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Dynamic Biochemical Tissue Analysis: A Novel In Situ Assay

动态生化组织分析：一种新颖的原位测定

基本信息

批准号：
8180472
负责人：
Monica Maki Burdick
金额：
$ 44.25万
依托单位：
OHIO UNIVERSITY ATHENS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8180472
关键词：
Adhesions Affinity Antigen Targeting Antigens Arterial Fatty Streak Binding Biochemical Biochemistry Biological Biological Assay Biomedical Research Cancerous Cell Adhesion Chemistry Colon Data Development Diagnostic Diagnostics Research E-Selectin Endothelium Grant Health Histological Techniques Histology Human Immunohistochemistry In Situ In Situ Hybridization Inflammation Investigation Kinetics Leukocyte Rolling Ligands Liquid substance Malignant Neoplasms Medical Research Methods Microspheres Molecular Probes Mus Nature Noise Normal tissue morphology P-Selectin Pathologic Processes Pathology Physiological Processes Property Relative (related person)Research Sampling Selectins Signal Transduction Surface Techniques Therapeutic Time Tissue Sample Tissues Variant Work cancer type clinical practice density disorder prevention graduate student human tissue insight novel novel diagnostics novel strategies particle prognostic response tumor

项目摘要

DESCRIPTION (provided by applicant): Histology is ubiquitous in biomedical research, clinical practice, and the development of diagnostics and therapeutics. Some of the most powerful histological techniques are those that characterize the biochemistry of tissue sections. This characterization is typically achieved by assaying the binding of a molecular probe to a tissue section under a single condition that maximizes specific recognition. We hypothesize that the full power of biochemical tissue analysis is unrealized due to the fact that (a) current assays do not allow systematic variation of the mode of contact between the probe and the tissue section and the force exerted on the bond and (b) only a single type of interaction, a high affinity interaction, between the probe and the tissue section is explored. We will investigate this hypothesis by completing the following specific aims: I. To determine the extent to which the method of contact between the molecular probe and the tissue section influences the results of a biochemical tissue analysis assay. We have developed a technique, termed dynamic biochemical tissue analysis (DBTA), which allows systematic investigation of the interaction of molecular probes with biological tissue samples. In this aim, we will definitively determine if the conditions under which the probing molecule interacts with the tissue (e.g., probes immobilized on microspheres, applied shear force) significantly influences the results of a biochemical tissue analysis. II. To determine if characterization of low affinity probe-tissue section interactions can reproducibly discriminate between cancerous and normal tissue, and between variants of cancerous tissue. Our preliminary studies with DBTA have revealed low affinity interactions between a probing molecule (E-selectin) and cancer tissue sections. Under one set of conditions, these interactions (a) are more numerous on cancerous tissue relative to normal tissue and (b) are statistically different amongst tumor variants. In this aim we will conduct a systematic DBTA to determine if the selectin binding profile for each cancer variant is unique and different from normal tissue. Completion of these aims will give insight into the validity of our hypothesis and will also (a) provide a new approach for analyzing biological tissue and identifying antigens in situ, (b) provide a framework for understanding relationships between the biophysical parameters operative in biochemical tissue analysis, (c) identify conditions under which DBTA can be performed to achieve identification of various tumor types, (d) suggest new ways to classify pathological tissue, and (e) open new avenues for the development of novel diagnostics. The project will provide significant research opportunities for undergraduate and graduate students, thus fulfilling the objectives of the R15 grant mechanism. PUBLIC HEALTH RELEVANCE: The biochemical analysis of tissue is germane to medical research and clinical practice and is used throughout the world to aid the identification, analysis, and prevention of disease. The proposed project seeks to develop a novel approach for analyzing the biochemistry of tissue sections that merges the fields of pathology and cell adhesion. The results of the proposed study will have a significant impact on how tissue samples are analyzed both for research and diagnostic/prognostic purposes.

描述（由申请人提供）：组织学在生物医学研究、临床实践以及诊断和治疗的发展中无处不在。一些最强大的组织学技术是那些表征组织切片的生物化学的技术。这种表征通常通过在最大化特异性识别的单一条件下测定分子探针与组织切片的结合来实现。我们假设生化组织分析的全部能力是未实现的，这是由于以下事实：（a）目前的测定不允许探针和组织切片之间的接触模式以及施加在结合上的力的系统变化，以及（B）仅探索探针和组织切片之间的单一类型的相互作用，即高亲和力相互作用。我们将通过完成以下具体目标来研究这一假设：确定分子探针和组织切片之间的接触方法对生化组织分析测定结果的影响程度。我们已经开发了一种技术，称为动态生化组织分析（DBTA），它允许系统的分子探针与生物组织样品的相互作用的调查。为此，我们将明确确定探测分子与组织相互作用的条件（例如，固定在微球体上的探针、施加的剪切力）显著影响生物化学组织分析的结果。二.确定低亲和力探针-组织切片相互作用的表征是否可以可重复地区分癌组织和正常组织以及癌组织的变体。我们对DBTA的初步研究揭示了探测分子（E-选择素）和癌组织切片之间的低亲和力相互作用。在一组条件下，这些相互作用（a）在癌组织上相对于正常组织更多，并且（B）在肿瘤变体之间统计学上不同。在这个目标中，我们将进行系统的DBTA，以确定每个癌症变体的选择素结合谱是否是独特的，并且与正常组织不同。这些目标的完成将使我们的假设的有效性得到深入了解，并且还将（a）提供用于分析生物组织和原位鉴定抗原的新方法，（B）提供用于理解在生物化学组织分析中起作用的生物物理参数之间的关系的框架，（c）鉴定可以进行DBTA以实现各种肿瘤类型的鉴定的条件，（d）提出病理组织分类的新方法，（e）为开发新的诊断方法开辟新的途径。该项目将为本科生和研究生提供重要的研究机会，从而实现R15赠款机制的目标。公共卫生关系：组织的生化分析与医学研究和临床实践密切相关，并在世界各地用于帮助识别，分析和预防疾病。拟议的项目旨在开发一种新的方法，用于分析组织切片的生物化学，合并病理学和细胞粘附领域。拟议研究的结果将对如何分析组织样本以用于研究和诊断/预后目的产生重大影响。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dynamic biochemical tissue analysis detects functional selectin ligands on human cancer tissues.

动态生化组织分析可检测人类癌症组织上的功能性选择素配体。

DOI：
10.1038/s41598-019-44838-4
发表时间：
2019
期刊：
Scientific reports
影响因子：
4.6
作者：
Martin,EricW;Malgor,Ramiro;Resto,VicenteA;Goetz,DouglasJ;Burdick,MonicaM
通讯作者：
Burdick,MonicaM

Mac-2 binding protein is a novel E-selectin ligand expressed by breast cancer cells.

DOI：
10.1371/journal.pone.0044529
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Shirure VS;Reynolds NM;Burdick MM
通讯作者：
Burdick MM

Expression of E-selectin ligands on circulating tumor cells: cross-regulation with cancer stem cell regulatory pathways?

E-选择素配体在循环肿瘤细胞上的表达：与癌症干细胞调控途径的交叉调控？

DOI：
10.3389/fonc.2012.00103
发表时间：
2012
期刊：
Frontiers in oncology
影响因子：
4.7
作者：
Burdick MM;Henson KA;Delgadillo LF;Choi YE;Goetz DJ;Tees DF;Benencia F
通讯作者：
Benencia F

Galectin-1 Influences Breast Cancer Cell Adhesion to E-selectin Via Ligand Intermediaries.

Galectin-1 通过配体中间体影响乳腺癌细胞对 E-选择素的粘附。

DOI：
10.1007/s12195-017-0512-9
发表时间：
2018
期刊：
Cellular and molecular bioengineering
影响因子：
2.8
作者：
Reynolds,NathanM;Mohammadalipour,Amina;Hall,ClaireR;AsghariAdib,Ali;Farnoud,AmirM;Burdick,MonicaM
通讯作者：
Burdick,MonicaM

An adhesion based approach for the detection of esophageal cancer.