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.

本研究利用吖啶橙子（AO）在各种动态能量波（如光束、X射线、电磁场或超声波）激发下的杀细胞作用，开发了一种新的手术策略，用于恶性骨和软组织肿瘤的切除。小鼠骨肉瘤细胞株体外实验表明，蓝光（466 nm）或低剂量X射线（5戈伊）激发的AO具有较强的杀伤细胞作用，而电磁场和超声波激发的AO则无杀伤细胞作用。用蓝光或X射线激发的AO在皮下接种小鼠骨肉瘤的体内研究中也有效地抑制肿瘤生长。AO具有如此强的细胞杀伤作用，其机制可能是蓝光或X射线激发AO后产生的单线态氧等细胞内自由基杀死肿瘤细胞。我们还发现AO具有特异性积聚于恶性肿瘤细胞，特别是恶性骨和软组织肿瘤细胞的生物学特性。基于这些结果，目前我们临床上将AO光动力学治疗和放射动力学治疗应用于恶性骨和软组织肿瘤的边缘或病灶内切除。

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.