LASER PHOTOTHERAPY FOR THE TREATMENT OF MALIGNANCIES

激光光疗治疗恶性肿瘤

• 批准号: 3080259
• 负责人: DAN J CASTRO
• 金额: $ 7.73万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3080259
• 关键词: adenosine triphosphate; antineoplastics; argon; disease /disorder model; electron microscopy; fluorescent dye /probe; head /neck neoplasm; histochemistry /cytochemistry; human subject; infrared radiation; laser therapy; membrane potentials; mitochondria; neoplasm /cancer photoradiation therapy; radiation therapy dosage; skin neoplasms; swine; thermography; tissue /cell culture

Photodynamic therapy with lasers may become an attractive adjunctive modality for early diagnosis and treatment of superficial malignancies when fluorochromes with high tumor specificity and low toxicity are developed. The specific aims of this study are to: 1. Develop a noninvasive, simple, accurate, and reproducible quantitiative method of dosimetry of laser induced damage in tissues. The beam scan technique will be developed to measure spatial profiles of laser beams. An infrared camera will allow measurement of thermal profiles in the porcine skin model after exposure to increasing levels of laser energies. Volume of damage will be quantitated by serial histological sections. Damage range constant, absorption coefficients and thresholds for lesions for the CO2, Argon and Nd:YAG lasers will be predicted. The "LAD" (laser absorptive dose) parallel to the RAD in radiology will be determined. 2. Define the basic intracellular events in laser "killing" of Rhodamine-123 sensitized human squamous carcinoma and melanoma cells in-vitro. Mitochondrial function, membrane potential and morphology will be assessed respectively by measuring oxygen consumption, 86Rb, 3H-thymidine assays and electron microscopy. ATP levels after laser and Rhodamine-123 phototherapy will be quantitated by luciferin-luciferase assays allowing measurement of mitochondrial oxidative phosphorilation. 3. Establish a randomized clinical protocol which will allow us to test the potentials of this new fluorochrome for the treatment of superficial malignancies of the head and neck with the Argon laser. Patients with recurrent Stage IV tumors (squamous cell carcinoma, melanoma) will be injected with a nontoxic, sensitizing dose of Rhodamine-123, then subjected to low energy Argon laser therapy. Optimal tumor response will be assessed according to the histological type, tumor size, dosages of Rhodamine-123, various laser energies and frequency of treatment. Potential local and systemic toxicity of Rhodamine- 123 will be evaluated. Our study promises to provide relevant information toward the elucidation of the mechanism of action of this promising new photochemosensitizing agent, and will define the potentials for treatment of human head and neck tumors. Furthermore, the basic unit of dosimetry that will be developed with the lasers ("LAD") will allow standardization of scientific clinical and biomedical research.

激光光动力疗法可能成为一种有吸引力的 早期诊断和治疗的辅助手段 荧光染料伴高肿瘤时的浅表恶性肿瘤 开发出了特异性和低毒性的药物。 这项研究的具体目的是： 1.开发一种非侵入性、简单、准确和可重复性的 激光损伤的剂量学定量方法 纸巾。光束扫描技术将被开发用于测量 激光的空间分布。红外线摄像机将允许 猪皮肤模型中温度分布的测量 暴露在不断增加的激光能量水平下。损毁体积 将通过连续的组织切片进行定量。毁伤范围 常量、吸收系数和病变阈值 对CO2、Ar和Nd：YAG激光器进行了预测。这位“小伙子” (激光吸收剂量)在放射学上将与RAD平行 下定决心。 2.定义激光杀伤中的基本细胞内事件 罗丹明-123致敏人鳞癌和 体外培养黑色素瘤细胞。线粒体功能，膜 潜力和形态将分别通过以下方式评估 测量耗氧量，86Rb，~3H-胸腺嘧啶核苷分析和 电子显微镜。激光和罗丹明-123治疗后的ATP水平 光疗将通过荧光素-荧光素酶分析进行定量。 允许测量线粒体氧化磷酸化。 3.建立随机临床方案，使我们能够 测试这种新的荧光色素治疗癌症的潜力 头部和颈部的浅表性恶性肿瘤伴氩 激光。复发的IV期肿瘤患者(鳞状细胞 癌症、黑色素瘤)将注射一种无毒、 罗丹明-123的增敏剂量，然后进行低能量 氩激光疗法。将评估最佳的肿瘤反应 根据组织学类型、肿瘤大小、剂量 罗丹明-123，各种激光能量和频率 治疗。罗丹明的潜在局部和全身毒性- 将对123个进行评估。 我们的研究承诺为 阐明这一有希望的新技术的作用机制 光化学增敏剂，并将定义潜在的 人类头颈部肿瘤的治疗。此外， 将与激光一起发展的剂量学基本单位 (“法援署”)将使科学临床和 生物医学研究。