Antivascular ultrasound therapy of primary liver neoplasia

原发性肝肿瘤的超声抗血管治疗

• 批准号: 9234984
• 负责人: CHANDRA M SEHGAL
• 金额: $ 38.97万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234984
• 关键词: Acoustics; Adverse effects; Affinity; Age; Angiogenesis Inhibitors; Animal Model; Animals; Blood Vessels; Blood flow; Cancer Etiology; Cells; Cessation of life; Clinical; Clinical Trials; Cytotoxic Chemotherapy; Deposition; Endothelial Cells; Endothelium; Energy Transfer; Exposure to; Feedback; Frequencies; Future; Goals; Heating; Image; Implant; Incidence; Individual; Knowledge; Laboratories; Liver; Liver neoplasms; Malignant Neoplasms; Measures; Methods; Microbubbles; Microscopic; Modeling; Monitor; Neoplasms; Neoplasms in Vascular Tissue; Outcome; Outcome Study; Patients; Pharmacologic Substance; Physical therapy; Population; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Process; Rattus; Research; Role; Sonication; Source; Techniques; Technology; Temperature; Testing; Time; Tissues; Translations; Treatment Efficacy; Ultrasonic Therapy; Ultrasonic wave; Ultrasonography; Width; absorption; base; cancer cell; cancer therapy; comparative; computer studies; contrast enhanced; cost; design; feeding; human subject; improved; insight; interest; intravenous administration; mathematical model; neovascularization; neovasculature; novel; novel strategies; quantitative ultrasound; response; simulation; tumor; tumor growth

ABSTRACT Hepatocellular carcinoma (HCC) accounts for 80 to 90% of primary liver cancer. It is the fifth most common malignancy and is the third most common cause of cancer-related death. This application will test the novel approach of antivascular ultrasound for treating HCC. Our preliminary studies show that low- level ultrasound with intensities comparable to those used in treating physiotherapy patients, when used with microbubbles, disrupts tumor neovasculature and improves the survival of animals with implanted tumors. The goals of the research are to demonstrate the efficacy of antivascular ultrasound for treating HCC, and to identify the conditions of treatment that have high efficacy as measured both by imaging and survival of the animals with implanted liver tumors. The proposal has three Specific Aims. Specific Aim 1 will investigate the relationship between blood flow and temperature change. Specific Aim 2 will determine the ultrasound exposure conditions that produce tumor antivascular activity at the lowest possible exposure to ultrasound. Specific Aim 3 will evaluate the short-term and the long term-term therapeutic efficacy of single and multiple ultrasound treatments. We anticipate that the knowledge gained from the proposed research will lead to a new form of antivascular or vascular disrupting treatment for HCC. Of particular interest would be the ability of antivascular ultrasound to treat non-resectable small and large cancers frequently observed clinical. Advantages include the simplicity and small cost of low-intensity ultrasound technology, the use of quantitative ultrasound imaging to assess and monitor therapeutic efficacy at the time of treatment, and fewer unwanted side effects from the low-intensity ultrasound therapy compared to cytotoxic therapies. We anticipate that the results of this study will facilitate the translation of a novel ultrasound technology to the treatment of patients with HCC.

抽象的 肝细胞癌（HCC）占原发性肝癌的80%至90%。这是第五大 常见的恶性肿瘤，是癌症相关死亡的第三大常见原因。该应用程序将测试 抗血管超声治疗 HCC 的新方法。我们的初步研究表明，低 使用时，超声波的强度与治疗物理治疗患者所用的强度相当 具有微泡，破坏肿瘤新血管系统并提高植入动物的存活率 肿瘤。 该研究的目标是证明抗血管超声治疗 HCC 的功效，以及 确定通过影像学和生存率衡量的高效治疗条件 植入肝肿瘤的动物。 该提案有三个具体目标。具体目标 1 将研究血流之间的关系 和温度变化。具体目标 2 将确定产生的超声波暴露条件 在尽可能低的超声暴露下肿瘤的抗血管活性。具体目标 3 将评估 单次和多次超声治疗的短期和长期治疗效果。 我们预计从拟议的研究中获得的知识将带来一种新形式的抗血管药物 或 HCC 的血管破坏治疗。特别令人感兴趣的是抗血管能力 超声治疗不可切除的小型和大型癌症在临床上经常观察到。优点包括 低强度超声技术简单且成本低，定量超声的使用 成像以评估和监测治疗时的治疗效果，并减少不需要的副作用 与细胞毒性疗法相比，低强度超声疗法的效果。我们预计 这项研究的结果将有助于将新型超声技术转化为治疗 肝癌患者。