Ingram S S, Samulski T, Dodge R, Prosnitz L R, Peters P, Vredenburgh J
Duke University Medical Center, Department of Radiation Oncology, Durham, North Carolina, USA.
Int J Hyperthermia. 1996 Jan-Feb;12(1):21-9. doi: 10.3109/02656739609023686.
The number of autologous bone marrow transplants done for solid tumours, particularly breast cancer, has risen steadily over the last ten years. The role of bone marrow or peripheral blood progenitor cell purging in transplantation is incompletely understood. Theoretically, the reinfusion of untreated bone marrow containing tumour cells might result in relapse in some patients treated with high-dose chemotherapy and hematopoietic support. Therefore, safe and effective purging techniques may increase long-term, disease-free survivorship. In this study, hyperthermia was evaluated for its ability to purge CAMA-1 breast cancer cells from normal human bone marrow. Between two and nine trials of a range of temperatures (42-45 degrees C) and durations of treatment (1-4 h) were performed. The effect of hyperthermia on normal bone marrow alone and in mixes with breast cancer cells was also evaluated. Hyperthermia (45 degrees C, 4 h) produced > 5 logs of CAMA-1 cell kill. Exposures of 45 degrees C for 2 h and 44 degrees C for 4 h resulted in approximately three logs of cell kill, corresponding to < 1% survival of clonogenic cells. Normal bone marrow was considerably more vulnerable to heat treatments, however, with approximately 1% of progenitors remaining clonogenic after exposure of 43 degrees C for 2 h and 44 degrees C for 1 h. Therefore, although hyperthermia is able to achieve adequate CAMA-1 breast cancer cell kill, it remains more toxic to normal bone marrow as a purging method. To make hyperthermia useful in purging systems, mechanisms to selectively alter thermal sensitivity must be pursued.
在过去十年中，用于实体瘤尤其是乳腺癌的自体骨髓移植数量稳步上升。骨髓或外周血祖细胞清除在移植中的作用尚未完全明了。从理论上讲，输注含有肿瘤细胞的未处理骨髓可能导致一些接受大剂量化疗和造血支持治疗的患者复发。因此，安全有效的清除技术可能会提高长期无病生存率。在本研究中，评估了热疗清除正常人骨髓中CAMA-1乳腺癌细胞的能力。进行了一系列温度（42-45℃）和治疗持续时间（1-4小时）的两到九次试验。还评估了热疗对单独的正常骨髓以及与乳腺癌细胞混合后的影响。热疗（45℃，4小时）可使CAMA-1细胞杀伤超过5个对数级。45℃暴露2小时和44℃暴露4小时导致约三个对数级的细胞杀伤，相当于克隆形成细胞存活率<1%。然而，正常骨髓对热处理的敏感性要高得多，在43℃暴露2小时和44℃暴露1小时后，约1%的祖细胞仍具有克隆形成能力。因此，尽管热疗能够充分杀伤CAMA-1乳腺癌细胞，但作为一种清除方法，它对正常骨髓的毒性仍然更大。为了使热疗在清除系统中发挥作用，必须探索选择性改变热敏感性的机制。
