNA复制与翻译过程为主的反义治疗技术其特点在于能特异性地与DNA核苷酸链结合并调节或降低其表达水平。这个方法可能比以蛋白质为靶点的治疗手段容易实现,原因就在于前者分子结构相对简单,进一步说就是如何将癌细胞阻滞在癌基因早期表达阶段。本文将简述近年来在这方面的研究进展以及必须解决的问题。

关键词： mRNA 特异性基团药物核昔酸磷酸化合物抑制基因校正基因靶分子细胞内治疗靶点成纤维细胞生长因子反义治疗生物活性

Combined collision-induced dissociation and photo-selected reaction monitoring mass spectrometry modes for simultaneous analysis of coagulation factors and estrogens

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Journal of Pharmaceutical Analysis 2014年第3期4卷 183-189页

作者： Quentin Enjalbert Marion Girod Jérémy Jeudy Jordane Biarc Romain Simon Rodolphe Antoine Philippe Dugourd Jér?me lemoine Arnaud Salvador Université Lyon 1 CNRS Université de Lyon 69622 Villeurbanne cedexFrance Institut Lumière Matière UMR5306France Institut des Sciences Analytiques UMR 5280France

Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring （SRM）, a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.

关键词： Estrogen Coagulation factorprotein Metabolite Photo-dissociation fragmentation SRM

Thermodynamic Properties of CaCl<sub>2</sub>-CaF<sub>2</sub>-CaO System: Phase Diagram Investigation

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Materials Sciences and Applications 2021年第4期12卷 139-151页

作者： Julien Claquesin Mathieu Gibilaro Laurent Massot Olivier lemoine Gilles Bourges Pierre Chamelot Laboratoire de Génie Chimique UMR 5503 UPS-CNRS-INP Université de Toulouse Toulouse France CEA DAM VALDUC Is-sur-Tille France

The CaCl2-CaF2-CaO phase diagram was investigated in the CaO low region (2-CaF2 and CaCl2-CaO binary diagrams, constituting the ternary system, were first studied by Differential Scanning Calorimetry (DSC) measurements and X-Ray Diffraction (XRD) characterization;a good agreement was obtained between the phase diagram models calculated with FactSage®software (FTsalt database) and present experimental data. As the CaF2-CaO liquidus could not be measured by DSC due to the high melting temperature, this diagram was calculated using FTsalt database combined with FToxid database of FactSage® software. The ternary phase diagram was obtained by calculations and exhibits an eutectic at the composition CaCl2-CaF2-CaO (78.2-15.7-6.1 mol.%) melting at 637°C, and five peritectic points. Measurements of relevant vertical cross-sections for three CaCl2-CaF2 compositions (50-50, 40-60 and 30-70 mol.%) up to 18 mol.% CaO are in agreement with the ternary phase diagram model. For each section, the liquidus temperature is constant up to around 11 mol.% CaO and then sharply increases. Moreover, an increase of CaF2 content in CaCl2-CaF2 melt leads to a decrease of the CaO solubility in isothermal condition.

关键词： Differential Scanning Calorimetry (DSC) Phase Diagram Calcium Chloride Calcium Fluoride Calcium Oxide Ternary System

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中法家庭消费的对比研究

国际商业技术 2011年第3期 24-31页

作者： Francoise lemoine[法] 法国国际展望与信息研究中心

促进消费是中国政府“十二五”规划的重要任务。通过中法两国、特别是中国城镇地区与法国在人均GDP、居民家庭收入之间的对比，探寻影响家庭消费的各项因素，寻找消费结构的变化规律，并最终提出：中国在下一阶段的发展中，要减少储蓄... 详细信息

促进消费是中国政府“十二五”规划的重要任务。通过中法两国、特别是中国城镇地区与法国在人均GDP、居民家庭收入之间的对比，探寻影响家庭消费的各项因素，寻找消费结构的变化规律，并最终提出：中国在下一阶段的发展中，要减少储蓄、鼓励信贷消费；在满足中低收入阶层对基础产品的需求的同时，也要满足中高收入家庭对更新换代产品以及高品质服务方面的需求。

关键词：中国法国家庭消费人均GDP 消费结构消费趋势

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长效支气管扩张剂作用机制探讨

中国医学科学院学报 1998年第3期20卷 191-196页

作者：包雅琳 Horst lemoine 中华医学会北京100710 德国海茵里希-海涅大学激光医学研究所杜塞尔多夫市40225

目的旨在比较长效支气管扩张剂福莫特罗(FOR)、沙美特罗(SLM)与短效支气管扩张剂芬诺特罗(FEN)、沙丁胺醇(SAL)及异丙肾上腺素(ISO)的内在活性(intrinsic activity,IA),受体亲和力及其在细胞膜的信号放大作用。方法采用酶解法制备牛支... 详细信息

目的旨在比较长效支气管扩张剂福莫特罗(FOR)、沙美特罗(SLM)与短效支气管扩张剂芬诺特罗(FEN)、沙丁胺醇(SAL)及异丙肾上腺素(ISO)的内在活性(intrinsic activity,IA),受体亲和力及其在细胞膜的信号放大作用。方法采用酶解法制备牛支气管平滑肌细胞膜,以^(32)P-ATP为底物,测定各激动剂作用于β_2受体,激活腺苷酸环化酶生成cAMP的IA及其生成半数最大量cAMP所需浓度(EC_(50)),并计算出各激动剂的相对效应pEC_(50);以放射性标记配体法测定各激动剂与β_2受体亲和力。结果 ISO、FOR、SLM、FEN和SAL的IA分别为1.00、1.00、0.76、0.81和0.83,上述各激动剂的亲和力分别为6.69、8.02、8.43、5.84和5.84 mol/L,pEC_(50)分别为7.68、9.10、8.70、6.79和6.78 mol/L。结论 FOR与ISO一样,为高效激动剂,其亲和力比ISO高约20倍,其他激动剂为部分激动剂。各激动剂作用于细胞膜均可产生信号放大作用,以FOR为著。FOR的高IA和高亲和力及其在细胞膜的信号放大作用可能是其长效作用的机制之一。

关键词：支气管扩张剂肾上腺素受体受体亲和力