Bloch W E, Lokeshwar B L, Ferrell S M, Block N L
Department of Urology, University of Miami, School of Medicine, FL 33101.
Prostate. 1994;24(3):131-8. doi: 10.1002/pros.2990240306.
Hyperthermia alone or with radiation is used therapeutically for localized solid tumors. Clinical experience shows that sustained tumor temperature exceeding 45 degrees C damages normal tissue. Any agent that enhances the effects of hyperthermia at or below this temperature may have clinical relevance. Lonidamine and hyperthermia were tested on the Dunning R3327G rat prostatic adenocarcinoma. Using colony-formation assays, cytotoxic effects of each agent alone and in combination were quantified. Lonidamine to 100 micrograms/ml was not significantly toxic, but in combination, it enhanced cytotoxicity. Survival patterns after fractionated hyperthermia revealed a rapid development and decay of thermotolerance. Measurement of cell-cycle progression following a single dose of hyperthermia revealed a reduction of S-phase cells, and subsequent accumulation in G1 over 24 hours. Combination treatment of tumor-bearing rats significantly reduced tumor growth rate when compared with individual agents. These results suggest a potential use of lonidamine in hyperthermic therapy of prostate tumors.
单独使用热疗或联合放疗可用于局部实体瘤的治疗。临床经验表明，持续的肿瘤温度超过45摄氏度会损害正常组织。任何在该温度或低于该温度时增强热疗效果的药物都可能具有临床意义。对Dunning R3327G大鼠前列腺腺癌进行了氯尼达明和热疗测试。使用集落形成试验，对每种药物单独使用和联合使用时的细胞毒性作用进行了量化。氯尼达明浓度达到100微克/毫升时毒性不显著，但联合使用时可增强细胞毒性。分次热疗后的存活模式显示热耐受性迅速发展和消退。单次热疗后细胞周期进程的测量显示S期细胞减少，随后在24小时内G1期细胞积累。与单独使用药物相比，联合治疗荷瘤大鼠可显著降低肿瘤生长速度。这些结果表明氯尼达明在前列腺肿瘤热疗中具有潜在用途。
