STUDIES OF PHOTOTHERAPY FOR THORACIC MALIGNANCIES

我们实验室对光动力疗法进行了持续的研究。 恶性细胞敏化治疗胸部恶性肿瘤 用双血卟啉乙醚，然后用630 nm的光照射。 自1989年10月以来，我们已经建立了不同肺的敏感性。 体外培养的癌细胞系。我们在试管中发现了微小的变异 光疗敏感度。我们已经从以下方面描述了这些变化 以双血卟啉醚含量、细胞大小、细胞体积、细胞蛋白为指标 以及电镀效率。我们已经公布了关于 肿瘤坏死因子和HAVE对小鼠巨噬细胞的作用 据透露，光动力疗法刺激这些巨噬细胞 增加巨噬细胞上清液中的肿瘤坏死因子。这可以是 在没有内毒素的情况下检测到。我们还有 建立了这种肿瘤坏死因子在24小时内产生的动力学。 这些数据代表了细胞因子释放的第一个证据，因为 光动力疗法，也可以解释光动力疗法的间接细胞毒性 作为血管效应。我们正在继续调查如何治疗 支气管腔内恶性肿瘤的PDT患者，我们现在已经治疗了 18例支气管腔内疾病伴PDT。70%的回复率 这些患者的发病率和患者都得到了很好的缓解和光动力 支气管治疗现在已成为我们首选的治疗方法。 经支气管镜治疗。我们现在还在进行光动力疗法 胸膜恶性肿瘤的治疗。我们目前已经治疗了7名患者 胸膜恶性肿瘤的清除和术中光动力疗法 心理治疗。这项试验现正作为经批准的第一阶段试验在 临床中心。在进行这些人体研究之前，我们进行了犬类实验 我们建立了正常胸部的剂量耐受性的实验 组织(食道、肺、心脏、胸壁和横隔膜)至PDT。

Our laboratory has continued investigation of photodynamic therapy for the treatment of thoracic malignancies by sensitization of, malignant cells with dihematoporphyrin ether followed by illumination by 630 nM light. Since October 1989 we have established the sensitivity of different lung cancer lines in vitro. We have found minor variations in vitro as far as phototherapy sensitivity. We have characterized these changes with regard to dihematoporphyrin ether content, cell size, cell volume, cell protein as well as plating efficiency. We have published investigations concerning the treatment of murine macrophages with tumor necrosis factor and have revealed that photodynamic therapy stimulates, these macrophages to increase tumor necrosis factor in the macrophage supernatants. This can be detected either in the presence of absence of endotoxin. We have also established the kinetics of such TNF production over a 24 hour period. These data represent the first demonstration of cytokine release due to photodynamic therapy and may explain indirect cytotoxicity of PDT as well as vascular effects. We are continuing investigations of the treatment of patients with endobronchial malignancies with PDT and we have now treated 18 patients with endobronchial disease with PDT. There is a 70% response rate in these patients and the patients are well palliated and photodynamic therapy of the bronchus has now become our preferred method of endobronchial therapy. We are also now performing photodynamic therapy for treatment of pleural malignancies. We have presently treated 7 patients with debulking of pleural malignancies and intraoperative photodynamic therapy. This is now being studied as an approved Phase I trial at the Clinical Center. Before performing these human studies we performed canine experiments in which we established the dose tolerance of normal thoracic tissue (esophagus, lung, heart, chest wall and diaphragm) to PDT.