METABOLIC IMPLICATIONS OF DIETARY ARGININE SUPPLEMENTS

膳食精氨酸补充剂的代谢影响

• 批准号: 2873495
• 负责人: Peter James Garlick
• 金额: $ 5万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2873495
• 关键词: aminoacid metabolism; arginine; cell proliferation; clinical research; dietary aminoacid; dietary supplements; human subject; human therapy evaluation; laboratory mouse; laboratory rat; neoplasm /cancer nutrition therapy; nonhuman therapy evaluation; nutrition related tag; proliferating cell nuclear antigen; protein biosynthesis

Dietary supplements of L-arginine have heen shown tO have a variety of potentially beneficial effects in animals and humans, including enhancement of the immune system, wound healing, recovery from surgery, and Inhibition of tumor growth. Consequently, arginine supplements have heen suggested for infection, trauma and cancer, as well as for a number of other conditions. However, the evidence of tumor inhibition obtained from cancer bearing animnls is paradoxical, with some studies indicating a stimulation rather than an inhibition of tumor growth by arginine. The only study to date in humans showed an enhancement of tumor protein synthesis and Ki67 expression when arginine supplements (3Ogid for 3d) were given to patients with breast cancer. In contrast, preliminary data from patients with head and neck cancer showed that arginine did not stimulate the tumor, suggesting that the effects of arginine supplements might be tumor type specific. Arginine supplements might therefore be used to advantage in some cancer patients to improve recovery from surgery, immunity and wound healing, but this surgery, immunity and wound healing, but this requires additional Knowledge of arginine's effects on human tumors other than those of the breast, as well as its effect on normal tissues. It is therefore proposed to investigate how arginine supplements influence protein synthesis rates and cell proliferation markers (Ki67 and proliferating cell nuclear antigen) in different malignant tumors and healthy tissues of surgical patients. Arginine supplements will be taken for three days and tissues will be sampled at surgery after injection of [2H5]phenyialanine. In a second experiment, tumors will he disaggregated and separate measurements made on malignant and tumor infiltrating cells, to examine whether it is the cancer or the host defences that are stimulated by arginine. A third experiment will test the assumption that the increase m tumor protein synthesis and cell proliferation resulting from arginine supplementation truly indicates a stimulation of tumor growth. In anir)l models of cancer, changes in tumor growth resulting from vaiiiations in dietary arginine intake will be correlated with changes in protein synthesis and cell proliferation. The ensuing knowledge will fill an existing void on the metabolic effects of dietary argliiine supplements on human tissues, and will provide information which is crucial if we are to realize the therapeutic potential of arginine, yet avoid harmful side effects.

L-精氨酸的饮食补充剂已显示出有多样性的Heen 对动物和人类的潜在有益影响，包括 免疫系统的增强，伤口愈合，从 手术和抑制肿瘤生长。因此，精氨酸 补充剂Heen建议感染，创伤和癌症，因为 以及许多其他条件。但是，证据 从癌症的动画中获得的肿瘤抑制是悖论性的， 一些研究表明刺激而不是抑制 精氨酸的肿瘤生长。迄今为止在人类的唯一研究表明 肿瘤蛋白合成和Ki67表达的增强 给予乳房患者的精氨酸补充剂（3D 3D） 癌症。相反，头颈患者的初步数据 癌症表明精氨酸没有刺激肿瘤，表明 精氨酸补充剂的作用可能是特定于肿瘤类型的。 因此，精氨酸补充剂可以用来在某些 癌症患者可以改善手术，免疫力和 伤口愈合，但是这种手术，免疫力和伤口愈合，但 需要更多了解精氨酸对人肿瘤的影响的知识 除了乳房及其对正常组织的影响。它 因此建议研究精氨酸如何补充 影响蛋白质的合成速率和细胞增殖标记（KI67 和在不同恶性肿瘤中增殖的细胞核抗原） 和外科患者的健康组织。精氨酸补充剂将是 服用三天，组织将在手术中采样 注射[2H5]苯丙氨酸。 在第二个实验中，肿瘤将 他分解了对恶性肿瘤和 肿瘤浸润细胞，检查是癌症还是宿主 精氨酸刺激的防御。第三个实验将测试 假设增加了M肿瘤蛋白合成和细胞 精氨酸补充产生的增殖确实表明 刺激肿瘤生长。在癌症模型中，变化 饮食精氨酸摄入量导致的肿瘤生长将 与蛋白质合成和细胞增殖的变化相关。 随后的知识将填补代谢的现有空隙 饮食中补充剂对人体组织的影响，并将 提供信息，如果我们要实现治疗性至关重要 精氨酸的潜力，但避免有害副作用。