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

淋巴细胞抗肺癌肺转移作用的活体显微镜研究

• 批准号: 09671392
• 负责人: SOHARA Yasunori
• 金额: $ 1.86万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671392/
• 关键词: vital microscopy; tumor microvessel; lung metastasis; ant-tumor lymphocyte; immunotherapy; 腫瘍微小循環; 佐藤肺癌; 肺転移; 癌細胞付着; 癌の成長

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

本研究旨在通过活体显微镜观察SATO肺癌血源性肺转移中的肿瘤微血管和抗肿瘤淋巴细胞的作用，开发有效的肺癌免疫疗法。方法（1）1997-1998年的研究：观察静脉输注单个SATO肺癌细胞到肺成熟肺转移的生长过程。 通过活体显微镜观察活体 Donryu 大鼠的微血管。 (2)1998-1999年的研究：通过生存率、外周血淋巴细胞分析和肿瘤微循环活体显微镜检查，研究了化疗、免疫治疗和化疗免疫联合化疗对肺癌成熟肺转移的治疗效果。结果(1)静脉输注以三种方式捕获肺微血管中的癌细胞。 91%的阻滞癌细胞被压入肺小动脉。它们必须承受来自周围血管壁的强大机械应力。 6% 的细胞被捕获在肺小动脉上。它们承受来自血流的强烈机械应力。 3%的细胞停在肺小动脉中，周围环绕着血浆，就像天空中的气球一样。它们可以通过逃避机械应力而生存。存活的癌细胞在输注三天后开始生长，并在输注七天后成为成熟的肺转移瘤，具有肿瘤小动脉、肿瘤毛细血管和肿瘤小静脉。所有肿瘤的肿瘤微血管均未见淋巴细胞粘附。 (2)非治疗组的生存率为17%，免疫治疗组的生存率为33%，化疗组的生存率为50%，免疫治疗联合化疗组的生存率为67%。淋巴细胞粘附仅在免疫治疗联合化疗组中出现。免疫治疗联合化疗组外周血中单核细胞、NK细胞和NKT细胞含量较高。结论肿瘤微血管壁干扰了肿瘤细胞与抗肿瘤淋巴细胞的直接接触。先前化疗对血管壁的破坏导致通过抗肿瘤淋巴细胞的后续作用减少肿瘤。较少的

项目成果

Y.Sohara et al.: The Third Asian Congress For Microcirculation, S.Patumraj et al.(1997)

Y.Sohara 等人：第三届亚洲微循环大会，S.Patumraj 等人(1997)

Y.Sohara et al.: "NKT cells induced by chemo-immunotherapy suppress tumor growth" Microcirculation annual. 13. 17-18 (1997)

Y.Sohara 等人：“化学免疫疗法诱导的 NKT 细胞抑制肿瘤生长”年度微循环。

Y.Sohara et al.: "NKT cells induced by chemo-immunotherapy suppress tumor growth" Microciculation annual. 13. 17-18 (1997)

Y.Sohara 等人：“化学免疫疗法诱导的 NKT 细胞抑制肿瘤生长”年度微循环。

Y.Sohara et al.: "Arrest styles of intravenously infused cancer cells in pulmonary microvessels" Microciculation annual. 14. 141-142 (1998)

Y.Sohara 等人：“肺微血管中静脉输注癌细胞的捕获方式”年度微循环。

Yasunori SOHARA: "NKT cells induced by chemo-immunothetrapy suppress tumor growth-studies by vital observation of tumor microcirculation and lymphocyte analysis of peripheral blood" Microcirculation anual. 13. 17-18 (1997)

Yasunori SOHARA：“化学免疫疗法诱导的 NKT 细胞抑制肿瘤生长——通过肿瘤微循环的活体观察和外周血淋巴细胞分析进行研究”微循环手册。