Chelvi T P, Ralhan R
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Tumour Biol. 1997;18(4):250-60. doi: 10.1159/000218038.
Malignant melanoma are chemoresistent tumors with poor prognosis. The aim of this study was to determine whether multimodality therapy of murine melanoma involving a combination of radiation with thermosensitive-liposome-encapsulated melphalan and local hyperthermia would result in enhancement of therapeutic efficacy for a more effective management of melanoma. Melphalan was entrapped in thermosensitive liposomes prepared from natural lipids: egg phosphatidyl choline, cholesterol and ethanol to show phase transition at 42 +/- 0.5 degrees C and used in combination with localized heating of B16F10 murine melanoma transplanted into the legs of C57B1/6 mice for selective drug targeting at the tumors and/or radiation for treatment of melanoma. Murine melanoma transplanted into C57B1/6 mice were subjected to bimodality treatments involving a combination of radiation, hyperthermia or melphalan. Partial tumor regression was observed in mice receiving a combination of hyperthermia and radiation (median tumor volume 427.3 mm3) or a combination of free melphalan and radiation (512.1 mm3) as compared to untreated controls (630.9 mm3). Each group consisted of 18 animals, and the results are expressed as median tumor volume +/- SD. Animals receiving multimodality therapy comprising irradiation followed by injection of thermosensitive liposomal melphalan and hyperthermic treatment of the tumor-bearing leg at 42 +/- 0.5 degrees C for 1 h showed marked tumor regression in comparison with untreated controls or animals treated with a combination of radiation and hyperthermia or radiation and free-drug melphalan. Animals receiving thermoradiochemotherapy also showed prolonged survival; 70% of animals survived for more than 3 months. The study shows greater tumor cell killing, tumor growth delay and prolonged survival produced by a combination of radiation, thermosensitive-liposome-entrapped melphalan and hyperthermia compared with animals receiving single-modality or bimodality treatments. It is concluded that this multimodality approach will be potentially useful for more effective management of melanoma.
恶性黑色素瘤是化疗抵抗性肿瘤，预后较差。本研究的目的是确定对小鼠黑色素瘤进行多模态治疗，即将放疗与热敏脂质体包裹的美法仑及局部热疗相结合，是否会提高治疗效果，从而更有效地治疗黑色素瘤。美法仑被包裹于由天然脂质（卵磷脂、胆固醇和乙醇）制备的热敏脂质体中，该脂质体在42±0.5℃时发生相变，并与移植到C57B1/6小鼠腿部的B16F10小鼠黑色素瘤的局部加热联合使用，以实现对肿瘤的选择性药物靶向治疗和/或用于黑色素瘤治疗的放疗。将移植到C57B1/6小鼠体内的小鼠黑色素瘤进行双模态治疗，包括放疗、热疗或美法仑联合治疗。与未治疗的对照组（中位肿瘤体积630.9mm³）相比，接受热疗与放疗联合治疗（中位肿瘤体积427.3mm³）或游离美法仑与放疗联合治疗（512.1mm³）的小鼠出现了部分肿瘤消退。每组有18只动物，结果以中位肿瘤体积±标准差表示。接受多模态治疗（包括放疗，随后注射热敏脂质体美法仑，并在42±0.5℃对荷瘤腿进行1小时热疗）的动物与未治疗的对照组或接受放疗与热疗联合治疗或放疗与游离药物美法仑联合治疗的动物相比，显示出明显的肿瘤消退。接受热放疗化疗的动物也显示出生存期延长；70%的动物存活超过3个月。该研究表明，与接受单模态或双模态治疗的动物相比，放疗、热敏脂质体包裹的美法仑和热疗联合使用可产生更强的肿瘤细胞杀伤作用、肿瘤生长延迟和生存期延长。结论是，这种多模态方法可能对更有效地治疗黑色素瘤有用。
