Reduced Temperature Thermal Ablation for HCC and other Liver Tumors

HCC 和其他肝脏肿瘤的低温热消融

基本信息

批准号：
8236877
负责人：
Michael Jude Borrelli
金额：
$ 18.92万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8236877
关键词：
Ablation Affect Antineoplastic Agents Blood Vessels Chemicals Chemoembolization Colon Carcinoma Diffusion Disease Dose Emulsions Excision Heating Human Incidence Liver Liver neoplasms Liver parenchyma Mediating Modeling Neoplasm Metastasis Normal tissue morphology Operative Surgical Procedures Organ Temperatures Patients Permeability Pharmaceutical Preparations Primary carcinoma of the liver cells Probability Procedures Property Quality of life Rattus Recurrence Resistance Safety Skin Solid Staging Structure Temperature Testing Thermal Ablation Therapy Time Tissues Treatment Efficacy Unresectable Viral Vector Walkers advanced disease chemotherapy cold temperature improved killings liver function liver transplantation nanoparticle neoplastic cell outcome forecast palliation patient population public health relevance radiofrequency research study targeted delivery treatment strategy tumor

项目摘要

DESCRIPTION (provided by applicant): Cyclopentadecanolide (CPDL) emulsions markedly lower the threshold temperature required to thermally ablate solid tissues. The proposed study will test the hypothesis that targeted delivery of CPDL into liver tumors will preferentially sensitize them to thermal ablation at temperatures of 44-55oC and that this CPDL-mediated reduced temperature thermal ablation (CPDL-RTTA) strategy will result in safer and more effective thermal ablation of liver tumors with improved sparing of normal liver tissue. Experiments will be performed using the rat Walker 256 liver tumor model. Specific aim one is to identify the most effective means for localizing delivery of effective doses of CPDL to liver tumors and to confirm that the prescribed CPDL dose has been delivered to tumors before initiating thermal ablation. The second aim is to demonstrate that CPDL-RTTA increases tumor ablation volume, can overcome the vascular heat sink effect, and will improve the ability to establish local tumor control. If this study is successful the developed treatment strategies can be directed towards treating patients that are currently ineligible for thermal ablation therapy for their liver tumors. Thermal ablation will then have broader applicability and utility as a treatment for establishing local tumor control, downstaging liver tumors so that resection or liver transplant become treatment options, or palliating advanced disease to improve quality of life. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to develop a better procedure for thermally ablating human hepatocellular carcinoma (HCC) and other liver tumors such that tumor killing is improved while more normal tissue is spared and remains functional. This will be accomplished by targeting delivery of a chemical emulsion (active ingredient cyclopentadecanolide (CPDL)) that markedly lowers the temperature threshold required to ablate the tumor. Effective tumor ablation will be performed using temperatures between 45-55oC, which will not harm normal liver tissues since they will not have received the thermal sensitizing CPDL. If successful, the CPDL procedure will improve tumor ablation efficacy and should make tumor thermal ablation available to patients that are currently excluded because their liver tumors are too numerous and/or massive.

描述（由申请人提供）：环十五内酯（CPDL）乳液显着降低了热消融实体组织所需的阈值温度。拟议的研究将测试以下假设：将 CPDL 靶向递送到肝脏肿瘤中将优先使它们对 44-55oC 温度下的热消融敏感，并且这种 CPDL 介导的低温热消融 (CPDL-RTTA) 策略将导致更安全、更有效的治疗。有效热消融肝脏肿瘤，并改善正常肝组织的保护。实验将使用大鼠 Walker 256 肝肿瘤模型进行。具体目标之一是确定将有效剂量的 CPDL 局部递送至肝脏肿瘤的最有效方法，并确认在开始热消融之前已将规定的 CPDL 剂量递送至肿瘤。第二个目的是证明CPDL-RTTA增加肿瘤消融体积，可以克服血管热沉效应，并将提高建立局部肿瘤控制的能力。如果这项研究成功，所开发的治疗策略可用于治疗目前不适合接受肝脏肿瘤热消融治疗的患者。热消融将具有更广泛的适用性和效用，作为一种治疗方法，用于建立局部肿瘤控制、使肝脏肿瘤降期以使切除或肝移植成为治疗选择，或缓解晚期疾病以提高生活质量。公共健康相关性：该提案的目的是开发一种更好的热消融人类肝细胞癌 (HCC) 和其他肝脏肿瘤的程序，从而提高肿瘤杀伤力，同时更多的正常组织得以幸免并保持功能。这将通过靶向递送化学乳液（活性成分环十五内酯（CPDL））来实现，该乳液显着降低消融肿瘤所需的温度阈值。有效的肿瘤消融将在 45-55oC 之间的温度下进行，这不会伤害正常肝组织，因为它们不会接受热敏化 CPDL。如果成功，CPDL 手术将提高肿瘤消融效果，并为目前因肝肿瘤数量过多和/或巨大而被排除在外的患者提供肿瘤热消融。