dc.contributor.author
Pötsch, Mareike S.
dc.contributor.author
Ishida, Junichi
dc.contributor.author
Palus, Sandra
dc.contributor.author
Tschirner, Anika
dc.contributor.author
Haehling, Stephan von
dc.contributor.author
Doehner, Wolfram
dc.contributor.author
Anker, Stefan D.
dc.contributor.author
Springer, Jochen
dc.date.accessioned
2021-11-22T14:14:16Z
dc.date.available
2021-11-22T14:14:16Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32806
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-32532
dc.description.abstract
Background:
Cachexia, a common manifestation of malignant cancer, is associated with wasting of skeletal muscle and fat tissue. In this study, we investigated the effects of a new first in class anabolic catabolic transforming agent on skeletal muscle in a rat model of cancer cachexia.
Methods:
Young male Wistar Han rats were intraperitoneally inoculated with 108 Yoshida hepatoma AH-130 cells and once daily treated with 0.3 mg kg−1, 3 mg kg−1 MT-102, or placebo by gavage.
Results:
Three mg kg−1d−1 MT-102 not only prevented progressive loss of fat mass (−6 ± 2 g vs -12 ± 1 g; P < 0.001); lean mass (+1 ± 10 g vs. −37 ± 2 g; P < 0.001) and body weight (+1 ± 13 g vs. −60 ± 2 g; P < 0.001) were remained. Quality of life was also improved as indicated by a higher food intake 12.9 ± 3.1 g and 4.3 ± 0.5 g, 3 mg kg−1d−1 MT-102 vs. placebo, respectively, P < 0.001) and a higher spontaneous activity (52 369 ± 6521 counts/24 h and 29 509 ± 1775 counts/24 h, 3 mg·kg-1d-1 MT-102 vs. placebo, respectively, P < 0.01) on Day 11. Most importantly, survival was improved (HR = 0.29; 95% CI: 0.16–0.51, P < 0.001). The molecular mechanisms behind these effects involve reduction of overall protein degradation and activation of protein synthesis, assessed by measurement of proteasome and caspase-6 activity or Western blot analysis, respectively.
Conclusions:
The present study shows that 3 mg kg−1 MT-102 reduces catabolism, while inducing anabolism in skeletal muscle leading to an improved survival.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
Cancer cachexia
en
dc.subject
Animal model
en
dc.subject
Drug development
en
dc.subject
Muscle wasting
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
MT‐102 prevents tissue wasting and improves survival in a rat model of severe cancer cachexia
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1002/jcsm.12537
dcterms.bibliographicCitation.journaltitle
Journal of Cachexia, Sarcopenia and Muscle
dcterms.bibliographicCitation.number
2
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
594
dcterms.bibliographicCitation.pageend
605
dcterms.bibliographicCitation.volume
11
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
32067370
dcterms.isPartOf.eissn
2190-6009