OPTIMIZATION OF HYPERTHERMIA--BIOL & PHYSICAL STUDIES

在20世纪70年代的S和80年代初的S，热疗被证明有实质性的 有可能提高人类癌症的治愈率，因为临床前 高温与X射线矿石相互作用的研究 抗癌药物是如此令人信服的积极。迄今为止，体温过高可能会 已被证明可以增加乳腺癌的放射治疗控制 头颈部复发的胸壁和大颈部结节 癌症，但对患者的可治愈性(即总存活率)有影响 与这些或其他肿瘤的关系还没有文献记载。我们相信， 热疗没有充分发挥其临床潜力的原因是 因为它的生物相互作用和它的传递的物理学 都还有待优化。这两个因素都将在 此应用程序中建议的工作。 该计划中的相关项目将试图改善 体温过高的临床有用生物学通过：1)更好地定义 负责耐热性的机制，所以我们可以尝试 选择性地抑制恶性组织中耐热性的发展，以及， 因此，使更频繁的热疗分级变得合理(Dr。 考德伍德，项目I)；2)探索全身热疗(WBH)为一体 一系列抗癌烷基化试剂(AA‘s)的正向调节剂 +复杂动物模型的局部辐射(Teicher博士，项目II)； 以及3)继续开发最有效的抗癌药物组合 临床中的药物、局部放射和体温过高(Herman博士，项目 v)。该计划项目还将尝试改善 通过以下方式提供热疗：1)测试和完善 临床上的新型聚焦、分段超声机(FSUM)(Herman博士， 项目V)；2)开发新的3-D计算机建模能力，以 与FSUM的接口(Svensson博士，项目III)；3)利用间隙 可以测量组织温度和组织温度的探头 灌注(鲍曼博士，项目IVA)；以及4)开发简化的3-D 可实时用于改善患者状况的温度模型 使用FSUM进行治疗(Newman博士，Project IVb)。

In the 1970's and early 1980's hyperthermia was shown to have substantial potential to increase the curability of human cancer because preclinical studies of the interaction between hyperthermia and x-irradiation or anticancer drugs were so compellingly positive. To date, hyperthermia may have been shown to increase radiotherapeutic control of breast cancer recurrent on the chest wall and large neck nodes from head and neck cancers, but an impact on curability (i.e. overall survival) of patients with these or other tumors has not been documented. We believe that the reasons why hyperthermia has not reached its full clinical potential are because both its biological interactions and the physics of its delivery have yet to be optimized. Both of these factors will be addressed in the work proposed in this application. The interrelated Projects in this program will attempt to improve the clinically useful biology of hyperthermia by: 1) better defining the mechanisms responsible for thermotolerance so that we can attempt to selectively inhibit thermotolerance development in malignant tissues, and, thus, make more frequent fractionation of hyperthermia rational (Dr. Calderwood, Project I); 2) exploring whole body hyperthermia (WBH) as one of a series of positive modulators of anticancer alkylating agents (AA's) + local radiation in sophisticated animal models (Dr. Teicher, Project II); and 3) continuing to develop maximally effective combinations of anticancer drugs, local radiation and hyperthermia in the clinic (Dr. Herman, Project V). The Program Project will also attempt to improve the physics of hyperthermia delivery by: 1) testing and refining the capabilities of a new Focused, Segmented Ultrasound Machine (FSUM) in the clinic (Dr. Herman, Project V); 2) developing new 3-D computer modelling capabilities to interface with FSUM (Dr. Svensson, Project III); 3) utilizing interstitial probes which can measure tissue temperatures densely as well as tissue perfusion (Dr. Bowman, Project IVa); and 4) developing simplified 3-D temperature models which can be used in real time to improve patient treatments with the FSUM (Dr. Newman, Project IVb).