Effect of Transfection with Human Interferon-β Gene Entrapped in Cationic Multilamellar Liposomes in Combination with 5-Fluorouracil on the Growth of Human Esophageal Cancer Cells

阳离子多层脂质体转染人干扰素-β基因联合5-氟尿嘧啶对人食管癌细胞生长的影响

基本信息

批准号：
15591397
负责人：
KODERA Yasuhiro
金额：
$ 1.92万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Antiproliferative potencies of humanrecombinantinterferon-β(hIFNβ) geneentrappedin cationic multilamellar liposomes (IAB-1) alone and in combination with antineoplastic agentswasevaluated, using a human esophageal cancer xenograft in vivo.hIFNβ or IAB-1 were injected into the subcutaneous tumor derived from a human esophageal cancer cell line, WSSC, in the dorsal flank of nude mice. Tumors were harvested 24 hours and 48 hours following the injection, and intratumoral concentrationof hIFNβ was quantified by ELISA. hIFNβ was detectable only in mice treated with IAB-1, suggesting that the production of hIFNβ as a result of gene transfection actually took place.Xenografts were then treated by intratumoral injection of IAB-1 alone and in combination with intraperitoneal 5FU or oral S-1,all at appropriatedoses. Onlyweak antiproliferative effects were observed, even with the combined treatments. Xenografts were then treated by intratumoral IAB-1, radiation (a single boost of 2 Gy on day 1), and a combination of IAB-1 and radiation. Although the treatment with radiation alone had little effect, a combination with radiation and IAB-1 exhibited an astonishing antiproliferative effect and the disease was stabilized for morethan 3 weeks. No adverse reaction in terms of significant body weight loss was observed in any of the treatment groups in comparison with the control mice. Current findings will become valuable information for clinical application of IAB-1 for patients with locally advanced esophageal cancer.

单独使用人类重组互入剂β（HIFNβ）的抗增殖功能，单独使用抗肿瘤的阳离子多层脂质体（IAB-1），并结合抗塑性的定位，并结合抗塑料的定位，使用人类癌症中的人类酸nifnbosogy.hifnbosogy.hifnbotem.hifnβ摄取的癌症。线，WSSC，在裸鼠的背侧。注射后24小时48小时收集肿瘤，并通过ELISA定量HIFNβ的肿瘤内浓度。仅在用IAB-1处理的小鼠中检测到HIFNβ，这表明实际上发生了基因转化的HIFNβ的产生。然后通过肿瘤内注射IAB-1单独注射IAB-1并与腹膜内5FU或口服S-1结合进行治疗。即使使用综合治疗，也只观察到只观察到伴随抗增生剂的作用。然后通过肿瘤内IAB-1，辐射（第1天的2 Gy提升）和IAB-1和辐射的组合处理异种移植物。尽管仅用辐射治疗几乎没有效果，但与辐射和IAB-1的结合暴露了惊人的抗增殖作用，疾病稳定了3周。与对照小鼠相比，在任何治疗组中，在任何治疗组中均未观察到体重减轻的不利反应。目前的发现将成为IAB-1临床应用的有价值信息，以在局部晚期食管癌患者中使用。