OVARIAN CANCER PROTEOME VIA TISSUE MICRODISSECTION AND GEMINI TECHNOLOGIES

通过组织显微切割和 Gemini 技术研究卵巢癌蛋白质组

基本信息

批准号：
7656860
负责人：
Satya Prakash Saxena
金额：
$ 26.03万
依托单位：
CALIBRANT BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-11 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7656860
关键词：
Adopted Archives Area Arizona Automobile Driving Back Behavior Benign Biochemical Biochemical Pathway Bioinformatics Biological Biological Markers Biological Markers Biological Products Biopsy Blood capillaries CA-125 Antigen Cancerous Carcinoma Cells Characteristics Classification Clinical Clinical Course of Disease Clinical Trials Collaborations Collection Complex Coupled Critical Pathways Cystadenoma DNA DNA copy number Data Detection Development Diagnosis Diagnostic Diagnostic Neoplasm Staging Disease Distant Metastasis Drug Approval Processes Electrophoresis Electrospray Ionization Environment Epidermal Growth Factor Receptor Epithelial Epithelium Evaluation Event Freezing Functional disorder Gel Genes Genetic Transcription Goals Gynecologic Gynecologic Oncology Group Gynecology Heterogeneity Histologic Human Human Genome Immunohistochemistry Industry Information Management Investigation Ions Isoelectric Focusing Label Lesion Liquid Chromatography Loss of Heterozygosity Malignant - descriptor Malignant Neoplasms Malignant neoplasm of ovary Manuals Mass Spectrum Analysis Measurement Medical Membrane Methods Microdissection Molecular Molecular Abnormality Molecular Profiling Monitor Neoplasm Metastasis Non-Malignant Normal Cell Organ Ovarian Ovarian Carcinoma Ovarian Serous Adenocarcinoma Ovarian Surface Epithelial-Stromal Tumor Ovarian Tissue Paraaortic Pathologist Pathology Patients Pelvic Examination Pelvis Performance Pharmaceutical Preparations Phase Plasma Play Polymorphism Analysis Population Post-Translational Protein Processing Preclinical Drug Evaluation Preclinical Testing Predictive Factor Preparation Process Protein Analysis Proteins Proteome Proteomics RNA Relative (related person)Reporting Reproducibility Research Role Sampling Serous Serum Serum Albumin Severities Shotguns Single Nucleotide Polymorphism Site Small Business Technology Transfer Research Specimen Staging Surface Surveys System TP53 gene Techniques Technology Testing Tissue Banks Tissue Sample Tissues Transvaginal Ultrasound Tumor Markers Two-Dimensional Polyacrylamide Gel Electrophoresis United States Food and Drug Administration Universities Validation Variant Western Blotting World Health Organization anticancer research base cDNA Arrays cancer cell capillary carcinogenesis clinically relevant comparative comparative genomic hybridization expectation human tissue improved laser capture microdissection lymph nodes medical schools neoplastic cell novel product development prognostic protein expression protein profiling public health relevance response success symposium therapeutic target tool tumor uncertain malignant potential neoplasm

项目摘要

DESCRIPTION (provided by applicant): Biologically and clinically relevant proteomics data can only be generated if organ or tissue samples investigated consist of homogeneous cell populations, in which no unwanted cells of different types and/or development stages obscure the results. Thus, several tissue microdissection technologies have been developed to provide a rapid and straightforward method for procuring homogeneous subpopulations of cells for biochemical and molecular biological analyses. However, current proteomic techniques, including 2-D PAGE, multidimensional liquid chromatography systems, and gel and gel-free isoelectric focusing approaches such as chromatofocusing, immobilized pH membranes, Rotofor, and free-flow electrophoresis, are all operated at the preparative-scale and are incompatible with small cell populations collected from microdissection-procured specimens. Thus, the reported tissue proteomics studies are mainly based on the analysis of entire tissue sections instead of targeted cell subpopulations. Clearly, development of the capability to enable tissue-based clinical proteomic studies will have far reaching impacts on protein biomarker investigations of disease through interrogation of the archived tissue collections. Our research goal is therefore to combine the novel tissue sample preparation and proteomic technologies that enable comprehensive and comparative survey of protein expression profiles in targeted tumor cell populations isolated from human tissues. By combining Calibrant's unique ability to perform proteomic profiling from minute samples with the expertise offered by Dr. Wenxin Zheng at the University of Arizona Medical College in cancer pathology, gynecology, and tissue microdissection, the proposed research represents a synergistic effort toward the evaluation and validation of a novel biomarker discovery paradigm for enabling the proteomic analysis of cancer cells and their micro-environment in support of cancer research, diagnosis, and treatment. Application of the resulting biomarker discovery platform for studying the molecular mechanisms associated with ovarian carcinoma will be realized also through the collaboration with Dr. Zheng, a gynecologic pathologist, to provide access to a collection of primary ovarian epithelial tumor specimens. PUBLIC HEALTH RELEVANCE:Comprehensive and comparative proteomics studies of microdissected ovarian epithelial tumor specimens are proposed in this STTR Phase I project and are expected to provide significant details at the global level on the molecular mechanisms associated with ovarian epithelial carcinogenesis. Identification of differentially expressed proteins that are characteristic of a clearly defined disease state paves the way for defining the molecular and biochemical pathways by which normal cells progress to cancerous states in addition to nurturing discovery of biological markers and therapeutic targets for ovarian cancer. The greatest expectations for targeted proteomics research using enriched non-malignant or malignant ovarian cells from high quality tissue specimens reside in the identification of diagnostic, prognostic, and predictive biological markers in the clinical setting, as well as the discovery and validation of new protein targets in the biopharmaceutical industry.

描述（由申请人提供）：只有在研究的器官或组织样品由均质细胞群组成时，才能生成生物学和临床相关的蛋白质组学数据，其中没有不同类型和/或发育阶段的不必要细胞掩盖结果。因此，已经开发了几种组织显微解剖技术，以提供一种快速，直接的方法来购买生化和分子生物学分析的细胞均匀亚群。然而，当前的蛋白质组学技术，包括2D页，多维液体色谱系统以及无凝胶和无凝胶的等电聚焦方法，例如染色体，固定的pH膜，旋转膜，旋转膜和自由流量电极，都在准备性尺度上均与小细胞分配不合格，并且都在小细胞分配中进行了处理。因此，报告的组织蛋白质组学研究主要基于对整个组织切片而不是靶向细胞亚群的分析。显然，通过通过询问存档的组织收集询问，可以开发能够实现基于组织的临床蛋白质组学研究的能力对蛋白质生物标志物的疾病研究产生巨大影响。因此，我们的研究目标是结合新型的组织样品制备和蛋白质组学技术，这些技术能够对从人体组织分离的靶向肿瘤细胞种群中进行全面和比较调查。通过结合校准剂的独特能力，可以从微小样本中进行蛋白质组织分析以及亚利桑那大学医学院的Wenxin Zheng博士提供的专业知识，癌症病理学，妇科学和组织显微回调，这项研究代表了对蛋白质发现的蛋白质癌症的评估和验证的协同努力，以促进型号的carradigry andiorment and Injortem and Injortem coneriquer conroice carrade parrosigent carrosigent，支持癌症研究，诊断和治疗。同时，还将通过与妇科病理学家Zheng博士合作实现生物标志物发现平台来研究与卵巢癌相关的分子机制，以提供访问原发性卵巢上皮肿瘤标本的访问。公共卫生相关性：在此STTR I期项目中提出了微分卵巢上皮肿瘤标本的全面和比较蛋白质组学研究，并有望在全球层面上有关与卵巢上皮癌相关的分子机制提供重要细节。鉴定差异表达的蛋白质是明确定义的疾病状态的特征，为定义分子和生化途径的方式铺平了道路，除了培育发现生物标记物和卵巢癌的治疗靶标，正常细胞通过该途径通过，正常细胞通过该途径进行癌细胞。对靶向蛋白质组学研究的最大期望是使用高质量组织标本中富集的非恶性或恶性卵巢细胞的预期，这是在临床环境中识别诊断，预后和预测性生物学标志物，以及生物体系工业中新蛋白质靶标的诊断，预后和预测性生物学标志物。