CHEMICAL MODIFICATION OF THE RADIATION RESPONSE

为了改善癌症治疗，相当多的关注 被放在修改辐射损害上，特别是针对 增强功能。多种化疗药物已证明具有辐射作用 敏感化，在过去的几年里，我们把注意力集中在 相对较新的药物紫杉醇(紫杉醇)。我们已经证明了紫杉醇 治疗诱导细胞周期的G2/M期阻滞)，并使放射增敏 多株人类肿瘤细胞株。特别值得注意的是 人乳腺腺癌细胞系MCF7的放射增敏作用。 紫杉醇联合放射治疗导致放射 增强比(RER)为1.9。根据我们的体外数据，乳腺癌 应该是最适合联合放射治疗和紫杉醇的。我们是在 最初的困惑是，人肺腺癌细胞没有 紫杉醇的放射增敏作用，尽管有明显的细胞诱导 G2/M中的周期阻塞。原因在于差动出口 细胞间S期(细胞周期中的辐射抗性部分)的时间 类型。虽然与辐射无关，但我们已经进行了初步的 临床前研究表明紫杉醇可以适当地联合 热疗(一种实验性的癌症治疗方法)只要 紫杉醇治疗先于热疗。这 这些信息将对临床医生设计人类非常有用 紫杉醇联合热疗的临床试验。 我们还启动了评估吉西他滨、奎诺霉素和 9-氨基喜树碱作为辐射增敏剂。初步研究表明 吉西他滨和9-氨基喜树碱提高辐射敏感性 人胰腺和肺的增强比为1.3~1.5 癌细胞系。其他化疗药物将被评估为辐射 致敏剂包括黄烷醇、瑞贝卡霉素和根霉毒素。

In the interest of improving cancer treatment, considerable attention has been placed on the modification of radiation damage, particularly toward enhancement. A variety of chemotherapy agents have demonstrated radiation sensitization and for the past few years we have focused attention on the relatively new agent paclitaxel (Taxol). We have shown that paclitaxel treatment induces a block in G2/M of the cell cycle) and radiosensitizes a number of human tumor cell lines. Of particular note was the radiosensitization of a human breast adenocarcinoma cell line MCF7. Paclitaxel treatment combined with radiation resulted in a radiation enhancement ratio (RER) of 1.9. Based on our in vitro data, breast cancer should be most suitable for combined radiation and paclitaxel. We were initially puzzled that human lung adenocarcinoma cells were not radiosensitized by paclitaxel despite the induction of a pronounced cell cycle block in G2/M. The reason for this resides in the differential exit times in S phase (a radioresistant portion of the cell cycle) among cell types. While not related to radiation, we have conducted preliminary pre-clinical studies which show that paclitaxel may be suitably combined with hyperthermia (an experimental cancer treatment modality) as long as the paclitaxel treatment precedes the hyperthermia treatment. This information will be extremely useful to clinicians designing human clinical trials combining paclitaxel and hyperthermia. We have also initiated studies evaluating gemcitabine, quinocarmycin, and 9-amino camptothecin as radiation sensitizers. Preliminary studies show that gemcitabine and 9-amino camptothecin enhance radiation sensitivity (enhancement ratios ranging from 1.3-1.5) of human pancreas and lung cancer cell lines. Other chemotherapy agents to be evaluated as radiation sensitizers include flavopiridol, rebeccamycin, and rhizoxin.