Manabe Tatsuya, Okino Hidenobu, Maeyama Ryo, Mizumoto Kazuhiro, Nagai Eishi, Tanaka Masao, Matsuda Takehisa
Division of Biomedical Engineering, Graduate School of Medicine, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
J Control Release. 2004 Dec 10;100(3):317-30. doi: 10.1016/j.jconrel.2004.09.007.
Local recurrence and hepatic metastasis are still the major causes of death of patients who have undergone resection for pancreatic cancer. To decrease the incidence of local recurrence, we have proposed and devised several trans-tissue and local delivery systems, all of which could be applied immediately after surgery at the resected sites: (1) System I: a drug-loaded photocured gelatinous tissue-adhesive gel (bioactive substance reservoir) that enables the sustained release of a drug, protein, or gene-encoding adenovirus, (2) System II: an anti-cytokine antibody-fixed photocured gelatinous, tissue-adhesive gel (cytokine barrier) that prevents cytokine permeation into the resected tissue, (3) System III: a gene-modified cell sheet that enables the sustained release of a very costly protein produced by gene-transduced cells and (4) System IV: a percutaneous drug-delivery device that enables continuous drug infusion and easy removal from the body. This review article is a summary of our several years of efforts and attempts, which are composed of integrated disciplines including active biomaterials and genetic- and tissue-engineerings, to overcome the recurrence of pancreatic cancer. Here, we outline our proposed strategies and therapeutic devices/materials and discuss their potential therapeutic effectiveness, promises and challenges in the clinical settings.
局部复发和肝转移仍然是接受胰腺癌切除术患者的主要死亡原因。为了降低局部复发率，我们提出并设计了几种跨组织和局部给药系统，所有这些系统都可以在手术后立即应用于切除部位：（1）系统I：一种载药的光固化凝胶状组织黏附凝胶（生物活性物质储存库），能够持续释放药物、蛋白质或编码腺病毒的基因；（2）系统II：一种固定有抗细胞因子抗体的光固化凝胶状组织黏附凝胶（细胞因子屏障），可防止细胞因子渗透到切除组织中；（3）系统III：一种基因修饰的细胞片，能够持续释放由基因转导细胞产生的非常昂贵的蛋白质；（4）系统IV：一种经皮给药装置，能够持续输注药物并易于从体内取出。这篇综述文章总结了我们多年来的努力和尝试，这些努力和尝试由包括活性生物材料以及基因和组织工程在内的综合学科组成，旨在克服胰腺癌的复发。在此，我们概述我们提出的策略以及治疗装置/材料，并讨论它们在临床环境中的潜在治疗效果、前景和挑战。
