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Proteolytic Beacons in the Non-invasive Assessment of Response to Cancer Therapy

蛋白水解信标在癌症治疗反应无创评估中的应用

基本信息

批准号：
7490272
负责人：
LYNN M MATRISIAN
金额：
$ 10.45万
依托单位：
VANDERBILT UNIVERSITY
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：
2008-09-22 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7490272
关键词：
AEE 788 Angiogenic Factor Animals Antibodies Benign Biological Availability Biometry Biostatistics Core Cell physiology Cells Cetuximab Chemicals Chemistry Chemotherapy-Oncologic Procedure Cleaved cell Clinical Collaborations Colorectal Cancer Complement Contrast Media Data Depth Detection Development Dose Dyes Endopeptidases Energy Transfer Enzymes Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Evaluation Experimental Designs Family Family member Fluorescence Gadolinium Gelatinase B Generations Goals Growth Factor Human Resources Image In Vitro Infiltration Inflammatory Intestinal Neoplasms Intestines Invasive Knowledge Laboratories Literature Liver MMP9 gene Magnetic Resonance Imaging Malignant - descriptor Malignant Neoplasms Matrix Metalloproteinases Mediating Metabolism Metalloendopeptidases Metalloproteases Microscopy Modeling Molecular Monitor Mus Neoplasm Metastasis Object Attachment Optics PTK787 Peptide Hydrolases Peptides Physiology Play Probability Proteins Reading Reagent Regulation Reporter Research Research Personnel Resolution Resources Role SU11248 Series Signal Pathway Solubility Standards of Weights and Measures Statistical Data Interpretation Surrogate Markers System Testing Therapeutic Studies Time Tissues Toxic effect Training Tumor Cell Invasion Tumor Volume Tyrosine Kinase Inhibitor Vascular Endothelial Growth Factor Receptor Vertebral column Xenograft Model adenoma aqueous base cancer care cancer therapy cellular imaging chemotherapeutic agent chemotherapy complement C2a design experience imaging probe in vivo in vivo Cellular and Molecular Imaging Centers inhibitor/antagonist interest member metastatic colorectal mouse model novel optical imaging optical switch research study residence response size tumor two-photon

项目摘要

Project 4, led by Drs. Lynn Matrisian and Wellington Pham, focuses on developing optical beacons and MRI contrast agents for the in vivo detection of tumor-associated metalloproteinase activity as a novel mechanism to monitor response to tumor therapy. Members of the matrix metalloproteinase (MMP) family are implicated in the matrix degradation associated with cancer invasion. There is substantial literature indicating the involvement of specific MMP family members in specific cellular processes related to cancer, including the activation of growth factors, angiogenesis, infiltration of inflammatory cells, and invasion. These investigators propose to take advantage of this knowledge to devise a series of non-invasive in vivo imaging reagents that will probe the proteolytic status of a tumor to aid in treatment decisions, and rapidly assess the response to standard and targeted cancer chemotherapies. Dr. Pham, a chemist by training, brings extensive experience with the design and synthesis of optical probes for proteolytic activity, and Dr. Matrisian, a cancer biologist, has extensive experience exploring the role of metalloproteinases in mouse models of cancer. Murine models of benign, malignant, and metastatic colorectal cancer will be used in this project, and the response to cancer therapies directed at the epidermal growth factor (EGF) receptor axis will be tested in collaboration with projects 1 and 3 of this ICMIC proposal.

项目4由林恩马特里西安博士和惠灵顿范博士领导，重点是开发光学信标和磁共振成像作为一种新机制的用于体内检测肿瘤相关金属蛋白酶活性的造影剂来监测肿瘤治疗的反应基质金属蛋白酶（MMP）家族的成员涉及与癌症侵袭相关的基质降解。有大量文献表明，特定MMP家族成员参与与癌症相关的特定细胞过程，包括生长因子的活化、血管生成、炎性细胞的浸润和侵袭。这些研究者提出利用这些知识来设计一系列非侵入性体内成像试剂，将探测肿瘤的蛋白水解状态，以帮助治疗决策，并快速评估对标准和靶向癌症化疗。Pham博士是一名训练有素的化学家，设计和合成了用于蛋白水解活性的光学探针，而癌症生物学家Matrisian博士探索金属蛋白酶在小鼠癌症模型中的作用的丰富经验。的鼠模型良性、恶性和转移性结直肠癌将用于本项目，针对表皮生长因子（EGF）受体轴的治疗将与项目1和项目3是ICMIC提案的一部分。