Targeting Cancer Chemotherapy : For the Control of Metastatic Liver Cancer

(1)为了传播治疗原发性癌症的最新技术，在英国伯明翰大学伊丽莎白二世医院进行了SMANCS/ lipodol与肝脏或肿瘤供血动脉的动脉注射，这种方法在欧洲是新的。(2)我们可以证实，日本开发的这种方法在英国的住院患者中同样有效。(3)英国伯明翰的肿瘤学家已经建立了对癌症化疗新概念的理解，即使肿瘤消退所需的药物量应该基于肿瘤大小，而不是旧概念中所实践的最大耐受剂量。也就是说，给药方案与肿瘤大小成正比，也与反应率平行，但与旧概念中患者的体重或表面积无关。这一理论背后的基本原理是，油性制剂的动脉给药最具选择性地靶向肿瘤（肿瘤/血液浓度的1000倍），但这种给药方式的药物分布很少被发现到其他异常组织或器官。因此，我们的系统不需要过量的药物剂量，因为过量的药物剂量会损害正常的组织或器官。(4)这些来自比里厄姆大学伊丽莎白二世医院的临床数据最近在两份期刊上发表，并于1998年6月在阿姆斯特丹举行的NCl（美国）EORTC（欧洲）联席会议上发表。(5)利用这种最有效的肿瘤传递系统，利用脂醇经肿瘤供血动脉，将干扰素- γ (ifn - γ)-聚l -赖氨酸复合物的重组DNA注射到患VX-2肝癌的家兔体内。结果表明，基因可选择性传递至肿瘤，表达β -半乳糖苷酶基因，但ifn - γ表达极少或不表达。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)在获得原发性肝癌治疗的令人信服的结果后，我们决定接近我们的最终目标；即控制结肠癌向肝脏的转移。结肠癌的首选治疗方法是手术切除，然而，约有一半的患者在手术切除肿瘤后发生肝转移。我们的方案是在手术（剖腹手术）时向门静脉注射SMANCS/ lipodol (1-2 ml)，因为考虑到在手术切除过程中会发生结肠肿瘤脱落或播散。我们在兔模型上的实验数据显示，通过门静脉注射SMANCS/ lipodol治疗门静脉SMANCS后，肿瘤转移的发生率降低到对照组的1%以下。如果我们能找到赞助商，合作研究将在六个月内启动。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