Summary of Study ST001064

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000714. The data can be accessed directly via it's Project DOI: 10.21228/M8CT1Z This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001064
Study TitleNude mice orthotopicly implanted with human glioma cell lines
Study SummaryMalignant gliomas are considered to be one of the deadliest human cancers, accounting for about 60% of all primary brain tumors. Cachexia is a complex metabolic derangement and muscle atrophy syndrome, which causes high mortalities in patients with advanced cancers including brain tumors. However, cachexia symptoms induced by gliomas and mechanisms underlying muscle atrophy are unclear. Herein, we developed a glioma cachexia model using nude mice orthotopicly implanted with two glioma cell lines (WHO II CHG5 and WHO IV U87). U87 mice developed more severe cachexia symptoms than CHG5 mice, including more evident anorexia, greater body weight loss and mortality. Unlike non-central nervous system cancer cachexia, glioma cachexia did not induce remarkable systemic inflammation but massive multi-organ atrophy. It also caused significantly decreased skeletal muscle mass and strength, which were associated with down-regulated myosin and AKT, and up-regulated AMPK, FOXO and Atrogin1. Interestingly, expressions of MuRF1, MyoD1, eIF3f, desmin and vimentin were not significantly changed. Consistently, NMR-based metabolomic analyses revealed pronounced metabolic derangements in cachectic gastrocnemius relative to controls. Glucose, glycerol, 3-hydroxybutyrate and glycine were remarkably down-regulated, whereas largely released amino acids due to proteolysis including glutamate, arginine, leucine and isoleucine were up-regulated in cachectic gastrocnemius. Moreover, glucose and lipid metabolism, protein biosynthesis and amino acid metabolism were disturbed dramatically in both glioma-bearing mice. U87 mice showed more changed metabolite levels and altered metabolic pathways. This work uncovers malignant grade-dependent glioma cachexia symptoms and metabolic derangements of skeletal muscle for the first time, and provides hints for new therapeutic approaches.
Institute
Xiamen University
Last NameCui
First NamePengfei
Address422 siming south road
Emailedmundcui@126.com
Phone15060796092
Submit Date2018-09-22
Analysis Type DetailNMR
Release Date2020-01-06
Release Version1
Pengfei Cui Pengfei Cui
https://dx.doi.org/10.21228/M8CT1Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Subject:

Subject ID:SU001175
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
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