Development of an Endoscopic System for Treating cancerous lesions by Immunological - and medico - technological Modification of Tissue Microcirculation.

本研究的目的是研究胃肠道紊乱组织的原位微循环，特别是在癌症和相关病变如肝硬化、慢性活动性肝炎、肠化生和腺瘤中的微循环，并阐明微循环在胃肠道细胞增殖和分化中的作用。此外，研究微循环免疫系统与组织或细胞功能障碍及其从无序状态修复过程的关系。首先，我们用体内显微镜过滤系统制作了组织氧合的图像。同时，结合显微图像对组织血容量和氧含量进行了显微分光光度分析。通过建立新的细胞修复模型，分析了分离培养的肝细胞双体和胃粘膜细胞（包括癌细胞）的增殖和分化情况，研究了各种细胞因子、生长因子、血管活性药物以及影响细胞-细胞通讯的药物等新开发药物的作用。最后，与奥林巴斯公司合作开发了一种新型的用于测量组织血容量和组织氧合水平的电子内窥镜模型，目前用于研究组织微循环变化，包括免疫小体的粘附和滚动与组织或细胞修复的关系，以及胃肠道细胞的增殖和去分化。

The aim of this research project was to investigate the micro-circulation in situ in the disorganized gastroenterological tissues especially in cancers and the related lesions like liver cirrhosis, chronic active hepatitis, intestinal metaplasia and adenomas and to clarify the role of microcirculation in proliferation and differentiation of the GI cells. Further, the microcirculatory immune systems was studied in relation with the processes of tissue or cellular dysfunction and of their repair from disorganized condition. First we made images of tissue oxygenation by using an in vivo microscope-filtering system. Also, microspectrophotometric analysis of tissue blood volume and oxygenation coupled with the microscopic images was made. The proliferation and differentiation of isolated and cultured hepato-cyte doublets and gastric mucosal cells including cancer cells were analyzed by developing a new cellular repair-model and the effects of various cytokines, growth factors, vasoactive agents and newly developing drugs like drugs affecting cell-cell communication were studied. Finally a new model of electronic endoscope applicable t o measurement of tissue blood volume and tissue oxygenation level was developed in collaboration with Olympus Co. Ltd. and is now used to study the relationship between the tissue microcirculatory changes including the sticking and rolling of immune corpuscles and the tissue or cellular repair, and proliferation and dedifferentiation of GI cells.