英文摘要翻译

2011硕士四教D1班学号：21100777 专业：药物化学

摘要一

文章来源：CANCER（Cancer CytoPath-ology）,June15,2004/V olume

100/Number12,Pages 2491-2499;2010SCI影响因子：5.131

Dietmar W. Siemann, Ph.D. David J. Chaplin, Michael R. Horsman, Ph.D., D.M.S Ph.D .Supported by the cancer Institute (Public Health Service Grants CA84408 and CA89655)and the Danish Cancer Society.

Vascular-Targeting Therapies for Treatment of Malignant Disease

血管靶向疗法治疗恶性瘤

ABSTRACT摘要

Background: Tumor endothelium represents a valuable target for cancer therapy. The vasculature plays a critical role in the survival and continued growth of solid tumor masses; in addition, the inherent differences between tumor blood vessels and blood vessels associated with normal tissue make the tumor vasculature a unique target on which to base the design of novel therapeutics, which may allow highly selective treatment of malignant disease. Therapeutic strategies that target and disrupt the already formed vessel networks of growing tumors are actively being pursued. The goal of these approaches is to induce a rapid and catastrophic shutdown of the vascular function of the tumor so that blood flow is arrested and tumor cell death due to the resulting oxygen and nutrient deprivation and buildup of waste products occurs. 背景：肿瘤的内皮细胞在癌症治疗中是一个非常重要的靶位。其脉管分布对实体肿瘤的生存和持续增长至关重要;此外,肿瘤血管和正常组织血管的内在差异使

得肿瘤脉管系统成为一个独特的靶位，并可以此为基础来设计高选择性的新型恶性瘤的治疗方法。靶向阻断肿瘤组织已有血管脉络的进一步生长的疗法备受推崇。上述疗法的最终目的是诱导肿瘤血管功能的快速和彻底丧失，从而切断其氧气和营养物质的供应，并导致代谢废物大量累积。

Methods: Biologic approaches and small-molecule drugs that can be used to damage tumor vasculature have been identified. Physiologic, histologic/morphologic, and immunohistochemical assessments have demonstrated that profound disruption of the tumor vessel network can be observed minutes to hours after treatment. The small-molecule agents that have made the greatest advances in the clinical setting(5,6-dimethylxanthenone-4-acetic acid [DMXAA], combretastatin A4 disodium phosphate [CA4DP], and ZD6126) are the focus of the current review.

方法：生物方法和小分子药物已经证明可以用来破坏肿瘤血管。生理学、组织学（形态学）和免疫学评估表明治疗后数分钟至数小时，肿瘤血管网络被完全破坏。小分子药物(如5,6-dimethylxanthenone-4-acetic acid [DMXAA], combretastatin A4 disodium phosphate [CA4DP], and ZD6126)在临床应用上的进展已成为现在的研究焦点。

Results: Loss of patent blood vessels, decreased tumor blood flow, extensive necrosis, and secondary ischemia-induced tumor cell death have been well documented in a variety of preclinical tumor models treated with agents such as DMXAA, CA4DP, and ZD6126. The use of such agents in conjunction with irradiation and other chemotherapeutic agents has led to improved treatment outcomes.

结果：在临床前期肿瘤模型中用DMXAA, CA4DP,和ZD6126等药物治疗后发现，其肿瘤血管被破坏，血流量减少，出现广泛坏死，局部缺血致使肿瘤细胞死亡。这类药物与放疗以及其他化疗药物联用可增强治疗效果。

Conclusions: The targeting of tumors’ supportive blood vessel networks could lead to improvements in cancer cure rates. It is likely that this approach will prove to be most efficacious when used in concert with conventional treatment strategies.

结论：以维持肿瘤生长的血管网络系统为靶点可提高癌症治愈率，该方法与传统的疗法相结合可能是最有效的。

摘要二

文章来源：Clinical Oncology, (2005) 17: 277–290;2010SCI影响因子：2.293 Department of Medical Oncology, Mount Vernon Cancer Centre, North-

wood, Middlesex, UK

Vascular Disrupting Agents: A New Class of Drug in Cancer Therapy

肿瘤血管生长抑制剂：一种新型癌症治疗方法

ABSTRACT摘要

Aims: To provide a comprehensive overview of the current state of development of a novel class of anti-cancer drugs, the vascular Disrupting agents (VDAs), previously known as vascular targeting agents (VTAs).

目的：为当前新型抗癌药物做一个全面的综述，肿瘤血管生长抑制剂（VDAS）曾被称为肿瘤血管靶向药物（VTAs）

Materials and methods: A comprehensive review, analysis and commentary of the published medical literature on VDAs was performed

材料与方法：全面概述，分析和评估与VDAs有关的已发表医学文献。Results: Tumour vascular targeting therapy exploits known differences between normal and tumour blood vessels. VDAs target the preexisting vessels of tumours (cf anti-angiogenics), and cause vascular shutdown leading to tumour cell death and rapid haemorrhagic necrosis within hours. It is becoming clear that VDAs have overlapping activity with anti-angiogenic drugs, which prevent the formation of new blood vessels. There are two types of VDA. First, biological or ligand-directed VDAs use antibodies, peptides or growth factors to target toxins or procoagulants to the tumour endothelium. In contrast, small molecule VDAs work either as tubulin-binding agents or through induction of local cytokine production. VDAs can kill tumour cells resistant to conventional chemotherapy and radiotherapy, and work best on cells in the poorly perfused hypoxic core of tumours, leaving a viable rim of well-perfused tumour tissue at the periphery, which rapidly regrows. Consequently, responses of tumours to VDAs