Antivascular ultrasound therapy of primary liver neoplasia

摘要 肝细胞癌占原发性肝癌的80%至90%。它是世界第五大 癌症是一种常见的恶性肿瘤，是癌症相关死亡的第三大常见原因。此应用程序将测试 抗血管超声治疗肝癌的新途径。我们的初步研究表明，低- 水平超声波，其强度与理疗患者使用的超声波相当 利用微泡，破坏肿瘤新生血管，并提高植入的动物的存活率 肿瘤。 这项研究的目的是证明抗血管超声治疗肝癌的有效性，以及 确定通过成像和生存来衡量具有高疗效的治疗条件 移植了肝脏肿瘤的动物。 该提案有三个具体目标。特定目标1将研究血液流动与 以及温度的变化。特定目标2将确定产生的超声波暴露条件 将肿瘤的抗血管活性降至最低，暴露在超声波下。《特定目标3》将评估 单次和多次超声治疗的近期和远期疗效比较。 我们预计，从拟议的研究中获得的知识将导致一种新形式的抗血管药物 或肝细胞癌的血管阻断治疗。特别令人感兴趣的是抗血管的能力 超声治疗不能切除的小癌和大癌临床上常被观察到。优势包括 低强度超声技术的简单性和低成本，使用定量超声 成像在治疗时评估和监测治疗效果，减少不良副作用 低强度超声波治疗与细胞毒治疗的效果比较。我们预计， 这项研究的结果将有助于将一种新的超声技术转化为治疗糖尿病的方法 肝细胞癌患者。

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.