Simultaneous Thermal and Osmotic Stresses in Tumor Ablation: Imaging and Biology

肿瘤消融中的同时热应力和渗透应力：成像和生物学

基本信息

批准号：
9315789
负责人：
ERIK N CRESSMAN
金额：
$ 37.35万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-14 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9315789
关键词：
Ablation Acetic Acids Acids Acute Address Adverse effects Affect BAY 54-9085 Biology Cell Death Cell physiology Cells Cellular Stress Cessation of life Characteristics Chemical Shift Imaging Chemicals Chemistry Clinic Clinical Clinical Trials Coagulation Process Combined Modality Therapy Disease Disease Management Dose Electrodes Ethanol Family suidae Funding Future Goals Image In Situ In Vitro Incidence Intervention Ions Lead Left Liver Local Therapy Magnetic Resonance Imaging Malignant Neoplasms Maps Medical Methods Modeling Molecular Monitor Natural Products Necrosis Needles Operative Surgical Procedures Oryctolagus cuniculus Outcome Pathway interactions Patient Selection Patients Pharmaceutical Preparations Pharmacotherapy Primary carcinoma of the liver cells Process Radiofrequency Interstitial Ablation Reaction Recording of previous events Recurrence Residual state Salts Sodium Sodium Chloride Solid Neoplasm Source Stress Technology Temperature Testing Therapeutic Embolization Thermography Tissues Toxic effect Tumor Cell Line Tumor Tissue United States base biological adaptation to stress cancer type chemical reaction cost cytotoxicity experimental study flexibility image guided improved improved outcome in vivo innovation killings mortality neoplastic cell novel response synergism systemic toxicity temporal measurement tumor tumor ablation

项目摘要

Abstract Hepatocellular carcinoma is a lethal disease and the fastest growing type of cancer in the United States. Most patients are not candidates for surgery and medical therapy has only recently achieved a limited survival benefit of 2-3 months with sorafenib. This drug is costly and has a number of side effects limiting its acceptance and impact. Locoregional therapies treating tumor in situ likewise have limitations, although the survival benefit is generally longer. Major clinical weaknesses of existing therapies such as ablation and embolization are incomplete treatment and local recurrence. In the current proposal, we seek to harness the exothermic chemical reaction between an acid and a base to release heat and a salt at high local concentration to kill tumor tissue. We hypothesize that the combination of simultaneous thermal and osmotic stress is highly effective in killing tumor cells and that the process can be imaged and controlled. In the first aim we propose to perform MRI temperature imaging to map the thermal dose, combined with multi-gradient echo recall chemical shift imaging to map the salt with high temporal resolution, and sodium MRI to map the concentration of the sodium in the treated volume. In the second aim we will perform in vitro experiments on tumor cell lines to understand how cells respond to this kind of combined stress and interrogate likely pathways for future intervention. In the final aim we propose to test the concept in vivo using the rabbit VX2 tumor model, which is large enough to allow for the thermal and sodium imaging.

抽象的肝细胞癌是一种致命的疾病，是美国增长最快的癌症。最多患者不是手术的候选者，并且医疗疗法最近才获得有限的生存率索拉非尼的好处2-3个月。该药物的昂贵，并且有许多副作用限制接受和影响。治疗肿瘤原位治疗的局部区域疗法也有局限性，尽管生存益处通常更长。现有疗法的主要临床弱点，例如消融和栓塞是不完整的治疗和局部复发。在当前的提议中，我们试图利用酸与碱之间的放热化学反应，以释放热量和盐分盐浓度杀死肿瘤组织。我们假设同时热和渗透的组合压力在杀死肿瘤细胞方面非常有效，并且可以成像和控制该过程。在第一个目标我们建议执行MRI温度成像以绘制热剂量，并结合多速率回声回忆化学移位成像以用高颞分辨率绘制盐，然后MRI钠MRI绘制钠在处理体积中的浓度。在第二个目标中，我们将在体外实验肿瘤细胞系以了解细胞如何响应这种综合应力并询问可能的途径用于将来的干预。在最终目标中，我们建议使用兔VX2肿瘤模型在体内测试概念，足够大，可以允许热成像和钠成像。