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4 results on '"Mark J. Kurth"'

3. Data from Halogenated Benzimidazole Carboxamides Target Integrin α4β1 on T-Cell and B-Cell Lymphomas

Author

Mark J. Kurth, Kit S. Lam, Sally J. DeNardo, Felice C. Lightstone, Danielle M. Solano, Mirela Andrei, Edmond Y. Lau, Arutselvan Natarajan, and Richard D. Carpenter

Abstract

Integrin α4β1 is an attractive but poorly understood target for selective diagnosis and treatment of T-cell and B-cell lymphomas. This report focuses on the rapid microwave preparation, structure-activity relationships, and biological evaluation of medicinally pertinent benzimidazole heterocycles as integrin α4β1 antagonists. We documented tumor uptake of derivatives labeled with 125I in xenograft murine models of B-cell lymphoma. Molecular homology models of integrin α4β1 predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. The high-affinity halogenated ligands identified offer attractive tools for medicinal and biological use, including fluoro and iodo derivatives with potential radiodiagnostic (18F) or radiotherapeutic (131I) applications, or chloro and bromo analogues that could provide structural insights into integrin-ligand interactions through photoaffinity, cross-linking/mass spectroscopy, and X-ray crystallographic studies. Cancer Res; 70(13); 5448–56. ©2010 AACR.

Published
2023

4. Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

Author

Franck Letourneur, Jérémy Augustin, Mark J. Kurth, Julie Le Naour, Sylvie Lachkar, Pamela Caudana, Eliane Piaggio, Youra Kim, Sarah Levesque, Jie S. Zhu, Guido Kroemer, Jonathan Pol, Bouchra Lekbaby, Andrea Checcoli, Patrick S.C. Leung, Allan Sauvat, Shashi Gujar, Agathe Delaune, Chantal Housset, Pierre de la Grange, Paule Opolon, Laura Fouassier, Noémie Robil, Laurence Zitvogel, Patrick Soussan, Juliette Paillet, Céleste Plantureux, Jimena Tosello Boari, M. Eric Gershwin, Isabelle Martins, Maria Chiara Maiuri, Cédric Coulouarn, Gautier Stoll, Norma Bloy, Gwennhael Autret, Juliette Hamroune, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Gustave Roussy (IGR), Institut Curie [Paris], Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), GenoSplice [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of California [Los Angeles] (UCLA), University of California, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dalhousie University [Halifax], Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CRLCC Eugène Marquis (CRLCC), Université Paris-Saclay, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska University Hospital [Stockholm], Association pour la lutte contre les maladies inflammatoires du foie et des voies biliaires, Dalhousie Medical Research Foundation, Agence National de la Recherche, ERA-Net for Research on Rare Diseases, Association pour la recherche sur le cancer, Cancéropôle Ile-de-France, Chancellerie des universités de Paris, Fondation pour la Recherche Médicale, Elior, European Research Area Network on Cardiovascular Diseases, Gustave Roussy Odyssea, European Union Horizon 2020, Canadian Cancer Society, Project Oncobiome, Fondation Carrefour, GDW20171100085, High-end Foreign Expert Program in China, Institut National du Cancer, Inserm, Institut Universitaire de France, LeDucq Foundation, LabEx, Recherche Hospitalo-Universitaire Torino Lumière, Seerave Foundation, Canadian Institutes of Health Research, Site de Recherche intégrée sur le Cancer Stratified Oncology Cell DNA Repair and Tumor Immune Elimination, Cancer Research and Personalized Medicine, Multi-Organism Institute (ITMO) Aviesan Cancer, Association Française d'Hépatologie, Site de Recherche intégrée sur le Cancer Cancer Research and Personalized Medicine, Ligue contre le Cancer, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of California (UC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
CD4-Positive T-Lymphocytes, Cholangitis, Autoimmunity, CD8-Positive T-Lymphocytes, Inbred C57BL, medicine.disease_cause, Medical and Health Sciences, Malignant transformation, Cholangiocarcinoma, Mice, 0302 clinical medicine, Immunologic, Neoplasms, 2.1 Biological and endogenous factors, Immunology and Allergy, Medicine, Aetiology, Cancer, 0303 health sciences, Tumor, Liver Disease, Forkhead Transcription Factors, 3. Good health, Immunosurveillance, medicine.anatomical_structure, Liver, Biliary tract, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, cardiovascular system, Cytokines, Female, Biotechnology, Liver Cancer, Monitoring, T cell, Chronic Liver Disease and Cirrhosis, Immunology, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Autoimmune Disease, digestive system, Cell Line, Primary sclerosing cholangitis, Experimental, 03 medical and health sciences, Rare Diseases, Monitoring, Immunologic, Cell Line, Tumor, parasitic diseases, Animals, cardiovascular diseases, Digestive Diseases - (Gallbladder), 030304 developmental biology, business.industry, Neoplasms, Experimental, medicine.disease, digestive system diseases, Mice, Inbred C57BL, Bile Duct Neoplasms, Cancer research, Digestive Diseases, business
Abstract

International audience; Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.

Published
2021

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