Development of a new surgical strategy in tumor resection for malignant bone and soft tissue tumors with cytocidal effect of acridine orange excited by various dynamic energy-wave.

在这项研究中，我们致力于开发一种新的手术策略来切除恶性骨和软组织肿瘤，利用各种动态能量波(如光束、X射线、电磁场或超声波)激发的吖啶橙(AO)的细胞杀伤作用。用小鼠骨肉瘤细胞株进行的体外研究表明，用蓝光(466 Nm)或低剂量X射线(5Gy射线)激发的AO具有很强的细胞杀伤作用，而电磁场刺激和超声场刺激都没有显示出明显的杀瘤作用。在皮下接种小鼠骨肉瘤的体内实验中，蓝光或X射线激发的AO也能有效地抑制肿瘤的生长。据推测，AO具有如此强的细胞杀伤作用的机制可能是在用蓝光或X射线激发AO后，细胞内的自由基以单线态氧的形式出现，从而可能对肿瘤细胞产生杀伤作用。我们还发现，AO具有特异性地聚集到恶性肿瘤细胞中的生物学特性，尤其是恶性骨和软组织肿瘤。基于这些结果，目前，我们在临床上应用光动力疗法和放射动力学疗法结合AO对恶性骨和软组织肿瘤进行边缘或病灶内切除。

In this study, we have undertaken to develop a new surgical strategy in tumor resection for malignant bone and soft tissue tumors, using cytocidal effect by acridine orange (AO) excited by various dynamic energy waves such as light-beam, X-ray, electro-magnetic field or ultra-sound. In vitro study using mouse osteosarcoma cell line revealed that AO excited with blue light beam (466 nm) or low-dose X-ray (5 Gy) showed a strong cytocidal effect, although both of an electro-magnetic field stimulation and ultra-sound did not. AO excited with blue light or X-ray was also effective to inhibit tumor growth in vivo study using mouse osteosarcoma inoculated subcutaneously. The mechanism of such a strong cytocidal effect of AO is speculated that intracellular free-radical as singlet oxygen which subsequently occurred after AO excitation with blue light or X-ray may kill tumor cells. We also found that AO has a biological feature to specifically accumulate into malignant tumor cells, especially, malignant bone and soft tissue tumors. Based on these results, at present, we clinically apply photodynamic therapy and radiodynamic therapy with AO to marginal or intra-lesional resection of malignant bone and soft tissue tumors.