COMBINATION THERAPY FOR CANCER AND AIDS

这个项目始于我们实验室小组发现的一种新的 艾滋病可能的“调节性”联合疗法(双脱氧核苷 加上核苷转运抑制剂)，我们和我们的合作者 通过I期临床试验开发。当我们找不到任何 发表的方法适用于我们的设计和分析 在对这种联合疗法进行实验后，我们决定开发自己的疗法。 结果产生了一系列新的概念、算法和计算机 程序，合并到一个称为COMBO的包中。组合组合 用于设计和分析联合疗法的算法现在形成了 这个项目的核心部分，尽管只占整个项目的一小部分 在研究小组中的努力。我们已经使用了新的算法和 计划(在癌症和艾滋病研究中)设计和分析 苏拉明、肿瘤等药物组合的实验研究 坏死因子、紫杉醇、潘生丁、AZT、DDI、ddC、CD4-假单胞菌 外毒素、HIV蛋白酶抑制剂和羟基脲等。 最近发表的分析包括关于组合的分析 使用蛋白酶抑制剂KNI-272治疗AZT或DDI(与 H.Mitsuya和他的同事，艾滋病研究和人类逆转录病毒 1994年；38：1036)以及双脱氧核苷和羟基脲的组合 (与R.Gallo和同事合作，例如《科学》 1994年；266：801)。

This project began with the discovery in our laboratory group of a new possible "modulatory" combination therapy for AIDS (dideoxynucleoside plus nucleoside transport inhibitor), which we and our collaborators developed through Phase I clinical trials. When we could not find any published method appropriate for the design and analysis of our experiments on this combination therapy, we decided to develop our own. The result was a set of new concepts, algorithms, and computer programs, incorporated into a package called COMBO. The COMBO algorithms for design and analysis of combination therapy now form the central portion of this project, albeit a small fraction of overall effort in the research group. We have used the new algorithms and programs (in both cancer and AIDS research) to design and analyze experiments on combinations involving such agents as suramin, tumor necrosis factor, taxol, dipyridamole, AZT, ddI, ddC, CD4-pseudomonas exotoxin, HIV protease inhibitors, and hydroxyurea, among others. Fairly recent published analyses have included those on combinations of AZT or ddi with protease inhibitor KNI-272 (in collaboration with H. Mitsuya and colleagues, AIDS Research and Human Retroviruses 1994;38:1036) and on combinations of dideoxynucleosides and hydroxyurea (in collaboration with R. Gallo and colleagues, e.g., Science 1994;266:801).