ESTABLISHMENT 0F MECHANISMS OF CRYODESTRUCTION

描述(改编自申请者摘要)：前列腺癌 预计今年将有超过30万名新患者被确诊。那里 关于冷冻外科治疗这种疾病的最佳治疗方案是否存在争议 一。根据目前已知的关于细胞水平的机制 损伤体积不到一半的组织被冷冻在典型的 冷冻外科冰球将被摧毁。体内的非定量研究， 然而，这表明体内被破坏的组织体积更接近于 冷冻外科冰球中冻结的组织的总体积。按顺序 为了坚定地将冷冻外科作为前列腺癌的治疗手段， 手术中形成的冰球与终极状态的关系 它在解冻后造成的损害必须是可控的和可重复的。 因此，这项工作旨在对这一机制有一个准确的理解。 低温外科冰球的形成和融化所造成的损害 在细胞、血管和整个组织(体外和体内)水平上。 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，这种损伤 在冷冻手术过程中主要依赖于细胞机制 冷冻手术中心冰球和以血管损伤为主的 冰球的边缘。 2.可以使用冷冻手术过程中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的数量。 具体目标：为了检验这些假设，以下具体目标 目标将会实现： 1.建立形成和解冻过程中的热历史 体外和体内的冷冻外科冰球。 2.量化生物物理和热变化之间的关系 在体外形成一个冰球。 3.建立热和生物物理介导的细胞损伤 冰球的体外解冻。 4.确定形成过程中的细胞生物物理变化，以及 冷冻冰球在体内解冻后的血管损伤。 5.将所有机制造成的组织全面破坏与热史联系起来 在体内形成冷冻外科冰球的过程中和解冻后。

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.