Kranjc Simona, Tevz Gregor, Kamensek Urska, Vidic Suzana, Cemazar Maja, Sersa Gregor
Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, Slovenia.
Radiat Res. 2009 Dec;172(6):677-85. doi: 10.1667/RR1873.1.
Electrochemotherapy can potentiate the radiosensitizing effect of bleomycin, as shown in our previous studies. To bring this treatment closer to use in clinical practice, we evaluated the interaction between electrochemotherapy with bleomycin and single-dose or fractionated radiation in two murine tumor models with different histology and radiosensitivity. Radiosensitive sarcoma SA-1 and radioresistant adenocarcinoma CaNT subcutaneous tumors grown in A/J and CBA mice, respectively, were used. The anti-tumor effect and skin damage around the treated tumors were evaluated after electrochemotherapy with bleomycin alone or combined with single-dose radiation or a fractionated radiation regimen. The anti-tumor effectiveness of electrochemotherapy was more pronounced in SA-1 than CaNT tumors. In both tumor models, the tumor response to radiation was not significantly influenced by bleomycin alone or by electroporation alone. However, electrochemotherapy before the first tumor irradiation potentiated the response to a single-dose or fractionated radiation regimen in both tumors. For the fractionated radiation regimen, normal skin around the treated tumors was damaged fourfold less than for the single-dose regimen. Electrochemotherapy prior to single-dose irradiation induced more damage to the skin around the treated tumors and greater loss of body weight compared to other irradiated groups, whereas electrochemotherapy combined with the fractionated radiation regimen did not. Electrochemotherapy with low doses of bleomycin can also be used safely for radiosensitization of different types of tumors in a fractionated radiation regimen, resulting in a good anti-tumor effect and no major potentiating effect on radiation-induced skin damage.
如我们之前的研究所示，电化学疗法可增强博来霉素的放射增敏作用。为了使这种治疗方法更接近临床应用，我们在两种具有不同组织学和放射敏感性的小鼠肿瘤模型中，评估了博来霉素电化学疗法与单剂量或分次放疗之间的相互作用。分别使用在A/J和CBA小鼠中生长的放射敏感肉瘤SA-1和放射抗性腺癌CaNT皮下肿瘤。在用博来霉素单独进行电化学疗法或联合单剂量放疗或分次放疗方案后，评估治疗肿瘤周围的抗肿瘤效果和皮肤损伤。电化学疗法在SA-1肿瘤中的抗肿瘤效果比在CaNT肿瘤中更明显。在两种肿瘤模型中，单独使用博来霉素或单独进行电穿孔对肿瘤对放疗的反应均无显著影响。然而，在首次肿瘤照射前进行电化学疗法可增强两种肿瘤对单剂量或分次放疗方案的反应。对于分次放疗方案，治疗肿瘤周围的正常皮肤损伤程度比单剂量方案小四分之一。与其他照射组相比，单剂量照射前进行电化学疗法对治疗肿瘤周围的皮肤造成的损伤更大，体重减轻也更明显，而电化学疗法与分次放疗方案联合使用则不会。低剂量博来霉素电化学疗法也可安全用于分次放疗方案中不同类型肿瘤的放射增敏，从而产生良好的抗肿瘤效果，且对放疗引起的皮肤损伤无明显增强作用。
