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Is inflammation resolution failing in adipose tissue of cachectic patients?

Grant number: 13/25207-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): February 01, 2014
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Marilia Cerqueira Leite Seelaender
Grantee:Katrin Radloff
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/50079-0 - Systemic inflammation in cachectic cancer patients: mechanisms and therapeutical strategies, a translational medicine approach, AP.TEM
Associated scholarship(s):16/09988-7 - Modulation by the fatty acid profile of inflammatory macrophage activity in cancer cachexia: consequences on cell function, BE.EP.DD


Cancer associated Cachexia is characterized by a progressive loss of muscle tissue and frequently of adipose tissue as well. Furthermore Cachexia is not only accompanied but also supposed to be partially caused by systemic inflammation leading to a low performance of cancer patients and an increased mortality. Elevated pro-inflammatory cytokines such as TNF-±, IL-6, IL-1² or IFN-³ are characteristic for systemic inflammation and are involved in metabolic changes, impairment of food intake and the degradation of tissue. During Cachexia the adipose tissue releases more fatty acids, potential precursor molecules for production of bioactive lipid compounds such prostaglandins and resolvins or lipoxins. Resolvins and lipoxins are already shown to resolve inflammation in other illnesses such as peritonitis. The adipose tissue itself contributes to the systemic inflammation and Cachexia in order to the increased immigration of macrophages and release of inflammation markers. We are hypothesizing that an improvement of the inflammatory processes in the adipose tissue could result in a systemic decrease of pro-inflammatory cytokines and an amelioration of cancer Cachexia. Thus we aim to resolve the inflammation of the adipose via treatment with resolvins and other lipid mediators. Therefore we evaluate the distribution patterns of lipid mediators in the adipose tissue of cachectic and non cachectic patients. Furthermore try to induce inflammation resolution via incubating adipose tissue explants with pro resolving compounds in an ex-vivo approach. (AU)