ESTABLISHMENT 0F MECHANISMS OF CRYODESTRUCTION

0F冷冻破坏机制的建立

• 批准号: 6173111
• 负责人: JOHN C BISCHOF
• 金额: $ 9.89万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-15 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173111
• 关键词: biochemistry; biophysics; biopsy; calorimetry; cell death; cryoelectron microscopy; cryosurgery; cytotoxicity; fluoroscopy; freezing; human tissue; laboratory rat; prostate neoplasms; prostate surgery; thermodynamics; tissue /cell culture; vascular endothelium

DESCRIPTION (Adapted from Applicant's Abstract): Prostate cancer is expected to be diagnosed in more that 300,000 new patients this year. There is debate as to the optimal treatment of the disease of which cryosurgery is one. Based on what is currently known about cellular level mechanisms of injury less than one half of the volume of tissue frozen in a typical cryosurgical iceball would be destroyed. Nonquantitative studies in vivo, however, suggest that the volume of tissue destroyed in vivo is closer to the total volume of the tissue frozen in the cryosurgical iceball. In order to firmly establish cryosurgery as a treatment of prostate cancer, the relationship between the iceball formed during the surgery and the ultimate damage it creates after thawing must be both controllable and reproducible. Therefore this work aims to develop a precise understanding of the mechanism of damage induced by the formation and thawing of the cryosurgical iceball at the cellular, vascular, and whole tissue (in vitro and in vivo) level. The following hypotheses and specific aims have been developed. Hypotheses: 1. Given that cryosurgery produces tissue death, the injury during cryosurgery depends on predominantly cellular mechanisms in the center of the cryosurgery iceball and predominately vascular injury at the periphery of the iceball. 2. The thermal history imposed on tissue during the cryosurgery can be used to predict the amount of tissue death by cellular and vascular mechanisms. Specific Aims: In order to test these hypotheses, the following specific aims will be accomplished: 1. Establish the thermal history during formation and thawing of a cryosurgical iceball in vitro and in vivo. 2. Quantify the relationship between biophysical and thermal changes during the formation of an iceball in vitro. 3. Establish thermally and biophysically mediated cellular injury after thawing of the iceball in vitro. 4. Establish cellular biophysical changes during the formation, and vascular injury after thawing, of the cryosurgical iceball in vivo. 5. Correlate total tissue destruction by all mechanisms to thermal history during the formation, and after thawing, of a cryosurgical iceball in vivo.

描述（改编自申请人的摘要）：前列腺癌是 预计今年将有超过30万名新患者被诊断出来。 那里 关于冷冻手术所适用的疾病的最佳治疗方法存在争议 一。 基于目前已知的细胞水平机制 损伤小于典型冷冻组织体积的一半 冷冻手术冰球会被破坏。 体内非定量研究， 然而，表明体内破坏的组织体积更接近 冷冻手术冰球中冷冻组织的总体积。 为了 为了牢固确立冷冻手术作为前列腺癌的治疗方法， 手术中形成的冰球与最终效果的关系 解冻后造成的损害必须是可控且可重现的。 因此，这项工作旨在深入了解该机制 冷冻手术冰球的形成和融化引起的损伤 在细胞、血管和整个组织（体外和体内）水平。 已经制定了以下假设和具体目标。 假设： 1. 鉴于冷冻手术会导致组织死亡，损伤 冷冻手术期间主要取决于细胞机制 冷冻手术冰球的中心和主要是血管损伤 冰球的外围。 2. 可以使用冷冻手术期间施加在组织上的热历史 通过细胞和血管机制预测组织死亡量。 具体目标：为了检验这些假设，以下具体目标 将实现的目标： 1. 建立形成和解冻过程中的热历史 体外和体内冷冻手术冰球。 2. 量化生物物理和热变化之间的关系 体外冰球的形成。 3. 建立热和生物物理介导的细胞损伤 体外冰球解冻。 4. 确定细胞形成过程中的生物物理变化，以及 体内冷冻手术冰球解冻后血管损伤。 5. 将所有机制的总组织破坏与热历史相关联 体内冷冻手术冰球形成期间和解冻后。