A novel strategy for treatment of cancer cachexia targeting xanthine oxidase in the brain.

Administration, Oral Animals Brain / enzymology Cachexia / drug therapy Disease Models, Animal Febuxostat / administration & dosage Male Mice, Inbred BALB C Neoplasms / complications Purines / metabolism Xanthine Oxidase / metabolism
Cancer cachexia Metabolome Xanthine oxidase

Journal

Journal of pharmacological sciences
ISSN: 1347-8648
Titre abrégé: J Pharmacol Sci
Pays: Japan
ID NLM: 101167001

Informations de publication

Date de publication:
May 2019
Historique:
received: 17 01 2019
revised: 12 03 2019
accepted: 01 04 2019
pubmed: 4 6 2019
medline: 18 12 2019
entrez: 4 6 2019
Statut: ppublish

Résumé

Cancer cachexia is a systemic wasting syndrome characterized by anorexia and loss of body weight. The xanthine oxidase (XO) inhibitor febuxostat is one of the promising candidates for cancer cachexia treatment. However, cachexic symptoms were not alleviated by oral administration of febuxostat in our cancer cachexia model. Metabolomic analysis with brains of our cachexic model showed that purine metabolism was activated and XO activity was increased, and thus suggested that febuxostat would not reach the brain. Accordingly, targeting XO in the brain, which controls appetite, may be an effective strategy for treatment of cancer cachexia.

Identifiants

DOI: 10.1016/j.jphs.2019.04.005 PMID: 31155393
pubmed: 31155393
pii: S1347-8613(19)31049-7
doi: 10.1016/j.jphs.2019.04.005
pii:
doi:

Substances chimiques

Purines 0
Febuxostat 101V0R1N2E
Xanthine Oxidase EC 1.17.3.2
purine W60KTZ3IZY

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

109-112

Informations de copyright

Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Auteurs

Miaki Uzu (M)

Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.

Miki Nonaka (M)

Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.

Kanako Miyano (K)

Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.

Hiromi Sato (H)

Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.

Nagomi Kurebayashi (N)

Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.

Kazuyoshi Yanagihara (K)

Division of Biomarker Discovery, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, 277- 8577, Japan.

Takashi Sakurai (T)

Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.

Akihiro Hisaka (A)

Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.

Yasuhito Uezono (Y)

Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan; Division of Supportive Care Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Tokyo, 104-0045, Japan; Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center Hospital, Tokyo, 104-0045, Japan. Electronic address: yuezono@ncc.go.jp.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie orale › A novel strategy for treatment of cancer...
questionsmedicales.fr › Eucaryotes › Animaux › A novel strategy for treatment of cancer...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › A novel strategy for treatment of cancer...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Cachexie › A novel strategy for treatment of cancer...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › A novel strategy for treatment of cancer...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Thiazoles › Fébuxostat › A novel strategy for treatment of cancer...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › A novel strategy for treatment of cancer...
questionsmedicales.fr › Tumeurs › A novel strategy for treatment of cancer...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › A novel strategy for treatment of cancer...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › Xanthine oxidase › A novel strategy for treatment of cancer...