STUDIES ON THE TREATMENT AND CHARACTERISTICS OF THORACIC MALIGNANCIES

我们的部门已经制定了治疗和研究 胸部恶性肿瘤，包括间皮瘤，转移性疾病， 肺癌和食道癌间皮瘤的主要协议有 在最大时间使用术中光动力疗法 切除疾病，这导致了一个完整的I期试验， 开胸时PDT的最大耐受剂量为30 光敏剂Photofrin II给药间隔24小时后的焦耳/厘米2。 我们已经在II期试验中开发了一种免疫化疗方案， 干扰素、顺铂和他莫昔芬（CIT）治疗伴胸膜间皮瘤 通过三维体积分析检测到20%的响应率 电脑断层扫描的反应。CIT方案也被用于 作为一种辅助治疗，在10名患者切除后，他们的 间皮瘤 一项比较手术、PDT和CIT与 外科手术和CIT已经发展并正在积累患者。间皮瘤 来自这些患者的组织已被用于开发9种新的细胞系， 用于疾病的分子生物学分析 包括p53状态、3 p缺失信息、Wilms肿瘤抑制因子 基因状态，生长因子产生，包括PDGF，IGF-2，TGF α， LIF等，以及SV 4 O掺入分析。我们正试图 将胸苷激酶基因整合到细胞系中用于发育 未来的治疗策略。体外化疗和体外放疗 敏感性、在无血清培养基中的细胞系生长和特异性分析 受体也在进行中。关于疾病的起源，我们有 表明特定类型的石棉纤维会导致人类单核细胞 产生TNF，IL-1和11-6，并且致癌性越高的石棉 纤维将在干扰素存在下上调NO的产生。我们 建立了一种猪离体肺灌注肿瘤模型 并已开始I期临床试验，以确定 这种疗法的最大耐受剂量。干扰素的新辅助试验， 顺铂5-FU和甲酰四氢叶酸也在进行中，其中标记指数 食管癌，食管内超声的效用，和反应 正在研究费率。

Our section has developed protocols for the treatment and study of thoracic malignancies including mesothelioma, metastatic disease to the lungs, and esophageal cancer. The primary protocols for mesothelioma have been using intraoperative photodynamic therapy at the time of maximal resection of disease, which led to a completed Phase I trial which defined the maximum tolerated dose of PDT at the time of thoracotomy to be 30 Joules/cm2 after a 24 hour dosing interval of the sensitizer Photofrin II. We have developed an immunochemotherapy regimen in a Phase II trial using interferon, cisplatinum and tamoxifen (CIT) for pleural mesothelioma with a 20% response rate as detected by three dimensional volumetric analysis of computerized tomographic responses. The CIT regimen has also been used as an adjuvant treatment in ten patients after resection of their mesothelioma. A Phase III trial comparing surgery, PDT, and CIT vs surgery and CIT has been developed and is accruing patients. Mesothelioma tissue from these patients has been used to develop 9 new cell lines, which are being used for molecular biologic analysis of the disease including p53 status, 3p deletional information, Wilms tumor suppressor gene status, growth factor production including PDGF, IGF-2, TGFalpha, LIF, etc, as well as analysis for SV4O incorporation. We are attempting to incorporate the thymidine kinase gene into the cell lines for development of future treatment strategies. In vitro chemo, and in vitro radiation sensitivity, growth of lines in serum free media and analysis of specific receptors is also ongoing. Regarding the genesis of the disease, we have shown that specific types of asbestos fibers will cause human monocytes to produce TNF, IL-I, and 11-6, and that the more carcinogenic asbestos fibers will upregulate NO production in the presence of interferon. We have developed a swine model of isolated lung perfusion with tumor necrosis factor and have started a Phase I clinical trial to define the maximum tolerated dose of this therapy. A neoadjuvant trial of interferon, cisplatinum 5-FU, and leucovorin is also ongoing in which labelling index of esophageal cancer, utility of endoesophageal ultrasound, and response rates are being studied.