STUDIES OF PHOTOTHERAPY AND FREE RADICAL LYMPHOKINE RELATIONSHIPS

光疗和自由基淋巴因子关系的研究

• 批准号: 3853218
• 负责人: H I PASS
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853218
• 关键词: bronchoscopy; bronchus neoplasm; clinical trials; cytotoxicity; disease /disorder model; dogs; free radicals; human subject; hydrogen peroxide; immunoconjugates; laboratory mouse; lung neoplasms; macrophage; metastasis; monoclonal antibody; neoplasm /cancer photoradiation therapy; oncogenes; phototherapy; pleural neoplasms; porphyrins; radiation sensitivity; radiation therapy dosage; superoxides; thorax neoplasm; tissue /cell culture; tumor necrosis factor alpha

Our laboratory has continued its investigation of photodynamic therapy (PDT) by sensitization of malignant cells with dihematoporphyrin ether followed by illumination by 630 nm light. Since October 1990, we have established an in vitro, in vivo model of PDT for cells transformed with the k-ras oncogene which is frequently activated in lung cancer. The model was found to exhibit (1) classic sensitizer retention characteristics of other models, and (2) predictable tumor regression with PDT. The model have been used to investigate the use of monoclonal antibody conjugated to the sensitizer, and superior PDT effects as well as greater sparing of normal tissue has been demonstrated. A murine model of solid peritoneal carcinomatosis, investigating sensitizer delivery, and maximal tolerated dose of PDT was published. A large animal model of PDT investigating the effects on intrathoracic organs revealed that focal PDT up to 40 Joules/cm2 was tolerated by heart, esophagus, chest wall, and lung. A Phase I human trial which combines radical debulking to 5 mm thickness of pleural malignancies followed by intrathoracic-intraoperative delivery of PDT for incurable, localized thoracic malignancies has been ongoing. Light dose escalation in cohorts of three patients has been performed from 15 Joules/cm2 to 32.5 Joules/cm2. We continue to treat patients with obstructing endobronchial malignancies with PDT delivered by bronchoscopy. As a followup on studies revealing PDT induction of tumor necrosis factor, our laboratory has demonstrated that free radical stress itself with hydrogen peroxide or superoxide can induce macrophages to produce TNF, and that radical-inducing chemotherapies can increase TNF production. Moreover, we have demonstrated that SOD-mimics can, at least, in vitro, abrogate TNF cytotoxicity. Investigations of other compounds which may be useful in protecting against cytokine toxicity is continuing in our section with in vitro and in vivo models.

我们实验室继续进行光动力疗法的研究 (PDT)用二血卟啉醚致敏恶性细胞 随后用630 nm光照射。 自1990年10月以来， 建立了体外，体内PDT模型，用于转化细胞， K-ras癌基因在肺癌中经常被激活。 的 发现模型表现出（1）经典的敏化剂保留 其他模型的特征，和（2）可预测的肿瘤消退 在PDT。 该模型已被用于研究使用单克隆 结合到敏化剂上的抗体，以及上级PDT效果 因为已经证明了正常组织的更大保留。 鼠 实体性腹膜癌转移模型，研究致敏剂 递送，和PDT的最大耐受剂量。 大 研究对胸腔内器官影响的PDT动物模型 显示心脏耐受高达40焦耳/cm 2的局灶性PDT， 食道胸壁和肺 第一阶段人体试验结合了 胸膜恶性肿瘤根治性减积至5 mm厚度， PDT的胸腔内-术中递送用于不可治愈的局部 胸部恶性肿瘤一直在持续。 轻度剂量递增， 三名患者的队列已经从15焦耳/平方厘米到32.5焦耳/平方厘米进行了测试。 焦耳/平方厘米。 我们继续治疗那些 支气管内恶性肿瘤，通过支气管镜进行PDT治疗。 作为 对揭示PDT诱导肿瘤坏死因子的研究进行了跟踪， 我们的实验室已经证明，自由基本身的压力， 过氧化氢或超氧化物可诱导巨噬细胞产生TNF， 而自由基诱导化疗可以增加TNF的产生。 此外，我们已经证明，SOD模拟物可以，至少，在体外， 消除TNF细胞毒性。 其他化合物的研究， 可用于保护免受细胞因子毒性的研究仍在继续， 体外和体内模型部分。