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老年小鼠与年轻小鼠肿瘤抗血管生成治疗的疗效

Efficacy of anti-angiogenic treatment of tumors in old versus young mice.

作者信息

Kaptzan Tatiana, Skutelsky Ehud, Itzhaki Orit, Sinai Judith, Huszar Monica, Siegal Annette, Ben-Zvi Ronen, Jossiphov Joseph, Michowitz Moshe, Schiby Ginnete, Leibovici Judith

机构信息

Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel.

出版信息

Mech Ageing Dev. 2006 Apr;127(4):398-409. doi: 10.1016/j.mad.2005.12.011. Epub 2006 Feb 14.

Abstract

Cancer treatment in the older population, the most afflicted by the disease, is as yet, inefficient. A reduced aggressiveness of tumors is often observed in the elderly, implying the necessity for therapeutic modalities adjusted to age. A rational design of age-related cancer therapy could be based on the mechanisms of this phenomenon. It is suggested that, in addition to the patient's old age-specific health problems (which prohibit the use of the aggressive cancer treatments now in use), the age-related differential tumor biology (apparently beneficial to the old) should also be considered for the design of treatment modalities suitable for the aged. Based on one mechanism of the reduced aggressiveness of tumors in the old (age-dependent decreased angiogenesis), we compared the effect of an anti-angiogenic treatment in young and old mice. TNP-470 treatment resulted in an inhibitory effect on B16 melanoma in both young and old mice but the effect was more pronounced in old animals. Moreover, a high percentage of long-term surviving animals was observed only in the old-treated mice. Treatment with TNP-470 of the AKR lymphoma produced similar results. We thus found a differential age-dependent therapeutic efficiency of an anti-angiogenic agent on two tumors. Importantly, the anti-angiogenic drug was more efficient against tumors of old animals.

摘要

癌症治疗在受该疾病影响最严重的老年人群中目前效率低下。在老年人中经常观察到肿瘤的侵袭性降低,这意味着需要有适合年龄的治疗方式。基于这一现象的机制,可以对与年龄相关的癌症治疗进行合理设计。有人提出,除了患者因年老而特有的健康问题(这使得目前使用的激进癌症治疗方法无法使用)之外,在设计适合老年人的治疗方式时,还应考虑与年龄相关的肿瘤生物学差异(显然对老年人有益)。基于老年人肿瘤侵袭性降低的一种机制(年龄依赖性血管生成减少),我们比较了抗血管生成治疗对年轻和老年小鼠的效果。TNP - 470治疗对年轻和老年小鼠的B16黑色素瘤均产生抑制作用,但在老年动物中效果更明显。此外,仅在接受治疗的老年小鼠中观察到高比例的长期存活动物。用TNP - 470治疗AKR淋巴瘤也产生了类似的结果。因此,我们发现抗血管生成药物对两种肿瘤具有不同的年龄依赖性治疗效果。重要的是,抗血管生成药物对老年动物的肿瘤更有效。

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