Improving cancer sample preservation through analyzing cell stress pathways

描述（由申请人提供）：本项目的目的是开发用于冷冻保存人类癌细胞系和肿瘤活检的改进方法。 虽然目前一直强调改善组织生物库的重要性（GEN，2005年2月1日），但很少有研究致力于改善癌症样本的档案储存。 细胞保存服务公司（CPSI）开发由CPSI的合作伙伴BioLife Solutions销售的低温储存（Hypothermosol，“HTS”）和冷冻保存（CryoTherapy）解决方案。 这些解决方案在再生医学应用中用作运输/储存解决方案，如细胞心肌成形术。 完全定义的无血清冷冻平台专为液氮中的细胞和组织储存而设计，与传统方案相比，需要降低DMSO水平，并将冷冻保存效率提高高达50%。 然而，即使是冷冻系列也只能保护癌细胞的活力最多70%。 因此，必须攻击该“低温保存帽”以实现最佳保存。 CPSI能够开发出改进的HTS和冷冻液，因为它能够研究和调节由于长期储存而可能引发的细胞死亡级联反应。 该一期项目的目的是开发一个名为CryoStor-CANCER的新解决方案平台-一系列专门为改善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微阵列来确定对经历冷冻保存的癌细胞激活的应激途径的分析是否可以导致癌细胞和肿瘤活检的改进的保存溶液;（2）确定对应激途径的相同分析是否可以导致可以逆转次优冷冻保存的不利影响的“救援溶液”;（3）确定次优保存是否导致癌症生物学中最常研究的400多种基因中的任何一种的表达的长期变化。 第二阶段研究将在更广泛的癌细胞和肿瘤类型上测试原型冷冻保存溶液，并确定冷冻保存和拟议的“拯救溶液”是否保存或拯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开发冷冻保存癌症标本生物库改进方法的机构来说非常重要。 因此，癌症组织的档案储存将得到改善，保存不佳的标本可以挽救。

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.