POTENTIATION OF CHEMOTHERAPY BY LOW-LEVEL ULTRASOUND

低强度超声增强化疗效果

• 批准号: 3197511
• 负责人: GEORGE H HARRISON
• 金额: $ 10.65万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3197511
• 关键词: breast neoplasms; cell line; cis platinum compound; combination cancer therapy; cytotoxicity; doxorubicin; drug screening /evaluation; fluorouracil; multidrug resistance; neoplasm /cancer chemotherapy; neoplasm /cancer photoradiation therapy; neoplasm /cancer thermotherapy; nitrogen mustard; nonhuman therapy evaluation; tamoxifen; tissue /cell culture; ultrasound therapy; vincristine

The objective of this project is to evaluate the hypothesis that chemotherapy can be potentiated by novel forms of low-level ultrasound (US) which by itself causes no tissue heating or cell killing. The main innovation of the project is the use of spatially uniform bursts of continuous-wave or pulsed US, including high-pressure amplitudes at low duty cycles. The specific goals related to US methodology are to develop US source/transducer systems producing a selected variety of treatment fields, and then to optimize field parameters (frequency, exposure time, temporal peak intensity, duty cycle, and wave-form shape) based on response of Chinese hamster ovary (CHO) cells to combined exposure to US and adriamycin at 1 microgram/ml. the US beam parameters producing the most effective combined treatment will serve as a baseline for testing other drugs and cell lines. Next, other anti-neoplastics (cisplatin, nitrogen mustard, hematoporphyrin derivative, r-fluorouracil, vincristine, and tamoxifen) will be screened using US and CHO cells. Effective drugs will then be tested against wild-type and multi-drug-resistant MCF-7 human breast carcinoma cell lines. In each test, survival curves will be obtained as a function of drug concentration, with and without US, to evaluate US enhancement. Mechanisms of US-enhanced drug activity will be investigated by in vitro measurements of US-induced changes in labelled drug uptake, free radical production, and treatment effectiveness in normal vs. drug-resistant cells. Any dependence of these endpoints with the US beam parameters mentioned above will provide valuable clues concerning possible athermal US interaction mechanisms such as intracellular streaming, finite amplitude effects, or transient cavitation. Primary emphasis in US technique development and biological experimentation will be placed on determining the potential of low-level US as a practical clinical adjuvant to improve chemotherapy.

本项目的目的是评估假设， 新形式的低强度超声（US）可增强化疗效果 其本身不会引起组织加热或细胞杀伤。 主要 该项目的创新之处在于使用空间均匀的 连续波或脉冲US，包括低压下的高压振幅 占空比 与美国方法论相关的具体目标是发展美国 产生选定的各种治疗场的源/换能器系统， 然后优化场参数（频率、曝光时间、时间 峰值强度、占空比和波形形状）的响应 联合暴露于US和阿霉素的中国仓鼠卵巢（CHO）细胞 1微克/毫升。 美国波束参数产生最有效的 联合治疗将作为测试其他药物的基线， 细胞系 接下来，其他抗肿瘤药物（顺铂，氮芥， 血卟啉衍生物、r-氟尿嘧啶、长春新碱和他莫昔芬） 将使用US和CHO细胞进行筛选。 有效的药物将 针对野生型和多药耐药MCF-7人乳腺癌进行了测试 癌细胞系。 在每项试验中，生存曲线将作为 使用和不使用US时的药物浓度函数，以评价US 增强 US增强药物活性的机制将通过体外研究 测量超声诱导的标记药物摄取、自由基 生产和治疗效果在正常与耐药细胞。 这些终点与所述US射束参数的任何相关性 以上所述将提供有关美国可能的非热性的有价值的线索 相互作用机制，如细胞内流，有限振幅 效应或瞬时空化。 美国技术开发和生物实验的主要重点 将被放置在确定低层次的美国作为一个实际的潜力， 临床辅助化疗提高疗效。