Enhancement of chemosensitivity of the quiescent call populations in murine solid tumor by combination treatment with antitumor drugs and vasoactive agent

抗肿瘤药物与血管活性药物联合治疗增强小鼠实体瘤静止细胞群的化疗敏感性

• 批准号: 05807076
• 负责人: KAWAI Kenichi
• 金额: $ 1.22万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807076/
• 关键词: chemotherapy; combination treatment; vasoactive agent; quiescent cell; hypoxic call; nicotinamide; ^<195m>Pt-carboplatin; ^<195m>Pt-254-S; ^<195m>Pt-標識-シスプラチン; ^<195m>Pt標識シスプラチン

The purpose of this project is to explore the role of a vasoactive agent such as nicotinamide to increase the cytotoxic effect of antitumor agents. The result of our investigation can be summarized as follows.1.We succeeded in synthesizing ^<195m>Pt radiolabelled DWA2114R,carboplatin and 254-S.2.By using the ^<195m>pt-antitumour compounds, above mentioned, we determined the target volumes, efficiencies of Pt atom to kill cells, of cultured HeLa cells.3.Furthermore, the target volume analysis was applied to examine the mechanism of hyperthermia-CDDP induced potentiation. A comparison of the Do's and efficiencies obtained at different temperatures, suggested that the supra-additive effect of the combination treatment could be explained by two mechanisms, i.e.the increased drug level in DNA (from 37 to 42 ﾟC) and the increased efficiency of the Pt atoms to kill the cells (>42 ﾟC) .4.Enhancement of chemosensitivity of the quiescent cell populations in murine solid tumours was confirmed between nicotinamide and CDDP.5.The exact mechanism of the radiation response of SCCVII tumor was elucidated.

本项目的目的是探索血管活性剂（如烟酰胺）增加抗肿瘤药物细胞毒性作用的作用。本研究的主要结果如下：1.成功地合成了~（18<195m>）Pt标记的DWA 2114 R、卡铂和~（254）S; 2.利用上述<195m>~（18）Pt标记的抗癌化合物，测定了它们对HeLa细胞的靶体积，即Pt原子对细胞的杀伤效率; 3.进一步用靶体积分析法探讨了顺铂对高血压的增效作用机制。在不同温度下获得的DO和效率的比较表明，组合处理的超加性效应可以通过两种机制来解释，即DNA中的药物水平增加（从37到42摄氏度）和铂原子杀死细胞的效率增加（&gt;42摄氏度）4.烟酰胺和顺铂对小鼠实体瘤静止期细胞群的化疗增敏作用得到证实。5.阐明了SCCVII肿瘤放射反应的确切机制。

项目成果

K.Ono, S.Masunaga, M.Akaboshi and K.Akuta: "Estimation of the initial slope of the cell survival curve after irradiation from micronucleus frequency in cytokinesis-blocked cells." Radiat.Res.138. S101-S104 (1994)

K.Ono、S.Masunaga、M.Akaboshi 和 K.Akuta：“根据胞质分裂阻断细胞中的微核频率估算辐射后细胞存活曲线的初始斜率。”

S.Masunaga: "The radiosensitivity of quiescent cell populations in murine solid tumors in irradiation with fast neutrons." Int.J.Radiation Oncology Biol.Phys.29. 239-242 (1994)

S.Masunaga：“快中子照射下小鼠实体瘤中静止细胞群的放射敏感性。”

Kenichi Kawai: "Synthesis of Platinum-195m radiolabeled(-)-(R)-2-aminomethyl pyrrobidine(I,I-oyclobutanedicarboxylato)-2-Platinum(II)monohydrate using high Performance liquid chromatography." J.Radioanal.Nucl.Chem.Letters. 164. 123-130 (1992)

Kenichi Kawai：“使用高效液相色谱法合成铂 195m 放射性标记的 (-)-(R)-2-氨甲基吡咯烷(I,I-环丁烷二羧基)-2-铂 (II) 一水合物。”

Mitsuhiko Akaboshi: "Binding characteristics of(-)-(R)-2-aminomethylpyrrolidine(1,1-oyclobutanedicarboxylato)-2-Platinum(II)to DNA,RNA and protein molecules in HeLa cells and its lethal effect." Jpn.J.Cancer Res.85. 106-111 (1994)

Mitsuhiko Akaboshi：“(-)-(R)-2-氨基甲基吡咯烷(1,1-环丁烷二羧基)-2-铂(II)与HeLa细胞中DNA、RNA和蛋白质分子的结合特性及其致死作用。”

K.Kawai: "Synthesis of ^<195m>Pt radiolabeled cis-diammine(glycolato)platinum(II)of high radionuclidic purity." J.Radioanal.Nucl.Chem.,Letters. 199. 207-215 (1995)

K.Kawai：“高放射性核素纯度的 ^<195m>Pt 放射性标记顺式二氨（乙醇酸）铂 (II) 的合成。”