Tissue Microarray Design and Development for Novel Gene and Gene Product Screeni

新基因和基因产品筛选的组织微阵列设计和开发

• 批准号: 7594818
• 负责人: DAVID E KLEINER
• 金额: $ 93.2万
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594818
• 关键词: Biological Markers; Breast; Breast Carcinoma; Bypass Budget; Cell Line; Colon; Communities; Cooperative Human Tissue Network; Core Facility; Development; Diagnosis; Educational workshop; Elements; Epithelial; Extramural Activities; Facility Construction Funding Category; Formalin; Genes; Genus Cola; Glass; Glioma; Goals; Histology; Human; Image; Immunohistochemistry; In Situ Hybridization; Lung; Lymphoma; Malignant Neoplasms; Mixed Neoplasm; National Cancer Institute; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Numbers; Ovary; Paper; Paraffin Embedding; Paraffin Tissue; Pathologist; Pathology; Pediatric Neoplasm; Phase; Prediction of Response to Therapy; Preparation; Procedures; Production; Prostate; Proteins; Publishing; Research Personnel; Sampling; Science; Seminal; Slide; Solutions; Spottings; Staining method; Stains; Standards of Weights and Measures; System; Techniques; Testing; Time; Tissue Array Research Program; Tissue Microarray; Tissue Sample; Tissues; United States National Institutes of Health; Work; Xenograft procedure; anticancer research; base; cost; design; falls; human tissue; interest; lung Carcinoma; melanoma; neoplastic cell; novel; outcome forecast; technology development; tumor; tumor molecular fingerprint; tumor xenograft

Identifying genes and gene products that are important in tumor cells is a high priority goal of the National Cancer Institute. In order to determine whether a gene of interest is expressed in human malignancy, investigators must be able to evaluate actual tissue samples of human tumors. Unfortunately, access to large numbers of well-characterized human tissue samples is difficult, and there is a large expense for the preparation of glass slides from tumor in order to perform immunohistochemistry or in-situ hybridization. As a partial solution to this problem, pathologists began to combine multiple tissue samples in one tissue block, in order to reduce the histology costs and the time and effort involved to perform the special studies. This technique has been refined to the point where hundreds of tissue samples can be placed in a grid arrangement in a single paraffin tissue block. Investigators in the NHGRI (Kohenen, Kallioniemi and others) demonstrated the utility of large scale tissue microarrays in a seminal paper published in Science.<BR><BR>Following a tissue microarray workshop hosted by NCI in Fall, 1999, a pathology-based tissue microarray core facility was established. This project is a direct outgrowth of the Extraordinary Opportunity to Define the Signatures of Cancer Cells identified in the 2001 Bypass Budget plan. The goals of the first year were to establish a core microarray production facility based on a similar facility in the NHGRI and to create the first mixed tumor microarrays for nationwide distribution. The initial product of the core was a mixed tumor block containing representative samples of the most common epithelial malignancies (breast, colon, lung, prostate, and ovary) as well as samples of melanoma, glioma and lymphoma. A selection of normal tissue and standard cell lines was also included to bring the total number of tissue spots to 500. Anonymized human tumor samples are obtained through the CHTN, and this organization will also handle distribution of arrays on glass slides to investigators in the intramural and extramural scientific community. Four sets of multi-tumor arrays were prepared in the first production year (FY2001), totaling more than 3000 slides for distribution. In the current phase of this project we are collaborating with mainly intramural investigators on tumor specific projects, both building arrays as well as staining and analyzing the pathology. This past year (FY2005) we have built arrays of the NCI60 cell lines and xenografts from those cell lines, pediatric tumors, breast carcinoma, non-small cell lung carcinoma, melanoma and general tumor arrays. In addition to slide production, the core facility has been engaged in technology development, from the basic histology procedures to array use to large-scale imaging of arrays. We have acquired an automated arrayer and have worked collaboratively on further technology development of the automated arrayer and an automated imaging system.

识别在肿瘤细胞中重要的基因和基因产物是国家癌症研究所的一个高度优先目标。为了确定感兴趣的基因是否在人类恶性肿瘤中表达，研究人员必须能够评估人类肿瘤的实际组织样本。不幸的是，获得大量的良好表征的人类组织样品是困难的，并且为了进行免疫组织化学或原位杂交，从肿瘤制备载玻片需要大量的费用。作为该问题的部分解决方案，病理学家开始将多个组织样本联合收割机组合在一个组织块中，以减少组织学成本以及进行特殊研究所涉及的时间和精力。这种技术已经被改进到可以将数百个组织样本以网格排列放置在单个石蜡组织块中的程度。NHGRI的研究人员（Kohenen，Kallioniemi等人）在《科学》杂志上发表的一篇开创性论文中证明了大规模组织微阵列的实用性。<BR><BR>继1999年秋季由NCI主办的组织微阵列研讨会之后，建立了基于病理学的组织微阵列核心设施。该项目是2001年旁路预算计划中确定的定义癌细胞特征的非凡机会的直接产物。第一年的目标是在NHGRI类似设施的基础上建立核心微阵列生产设施，并创建第一个全国分布的混合肿瘤微阵列。核心的初始产品是混合肿瘤块，含有最常见的上皮恶性肿瘤（乳腺、结肠、肺、前列腺和卵巢）的代表性样品以及黑色素瘤、神经胶质瘤和淋巴瘤的样品。还包括正常组织和标准细胞系的选择，以使组织点的总数达到500。通过CHTN获得了经分析的人类肿瘤样本，该组织还将处理将载玻片上的阵列分发给校内和校外科学界的研究人员。在第一个生产年度（2001财年）制备了四套多肿瘤阵列，总计超过3000张载玻片用于分发。在该项目的当前阶段，我们主要与校内研究人员合作开展肿瘤特异性项目，包括构建阵列以及染色和病理分析。去年（2005财年），我们建立了NCI60细胞系阵列和这些细胞系的异种移植物、儿科肿瘤、乳腺癌、非小细胞肺癌、黑色素瘤和一般肿瘤阵列。除了制作载玻片外，核心设施还从事技术开发，从基本的组织学程序到阵列的使用，再到阵列的大规模成像。我们已经获得了一个自动化的阵列，并已合作的自动化阵列和自动成像系统的进一步技术开发。

项目成果

Perspectives in tissue microarrays.

组织微阵列的前景。

• DOI: 10.2174/1386207043328445
• 发表时间: 2004
• 期刊: Combinatorial chemistry & high throughput screening
• 影响因子: 1.8
• 作者: Braunschweig,Till;Chung,Joon-Yong;Hewitt,StephenM
• 通讯作者: Hewitt,StephenM

Transfer and multiplex immunoblotting of a paraffin embedded tissue.

石蜡包埋组织的转移和多重免疫印迹。

• DOI: 10.1002/pmic.200401343
• 发表时间: 2006
• 期刊: Proteomics
• 影响因子: 3.4
• 作者: Chung,Joon-Yong;Braunschweig,Till;Baibakov,Galina;Galperin,Mike;Ramesh,Arun;Skacel,Marek;Gannot,Gallya;Knezevic,Vladimir;Hewitt,StephenM
• 通讯作者: Hewitt,StephenM

Tissue microarrays as a platform for proteomic investigation.

组织微阵列作为蛋白质组研究的平台。

• DOI: 10.1007/s10735-006-9049-2
• 发表时间: 2007
• 期刊: Journal of molecular histology
• 影响因子: 3.2
• 作者: Chung,Joon-Yong;Braunschweig,Till;Tuttle,Kimberly;Hewitt,StephenM
• 通讯作者: Hewitt,StephenM

Heterogeneous expression of the aquaporin 1 (AQP1) water channel in tumors of the prostate, breast, ovary, colon and lung: a study using high density multiple human tumor tissue microarrays.

• DOI: 10.3892/ijo.26.5.1149
• 发表时间: 2005-05
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: A. Mobasheri;R. Airley;S. Hewitt;D. Marples

Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.

人FRAT1表达的组织微阵列分析及其与β-catenin在卵巢肿瘤中的亚细胞定位的相关性。

• DOI: 10.1038/sj.bjc.6602988
• 发表时间: 2006-03-13
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Wang, Y;Hewitt, SM;Liu, S;Zhou, X;Zhu, H;Zhou, C;Zhang, G;Quan, L;Bai, J;Xu, N
• 通讯作者: Xu, N