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

本项目的目的是探索一种血管活性物质，如烟酰胺，在增加抗肿瘤药物的细胞毒作用方面的作用。我们的研究结果概括如下：1.我们成功地合成了放射性标记的DWA2114R、卡铂和254-S2。利用上述抗肿瘤化合物，我们测定了铂原子对培养的HeLa细胞的靶向体积、杀伤细胞的效率。3.利用靶向体积分析研究了高温-顺铂诱导HeLa细胞增殖的机制。对不同温度下的DO和效率的比较表明，联合治疗的超相加效应可以由两种机制解释，即DNA中药物浓度的增加(从37ﾟC增加到42ﾟC)和铂原子对细胞杀伤效率的增加(&GT；42 GMT C)。4.烟酰胺和CDDP提高了小鼠实体瘤静止细胞群的化疗敏感性。5.阐明了SCCVII肿瘤辐射反应的确切机制。

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.