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

• 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
• 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

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.

摘要 肝癌是一种致命的疾病，也是美国增长最快的癌症类型。最 患者不是手术的候选者，并且药物治疗最近才实现有限的存活 索拉非尼2-3个月的益处。这种药物价格昂贵，而且有许多副作用，限制了它的 接受和影响。原位治疗肿瘤的局部区域疗法同样具有局限性，尽管 生存期一般较长。现有疗法的主要临床弱点，如消融和 栓塞是治疗不完全和局部复发。在目前的建议中，我们寻求利用 酸和碱之间发生放热化学反应，在高温下释放热量和盐 浓度杀死肿瘤组织。我们假设同时发生的热力和渗透作用 压力在杀死肿瘤细胞方面非常有效，并且该过程可以被成像和控制。在第一个目标中 我们建议进行MRI温度成像来映射热剂量，结合多梯度回波 召回化学位移成像以高时间分辨率映射盐，钠MRI以映射盐。 处理体积中的钠浓度。在第二个目标中，我们将进行体外实验， 肿瘤细胞系，以了解细胞如何应对这种组合压力，并询问可能的途径 未来的干预。在最后的目标中，我们建议使用兔VX 2肿瘤模型在体内测试该概念， 其足够大以允许热和钠成像。