[Systemic and local mechanisms leading to cachexia in cancer].

Ogólnoustrojowe i miejscowe mechanizmy prowadzące do kacheksji w chorobach nowotworowych.

Publisher: Medical Science International Country of Publication: Poland NLM ID: 101206517 Publication Model: Electronic Cited Medium: Internet ISSN: 1732-2693 (Electronic) Linking ISSN: 00325449 NLM ISO Abbreviation: Postepy Hig Med Dosw (Online) Subsets: MEDLINE

Original Publication: [Warsaw, Poland] : Medical Science International, [2004]-

Cachexia/*etiology ; Cachexia/*metabolism ; Neoplasms/*complications ; Neoplasms/*metabolism; Adipose Tissue/metabolism ; Animals ; Anorexia/etiology ; Anorexia/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Energy Metabolism/physiology ; Humans ; Interleukin-6/metabolism ; Lipid Metabolism ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/pathology ; Myostatin/metabolism ; NF-kappa B/metabolism ; Tumor Necrosis Factor-alpha/metabolism

Cachexia is a multifactorial syndrome of atrophy of skeletal muscle and adipose tissue, resulting in progressive loss of body weight associated with low quality of life and poor prognosis in cancer. Studies on experimental animal models and observations on patients have shown that the soluble factors secreted by tumor cells and tissues of the patient can participate in regulation of the wasting process. Cachexia is often accompanied by anorexia, which is caused by predominance of signals inhibiting appetite in the hypothalamus, such as release of proopiomelanocortin and anorexigenic action of proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α). Cachexia is also accompanied by extensive metabolic changes consisting of increase of resting energy expenditure and disturbance of carbohydrate, protein and lipid metabolism. Increased expression of protein uncoupling phosphorylation leads to increased thermogenesis in skeletal muscle. Tumor tissue hypoxia caused by its growth beyond blood vessels activates the transcription factor HIF-1, which results in increase in glycolysis, and leads to lactic acid accumulation and activation of the energy inefficient Cori cycle. Loss of fat tissue is caused by increase of lipolysis induced by lipid-mobilizing factor (LMF) and proinflammatory cytokines. Skeletal muscle wasting in cachexia is caused by a reduction of protein synthesis at the stage of initiation and elongation of translation and the simultaneous increase of protein degradation via ubiquitin-dependent and lysosomal pathways. The main mediators of skeletal muscle wasting in cancer are proteolysis-inducing factor (PIF), proinflammatory cytokines, and angiotensin II acting through increased levels of reactive oxygen species (ROS) and nuclear factor NF-κB activation, as well as glucocorticoid activated FOXO transcription factors and myostatin. Understanding of the complexity of the interaction of factors produced by the tumor and the patient's body may form the basis for the development of effective treatments for cachexia in cancer and other pathological conditions.

0 (Cytokines)
0 (Interleukin-6)
0 (MSTN protein, human)
0 (Myostatin)
0 (NF-kappa B)
0 (Tumor Necrosis Factor-alpha)

Date Created: 20140205 Date Completed: 20140529 Latest Revision: 20220330

20221213

10.5604/17322693.1085135

24493689