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

我们在获得机构伦理委员会的批准和患者的书面知情同意后开始实验。(1)通过肝癌细胞系的生物筛选，获得HCC特异性结合肽。所鉴定的肽显示出对接受外科手术（肝切除术）的患者的肝细胞癌的结合能力。(2)通过将导管置入外科手术（结肠切除术）患者的结直肠癌标本的喂养动脉和引流静脉，开发出离体生物筛选系统。将噬菌体文库经供血动脉注入系统，鉴定结直肠癌结合肽。(3)利用荷瘤小鼠（人胃癌腹腔注射）的生物筛检方法，发现了与胃癌腹膜转移的肽结合。与对照噬菌体载体相比，肽偶联噬菌体载体对胃癌恶性腹水细胞的结合能力明显增强。接下来，肽偶联脂质体（由静冈大学naoto Oku教授提供）在小鼠腹膜肿瘤上的结合能力明显高于对照脂质体。此外，肽偶联脂质体与阿霉素在体外对胃癌细胞的细胞毒性作用明显强于非肽脂质体+阿霉素。现就上述实验提交三篇英文论文。此外，上述结果已在以下科学大会上发表，并感谢日本科学促进会的资助：日本临床肿瘤学会年会（研讨会，2004年10月27日），日本癌症协会年会（研讨会，2004年9月30日），日本胃肠病学学会年会（研讨会，2005年4月14日），日本DDW年会（研讨会，2004年10月6日），日本胃肠外科学会年会（研讨会，2005年7月20日），等等。少

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