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INVOLVEMENT OF TRANSPORTERS IN NEuROTOXICITY

第十五届国际药理学大会

作者： Boczkowski Jorge inserm u700 Paris FRANCE

＜正＞ Chronic obstructive pulmonary disease （COPD） is a major public health problem that is related to cigarette smoke exposure. COPD is characterized by non reversible airflow obstruction, secondary to airways and lung parenchyma inflammation and remodeling. An increased airway smooth muscle mass and mucus hypersecretionare characteristic features of airways remodeling whereas a proteases/antiproteasesimbalance is characteristic of lung remodeling （also know as emphysema）.Heme oxygenase （HO） and NADPH oxidase （NOX） are anti and pro - oxidant proteins respectively, that are involved in the control of smooth muscle proliferation, mucus protein expression and proteases/antiproteases balance, via oxidants signaling and mitogen activated protein kinases. We have shown that a decreased HO expression, secondary to a promoter polymoprhism in HO - 1 gene, is asso- dated with an accelerated decline in lung function in smokers, and that experimental up regulation of HO and down regulation of NOX proteins prevent airway and lung remodeling after cigarette smoke exposure in vivo and in vitro. Therefore, modulation of oxidants signaling by acting on HO and/or NOX could be proposed as new therapeutic approachs of COPD.

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INVOLVEMENT OF TRANSPORTERS IN NEUROTOXICITY

Roles of macrophages in tumor development: a spatiotemporalperspective

第十五届国际药理学大会

作者： Scherrmann Jean-Michel university Paris 5 inserm u 705

＜正＞ The blood - brain barrier （BBB） and the blood - cerebrospinal fluid barrier （BCSFB）. are the first lines for protecting the brain. A complex network of transporters expressed at BBB and BCSFB participates to solute exchanges between blood and brain. Influx transporters belonging to the Solute Carrier super-family may facilitate the occurence of neurotoxic effects. Thus, the monocar-boxylate transporter MCT1 transports across BBB the recreational drug of abuse g - hydroxybutyrate leading to seizures, respiratory depression and impaired consciousness . In contrast, efflux transporters like P - glycoprotein （Pgp）. acts by pumping out endothelial cells towards the blood a wide variety of substrates including potential neurotoxic compounds. More recently, a second member, the Breast Cancer Resistance Protein （BCRP） was found co - localized with Pgp at BBB. The neuroprotective effect of these ABC transporters was demonstrated a-gainst xenobiotics like ivermectin. an antiparasite agent substrate of Pgp and dietary phototoxins which are substrates of BCRP. All these transporters play a critical role for protecting the brain from neurotoxic events.

关键词： neurotoxicity ABC SLC transporter

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Cellular & Molecular Immunology 2023年第9期20卷 983-992页

作者： Mathilde Bied William W.Ho Florent Ginhoux Camille Blériot Institut Gustave Roussy INSERM U1015VillejuifFrance Singapore Immunology Network(SIgN) Agency for ScienceTechnology and Research(A∗STAR)SingaporeSingapore Shanghai Institute of Immunology Shanghai JiaoTong University School of MedicineShanghaiChina Translational Immunology Institute SingHealth Duke-NUSSingaporeSingapore Institut Necker des Enfants Malades INSERMCNRSUniversitéParis CitéParisFrance

Macrophages are critical regulators of tissue homeostasis but are also abundant in the tumor microenvironment (TME). In bothprimary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support tumor development. While we knowthat TAMs are the dominant immune cells in the TME, their vast heterogeneity and associated functions are only just beingunraveled. In this review, we outline the various known TAM populations found thus far and delineate their specialized rolesassociated with the main stages of cancer progression. We discuss how macrophages may prime the premetastatic niche to enablethe growth of a metastasis and then how subsequent metastasis-associated macrophages can support secondary tumor ***, we speculate on the challenges that remain to be overcome in TAM research.

关键词： Macrophages Tumor associated macrophages Tumor microenvironment Metastasis

Circulating tumor cell isolation:the assets of filtration methods with polycarbonate track-etched filters

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Chinese Journal of Cancer Research 2015年第5期27卷 479-487页

作者： Claire Dolfus Nicolas Piton Emmanuel Toure Jean-Christophe Sabourin Department of Pathology Rouen University Hospital inserm u1079 Institute for Biomedical Research and InnovationUniversity of Rouen

Circulating tumor cells （CTCs） arise from primary or secondary tumors and enter the bloodstream by active or passive intravasation. Given the low number of CTCs, enrichment is necessary for detection. Filtration methods are based on selection of CTCs by size using a filter with 6.5 to 8 pm pores. After coloration, collected CTCs are evaluated according to morphological criteria. Immunophenotyping and fluorescence in situ hybridization techniques may be used. Selected CTCs can also be cultivated in vitro to provide more material. Analysis of genomic mutations is difficult because it requires adapted techniques due to limited DNA materials. Filtration-selected CTCs have shown prognostic value in many studies but multicentric validating trials are mandatory to strengthen this assessment. Other clinical applications are promising such as follow-up, therapy response prediction and diagnosis. Microfluidic emerging systems could optimize filtration-selected CTCs by increasing selection accuracy.

关键词： Circulating tumor ceils (CTCs) biological markers filtration

Insights into the 2023 multidisciplinary surgical treatment guidelines for hepatocellular carcinoma:perspectives from Italian Professional Associations

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 861-864页

作者： Mohamed Bouattour Julie Devictor Clemence Hollande AP-HP Hôpital BeaujonLiver Cancer and Innovative Therapy UnitClichyFrance universitéParis Cité Centre de Recherche sur l’Inflammation(CRI)INSERMU1149ParisFrance universitéParis Cité ECEVEINSERM UMR 1123ParisFrance

The collaboration among various Italian scientific societies to establish recommendations for the surgical management of hepatocellular carcinoma(HCC),recently published in Digestive and Liver Disease(1),is a worthy *** multidisciplinary approach,which includes input from different disciplines such as surgery,hepatology,gastroenterology,oncology,pathology,radiology,and patient associations,underscores the commitment to placing patients at the center of *** a holistic and inclusive approach enhances the relevance and applicability of these guidelines in clinical *** several scientific associations have previously issued guidelines for managing HCC,the Italian colleagues have adopted a comprehensive methodology.

关键词： Multidisciplinary patient-centered surgery recommendation

Hepatitis C in Laos： A 7-Year Retrospective Study on 1765 Patients

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Virologica Sinica 2018年第4期33卷 295-303页

作者： Phimpha Paboriboune Thomas Vial Philavanh Sitbounlang Stephane Bertani Christian Trepo Paul Deny Francois-Xavier Babin Nicolas Steenkeste Pascal Pineau Eric Deharo Centre d'Infectiologie Lao-Christophe Merieux 3888 Vientiane Laos uMR 152 PHARMADEV IRD Universite de ToulouseUPS 31062 Toulouse France inserm u1052 CNRS UMR 5286 Cancer Research Centre of Lyon 69008 Lyon France universite Paris 13 Sorbonne Paris Cite Hopitaux Universitaires Paris Seine Saint Denis 93000 Bobigny France Fondation Merieux 69002 Lyon France inserm u993 Institut Pasteur Unite 'Organisation Nucleaire et Oncogenese' 75015 Paris France

Hepatitis C virus （HCV） is a global health concern, notably in Southeast Asia, and in Laos the presentation of the HCV- induced liver disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients, their infection status （viral load： VL）, liver function （aminotransferases） and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6 years for women （13-86 years）. The majority of patients （72%） were confirmed positive （VL 〉 50 Iu/mL） and 28% of them had high VL （〉 61oglo）. About 23% of patients had level of aminotransferases indicative of liver damage （〉 40 Iu/mL）; but less than 20% of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff, without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines. However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.

关键词： Hepatitis C virus (HCV) HCV incidence Antiviral agents Laos

Glutamine metabolism in cancer therapy

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Cancer Drug Resistance 2018年第3期1卷 126-138页

作者： Tra-Ly Nguyen Raúl V.Durán Institut Européen de Chimie et Biologie INSERM U1218Universitéde Bordeaux2 Rue Robert Escarpit33607 PessacFrance.

The amino acid glutamine plays a key role in the metabolism of highly proliferating *** malignant transformation,cancer cells modify the consumption and processing of glutamine to sustain cell growth and *** some cases,these cancer cells become addicted to ***,targeting the metabolism of glutamine has been developed during last years as a potential strategy against *** this review,we summarized the last advances in our knowledge about the role of glutamine metabolism in cancer therapy.

关键词： Cancer glutamine glutamoptosis metabolism mammalian target of rapamycin

Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

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World Journal of Gastroenterology 2019年第19期25卷 2354-2364页

作者： Elisa Sollelis Régine Minet Quinard Guillaume Bouguen Marion Goutte Félix Goutorbe Damien Bouvier Bruno Pereira Gilles Bommelaer Anthony Buisson inserm 3i HP CHU Clermont-Ferrand Service d’Hépato-Gastro Entérologie Université Clermont Auvergne inserm u1071 M2i SH USC-INRA 2018 Université Clermont Auvergne Biochemistry laboratory University Hospital G.Montpied CHu Rennes Univ Rennes INSERM CIC1414 Institut NUMECAN (Nutrition Metabolisms and Cancer) Gastroenterology Department Hospital of Bayonne Biostatistics unit DRCI University Hospital

BACKGROuND The individual performances and the complementarity of Crohn's disease(CD)activity index(CDAI), C-reactive protein(CRP) and faecal calprotectin(Fcal) to monitor patients with CD remain poorly inves-tigated in the era of "tight control"and "treat to target" *** To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk(W12) of anti-tumor necrosis factor(TNF) therapy to predict corticosteroids-free remission(CFREM = CDAI utic intensification and no surgery) at *** CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP >2.9 mg/L or Fcal > 250 μg/g were prospectively *** Among the 40 included patients, 13 patients(32.5%) achieved CFREM at W52. In univariable analysis, CDAI ue = 100.0%(100.0-100.0)and negative predictive value = 87.1%(75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio(OR) = 45.1(2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI uSION The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

关键词： Biomarkers Crohn's disease Faecal calprotectin Crohn's disease activity index C-reactive protein Tight control Anti-tumor necrosis factor

Comment on“Hypothermic machine perfusion in liver transplantation-a randomized trial”

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 364-366页

作者： Fabien Robin Heithem Jeddou Department of Hepatobiliary and Digestive Surgery University HospitalRennes 1 UniversityRennesFrance inserm u1242 Chemistry Oncogenesis Stress SignalingRennes 1 UniversityRennesFrance

We read with great interest the article by van Rijn et *** in March 2021,in The New England Journal of Medicine(1).In this multicenter,randomized controlled trial,the authors investigated the efficacy of dual hypothermic oxygenated perfusion(D-HOPE)versus static cold storage(SCS)in grafts from donors after cardiac death(DCD)to decrease the rate of non-anastomotic biliary stenosis(NAS)within the first 6 post-transplant months.

关键词： randomized therm perfusion