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Immune precision medicine for cancer:a novel insight based on the efficiency of immune effector cells

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Cancer Communications 2019年第1期39卷 318-333页

作者： jean-françois rossi Patrice Céballos Zhao-Yang Lu Institut Sainte Catherine 84918 AvignonFrance UniversitéMontpellier 1 UFR Médecine34396 MontpellierFrance Département d’Hématologie CHU de Montpellier34295 MontpellierFrance Unitéde Thérapie Cellulaire CHU Saint-Eloi34295 MontpellierFrance

Cancer cell growth is associated with immune surveillance ***,restoring the desired immune response against cancer cells remains a major therapeutic *** to the recent advances in biological knowledge,efficient therapeutic tools have been developed to support the best bio-clinical approaches for immune precision *** of the most important successes in immune therapy is represented by the applicational use of monoclonal antibodies,particularly the use of rituximab for B-cell lymphoproliferative *** recently,other monoclonal antibodies have been developed,to inhibit immune checkpoints within the tumor microenvironment that limit immune suppression,or to enhance some immune functions with immune adjuvants through different targets such as Toll-receptor *** aim is to inhibit cancer proliferation by the diminishing/elimination of cancer residual cells and clinically improving the response duration with no or few adverse *** effect is supported by enhancing the number,functions,and activity of the immune effector cells,including the natural killer(NK)lymphocytes,NKT-lymphocytes,γδT-lymphocytes,cytotoxic T-lymphocytes,directly or indirectly through vaccines particularly with neoantigens,and by lowering the functions of the immune suppressive *** these new therapeutics and their personalized usage,new considerations have to be taken into account,such as epigenetic regulation particularly from microbiota,evaluation of transversal functions,particularly cellular metabolism,and consideration to the clinical consequences at the body *** aim of this review is to discuss some practical aspects of immune therapy,giving to clinicians the concept of immune effector cells balancing between control and *** precision medicine is a combination of modern biological knowledge and clinical therapeutic decisions in a global vision of the patient.

关键词： Precision therapy Immunotherapy NK lymphocytes T-lymphocytes Dendritic cells Vaccination Cancer

癌症的免疫精准医学:一种基于免疫效应细胞作用的新策略

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癌症 2020年第2期39卷 51-70页

作者： jean‑françois rossi Patrice Céballos Zhao‑Yang Lu Institut Sainte Catherine 84918 AvignonFrance UniversitéMontpellier 1 UFR Médecine34396 MontpellierFrance Département d’Hématologie CHU de Montpellier34295 MontpellierFrance Unitéde Thérapie Cellulaire CHU Saint-Eloi34295 MontpellierFrance.

癌细胞生长与免疫监视逃逸相关。目前,恢复对癌细胞的免疫应答仍是一种主要的治疗策略。得益于生物学领域的最新研究成果,人们已经开发出了可支持免疫精准治疗相关的最佳生物临床途径的有效治疗工具。免疫治疗中最重要的、有效的成果之... 详细信息

癌细胞生长与免疫监视逃逸相关。目前,恢复对癌细胞的免疫应答仍是一种主要的治疗策略。得益于生物学领域的最新研究成果,人们已经开发出了可支持免疫精准治疗相关的最佳生物临床途径的有效治疗工具。免疫治疗中最重要的、有效的成果之一是单克隆抗体的应用,特别是利妥昔单抗在B细胞淋巴增生性疾病中的应用。最近,也开发出一些其他的单克隆抗体,通过抑制限制免疫抑制的肿瘤微环境中的免疫检查点,或者通过联合如Toll受体激动剂等免疫佐剂针对不同靶点来增强免疫功能。其目的是通过减少/消除癌症残留细胞来抑制癌症增殖,在临床上改善反应持续时间而无副作用或副作用较小。该效应是依靠直接或间接通过疫苗特别是新抗原来增强免疫效应细胞[包括自然杀伤(natural killer,NK)淋巴细胞、NKT-淋巴细胞、γδT-淋巴细胞、细胞毒性T-淋巴细胞]的数量、功能和活性,以及依靠降低免疫抑制细胞的功能而产生的。除了这些新疗法及其个体化治疗外,还必须考虑新的因素,例如表观遗传调控(特别是来自微生物菌群)、横向功能的评估(特别是细胞代谢),以及对身体整体的临床疗效。本综述旨在探讨免疫治疗的一些实践,向临床医生介绍如何在免疫效应细胞的控制和耐受之间取得平衡。免疫精准医学是现代生物学知识和着眼于患者全局的临床治疗决策的结合。

关键词：精准治疗免疫治疗 NK淋巴细胞 T-淋巴细胞树突状细胞疫苗接种癌症

Genotype phenotype classification of hepatocellular adenoma

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World Journal of Gastroenterology 2007年第19期13卷 2649-2654页

作者： Paulette Bioulac-Sage jean Frédéric Blanc Sandra Rebouissou Charles Balabaud Jessica Zucman-rossi CHU Bordeaux Hpital Pellegrin Department of Pathology Bordeaux F-33076 France Charles Balabaud Inserm U889 Bordeaux F-33076 GREF Univ Victor Segalen Bordeaux 2 Bordeaux F-33076 France Charles Balabaud CHU Bordeaux Hpital Saint André Department of Hepatology Bordeaux F-33075 France Inserm U674 CEPH Univ Paris 7 Paris F-75010 France CHU Bordeaux Hpital Saint André Department of Hepatology Bordeaux F-33075 France

Studies that compare tumor genotype with phenotype have provided the basis of a new histological/molecular classification of hepatocellular adenomas. Based on two molecular criteria （presence of a TCFI/HNF1α or β-catenin mutation）, and an additional histological criterion （presence or absence of an inflammatory infiltrate）, subgroups of hepatocellular adenoma can be defined and distinguished from focal nodular hyperplasia. Analysis of 96 hepatocellular adenomas performed by a French collaborative network showed that they can be divided into four broad subgroups： the first one is defined by the presence of mutations in TCF1 gene inactivating the hepatocyte nuclear factor 1 （HNF1α）, the second by the presence of β-catenin activating mutations; the category without mutations of HNF1α or β-catenin is further divided into 2 subgroups depending on the presence or absence of inflammation. Therefore, the approach to the diagnosis of problematic benign hepatocytic nodules may be entering a new era directed by new molecular information. It is hoped that immunohistological tools will improve significantly diagnosis of liver biopsy in our ability to distinguish hepatocellular adenoma from focal nodular hyperplasia （FNH）, and to delineate clinically meaningful entities within each group to define the best clinical management. The optimal care of patients with a liver nodule will benefit from the recent knowledge coming from molecular biology and the combined expertise of hepatologists, pathologists, radiologists, and surgeons.

关键词： Hepatocellular adenoma HNF1α mutation β-catenin mutation Inflammatory adenoma Telangiectatic adenoma Maturity-onset diabetes of theyoung Hepatocyte nuclear factor 1 CTNNB1 Focal nodular hyperplasia

DIMZAL:A Software Tool to Compute Acceptable Safety Distance

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Open Journal of Forestry 2017年第1期7卷 11-33页

作者： Paul-Antoine Bisgambiglia jean-Louis rossi Romain franceschini francois-Joseph Chatelon Paul Antoine Bisgambiglia Lucile rossi Thierry Marcelli University of Corsica CorteFrance

The scope of this work is to present a multidisciplinary study in order to propose a tool called DIMZAL. DIMZAL forecasts fuelbreak safety zone sizes. To evaluate a safety zone and to prevent injury, the Acceptable Safety Distance (ASD) between the fire and firefighters is required. This distance is usually set thanks to a general rule-of-thumb: it should be at least 4 times the maximum flame length. A common assumption considers an empirical relationship between fireline intensity and flame length. In the current work which follows on from an oral presentation held at the VII International Conference on Forest Fire Research in Coimbra in 2014, an alternative way is proposed: a closed physical model is applied in order to quantize the ASD. This model is integrated in a software tool, which uses a simulation framework based on Discrete EVent system Specification formalism (DEVS), a 3D physical real-time model of surface fires developed at the University of Corsica and a mobile application based on a Google SDK to display the

关键词： Decision-Making Tool Fire Model Acceptable Safety Distance ASD Calculation Tool DEVS Mobile Application

Modelling of Eruptive Fire Occurrence and Behaviour

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Journal of Environmental Science and Engineering(B) 2014年第3期3卷 115-132页

作者： Jacques-Henri Balbi frangois Joseph Chatelon jean Louis rossi Albert Simeoni Domingos Xavier Viegas Carlos Rossa Research Laboratory 6134 National Center for Scientific Research University of Corsica Corte 20250 France Building Research Establisment Centre for Fire Safety Engineering University of Edinburgh Edinburgh EH93JL Scotland Centre of Studies on Forest Fires Association for the Development of the Industrial Aerodynamics University of CoimbraCoimbra 3030-790 Portugal Department of Mechanical Engineering University of Coimbra Coimbra 3030-790 Portugal School of Technology and Management Polytechnic Institute of Leiria Leiria 2411-901 Portugal

Eruptive fires are one of the main causes of human losses in forest fire fighting. The sudden change in fire behaviour due to a fire eruption is extremely dangerous for fire-fighters because it is unpredictable. Very little literature is available to support either modelling or occurrence prediction for this phenomenon. In this study, an unsteady physical model of fire spread is detailed, which describes the initiation and development of eruptive fires with an induced wind sub-model. The latter phenomenon is proposed as the mainspring of fire eruptions. Induced wind is proportional to the rate of spread and the rate of spread is in a non-linear relationship with induced wind. This feedback can converge or diverge depending on the conditions. The model allows both explaining why an eruption can occur and predicting explicitly its occurrence according to meteorological conditions, topographic parameters, fuel bed properties and fire front width. The model is tested by comparing its results to a set of experiments carried out at laboratory scale and during an outdoor wildfire, the Kornati accident.

关键词： Eruptive fire unsteady solutions fire spread physical model.

Surface Fires： No Wind, No Slope, Marginal Burning

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Journal of Environmental Science and Engineering(A) 2014年第2期3卷 73-86页

作者： Jacques-Henry Balbi Domingos Xavier Viegas jean-Louis rossi Carlos Rossa francois Joseph Chatelon Dominique Cancellieri Albert Simeoni Thierry Marcelli Research Laboratory 6134 National Center for Scientific Research University of Corsica Corte 20250 France Centre of Studies on Forest Fires~Association for the Development of the Industrial Aerodynamics University of CoimbraCoimbra 3030-790 Portugal Department of Mechanical Engineering University of Coimbra Coimbra 3030-790 Portugal School of Technology and Management Polytechnic Institute of Leiria Leiria 2411-901 Portugal Building Research Establisment Centre for Fire Safety Engineering University of Edinburgh Edinburgh EH9 3JL Scotland

The first aim of this work is to provide an analytical expression to calculate the rate of spread of surface fires under no wind and no slope conditions. A previous simplified model was improved for this particular case of fire propagation. The test of this proposed model was performed by using two complete sets of experimental results with several fuel beds and variable parameters such as moisture content or bulk density. The second aim of this article is to highlight two conditions that allow stopping a fire： the low leaf area and the high value of the moisture content.

关键词： Surface fire spread marginal burning extinction conditions

Development and validation of an artificial intelligence model for predicting post-transplant hepatocellular cancer recurrence

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Cancer Communications 2023年第12期43卷 1381-1385页

作者： Quirino Lai Carmine De Stefano jean Emond Prashant Bhangui Toru Ikegami Benedikt Schaefer Maria Hoppe-Lotichius Anna Mrzljak Takashi Ito Marco Vivarelli Giuseppe Tisone Salvatore Agnes Giuseppe Maria Ettorre Massimo rossi Emmanuel Tsochatzis Chung Mau Lo Chao-Long Chen Umberto Cillo Matteo Ravaioli Jan Paul Lerut the EurHeCaLT and the West-East LT Study Group General Surgery and Organ Transplantation Unit AOU Policlinico Umberto I Sapienza University of Rome Rome Italy Data Science and Engineering Polytechnic of Turin Turin Italy Division of Liver Transplantation and Hepatobiliary Surgery Department of Surgery Weill Cornell Medicine-Columbia University New York US Medanta Institute of Liver Transplantation and Regenerative Medicine Medanta-The Medicity Gurgaon India Department of Surgery and Science Kyushu University Fukuoka Japan Department of Medicine I Gastroenterology Hepatology and Endocrinology Medical University of Innsbruck Innsbruck Austria Klinik für Allgemein- Viszeral- und Transplantationschirurgie Universitätsmedizin Mainz Mainz Germany Liver Transplant Centre Merkur University of Zagreb Zagreb Croatia Division of Hepato-Biliary-Pancreatic and Transplant Surgery Department of Surgery Graduate School of Medicine Kyoto Japan Unit of Hepatobiliary Surgery and Transplantation AOU Ospedali Riuniti Polytechnic University of Marche Ancona Italy Department of Surgical Sciences and Medical Sciences University of Rome-Tor Vergata Rome Italy Liver Unit Department of Surgery Catholic University-Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy Department of Transplantation and General Surgery San Camillo Hospital Rome Italy UCL Institute for Liver and Digestive Health and Royal Free Sheila Sherlock Liver Centre Royal Free Hospital London UK Hong Kong University–Department of Surgery Queen Mary Hospital University of Hong Kong Hong Kong P. R. China Department of Surgery Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan P. R. China Department of Surgery Oncology and Gastroenterology University of Padua Padua Italy Department of General Surgery and Transplantation IRCCS Azienda Ospedaliero-Universitaria di Bologna Bologna University Bologna Italy Institut de Recherche Clinique Université catholique de Louvain Brussels Belgium 不详

Dear Editor,In recent years,criteria based on the combinationof morphology and biology have been proposed forimproving the selection of hepatocellular cancer(HCC)patients waiting for liver transplantation(LT)[1,2].Since all the proposed models showed suboptimalresults in predicting the risk of postLT recurrence,aprediction model constructed using artificial intelligence(Al)could be an attractive way to surpass this limit[3,4].Therefore,the Time_Radiological-response_Alpha-fetoproteIN_Artificial-Intelligence(TRAIN-AI)modelwas developed,combining morphology and biology tumorvariables.

关键词： hepatocellular cancer artificial

Active surveillance of adverse drug reactions in children in five Italian paediatric wards

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Open Journal of Pediatrics 2012年第2期2卷 111-117页

作者： Mariapina Gallo Antonio Clavenna Maurizio Bonati Paolo Siani Antonio Irpino francesco rossi Annalisa Capuano Department of European and Mediterranean Studies Faculty of Political Studies and Higher European Education Jean Monnet Second University of Naples Naples Italy Department of Experimental Medicine Section of Pharmacology “Leonardo Donatelli” Center of Pharmacosurveillance and Phar-macoepidemiology Faculty of Medicine and Surgery Second University of Naples Naples Italy Laboratory for Mother and Child Health Department of Public Health Mario Negri Institute for Pharmacological Research Milan Italy Pediatric Department AORN A. Santobono-Pausillipon Hospital Naples Italy

Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.

关键词： Child Prospective Studies Drug Therapy/Adverse Effects Adverse Drug ReactionReporting System Hospital

肝细胞腺瘤相关的基因型-表现型:新的分类及与HCC的关系

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世界核心医学期刊文摘（胃肠病学分册） 2006年第9期2卷 47-47页

作者： Zucman-rossi J. jeannot E. Van Nhieu J.T. 陈云茹 Inserm U674 IUH Paris Saint-LouisCEPH Fondation Jean Dausset27 rue Juliette Dodu75010 ParisFrance

Hepatocellular adenomas are benign tumors that can be difficult to *** refine their classification,we performed a comprehensive analysis of their genetic,pathological,and clinical features.A multicentric series of 96 liver tumors with a firm or possible diagnosis of hepatocellular adenoma was reviewed by liver *** all cases,the genes coding for hepatocyte nuclear factor 1α(HNF1α)and β-catenin were *** tumors were mutated in both HNF1αand β-catenin enabling tumors to be classified into 3 groups,according to *** with HNF1αmutations formed the most important group of adenomas(44 cases).They were phenotypically characterized by marked steatosis(P < 10-4),lack of cytological abnormalities(P < 10-6),and no inflammatory infiltrates(P < 10-4).In contrast,the group of tumors defined by β-catenin activation included 13 lesions with frequent cytological abnormalities and pseudo-glandular formation(P < 10-5).The third group of tumors without mutation was divided into two subgroups based on the presence of inflammatory *** subgroup of tumors consisting of 17 inflammatory lesions,resembled telangiectatic focal nodular hyperplasias,with frequent cytological abnormalities(P = 10-3),ductular reaction(P < 10-2),and dystrophic vessels(P =.02).In this classification,hepatocellular carcinoma associated with adenoma or borderline lesions between carcinoma and adenoma is found in 46%of the β-catenin-mutated tumors whereas they are never observed in inflammatory lesions and are rarely found in HNF1αmutated tumors(P =.004).In conclusion,the molecular and pathological classification of hepatocellular adenomas permits the identification of strong genotype-phenotype correlations and suggests that adenomas with β-catenin activation have a higher risk of malignant transformation.

关键词：肝细胞腺瘤基因型表现型分类 β-连环蛋白 HCC α基因突变良性肿瘤