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脂质 A 的抗肿瘤作用,临床研究。

Antitumoral effects of lipids A, clinical studies.

机构信息

Clinical Pharmacology Unit & Laboratory of Cardiovascular Experimental Physiology and Pharmacology, Faculty of Medicine, 7 Bd Jeanne d'Arc, BP87900, 21079 Dijon, France.

出版信息

Adv Exp Med Biol. 2010;667:125-31. doi: 10.1007/978-1-4419-1603-7_11.

DOI:10.1007/978-1-4419-1603-7_11
PMID:20665205
Abstract

Cancer remains the second leading cause of death, after cardiovascular diseases, in industrialized countries. The first goal to achieve is to prevent cancer occurrence or to diagnose it at an early and curable stage. Some screening strategies have been developed, with controversies across countries, for several cancer type; colorectal, breasts or prostate cancer for example.Treatment of cancer is generally based on surgery and radiotherapy for localized and attainable tumors, associated, in some cases, with adjuvant chemotherapy. Chemotherapy can also be used as first line treatment for disseminated diseases.The formulation of therapeutic strategies to enhance immune-mediated tumor destruction is a central goal of cancer immunology. Substantive progress toward delineating the mechanisms involved in innate and adaptive tumor immunity has improved the prospects for crafting efficacious treatments LPS and their active component lipid A, have been used in tumor therapy since the 19th century.Studies in animal models have shown promising results on different models of cancer but data from human trial are scarce. The published Phase-1 cancer studies have shown that lipid A analogues are usually well tolerated, most of the side effects being likely related to immune response, i. e., fever, chills and rigor. The administration of several lipids A analogues was shown to result in a significant increase in circulating levels of several cytokines but no objective antitumor responses were observed. Therefore clinical activity of such molecules deserves further experiments, likely in conjunction with chemotherapy.

摘要

在工业化国家,癌症仍然是仅次于心血管疾病的第二大死亡原因。首要目标是预防癌症的发生,或在早期和可治愈阶段诊断癌症。针对几种癌症类型(例如结直肠癌、乳腺癌或前列腺癌)已经制定了一些筛查策略,但在各国存在争议。癌症的治疗通常基于手术和放疗,适用于局部和可达到的肿瘤,并在某些情况下与辅助化疗联合使用。化疗也可用于治疗扩散性疾病。制定增强免疫介导的肿瘤破坏的治疗策略是癌症免疫学的核心目标。在阐明先天和适应性肿瘤免疫中涉及的机制方面取得了实质性进展,提高了制定有效治疗方法的前景。脂多糖及其活性成分脂 A 自 19 世纪以来就已用于肿瘤治疗。动物模型研究显示出不同癌症模型的有希望的结果,但人类试验数据很少。已发表的 I 期癌症研究表明,脂 A 类似物通常耐受性良好,大多数副作用可能与免疫反应有关,即发热、寒战和肌强直。几种脂 A 类似物的给药导致几种细胞因子的循环水平显著增加,但未观察到客观的抗肿瘤反应。因此,此类分子的临床活性值得进一步实验,可能与化疗联合进行。

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