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癌症代谢与线粒体功能障碍、疲劳及癌症治疗不良反应的分子替代疗法

Molecular Replacement for Cancer Metabolic and Mitochondrial Dysfunction, Fatigue and the Adverse Effects of Cancer Therapy.

作者信息

Nicolson Garth L, Conklin Kenneth A

机构信息

Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA 92647

Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, U.S.A.

出版信息

Cancer Genomics Proteomics. 2006 May-Aug;3(3-4):159-168. Epub 2006 Jan 1.

Abstract

During cancer treatment drug-induced oxidative stress can limit the effectiveness of therapy and cause a number of side effects such as fatigue, nausea, vomiting and diarrhea, as well as more serious adverse effects including cardiomyopathy, peripheral neuropathy, hepatotoxicity and pulmonary fibrosis. Many of these adverse effects are due to oxidative stress-mediated damage to normal tissues. Antioxidant administration and molecular replacement can mitigate the damage to normal tissues and reduce the adverse effects of cancer therapy without loss of therapeutic potential. For example, loss of efficiency in the electron transport chain caused by membrane peroxidation and reduction in coenzyme Q can occur during cytotoxic therapy. Molecular replacement of membrane lipids and enzymatic cofactors administered as nutritional supplements with antioxidants can prevent oxidative membrane damage and reduction of cofactors in normal tissues, restore mitochondrial and other cellular functions and reduce the adverse effects of cancer therapy. Recent clinical trials using cancer and non-cancer patients with chronic fatigue have shown the benefit of Molecular Replacement Therapy plus antioxidants in restoring mitochondrial electron transport function, reducing moderate to severe chronic fatigue and protecting mitochondrial and other cellular structures and enzymes from oxidative or other damage due to cytotoxic therapy.

摘要

在癌症治疗期间,药物诱导的氧化应激会限制治疗效果,并引发一系列副作用,如疲劳、恶心、呕吐和腹泻,以及更严重的不良反应,包括心肌病、周围神经病变、肝毒性和肺纤维化。这些不良反应中的许多都是由于氧化应激介导的对正常组织的损害。给予抗氧化剂和进行分子替代可以减轻对正常组织的损害,并减少癌症治疗的不良反应,同时不损失治疗潜力。例如,在细胞毒性治疗期间,可能会发生由膜过氧化和辅酶Q减少导致的电子传递链效率降低。用抗氧化剂作为营养补充剂对膜脂质和酶辅因子进行分子替代,可以防止正常组织中的氧化膜损伤和辅因子减少,恢复线粒体和其他细胞功能,并减少癌症治疗的不良反应。最近针对患有慢性疲劳的癌症患者和非癌症患者进行的临床试验表明,分子替代疗法加抗氧化剂在恢复线粒体电子传递功能、减轻中度至重度慢性疲劳以及保护线粒体和其他细胞结构及酶免受细胞毒性治疗引起的氧化或其他损伤方面具有益处。

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