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Tailor-made Cancer Targeted Therapy using Real-time Biopanning Procedure -Novel Methodology in the Treatment for Advanced/Recurrent Cancer-

使用实时生物淘选程序的定制癌症靶向治疗 -治疗晚期/复发癌症的新方法 -

基本信息

批准号：
16591306
负责人：
MARUTA Fukuto
金额：
$ 2.18万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

The experiments were started after we obtained approval from institutional ethical committee and written informed consent from patients.(1) HCC-specific binding peptide was developed by biopanning procedure on HCC cell line. The identified peptide showed the binding ability on HCC derived from patients who received surgical operation (hepatectomy).(2) The ex vivo biopanning system was developped by cannulation of catheter into feeding artery and drainage vein of colorectal cancer specimens derived from patients who received surgical operation (colectomy). The phage library was injected into the system via feeding artery, and the binding peptide to colorectal cancer was identified.(3) The peptide binding to peritoneal metastasis of gastric cancer was developed using biopanning procedure on tumor-bearing mice (peritoneal injection of human gastric cancer). The peptide-conjugated phage-vector showed binding ability to cells in malignant ascites from a patient with carcinomatosa peritoniti … More s (gastric cancer) significantly more than control phage-vector. Next, the peptide-conjugated liposome (supplied by Prof.Naoto Oku, University of Shizuoka) showed binding ability to peritoneal tumor in mice significantly more than control liposome. In addition, the peptide-conjugated liposome coupled with Adriamycin showed cell-toxicity effect on gastric cancer cells in vitro significantly stronger than non-peptide liposome + Adriamycin.Three English papers regarding the above experiments are now submitting. In addition, the above results have been published in the following scientific congress with acknowledgements for support by grant from the Japan Society for the Promotion of Science : 42^<nd> Annual Congress of the Japan Society of Clinical Oncology (Symposium, 27/October/2004), 63^<rd> Annual Congress of the Japanese Cancer Association (Workshop, 30/September/2004), the 91^<st> Annual Congress of the Japanese Society of Gastroenterology (Symposium, 14/April/2005), the 13^<th> DDW Japan (Symposium, 6/October/2004), 60^<th> Annual Congress of the Japanese Society of Gastroenterological Surgery (Symposium, 2O/July/2005), and so on. Less

实验在获得机构伦理委员会批准并获得患者书面知情同意后开始。(1)通过对HCC细胞系进行生物淘选程序开发HCC特异性结合肽。鉴定出的肽显示出对来自接受外科手术（肝切除术）的患者的HCC的结合能力。（2）通过将导管插入来自接受外科手术（结肠切除术）的患者的结直肠癌标本的供血动脉和引流静脉，开发了离体生物淘选系统。通过饲喂动脉将噬菌体文库注射到系统中，鉴定出与结直肠癌的结合肽。(3)利用荷瘤小鼠（人胃癌腹膜注射）的生物淘选程序开发了与胃癌腹膜转移结合的肽。肽缀合噬菌体载体显示出与癌性腹膜炎（胃癌）患者恶性腹水中细胞的结合能力显着高于对照噬菌体载体。接下来，肽缀合脂质体（由静冈大学 Naoto Oku 教授提供）对小鼠腹膜肿瘤的结合能力显着高于对照脂质体。此外，肽脂质体与阿霉素偶联在体外对胃癌细胞的细胞毒作用明显强于非肽脂质体+阿霉素。目前正在提交有关上述实验的三篇英文论文。此外，上述结果已在以下科学大会上发表，并感谢日本学术振兴会的资助：第 42 届日本临床肿瘤学会年会（研讨会，2004 年 10 月 27 日）、第 63 届日本癌症协会年会（研讨会，2004 年 9 月 30 日）、第 91 届日本临床肿瘤学会年会（研讨会，2004 年 10 月 27 日）日本学会年会胃肠病学（研讨会，2005 年 4 月 14 日）、第 13 届 DDW 日本（研讨会，2004 年 10 月 6 日）、第 60 届日本胃肠外科学会年会（研讨会，2005 年 7 月 2O 日）等。较少的