Improving cancer sample preservation through analyzing cell stress pathways

描述(由申请人提供)：这个项目的目的是开发改进的方法来冷冻保存人类癌细胞系和肿瘤活检组织。虽然目前人们一直强调改善组织生物库的重要性(GEN，2/1/05)，但致力于改善癌症样本档案储存的研究很少。细胞保存服务公司(CPSI)开发低温储存(HypoThermosol，HTS)和冷冻保存(CryoStor)解决方案，由CPSI的合作伙伴BioLife Solutions销售。这些解决方案被用作再生医学应用中的运输/储存解决方案，例如细胞心肌成形术。全定义、无血清的CryoStor平台专为液氮中的细胞和组织存储而设计，需要降低DMSO水平，与传统方案相比，低温保存效率最高可提高50%。然而，即使是CryoStor系列也只能保护癌细胞的活力，最高可达70%。因此，必须对这一“冷冻保存帽”进行攻击，以实现最佳保存。CPSI能够开发改进的HTS和CryoStor解决方案，因为它有能力调查和调节因延长存储而引发的细胞死亡级联。这一第一阶段项目的目的是开发一种新的解决方案平台，称为低温存储-癌症--一系列专门为改进人类癌细胞和肿瘤活检的冷冻保存而设计的解决方案。CPSI将(1)使用cDNA微阵列来确定对低温保存的癌细胞激活的应激信号的分析是否可以改进癌细胞和肿瘤活检的保存方案；(2)确定是否对应激信号的相同分析可能导致“拯救方案”，从而逆转次最佳冷冻保存的不利影响；以及(3)确定次优保存是否会导致癌症生物学中最常研究的400多个基因中的任何一个的表达发生长期变化。第二阶段的研究将在更广泛的癌细胞和肿瘤类型上测试CryoStor解决方案的原型，并确定冷冻保存和拟议的“拯救方案”是否保留或挽救癌细胞系和肿瘤组织的肿瘤学指纹。这项工作对于目前正在为低温保存的癌症标本开发改进的生物库方法的机构来说将是重要的。因此，癌症组织的档案存储将得到改善，保存不良的标本可以被挽救。

DESCRIPTION (provided by applicant): The intent of this project is to develop improved methods for the cryopreservation of human cancer cell lines and tumor biopsies. While there has been a current emphasis on the importance of improving biobanking of tissues (GEN, 2/1/05), there has been little research dedicated to improving the archival storage of cancer samples. Cell Preservation Services Inc. (CPSI) develops hypothermic storage (HypoThermosol, "HTS") and cryopreservation (CryoStor) solutions marketed by CPSI's partner, BioLife Solutions. These solutions are used as the shipping/storage solutions in Regenerative Medicine applications such as cellular cardiomyoplasty. The fully defined, serum-free CryoStor platform is designed for cell and tissue storage in liquid nitrogen, requires reduced DMSO levels, and improves cryopreservation efficacy up to 50% compared to traditional protocols. Yet, even the CryoStor series can only protect the viability of cancer cells to a maximum of 70%. Thus, this "cryopreservation cap" must be attacked so as to achieve optimal preservation. CPSI is able to develop improved HTS and CryoStor solutions given its ability to investigate and modulate the cell death cascades that can be initiated due to extended storage. The purpose of this Phase I Project is to develop a new platform of solutions called CryoStor-CANCER - a series of solutions expressly designed for the improved cryopreservation of human cancer cells and tumor biopsies. CPSI will (1) use cDNA microarrays to determine if the analysis of stress pathways activated by cancer cells undergoing cryopreservation can lead to improved preservation solutions for cancer cells and tumor biopsies; (2) determine if the same analysis of stress pathways might lead to "rescue solutions" that can reverse the adverse effects of sub-optimal cryopreservation and; (3) determine if sub-optimal preservation results in a long term change to the expression of any of the 400+ genes that are most often studied in cancer biology. Phase 2 studies will test the prototype CryoStor solutions on a wider variety of cancer cell and tumor types, and determine if cryopreservation and the proposed "rescue solution" preserve or rescue the oncological fingerprint of cancer cell lines and tumor tissues. This work will be important to agencies that are currently developing improved methods for biobanking of cryopreserved cancer specimens. As a result, archival storage of cancer tissues will be improved and poorly preserved specimens can be rescued.