Targeting Cancer Chemotherapy : For the Control of Metastatic Liver Cancer

(1)为了传播治疗原发癌症的最新技术，英国伯明翰大学伊丽莎白二世医院进行了SMANCS/碘化油与肝脏或肿瘤供血动脉的动脉插入术。这种方法在欧洲是新的。(2)我们可以证实，这种由日本发展的方法在英国住院患者中也同样有效。(3)英国伯明翰的肿瘤学家现在已经对癌症化疗的新概念建立了理解。也就是说，剂量方案与肿瘤大小成正比，这也与应答率平行，而不是像旧观念中那样，患者的体重或表面积。这一理论背后的理论基础是，动脉注射油性制剂最有选择性地针对肿瘤(肿瘤/血液浓度是肿瘤的1000倍)，但…更多的是给药方式，在正常组织或器官中很少有药物分布到其他地方。(4)这些临床数据最近发表在两本杂志上，以及1998年6月在阿姆斯特丹举行的NCL(美国)EORTC(欧洲)联席会议上。(5)利用这一最有效的肿瘤给药系统，通过肿瘤供血动脉，将重组的干扰素-γ-多聚L-赖氨酸复合体注射到荷VX-2肝癌的兔体内。结果表明，表达β-半乳糖苷酶基因的基因被选择性地输送到肿瘤组织中，而干扰素-γ基因的表达很少或不表达。这表明，增强和持续的基因表达是目前基因治疗的关键问题，但还为时过早。(6)在对原发性肝癌的治疗取得令人信服的结果后，我们决定接近我们的最终目标，即控制结肠癌的肝脏转移。结肠癌的首选治疗方法是手术切除，但手术切除的患者中约有一半发生肝转移。我们的方案是在手术(肾癌手术)时向门静脉注射SMANCS/碘化油(1-2毫升)，因为人们认为在手术切除过程中会发生结肠癌的脱落或扩散。我们利用兔模型的实验数据显示，经门静脉注射SMANCS/碘化油后，肿瘤转移率降至对照组的1%以下。合作研究将在六个月内启动，如果我们可以找到赞助商的话。较少

(1)To disseminate the state of the art for the treatment of primary cancer, the arterialinlection of SMANCS/Lipiodol with the hepatic or tumor feeding artery was performed at Queen Elizabeth II Hospital of the University of Birmingham, U.K.This method was new in Europe.(2)We could confirm that this method, developed in Japan, is similarly effective inpatients in U.K.(3)The understanding of the new concept for cancer chemotherapy is now established among oncologists in Birmingham, U.K.Namely, the amount of drug needs to result in regression of tumor should be based on the tumor size but not maximum tolerable dose as practiced in old concept. That is, dose regimen is proportional to the tumor size, which is also parallel to the response rate, but not body weight or surface area of the patients as in old concept. The rationale behinds this theory is that arterial administration of oily formulation is most selectively targeted to the tumor (> 1000-fold in tumor/blood concentration), but th … More is delivery method drug distribution was found of very little to elsewhere innormal tissues or organs. Thus, excessive amount of drug dosage is not needed in our system, which could damage normal tissues or organs.(4)These clinical data from Queen Elizabeth II Hospital of the University of Biririgham were reported recently in two journals, and also in Joint Meeting of NCl (USA) EORTC (Europe) in June, 1998, Amsterdam.(5)Utilizing this most effective tumor delivery system using lipiodol via tumor feeding artery, recombinant DNA of interteron-gamma (IFN-gamma)-poly L-lysine complex was injected into rabbit bearing VX-2 carcinoma in the liver. The result showed that gene was delivery to the tumor selectively, which expressing beta-galactosidase gene, but expression of IFN-gamma was very little or none. This indicates that enhanced and sustained gene expression is the key issue at this point for gene therapy, and yet premature.(6)After obtaining a convincing result for the treatment of the primary liver cancer, we decided to approach our final goal ; that is, the control of colon cancer metastasis to the liver. The first choice of the treatment of colon cancer is surgical resection, however, about half of the patients undergo surgical removal of tumor develops liver metastasis. Our protocol is to inject SMANCS/Lipiodol (1-2 ml) into the portal vein upon surgery (laporatomy) because it is considered that colon tumor shedding or dissemination occurs during the surgical resection. Our experimental data using rabbit model showed that the incidence of cancer metastasis is reduced to less than 1 % of control without portal SMANCS treatment by SMANCS/Lipiodol via the portal vein. The collaborative study will be initiated within six months it we could find a sponsor. Less