Severe Hepatotoxicity of Mithramycin Therapy Caused by Altered Expression of Hepatocellular Bile Transporters.

ATP Binding Cassette Transporter, Subfamily B / genetics ATP Binding Cassette Transporter, Subfamily B, Member 11 / genetics Adult Aged Antibiotics, Antineoplastic / adverse effects Cell Line, Tumor Chemical and Drug Induced Liver Injury / genetics Clinical Trials, Phase II as Topic Female Gene Expression Regulation, Neoplastic / drug effects Humans Male Membrane Transport Proteins / genetics Middle Aged Plicamycin / adverse effects Receptors, Cytoplasmic and Nuclear / genetics Thoracic Neoplasms / drug therapy

Journal

Molecular pharmacology
ISSN: 1521-0111
Titre abrégé: Mol Pharmacol
Pays: United States
ID NLM: 0035623

Informations de publication

Date de publication:
08 2019
Historique:
received: 12 10 2018
accepted: 15 05 2019
pubmed: 9 6 2019
medline: 18 12 2019
entrez: 9 6 2019
Statut: ppublish

Résumé

Mithramycin demonstrates preclinical anticancer activity, but its therapeutic dose is limited by the development of hepatotoxicity that remains poorly characterized. A pharmacogenomics characterization of mithramycin-induced transaminitis revealed that hepatotoxicity is associated with germline variants in genes involved in bile disposition:

Identifiants

DOI: 10.1124/mol.118.114827 PMID: 31175181 PMC: PMC6608607
pubmed: 31175181
pii: mol.118.114827
doi: 10.1124/mol.118.114827
pmc: PMC6608607
doi:

Substances chimiques

ABCB11 protein, human 0
ATP Binding Cassette Transporter, Subfamily B 0
ATP Binding Cassette Transporter, Subfamily B, Member 11 0
Antibiotics, Antineoplastic 0
Membrane Transport Proteins 0
Receptors, Cytoplasmic and Nuclear 0
farnesoid X-activated receptor 0C5V0MRU6P
multidrug resistance protein 3 9EI49ZU76O
Plicamycin NIJ123W41V

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

158-167

Subventions

Organisme : Intramural NIH HHS
ID : ZIA BC010627
Pays : United States

Informations de copyright

U.S. Government work not protected by U.S. copyright.

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Auteurs

Tristan M Sissung (TM)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Phoebe A Huang (PA)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Ralph J Hauke (RJ)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Edel M McCrea (EM)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Cody J Peer (CJ)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Roberto H Barbier (RH)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Jonathan D Strope (JD)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Ariel M Ley (AM)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Mary Zhang (M)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Julie A Hong (JA)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

David Venzon (D)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Jonathan P Jackson (JP)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Kenneth R Brouwer (KR)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Patrick Grohar (P)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Jon Glod (J)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Brigitte C Widemann (BC)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

Theo Heller (T)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

David S Schrump (DS)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.).

William D Figg (WD)

Clinical Pharmacology Program (T.M.S., C.J.P., W.D.F.), Molecular Pharmacology Section (P.A.H., R.J.H., E.M.M., R.H.B., J.D.S., A.M.L., W.D.F.), Biostatistics and Data Management Section (M.Z., J.A.H., D.V.), Pediatric Oncology Branch (P.G., J.G., B.C.W.), Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (D.S.S.), and Translational Hepatology Section (T.H.), Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and BioIVT, ADME-Tox Division, Durham, North Carolina (J.P.J., K.R.B.) figgw@mail.nih.gov.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Sous-famille B de transporteurs à cassette liant l'ATP › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Sous-famille B de transporteurs à cassette liant l'ATP › Membre-11 de la sous-famille B à cassette liant l'ATP › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antibiotiques antinéoplasiques › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Troubles dus à des produits chimiques › Intoxication › Lésions hépatiques dues aux substances › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques de phase II comme sujet › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Glucides › Hétérosides › Aminosides › Anthracyclines › Mithramycine › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Severe Hepatotoxicity of Mithramycin Therapy...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs du thorax › Severe Hepatotoxicity of Mithramycin Therapy...