Saad A H, Hahn G M
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305-5468.
Ultrasound Med Biol. 1992;18(8):715-23. doi: 10.1016/0301-5629(92)90122-q.
Earlier studies from our and other laboratories have demonstrated that ultrasound (US) enhances the cytotoxicity in vitro of the antitumor agent Adriamycin (Adr) (Harrison et al. 1991; Loverock et al. 1990; Saad and Hahn 1987, 1989; Yang et al. 1991; Yumita et al. 1987, 1989). We have now tested the possibility that this additional cytotoxicity can be translated into antitumor activity in vivo. Mice, bearing either a fibrosarcoma (RIF-1) or a melanoma (B-16) on their thighs, were injected with a single dose of Adr (10-20 mg/kg). The tumors were then heated locally to 41 degrees -43 degrees C for 30 min, either by insonation with US or by immersion of the animals' limbs into hot water baths. Antitumor efficacy was scored two ways: by serial measurements of tumor volume to determine the time for the tumor to double in size, or by determining the X-ray dose required to sterilize 50% of the tumors (TCD50) after the Adr-hyperthermia treatment. Both assays gave similar results. Ultrasound-induced hyperthermia was substantially more effective in enhancing Adr activity than was hyperthermia induced by the water bath. The mean-doubling time was 13 days for tumors treated with the combination of Adr and US and 6 days for tumors heated with a water bath immediately after injection of Adr. The TCD50 was 21.2 +/- 0.8 Gy for the combination of US and Adr and 36.1 +/- 0.9 Gy for the water bath heating and Adr.(ABSTRACT TRUNCATED AT 250 WORDS)
我们实验室及其他实验室早期的研究表明，超声（US）可增强抗肿瘤药物阿霉素（Adr）的体外细胞毒性（哈里森等人，1991年；洛夫罗克等人，1990年；萨德和哈恩，1987年、1989年；杨等人，1991年；弓田等人，1987年、1989年）。我们现在测试了这种额外的细胞毒性能否转化为体内抗肿瘤活性的可能性。在大腿上长有纤维肉瘤（RIF-1）或黑色素瘤（B-16）的小鼠，注射单剂量的阿霉素（10 - 20毫克/千克）。然后通过超声照射或把动物肢体浸入热水浴，将肿瘤局部加热至41摄氏度 - 43摄氏度，持续30分钟。通过两种方式评估抗肿瘤效果：通过连续测量肿瘤体积以确定肿瘤体积翻倍的时间，或通过确定在阿霉素 - 热疗治疗后使50%的肿瘤无菌所需的X射线剂量（TCD50）。两种检测方法得出了相似的结果。超声诱导的热疗在增强阿霉素活性方面比水浴诱导的热疗有效得多。阿霉素与超声联合治疗的肿瘤平均倍增时间为13天，注射阿霉素后立即用水浴加热的肿瘤平均倍增时间为6天。超声与阿霉素联合治疗的TCD50为21.2±0.8戈瑞，水浴加热与阿霉素联合治疗的TCD50为36.1±0.9戈瑞。（摘要截选至250字）
