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癌症恶病质的病理生理学和草药的转化研究。

Cancer cachexia pathophysiology and translational aspect of herbal medicine.

机构信息

Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.

出版信息

Jpn J Clin Oncol. 2013 Jul;43(7):695-705. doi: 10.1093/jjco/hyt075. Epub 2013 Jun 4.

Abstract

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.

摘要

大约一半的癌症患者表现出恶病质综合征,其特征为厌食和脂肪组织及骨骼肌质量的丧失。许多细胞因子被认为在癌症恶病质的病因中起作用。细胞因子可以引发类似于瘦素信号的作用,并抑制食欲肽 ghrelin 和神经肽 Y 的信号,导致持续的厌食和恶病质,而没有通常的代偿反应。此外,细胞因子与癌症相关的肌肉消耗有关。具体而言,肿瘤坏死因子-α、白细胞介素-1、白细胞介素-6 和干扰素-γ已被牵涉到诱导癌症相关的肌肉消耗。细胞因子诱导的骨骼肌消耗可能是一个多因素的过程,涉及蛋白质合成的抑制、蛋白质降解的增加或两者的结合。癌症患者遭受身体功能、对癌症治疗的耐受性和生存能力的降低,而许多有效的癌症化疗药物都存在毒性,这些毒性会降低患者的生活质量或阻碍其有效使用。草药已被广泛用于帮助改善这些状况。最近的研究表明,例如六君子汤等草药可以增强 ghrelin 信号,从而改善与癌症或癌症化疗相关的恶心、食欲减退和恶病质,提高患者的生活质量和预期寿命。能够针对多个靶点的多成分草药可能对未来的药物发现有用。机制研究和活性化合物的鉴定可能会导致生物和生物医学科学的新发现。

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