Harrison L H, Schwarzenberger P O, Byrne P S, Marrogi A J, Kolls J K, McCarthy K E
Department of Surgery, Louisiana State University Health Sciences Center, New Orleans 70112-2822, USA.
Ann Thorac Surg. 2000 Aug;70(2):407-11. doi: 10.1016/s0003-4975(00)01557-5.
Malignant mesothelioma is an uncommon but lethal cancer of increasing incidence, particularly among patients with a history of exposure to asbestos. Although numerous treatments have been employed, including chemotherapy, radiation therapy, surgical resection, and combinations of the above, no satisfactory treatment yet exists, and affected patients will die of this disease, usually within 12 months. Gene-based therapies constitute a new approach that offers hope of improved control of these tumors while being associated with less morbidity than conventional chemotherapeutic or surgical regimens. We demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a phenomenon that is required for optimal exertion of this therapeutic concept.
Gene-modified ovarian cancer cells expressing the thymidine-kinase gene (PA1-STK) were radiolabeled with 99Tc and infused into the pleural space of 4 patients with malignant pleural mesothelioma, then scanned to determine distribution of the cells.
PA1-STK cells recognized and adhered preferentially to mesothelioma lining the chest wall.
Cell-based "suicide gene" therapy utilizing the "bystander effect" with the gene-modified ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We have shown that this trafficking and homing of the therapeutic cells to the intrapleural tumor sites, a requirement for success with this novel therapeutic concept, is also valid in humans.
恶性间皮瘤是一种不常见但致命的癌症，其发病率在不断上升，尤其是在有石棉接触史的患者中。尽管已经采用了多种治疗方法，包括化疗、放疗、手术切除以及上述方法的联合应用，但仍不存在令人满意的治疗方法，受影响的患者通常会在12个月内死于这种疾病。基于基因的疗法是一种新方法，有望更好地控制这些肿瘤，同时与传统化疗或手术方案相比，发病率更低。我们证明了PA1-STK细胞在体内归巢于间皮瘤沉积物，这一现象是这种治疗理念最佳发挥作用所必需的。
将表达胸苷激酶基因的基因修饰卵巢癌细胞（PA1-STK）用99Tc进行放射性标记，然后注入4例恶性胸膜间皮瘤患者的胸腔，随后进行扫描以确定细胞的分布情况。
PA1-STK细胞优先识别并黏附于胸壁上的间皮瘤。
利用基因修饰卵巢癌细胞系PA1-STK的“旁观者效应”进行基于细胞的“自杀基因”疗法在人类胸膜间皮瘤中是可行的。我们已经表明，治疗性细胞向胸膜内肿瘤部位的这种运输和归巢，是这种新治疗理念成功的必要条件，在人类中也是有效的。
