The immunopotentiation effects of low neurotoxic radiosensitizers KIN806 and KIN896

低神经毒性放射增敏剂 KIN806 和 KIN896 的免疫增强作用

• 批准号: 08671036
• 负责人: INOMATA Taisuke
• 金额: $ 1.41万
• 依托单位: Kochi 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: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671036/
• 关键词: Radiosensitizer; Radiotherapy; KIN806; KIN896; Metastasis; BRM; 腫瘍浸潤単核球; 免疫賦活作用; KIN804; KIN844

K1N806 and K1N896 belong to the 2- nitroimidazole derivative hypoxic cell radiosensitizers. The radiosensitizing and anti- tumor effects of these sensitizers' were evaluated and compared with their analogs KTN8O4 and KIN844. For materials, C3H/He mice / SCCVII tumor cells, and C57BL/6 mice / Lewis lung cancer cells were used. 30 Gy or 40 Gy was delivered as local irradiation. KIN- 806, K1N896, KTN8O4, and K1N844, administered before irradiation, suppressed tumor regrowth in comparison with irradiation alone. Tumor regrowth was more suppressed in the 40 Gy- irradiated groups and the 0.4mg/g of the radiosensitisers- administered groups than in the 30 Gy irradiated groups and the 0.2mg/g administered groups, respectively. There was no significant difference in the radiosensitizing effects among these four radiosensitizers. A marked suppression of lung metastasis and macrophage / T lymphocyte infiltration into the tumor were observed in the K1N806 and K1N896- administered groups, regardless of radiation therapy, and these effects were dose dependent. It therefore appears likely that the lung metastasis suppression was caused by the immune reaction elicited KIN806 and KIN896, which are excellent immunopotentiators as well as effective radiosensitizers. K1N806 and K1N896 are expected to be hopeful radiosensitizers for clinical use.

K1N806和K1N896属于2-硝基咪唑衍生物缺氧细胞放射增敏剂。评价这些增敏剂的放射增敏和抗肿瘤作用，并与类似物KTN8O4和KIN844进行比较。材料采用C3H/He小鼠/ SCCVII肿瘤细胞，C57BL/6小鼠/ Lewis肺癌细胞。30gy或40gy作为局部照射。与单独放疗相比，放疗前给药的KIN- 806、K1N896、KTN8O4和K1N844抑制了肿瘤的再生。与30 Gy和0.2mg/g剂量组相比，40 Gy剂量组和0.4mg/g剂量组的肿瘤再生受到更大的抑制。4种放射增敏剂的放射增敏效果无显著差异。无论放射治疗如何，K1N806和K1N896给药组均显著抑制肺转移和巨噬细胞/ T淋巴细胞浸润到肿瘤中，且这些作用是剂量依赖性的。因此，肺转移抑制可能是由KIN806和KIN896引发的免疫反应引起的，它们是优秀的免疫增强剂和有效的放射增敏剂。K1N806和K1N896有望成为临床应用的放射增敏剂。

项目成果

T.INOMATA: "The Immunopotentiation Effects of the Bifunctional Radiosensitizer KIN806 in Comparison with its Analogs KIN804 and KIN896" Radiotherapy and Oncology. 32. 未定 (1999)

T.INOMATA：“双功能放射增敏剂 KIN806 与其类似物 KIN804 和 KIN896 的免疫增强作用”放射治疗和肿瘤学 32。待定（1999 年）。

T.INOMATA: "The Immunopotentiation Effects of the Bifunctional Radio sensitiger KIN806 in Comparisar of with its Analogs KIN804 ad KIN844" Radiotherapy and Oncology. 32. (1999)

T.INOMATA：“双功能放射敏剂 KIN806 与其类似物 KIN804 和 KIN844 的免疫增强作用”放射治疗和肿瘤学。

T.Inomata, A.Nishioka, N.Hamada, S.Ito, S.Kariya, S.Yoshida, H.Nagasawa, H.Hori, S.Inayama: "The Immunopotentiation Effects of the Bifunctional Radiosensitizer KIN806 in Comparison with its Analogs KIN804 and KIN844." Radiotherapy and Oncology. 32. (1999)

T.Inomata、A.Nishioka、N.Hamada、S.Ito、S.Kariya、S.Yoshida、H.Nagasawa、H.Hori、S.Inayama：“双功能放射增敏剂 KIN806 与其类似物的免疫增强作用