Improving cancer sample preservation through analyzing cell stress pathways

描述（由申请人提供）：本项目旨在开发人类癌细胞系冷冻保存和肿瘤活检的改进方法。虽然目前强调改善组织生物银行的重要性（GEN, 2/1/05），但很少有研究致力于改善癌症样本的档案储存。Cell Preservation Services Inc. （CPSI）开发低温储存（HypoThermosol，“HTS”）和低温保存（CryoStor）解决方案，由CPSI的合作伙伴BioLife solutions销售。这些溶液被用作再生医学应用的运输/储存溶液，如细胞心肌成形术。完全定义的无血清CryoStor平台专为细胞和组织在液氮中储存而设计，需要降低DMSO水平，与传统方案相比，冷冻保存效率可提高50%。然而，即使是CryoStor系列也只能最多保护70%的癌细胞的生存能力。因此，必须突破这一“低温保存帽”，才能达到最佳保存效果。CPSI能够开发改进的HTS和CryoStor解决方案，因为它能够调查和调节由于延长存储而启动的细胞死亡级联。本一期项目的目的是开发一个名为CryoStor-CANCER的新解决方案平台，这是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微阵列来确定对冷冻保存的癌细胞激活的应激途径的分析是否可以改善癌细胞和肿瘤活检的保存方案；(2)确定对应力路径的相同分析是否可能导致“拯救方案”，从而扭转次优低温保存的不利影响；(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基因的长期表达变化。二期研究将在更广泛的癌细胞和肿瘤类型上测试CryoStor原型解决方案，并确定冷冻保存和提出的“拯救方案”是否保留或拯救了癌细胞系和肿瘤组织的肿瘤指纹。这项工作将是重要的机构，目前正在开发改进的方法冷冻保存癌症标本的生物银行。因此，癌症组织的档案储存将得到改善，保存不良的标本可以抢救出来。

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.