COMBINATION THERAPY OF CANCER AND AIDS

我们开发了一种新的艾滋病“调节性”联合疗法。 双嘧达莫（Dipyridamole，Dipyridamole），一种有效的核苷抑制剂 广泛用于心血管适应症。 我们发现 叠氮胸苷（AZT）对人 免疫缺陷病毒（HIV-1）在培养的人单核细胞/巨噬细胞中的作用， 刺激的T细胞 在培养的人类睾丸成纤维细胞中， 增强抗病毒活性，同时保护细胞， AZT的细胞毒性 AZT不会增强AZT的细胞毒性作用 对人类骨髓祖细胞的影响。 综上所述各项 研究结果表明，AZT可能会增加AZT的治疗指数， vivo.我们目前正与另外两个机构合作， AZT/AZT联合用药的临床试验 正在研究的其他方面 包括以下步骤： 1. 作用机制：顺铂阻断细胞对生理性核苷的摄取 但不是AZT 因此，AZT的增效作用可能部分来自于 减少与AZT竞争病毒的核苷的流入， 逆转录酶 2. 分子结构：已根据分子结构计算出 结晶学 定量构效关系（3D-QSAR） 正在研究预测核苷的哪些特征 转运抑制分子是活性所必需的。 3.分子生物学：基于聚合酶链反应的方法是 被用来克隆核苷转运蛋白，一个主要目标， - 是的 4.联合治疗分析：因为没有发表的算法或 计算机软件包足以分析我们的抗病毒药物数据 结合，我们开发了一种新的方法。 新概念和 原型计算机程序包（COMBO），将是有用的，在上下文 癌症和艾滋病。

We developed a new "modulatory" combination therapy for AIDS. Dipyridamole (DPM; Persantin) , a potent inhibitor of nucleoside transport, is widely used for cardiovascular indications. We found that DPM potentiates the activity of azidothymidine (AZT) against human immunodeficiency virus (HIV-1) in cultured human monocyte/macrophages and stimulated T-cells. In cultured human Tlympboblastoid cells, DPM potentiates the antiviral activity and simultaneously protects the cells from AZT's cytotoxicity. DPM does not potentiate AZT's cytotoxic effect on human bone marrow progenitor cells in vitro. Taken together, these findings suggest that DPM may increase the therapeutic index of AZT in vivo. we are currently collaborating with two other institutions on clinical trials of the AZT/DPM combination. Other aspects under study include: 1. Mechanism: DPM blocks cellular uptake of physiological nucleosides but not of AZT. The potentiation of AZT may thus result, in part, from decreased influx of the nucleosides that compete with AZT for viral reverse transcriptase. 2. Molecular structure: A structure for DPM has been computed from the crystallography. Quantitative structure-activity relationships (3D-QSAR) are being studied to predict which features of nucleoside transport-inhibiting molecules are required for activity. 3. Molecular biology: Methods based on polymerase chain reaction are being used to clone the nucleoside transport protein, a major target for DPM. 4. Analysis of combination therapy: Because no published algorithm or computer package was adequate for analysis of our data on antiviral drug combinations, we have developed a new approach. The new concepts and prototype computer program package (COMBO), will be useful in the context of cancer as well as AIDS.