A Novel Approach to Nerve-Sparing Prostate Cryosurgery

描述(由申请人提供)：细胞保存服务公司(CPSI)是一家生物技术公司，专注于开发新的创新方法，利用低温和冷冻温度来支持细胞治疗和癌症领域。在前者中，CPSI研究低温储存(4C)和低温保存(-196)期间激活的应力通路，以便开发改进的工艺。关于应激途径的类似数据也被用于增强消融性冷冻过程中癌细胞的死亡-这是一种将传统冷冻手术与辅助(例如5-FU、顺铂)治疗相结合的方法。这种方法最近导致了医生赞助的IND治疗晚期前列腺癌的启动。这个第一阶段的项目建议开发一种新的治疗设备(Neuprosol)，用于在前列腺癌的冷冻外科治疗中保护神经血管束(NVB)并最终保护勃起功能。开发该设备的理由如下：(1)NeuprosolTM将在冷冻手术应用时直接应用于NVB；(2)将通过分子分析设计针对神经细胞的保护剂；(3)还将开发保护剂以提供不同程度的分区(热)保护；(4)该设备的使用将成为一种有效的神经保护药物，并最终还可能用于尿路保护。第一阶段的具体目标是：SA1确定冷冻对神经细胞活性的影响；SA2确定细胞凋亡在冷冻诱导的神经细胞死亡中所起的作用；SA3确定哪些新型药物可用于保护神经细胞免受冷冻破坏机制的影响；SA4使用犬冷冻外科模型测试NeuprosolTM作为神经保留概念的有效性。第一阶段和第二阶段的成功完成将导致NeuprosolTM的开发，NeuprosolTM随后可以在前列腺癌的冷冻外科消融术中用作有效的神经保留剂。一旦开发和测试，NeuprosolTM可能会成为一种保留神经的治疗方法，以及保护其他组织(如尿路)的另一种方法。因此，这一新的治疗设计将为临床领域提供重大好处，并为未来癌症治疗策略的发展提供平台。

DESCRIPTION (provided by applicant): Cell Preservation Services Inc. (CPSI) is a biotechnology corporation focused on developing new and innovative approaches to the use of chilling and freezing temperatures in support of the cell therapy and cancer arenas. In the former, CPSI studies stress pathways activated during hypothermic storage (4C) and cryopreservation (-196) so that improved processes can be developed. Similar data on stress pathways are also being used to potentiate cell death in cancer cells during ablative freezing processes - a regime that couples traditional cryosurgery with adjuvant (e.g. 5-FU, cisplatin) treatments. This approach has recently led to the initiation of a physician sponsored IND for the treatment of advanced stage prostate cancer. This Phase I project proposes to develop a novel therapeutic device (Neuprosol") for the protection of the neural vascular bundles (NVB) and ultimately erectile function during the cryosurgical treatment of prostate cancer. The reasoning behind the development of the device are as follows: (1) NeuprosolTM will be applied directly to the NVB at the time of the cryosurgical application; (2) The protective agents will be designed through molecular analysis to be nerve cell specific; (3) The agents will also be developed to provide varying levels of zonal (thermal) protection; (4) The utilization of this device will be an effective nerve-sparing agents and may also eventually be applied for urethral protection. The Specific Aims of the Phase 1 are: SA1 Determine the effects of freezing on nerve cell viability; SA2 Determine the role played by apoptosis in freezing-induced cell death of neuronal cells; SA3 Determine which novel agents can be used to protect nerve cells from the destructive mechanisms of freezing; SA4 Test the efficacy of NeuprosolTM as a nerve-sparing concept using a canine cryosurgical model. Successful completion of Phase I and 2 will lead to the development of NeuprosolTM which can then be used as an effective nerve-sparing agent during cryosurgical ablation of prostate cancer. Once developed and tested, NeuprosolTM may become useful as a nerve-sparing treatment as well as an alternative method for protecting other tissues, such as the urethra. Consequently, this novel therapeutic design will provide a major benefit to the clinical area as well as provide a platform for future development of therapeutic strategies for the treatment of cancer.