INTRA VITAL MICROSCOPIC STUDIES FOR ANTI-TUMOR LYMPHOCYTE ACTIONS TO LUNG METASTASIS OF LUNG CANCER

本研究旨在通过活体显微镜观察肿瘤微血管及抗肿瘤淋巴细胞在佐藤肺癌血行性肺转移中的作用，开发有效的肺癌免疫治疗方法。方法(1)1997 - 1998年研究：采用活体显微镜观察经静脉注射的佐藤肺癌单个癌细胞在东流大鼠肺微血管中向成熟肺转移的生长过程。(2) 1998 - 1999年的研究：通过生存率、外周血淋巴细胞分析、肿瘤微循环活体显微镜观察，研究了化疗、免疫治疗、免疫治疗联合化疗对肺癌成熟肺转移的治疗效果。结果(1)静脉输注的癌细胞在肺微血管中有三种类型的阻滞。91%的癌细胞被压入肺小动脉。它们必须有来自周围血管壁的强机械应力。6%的细胞被捕获…更多的是肺小动脉。它们从血流中接受强大的机械应力。3%的细胞停在被血浆包围的肺小动脉中，就像天空中的气球。它们可能通过逃避机械压力而存活下来。存活的癌细胞在输注后3天开始生长，7天后成为肿瘤小动脉、肿瘤毛细血管和肿瘤小静脉的成熟肺转移灶。所有肿瘤微血管均未见淋巴细胞粘连。(2)非治疗组生存率为17%，免疫治疗组生存率为33%，化疗组生存率为50%，免疫治疗联合化疗组生存率为67%。淋巴细胞粘连仅见于免疫联合化疗组。免疫联合化疗组外周血单核细胞、NK细胞和NKT细胞含量较高。结论肿瘤微血管壁干扰肿瘤细胞与抗肿瘤淋巴细胞的直接接触。前期化疗破坏血管壁，通过抗肿瘤淋巴细胞的后续作用使肿瘤缩小。少

This study was projected to develop effective immunotherapy to lung cancer through intravital microscopic observations for tumor microvessels and anti-tumor lymphocyte actions in hematogenous lung metastasis of SATO lung cancer.METHODS (1) Studies in 1997 - 1998 : We observed growth process of intravenously infused sigle cancer cell of SATO lung cancer to mature lung metastasis in pulmonary microvessels of living Donryu rats by a vital nicroscope. (2) Studies in 1998 - 1999 : We studied therapeutic effect of chemotherapy, immunotherapy and immunotherapy with chemothertapy toward mature lung metastasis of lung cancer by using survival rate, lymphocyte analysis of peripheral blood and intravital microscopy of tumor microcirculation.RESULTS (1) Intravenously infused cancer cells arrested in pulmonary microvessels in three styles. 91% of arrest cancer cells were pressed into the pulmonary arterioles. They must have strong mechanical stress from surrounding vessel wall. 6% cells were caught … More on the pulmonary arterioles. They receive strong mechanical stress from blood stream. 3% cells stopped in the pulmonary arterioles surrounded with plasma like a balloon in the sky. They may survive by escaping from mechanical stress. Survival cancer cells started their growth three days after the infusion and became mature lung metastases with tumor arterioles, tumor capillaries and tumor venules seven days after. No lymphocyte adhesion was seen in tumor microvessels of all tumors. (2) Survival rate was 17% in non treatment group, 33% in immunotherapy group, 50% in chemotherapy group and 67% in immunotherapy with chemotherapy group. Lymphocyte adhesion was only seen on immunotherapy with chemotherapy group. Immunotherapy with chemotherapy group had high values of monocyte, NK cells and NKT cells in peripheral blood.CONCLUSIONS Tumor microvessel wall disturb direct contact between tumor cells and anti-tumor lymphocytes. Previous destruction of vessel wall by chemotherapy results in tumor reduction through following work of anti-tumor lymphocyte. Less