HYPERTHERMIA AND PERFUSION EFFECTS IN CANCER THERAPY

该项目的长期目标是优化热疗（HT）作为放疗（RT）和/或化疗（CT）辅助的应用。这个项目的优势在于它强调热剂量学和高温疗法与肿瘤生理学之间的相互关系。优势仍在继续，但在新的临床试验和新的治疗方法的背景下。这一竞争性更新的一个主要基石是在人类四肢软组织肉瘤患者中进行非侵入性测温的首次临床试验。我们之前对肿瘤氧合与治疗结果的观察使我们继续对软组织肉瘤和局部晚期乳腺癌进行生理学研究。激动人心的临床前研究和I期试验结果使我们能够用含药脂质体、HT介导的免疫基因治疗来测试HT，并继续研究腹腔内（IP）顺铂热化疗卵巢癌。项目1，人体临床研究，将进行9项临床试验，进入4个具体目标。(1)无创测温。(2)多机构III期试验测试HT作为潜在可治愈患者（晚期高级别软组织肉瘤和直肠癌）CT和RT的辅助手段。(3) HT联合含阿霉素脂质体和IP顺铂的新治疗试验。(4)继续探讨肿瘤生理学在HT+RT和HT+CT试验中的作用。项目2。新热疗在犬和猫肿瘤中的应用，重点研究了一种新的低温敏感脂质体制剂和使用HSP70启动子的高温触发免疫基因治疗的新临床试验。项目3，脂质体药物递送和热基因治疗，将与项目1和项目2相互作用，测量HT后患者的脂质体摄取，药物水平和基因治疗产品。项目4的重点是实施无创测温试验。四个核心（行政，动物，成像和工程）将支持该计划。

The long-term goal of this program is to optimize the application of hyperthermia (HT) as an adjuvant to radiotherapy (RT) and/or chemotherapy (CT). The strengths of this program have been its emphasis on thermal dosimetry and the inter-relationships between HT and tumor physiology. The strengths continue, but in the context of new clinical trials and novel therapeutics. A major cornerstone of this competing renewal is the first clinical trial testing non-invasive thermometry in human patients with extremity soft tissue sarcomas. Our prior observations of tumor oxygenation vs. treatment outcome lead us to continue physiologic studies of soft tissue sarcomas and locally advanced breast cancers. Provocative pre-clinical studies and phase I trial results lead us to test HT with drug-containing liposomes, HT mediated immunogene therapy and to continue studies of intraperitoneal (IP) cisplatin thermochemotherapy of ovarian cancer. Project 1, Human Clinical Studies, will conduct nine clinical trials entered on four specific aims. (1) Non-invasive thermometry. (2) Multi- institutional phase III trials testing HT as an adjuvant to CT and RT in potentially curable patients (advanced high grade soft tissue sarcoma and rectal cancer). (3) Novel therapeutic trials combining HT with doxorubicin-containing liposomes and with IP cisplatin. (4) Continued examination of the role of tumor physiology in HT+RT and HT+CT trials. Project 2. New Hyperthermia Applications in Canine and FELINE Tumors, focuses on novel clinical trials investigating a new low temperature-sensitive liposome formulation and HT triggered immunogene therapy using the HSP70 promoter. Project 3, Delivery of liposomal drugs and gene therapy with heat, will interact with projects 1 and 2 to measure liposomal uptake, drug levels and gene therapy products in patients after HT. The focus of project 4 is on the implementation of the non-invasive thermometry trial. Four cores (Administrative, Animal, Imaging and Engineering) will support the program.