2014-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656461摘要：全世界每年有幾百萬人死於癌症，因此癌症仍是目前醫學重要課題。癌症病人的存活期是癌症病人照顧非常重的指標。癌症的期別、惡病質以及身體功能是癌症病人存活期的重要決定因子。影響癌症病人存活期的最重要原因之一就是慢性發炎反應。發炎反應就是導致癌症惡病質能量平衡失調的重要原因。單核球及巨噬細胞扮演重要的角色。它們會跟癌細胞發生交互作用，同時釋放許多發炎細胞激素造成肌肉及脂肪組織的消瘦，導致惡病質的產生。因此發炎細胞激素的不當製造或功能異常是造成惡病質的重要原因。許多證據顯示癌症病人周邊血液單核球及癌組織內的巨噬細胞功能不但會受到腫瘤的影響，而且跟癌症的進程及病人的預後有關。而且周邊血液單核球被證實跟將來變成的巨噬細胞有類似的表現。脂締素是具有抗發炎作用及抑制癌細胞的脂肪專一性細胞激素。過去我們已經發表單核球不僅會表現的脂締素，而且會抑制單核球的黏著作用。今年我們更發表了胃癌病人周邊血液單核細胞表現脂締素的量和病人存活期呈現正相關，強化了癌症病人單核球功能的改變跟病人預後有關的證據。目前我們又進一步發現胃癌病人單核細胞表現脂締素的量明顯和腫瘤壞死因子正相關，同時也與病人的存活期有關。我們實驗室研究也證實腫瘤壞死因子會增加巨噬細胞脂締素的表現。我們需要進一步研究癌細胞或發炎反應影響單核球表現脂締素的機轉及其對單核球分化極性與腫瘤進程的關係。同時探討單核球表現脂締素對癌症惡病質中肌肉、脂肪組織及肝臟代謝的影響。研究結果有助於癌症病人預後的評估、癌症治療效果的評估及發展癌症免疫治療的基礎。 <br> Abstract: Cancer is a great challenge in medicine, because several million people die of cancer each year. Survival is an important outcome indicator in the care of cancer patients. Tumor stage, presence of cachexia and functional performance have been shown to be important factors for survival in cancer patients. Cancer cachexia is a situation of disturbances in energy homeostasis. Monocytes and macrophages have been shown to be important roles in cancer cachexia. They interact with cancer cells and secret proinflammatory cytokines, resulting in metabolic disturbances. Abnormal production and dysfunction of these cytokines plays an important role in cancer cachexia. Several lines of evidence have demonstrated that functions of circulating monocytes and tumor-associated macrophages are altered in cancer patients, which is closely associated with cancer progression. In addition, blood monocytes from tumor-bearing mice are similar to the macrophages they later become. Adiponectin is an important adipocyte-specific adipokine with anti-inflammatory and anti-cancer properties. We had published that monocyte-expressed adiponectin inhibits monocyte adhesion. This year, we published that adiponectin mRNA levels in peripheral mononuclear cells are positively correlated with survival in gastric cancer patients. Thus, these results reinforce survival is related to the altered monocyte functions in cancer patients. We have found that adiponectin mRNA levels in peripheral mononuclear cells are positively correlated with those of tumor necrosis factor alpha in gastric cancer patients. Tumor necrosis factor alpha mRNA in peripheral mononuclear cells are also correlated with survival in gastric cancer patients. Thus, we will further investigate the mechanism for cancer and inflammatory cells to regulate adiponectin expression in monocytes/macrophages, and the roles of monocyte-expressed adiponectin in monocyte/macrophage functions, differential polarization and cancer progression. Meanwhile, we will investigate the role of adiponectin expressed by monocytes/macrophages in metabolic disorders of skeletal muscle, adipose tissue and liver in cancer cachexia. In addition to prognostic prediction, the results may be outcome indicators of anti-cancer therapy. Furthermore, to regulate adiponectin expression in monocytes/macrophages may be potential strategies for cancer treatment.癌症惡病質存活期巨噬細胞單核球細胞激素脂締素cancercachexiasurvivalmacrophagemonocytecytokineadiponectin