CORTICOSTEROIDS CYTOKINETIC AND BIOCHEMICAL STUDIES

前期在多种实验性小鼠实体瘤模型上的研究

Previous studies in a variety of experimental solid tumor models in mice and rats indicated that dexamethasone (dex) can induce a reversible G1 block in cell cycle progression. Following cessation of treatment, the time for cell cycle progression (delta t) is directly related to dex dose and glucocorticoid receptor content (GR) of the tumor and can be described by delta t = (Tc) (mg/m2) (2.2 x 10-4 GR + 2.3 x 10-3). Studies employing 5FU, VCR, 5FU + VCR, and CP indicated that the effectiveness of these agents could be significantly increased if administered during the delta t interval. The purpose of this project is to investigate the predictability of the dex response model as xenograft models of human melanoma and lung cancer, as well as in selected patients with advanced metastatic disease. Other studies are designed to evaluate the feasibility of using corticosteroid hormone treatments to predictably manipulate the timing of proliferative recovery in solid tumors after cytotoxic cytoreduction and how such strategies effect recovery and chemosensitivity of critical normal tissues. (D)