Transcriptome data derived from muscle and brain in CT-26-induced mouse cancer cachexia models
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE281701 | GEO | 2024/11/19
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome data derived from muscle and brain in CT-26-induced mouse cancer cachexia models
| PRJNA1185256 | ENA
Project description:To determine the transcriptomic differences between CT-26 and Colon 26, we sequenced RNA from these cell lines as well as tumors isolated ex vivo from tumor bearing animals at sizes 100, 400 and 800 mm3
2021-11-08 | GSE185023 | GEO
Project description:Forkhead BoxO (FoxO) transcription factors expressed in adult skeletal muscle promote muscle atrophy during various catabolic conditions. We have identified the genome wide target genes and biological networks regulated by FoxO in skeletal muscle during Colon-26 (C-26) cancer cachexia. In this dataset, we include the expression data obtained from the tibialis anterior muscles of control and severely cachectic Colon-26 mice in which FoxO-dependent transcription was either intact (AAV9-EV) or inhibited (AAV9-d.n.FoxO). These data were used to obtain 543 FoxO target genes during cancer. These target genes were identified as those genes whose expression was both differentially regulated in skeletal muscle in response to cancer (control AAV9-EV vs. C26 AAV9-EV), and differentially regulated in the presence of d.n.FoxO (C26 AAV9-EV vs. C26 AAV9-d.n.FoxO).
2014-12-31 | GSE56555 | GEO
Project description:No approved therapy exists for cancer-associated cachexia. The colon-26 mouse model of cancer cachexia mimics recent late stage clinical failures of anabolic anti-cachexia therapy, and was unresponsive to anabolic doses of diverse androgens, including the selective androgen receptor modulator (SARM) GTx-024. The histone deacetylase inhibitor (HDACi) AR-42 exhibited anti-cachectic activity in this model. We explored combined SARM/AR-42 therapy as an improved anti-cachectic treatment paradigm. A reduced dose of AR-42 provided limited anti-cachectic benefits, but, in combination with GTx-024, significantly improved body weight, hind limb muscle mass, and grip strength versus controls. AR-42 suppressed the IL-6/GP130/STAT3 signaling axis in muscle without impacting circulating cytokines. GTx-024-mediated β-catenin target gene regulation was apparent in cachectic mice only when combined with AR-42. Our data suggest cachectic signaling in this model involves catabolic signaling insensitive to anabolic GTx-024 therapy and a blockade of GTx-024-mediated anabolic signaling. AR-42 mitigates catabolic gene activation and restores anabolic responsiveness to GTx-024. Combining GTx-024, a clinically established anabolic therapy, with AR-42, a clinically evaluated HDACi, represents a promising approach to improve anabolic response in cachectic patients.
2019-11-20 | GSE138464 | GEO
Project description:Here, we investigate the systematic impact of tumor cachexia on muscle function. From a nutritional supplementation perspective, we examine the influence of fatty acid metabolism on the cachectic state, revealing that dietary supplementation with high-fat diet does not alleviate the muscle and fat dysfunction induced by tumors but instead accelerates muscle degradation. Utilizing RNA-seq transcriptome data from muscle tissue, we identify metabolic abnormalities in muscle during cachexia, with the PDK4 gene being activated initially and showing significant enrichment of PPARδ targets. We find that inhibiting PDK4 can mitigate the cachectic state and observe a relationship between the activation of muscle PDK4 and PPARδ during cachexia. This is supported by epigenomic data revealing that PDK4 is a transcriptional target gene of PPARδ in muscle. Activation and mechanical modulation of PPARδ in vivo significantly impact muscle atrophy caused by cachexia. Our research suggests that targeting PPARδ could serve as a therapeutic drug target for tumor cachexia.
2024-12-18 | GSE246122 | GEO
Project description:Background: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of amiloride for ameliorating muscle wasting in murine models of cancer cachexia. Methods: CT26 and LLC tumor cells were subcutaneously injected into mice to induce cancer cachexia. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 and LLC models, respectively, were characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius. Results: The CT26 and LLC models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. The CT26 and LLC cachexia mice showed increased particle density of plasma exosomes which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius. Conclusions: Our results demonstrated the efficacy of amiloride in ameliorating cachectic muscle wasting and elucidated the underlying mechanistic rationale for its use as an alternative strategy to improve CAC treatments.
2021-07-14 | GSE173250 | GEO
Project description:Background Loss of skeletal muscle mass in advanced cancer is recognized as an independent predictor of mortality. Mechanisms involved in this wasting process and parameters for early diagnosis are still lacking. As skeletal muscle is considered as a secretory organ, the aim of this present experimental work was to characterize the changes in muscle proteome and secretome associated with cancer-induced cachexia to better understand cellular mechanisms involved in this wasting process and to identify secreted proteins which might reflect the ongoing muscle atrophy process. Methods We investigated first the changes in the muscle proteome associated with cancer-induced cachexia by using differential label-free proteomic analysis on muscle of the C26 mouse model. The differentially abundant proteins were submitted to sequential bioinformatic secretomic analysis in order to identify potentially secreted proteins. Selected reaction monitoring and Western blotting were used to verify the presence of candidate proteins at the circulating level. Their muscle source was demonstrated by assessing their gene expression in skeletal muscle and in cultured myotubes. Finally, we also investigated their regulation in muscle cells. Alterations in several molecular pathways potentially involved in muscle atrophy were highlighted using Gene ontology enrichment analyses. Results Our results revealed a dramatic increased production (2-to 25-fold) by the muscle of several acute phase reactants (APR: Haptoglobin, Serpina3n, Complement C3, Serum amyloid A1) which are also released in the circulation during C26 cancer cachexia. Their production was confirmed in other preclinical models of cancer cachexia as well as in cancer patients. The muscular origin of these APR was demonstrated by their increased expression in skeletal muscle and myotubes. Glucocorticoids and pro-inflammatory cytokines contribute directly to their increased expression in muscle cells in vitro, while the role of IL-6 in the muscular induction of these APR was demonstrated in vivo. Conclusions Cancer is associated with marked changes in muscle secretome during muscle wasting. Our study demonstrates a marked increased production of APR by skeletal muscle in pre-clinical models of cancer cachexia and in cancer patients. Further studies are required to unravel the potential role of these proteins in muscle atrophy and their interest as biomarkers of cancer cachexia.
2020-10-28 | PXD016474 | Pride
Project description:RAW cells,ABHD5-KD RAW cells or those macrophage-primed CT-26 cells were subjected to microarray assays.Each group contain 3 samples.
2019-08-11 | GSE135673 | GEO
Project description:Cancer cachexia has been linked to gut bacterial alterations, but alterations of gut viruses, mostly bacteriophages, have not yet been explored. We performed shotgun metagenomic sequencing of DNA from stool samples of 78 cachectic and 42 non-cachectic cancer patients. K-mer-based matching to reference databases revealed abundance variations of bacteria and viruses. Beyond bacterial alterations, cachectic patients exhibited significantly lower bacteriophage abundance, predominantly affecting Caudovirales and Siphoviridae species (double-stranded DNA) but also Inoviridae and Microviridae families (single-stranded DNA).
| EGAS00001007156 | EGA
Project description:Cancer cachexia is a disorder characterized by both involuntary weight loss and impaired physical performance. Decline in physical performance of patients with cachexia is associated with poor quality of life, and currently there are no effective pharmacological interventions that restore physical performance. Here we examined the effect of GDF15 neutralization in a mouse model of cancer-induced cachexia (TOV21G) that manifested weight loss and muscle function impairments. With comprehensive assessments, our results demonstrated that cachectic mice treated with the anti-GDF15 antibody mAB2 exhibited body weight gain with near-complete restoration of muscle mass and markedly improved muscle function and physical performance. Mechanistically, the improvements induced by GDF15 neutralization were primarily attributed to increased caloric intake, while altered gene expressions in cachectic muscles were restored in both caloric intake-dependent and -independent manners. The findings implicate the potential of GDF15 neutralization as an effective therapy to enhance physical performance of patients with cachexia.
2023-01-11 | GSE214603 | GEO