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- W3037877431 endingPage "2029" @default.
- W3037877431 startingPage "2029" @default.
- W3037877431 abstract "Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass, which negatively impacts patients’ quality of life, reduces their ability to sustain anti-cancer therapies, and increases the risk of mortality. Recent discoveries have identified the myostatin/activin A/ActRIIB pathway as critical to muscle wasting by inducing satellite cell quiescence and increasing muscle-specific ubiquitin ligases responsible for atrophy. Remarkably, pharmacological blockade of the ActRIIB pathway has been shown to reverse muscle wasting and prolong the survival time of tumor-bearing animals. To explore the implications of this signaling pathway and potential therapeutic targets in cachexia, we construct a novel mathematical model of muscle tissue subjected to tumor-derived cachectic factors. The model formulation tracks the intercellular interactions between cancer cell, satellite cell, and muscle cell populations. The model is parameterized by fitting to colon-26 mouse model data, and the analysis provides insight into tissue growth in healthy, cancerous, and post-cachexia treatment conditions. Model predictions suggest that cachexia fundamentally alters muscle tissue health, as measured by the stem cell ratio, and this is only partially recovered by anti-cachexia treatment. Our mathematical findings suggest that after blocking the myostatin/activin A pathway, partial recovery of cancer-induced muscle loss requires the activation and proliferation of the satellite cell compartment with a functional differentiation program." @default.
- W3037877431 created "2020-07-02" @default.
- W3037877431 creator A5061050808 @default.
- W3037877431 creator A5068704751 @default.
- W3037877431 date "2020-06-28" @default.
- W3037877431 modified "2023-09-24" @default.
- W3037877431 title "Mathematical Model of Muscle Wasting in Cancer Cachexia" @default.
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