ESTABLISHMENT 0F MECHANISMS OF CRYODESTRUCTION

描述（改编自申请人的摘要）：前列腺癌是一种 预计今年将有超过30万新患者被诊断出来。 那里 关于冷冻手术治疗疾病的最佳治疗方法， 一个. 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 冷冻手术冰球就会被摧毁 体内非定量研究， 然而，这表明体内破坏的组织体积更接近于 冷冻手术冰球中冷冻的组织的总体积。 为了 为了牢固确立冷冻手术作为前列腺癌的治疗方法， 手术过程中形成的冰球与最终的 解冻后产生的损害必须是可控的和可再生的。 因此，这项工作的目的是发展一个精确的理解的机制 由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。 提出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， 在冷冻外科手术中主要取决于细胞机制， 冷冻手术冰球的中心和主要的血管损伤 冰球的边缘 2. 可以使用在冷冻外科手术期间施加在组织上的热历史 通过细胞和血管机制来预测组织死亡的数量。 具体目标：为了检验这些假设，以下具体目标 目标将实现： 1. 建立在形成和融化过程中的热历史 体外和体内的冷冻手术冰球。 2. 量化生物物理和热变化之间的关系， 在试管中形成冰球。 3. 建立热和生物病理学介导的细胞损伤后， 体外解冻冰球。 4. 在形成过程中建立细胞生物物理变化，以及 血管损伤后解冻，冷冻外科冰球在体内。 5. 通过所有机制将总组织破坏与热历史相关联 在体内冷冻手术冰球的形成过程中和解冻后。

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.