Buchsbaum D J, Raben D, Stackhouse M A, Khazaeli M B, Rogers B E, Rosenfeld M E, Liu T, Curiel D T
Department of Radiation Oncology, University of Alabama at Birmingham 35294-3300, USA.
Gene Ther. 1996 Dec;3(12):1042-68.
This review presents an overview and discussion of the potential synergistic strategies of radiation therapy and gene transfer for treating neoplastic disease. Topics discussed include radiation-inducible promoters coupled to genes which produce proteins that are cytotoxic or enhance radiosensitivity, employment of molecular chemotherapy approaches in conjunction with radiation therapy, and genetic induction of radiosensitization through modification of DNA repair, signal transduction, and cell cycle control genes. Additional topics discussed relate to gene transfer augmentation of radioimmunotherapy of cancer. Specifically, gene transfer methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to increase radiolabeled antibody and peptide targeting and thus increase their therapeutic effect, selection of radionuclides for therapeutic ligand labeling, and computer simulation of genetic tumor-specific delivery of radiolabeled ligands are proposed.
本综述介绍并讨论了放射治疗与基因转移联合治疗肿瘤疾病的潜在协同策略。讨论的主题包括与产生细胞毒性蛋白或增强放射敏感性的基因偶联的辐射诱导启动子、分子化疗方法与放射治疗的联合应用,以及通过修饰DNA修复、信号转导和细胞周期控制基因进行放射增敏的基因诱导。讨论的其他主题涉及基因转移增强癌症放射免疫治疗。具体而言,提出了基因转移方法,即通过基因诱导肿瘤细胞表达更高水平的细胞表面抗原和受体,以增加放射性标记抗体和肽的靶向性,从而提高其治疗效果,还包括用于治疗性配体标记的放射性核素的选择,以及放射性标记配体基因肿瘤特异性递送的计算机模拟。