Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effects of doxorubicin and blocking activin receptor 2B ligands in mice [heart]

ABSTRACT: Doxorubicin is a widely used and effective anthracycline chemotherapy drug. However, it causes cardiotoxicity and also a few negative effects on skeletal muscle as well. As a result, cancer treatment might actually worsen cancer-induced cachexia and consequently the prognosis of the disease. Inhibiting myostatin/activin signaling is known to increase muscle size. This pathway blockade by soluble activin receptor IIB (sAcvR2B-Fc) has also prolonged survival in cancer, even of animals in which tumor growth is not inhibited. It is not known, however, whether blocking this pathway affects chemotherapy-induced muscle wasting. We found that doxorubicin induces muscle atrophy which is prevented by a blocker for activin receptor 2B ligands (sAcvR2B-Fc)

ORGANISM(S): Mus musculus

PROVIDER: GSE97642 | GEO | 2017/12/04

SECONDARY ACCESSION(S): PRJNA382543

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The effects of doxorubicin and blocking activin receptor 2B ligands in mice [muscle]

Project description:Doxorubicin is a widely used and effective anthracycline chemotherapy drug. However, it causes cardiotoxicity and also a few negative effects on skeletal muscle as well. As a result, cancer treatment might actually worsen cancer-induced cachexia and consequently the prognosis of the disease. Inhibiting myostatin/activin signaling is known to increase muscle size. This pathway blockade by soluble activin receptor IIB (sAcvR2B-Fc) has also prolonged survival in cancer, even of animals in which tumor growth is not inhibited. It is not known, however, whether blocking this pathway affects chemotherapy-induced muscle wasting. We found that doxorubicin induces muscle atrophy which is prevented by a blocker for activin receptor 2B ligands (sAcvR2B-Fc).

2016-09-25 | GSE77745 | GEO

Gene expression profiling of skeletal muscles treated with a soluble activin type IIB receptor

2011-02-04 | GSE25306 | GEO

Gene expression profiling of skeletal muscles treated with a soluble activin type IIB receptor

Project description:Inhibition of the myostatin signaling pathway is emerging as a promising therapeutic means to treat muscle wasting disorders. Activin type IIB receptor is the putative myostatin receptor, and a soluble activin receptor (ActRIIB-Fc) has been demonstrated to potently inhibit a subset of TGF-β family members including myostatin. In order to determine reliable and valid biomarkers for myostatin pathway inhibition, we assessed gene expression profiles for quadriceps muscles from mice treated with ActRIIB-Fc compared to mice genetically lacking myostatin and control mice. RNA extracted from quadriceps muscles of four classes of two-month-old female mice were analyzed with Affymetrix microarrays: control mice, myostatin-null mice, mice treated with one dose of ActRIIB-Fc and mice treated with four doses of ActRIIB-Fc. An initial study used 3 mice from each class, and an independent follow-up study used 8 myostatin-null mice and 5 mice from each of the other 3 classes.

2011-02-04 | E-GEOD-25306 | biostudies-arrayexpress

Comparing effects of inhibition of activin receptor type IIB (ActRIIB), myostatin (GDF8) and/or activinA in mouse muscle

Project description:This study was to compare the gene expression of our anti-GDF8 (i.e. anti-myostatin) and anti-activin A antibody combination to that of the activin receptor type IIB (ActRIIB.hFc) trap in SCID mice. The study was conducted in tibialis anterior muscle that is a common muscle type for the hypertrophy study. The combination treatment produces very similar muscle growth in tibialis muscle as the ActRIIB.hFc trap, however our combination blocks two specific ligands compared to the many ligands the receptor trap will inhibit. The difference in gene expression between these groups demonstrates that despite producing similar muscle growth, the trap affecting more genes in muscle without producing additional muscle hypertrophy.

2017-06-01 | E-MTAB-4943 | biostudies-arrayexpress

The effects of muscular dystrophy, exercise and sActRIIB-Fc on molecular signature of skeletal muscle in mice

2014-10-13 | GSE52766 | GEO

The effects of muscular dystrophy, exercise and sActRIIB-Fc on molecular signature of skeletal muscle in mice

Project description:To study the combined effect of myostatin/activin inhibition and exercise on muscle mass and pathophysiology, young mdx mice, a model for Duchenne Muscular Dystrophy, were injected with soluble activin receptor-Fc (sActRIIB-Fc) or placebo (PBS) 1x/week for a 7-week period, in combination with or without voluntary running. C57Bl/10ScSnJ mice injected with PBS acted as wildtype controls. Microarray expression analysis from skeletal muscle was performed using m. gastrocnemies as the sample. We found thatexercise or a combination of exercise and sActRIIB-Fc treatment is more effective in correcting gene expression profiles of dystrophic muscles than the sActRIIB-Fc treatment alone. We also identified several pathways and proteins that were affected by exercise and sActRIIB-Fc together or independently. Total RNA obtained from gastrocnemius muscle of mdx mice divided into four groups: 1) control (injected with PBS, n=5), 2) runners (voluntary wheel running for 7 weeks, injected with PBS, n=5), 3) sActRIIB-Fc -treated (n=5), and 4) runners with sActRIIB-Fc-treatment (n=5). sActRIIB-Fc or PBS was injected intraperitoneally once a week with a 5-mg/kg dose of sActRIIB-Fc. In addition, wildtype mice served as healthy controls (n=4).

2014-10-13 | E-GEOD-52766 | biostudies-arrayexpress

Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington’s disease mice.

Project description:Huntington’s disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Transcriptional profiling of muscle in treated and untreated wild-type and R6/2 mice was performed to analyze the effect of the ActRIIB decoy on genes and pathways involved in maintaining normal muscle physiology as well as those dysregulated due to the mutant HTT gene mutation.

2017-10-29 | GSE81367 | GEO

Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight

Project description:Among the physiological consequences of extended space flight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin and activin A. Here, we used both pharmacological and genetic approaches to investigate the effect of targeting myostatin/activin A signaling in mice that were sent to the International Space Station. We show that inhibition of myostatin/activin A signaling has a significant protective effect against microgravity-induced muscle and bone loss. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions.

2020-09-16 | GSE156321 | GEO

Targeting histone methylation to reprogram the transcriptional state that drives survival of drug-tolerant myeloid leukemia persisters

Project description:Although chemotherapy induces complete remission in the majority of acute myeloid leukemia (AML) patients, many face a relapse. This relapse is caused by survival of chemotherapy-resistant leukemia (stem) cells, called measurable residual disease (MRD). Here, we demonstrate that the anthracycline doxorubicin epigenetically reprograms leukemia cells by inducing tri-methylation of histone 3 lysine 27 (H3K27) and H3K4. Moreover, within a doxorubicin-sensitive leukemia cell population, we identified a subpopulation of reversible anthracycline-tolerant cells (ATCs) with leukemic stem cell (LSC) features lacking upregulation of doxorubicin-induced H3K27me3 or H3K4me3. These ATCs have a distinct transcriptional landscape than the leukemia bulk and could be eradicated by inhibition of KDM6. In primary AML, reprogramming the transcriptional state by targeting KDM6 reduced MRD load and survival of LSCs residing within MRD, and enhanced the response to chemotherapy in vivo. Together, our results reveal plasticity of anthracycline resistance in AML cells and highlight the potential of transcriptional reprogramming by epigenetic-based therapeutics to target chemotherapy-resistant AML cells.

2022-08-15 | GSE210916 | GEO

Effects of VEGF-B on doxorubicin-induced cardiotoxicity

Project description:Doxorubicin is a widely used and effective anthracycline chemotherapy drug, which use is limited due to its cardiotoxic side effects. We show that gene therapy with AAV-VEGF-B can inhibit the doxorubicin-induced cardiac atrophy and whole body cachexia.

2016-09-30 | GSE81448 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data