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采用综合癌症疗法靶向血管生成。

Targeting angiogenesis with integrative cancer therapies.

作者信息

Yance Donald R, Sagar Stephen M

机构信息

Center for Natural Healing, Ashland, Oregon, USA.

出版信息

Integr Cancer Ther. 2006 Mar;5(1):9-29. doi: 10.1177/1534735405285562.

Abstract

An integrative approach for managing a patient with cancer should target the multiple biochemical and physiological pathways that support tumor development while minimizing normal tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The authors will focus on natural health products (NHPs) that have a high degree of antiangiogenic activity but also describe some of their many other interactions that can inhibit tumor progression and reduce the risk of metastasis. NHPs target various molecular pathways besides angiogenesis, including epidermal growth factor receptor (EGFR), the HER-2/neu gene, the cyclooxygenase-2 enzyme, the NF-kB transcription factor, the protein kinases, Bcl-2 protein, and coagulation pathways. The herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are confirming the knowledge that is already documented in traditional texts. The following herbs are traditionally used for anticancer treatment and are antiangiogenic through multiple interdependent processes that include effects on gene expression, signal processing, and enzyme activities: Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (turmeric), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinale (ginger), Panax ginseng, Rabdosia rubescens (rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking on clinical trials. More data are required on dose response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as biological response modifiers and adaptogens, potentially enhancing the efficacy of the so-called conventional therapies. Their effectiveness may be increased when multiple agents are used in optimal combinations. New designs for trials to demonstrate activity in human subjects are required. Although controlled trials might be preferred, smaller studies with appropriate end points and surrogate markers for antiangiogenic response could help prioritize agents for the larger resource-intensive phase 3 trials.

摘要

管理癌症患者的综合方法应针对支持肿瘤发展的多种生化和生理途径,同时将正常组织毒性降至最低。血管生成是促进癌症发展的关键过程。许多抑制血管生成的天然健康产品也表现出其他抗癌活性。作者将重点关注具有高度抗血管生成活性的天然健康产品(NHPs),同时也描述它们的许多其他相互作用,这些相互作用可以抑制肿瘤进展并降低转移风险。NHPs除了作用于血管生成外,还靶向多种分子途径,包括表皮生长因子受体(EGFR)、HER-2/neu基因、环氧合酶-2酶、NF-κB转录因子、蛋白激酶、Bcl-2蛋白和凝血途径。草药医生可以获取数百年关于许多草药抗癌活性的观察数据。实验室研究正在证实传统文献中已记载的知识。以下草药传统上用于抗癌治疗,并且通过多种相互依存的过程具有抗血管生成作用,这些过程包括对基因表达、信号处理和酶活性的影响:青蒿(中国艾草)、欧洲槲寄生、姜黄、黄芩、白藜芦醇和原花青素(葡萄籽提取物)、厚朴(中国木兰树)、茶树(绿茶)、银杏、槲皮素、茯苓、生姜、人参、冬凌草以及中国的消滞草药。在开展临床试验之前,确保适当提取物的质量至关重要。需要更多关于剂量反应、合适组合和潜在毒性的数据。鉴于这些药物的多种作用,它们未来在癌症治疗中的应用可能在于协同组合。在积极的癌症治疗期间,通常应将它们与化疗和放疗联合评估。在这种情况下,它们作为生物反应调节剂和适应原,有可能提高所谓传统疗法的疗效。当多种药物以最佳组合使用时,其有效性可能会增加。需要新的试验设计来证明在人体中的活性。虽然对照试验可能更可取,但具有适当终点和抗血管生成反应替代标志物的小型研究可以帮助为大型资源密集型3期试验确定药物的优先顺序。

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