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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Project:

Project ID:PR000714
Project DOI:doi: 10.21228/M8CT1Z
Project Title:Cachexia symptoms induced by Gliomas - NMR metabolomics
Project Summary:Malignant 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
Department:Chemistry
Last Name:Cui
First Name:Pengfei
Address:422 siming south road
Email:edmundcui@126.com
Phone:86-15060796092

Subject:

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

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Celltype Treatment
SA077661C2CHG5 lowgrade
SA077662C4CHG5 lowgrade
SA077663C6CHG5 lowgrade
SA077664C1CHG5 lowgrade
SA077665C5CHG5 lowgrade
SA077666C3CHG5 lowgrade
SA077667H7HEB control
SA077668H2HEB control
SA077669H3HEB control
SA077670H4HEB control
SA077671H6HEB control
SA077672H1HEB control
SA077673H5HEB control
SA077674U6U87 highgrade
SA077675U5U87 highgrade
SA077676U1U87 highgrade
SA077677U2U87 highgrade
SA077678U3U87 highgrade
SA077679U4U87 highgrade
Showing results 1 to 19 of 19

Collection:

Collection ID:CO001169
Collection Summary:Muscles were rapidly dissected, weighted and frozen in liquid nitrogen and stored at -80 °C until analyses.
Sample Type:Muscle

Treatment:

Treatment ID:TR001189
Treatment Summary:Right caudate nuclei of mice were separately injected with 2.0 μL of the suspension of 2.0 × 105 of HEB, CHG5 and U87 cells. muscles were rapidly dissected, weighted and frozen.

Sample Preparation:

Sampleprep ID:SP001182
Sampleprep Summary:Generally, gastrocnemius muscle samples were homogenized after adding ice-cold methanol, chloroform and water at a volume ratio of 4:4:2.85 to obtain a two-phase extract.

Analysis:

Analysis ID:AN001829
Analysis Type:NMR
Num Factors:3

NMR:

NMR ID:NM000142
Analysis ID:AN001829
Instrument Name:Bruker Avance III
Instrument Type:FT-NMR
NMR Experiment Type:1D 1H
Spectrometer Frequency:850 MHz
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