Effective tumor regression by anti-neovascular therapy in hypovascular orthotopic pancreatic tumor model
Effective tumor regression by anti-neovascular therapy in hypovascular orthotopic pancreatic tumor model
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DOI：
10.1016/j.jconrel.2006.12.024
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发表时间：
2007-04-23
影响因子：
10.8
通讯作者：
Oku, Naoto
中科院分区：
文献类型：
--
作者：
Yonezawa, Sei;Asai, Tomohiro;Oku, Naoto
胰腺癌是最严重的癌症之一，治疗效果差，预后差。在此，我们提出了一种新的治疗胰腺癌的策略，即用阿霉素脂质体损伤有限的新生血管。首先，我们建立了一个具有胰腺肿瘤低血供特点的原位肿瘤模型。在此模型中，我们用聚乙二醇（PEG）和具有对新生血管亲和力的肽Ala-Pro-Arg-Pro-Gly（APRPG）修饰的脂质体获得了增强的治疗效果。组织化学分析表明，用APRPG-PEG-脂质体阿霉素处理后，血管生成的血管降解。此外，我们观察到荧光标记的APRPG-PEG-脂质体与血管生成内皮细胞的共定位，虽然H-3标记的脂质体的生物分布没有显示PEG修饰的脂质体和APRPG-PEG-i-nodified脂质体之间的蓄积量的差异。这些结果提示抗胰腺癌新生血管治疗的有效性，为胰腺癌化疗药物的应用提供了新的视觉指标。(c)2007 Elsevier B. V.保留所有权利。
Pancreatic cancer is one of the most serious cancers with poor therapeutic results and prognosis. In here, we proposed a novel treatment strategy of pancreatic cancer by injuring limited angiogenic vessels with liposome containing adriamycin. At first, we established an orthotopic tumor model, which has a hypovascular characteristic of pancreatic tumor. In this model, we obtained the enhanced therapeutic efficacy with liposome that modified by polyethylene glycol (PEG) and a peptide, Ala-Pro-Arg-Pro-Gly (APRPG), having an affinity to neovessels. Histochemical analysis suggested the degradation of angiogenic vessels after treatment with APRPG-PEG-liposomal adriamycin. In addition, we observed colocalization of fluorescence-labeled APRPG-PEG-liposome with angiogenic endothelial cells, although the biodistribution of H-3-labeled liposome did not show the difference in the amount of accumulation between PEG-modified liposome and APRPG-PEG-i-nodified liposome. These results suggested the availability of the anti-neovascular therapy against pancreatic cancer and supply a new sight indication on chemotherapeutics against pancreatic cancer. (c) 2007 Elsevier B.V. All rights reserved.