Clinical Gastroenterology Vol.28 No.6(13)

Theme The Roles of Gut Physiological Active Peptides in the Control of Nutrition and Metabolism
Title Cancer Cachexia and Ghrelin -- Improving Cachexic Symptoms Through Potentiation of Endogenous Ghrelin Signaling
Publish Date 2013/06
Author Yasuhito Uezono Division of Cancer Pathophysiology, National Cancer Center Research Institute
Author Kiyoshi Terawaki Division of Cancer Pathophysiology, National Cancer Center Research Institute
Author Yumi Sawada Division of Cancer Pathophysiology, National Cancer Center Research Institute
Author Yohei Kashiwase Division of Cancer Pathophysiology, National Cancer Center Research Institute / Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science
Author Yuka Sudo Division of Cancer Pathophysiology, National Cancer Center Research Institute / Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science
[ Summary ] Cachexia induced by cancer is characterized by anorexia and weight loss. Associated symptoms affect the quality of life of cancer patients. To improve the symptoms of cachexia, three independent approaches are suggested ; improvement of gastrointestinal-related symptoms, control of metabolic balance and increasing the mass of skeletal muscles. Improving gastrointestinal symptoms with the orexigenic peptide ghrelin is now being examined in basic and clinical trials. Ghrelin controls gastrointestinal functions through activation of dedicated receptors. However, in patients with cancer-induced cachexia, blood ghrelin concentrations are already high, possibly due to compensatory mechanisms. Thus, they may be in a state of ghrelin resistance. Rikkunshito, a traditional Japanese Kampo medicine, has been reported to improve various gastrointestinal tract disorders due to increases in ghrelin levels. Although ghrelin and rikkunshito are anticipated to improve symptoms of cancer patients, we postulate that rikkunshito has additional mechanisms other than elevation of ghrelin concentrations. These medications may improve gastrointestinal symptoms without producing ghrelin resistance.
Our experimental results exhibited that rikkunshito potentiated ghrelin-induced cellular responses. Therefore, we conclude that rikkunshito as well as ghrelin alone may contribute to the development of novel treatments for cancer-induced cachexia conditions.
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