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High-Resolution Dynamic Imaging of Ovarian Cancer Metastasis Post Chemotherapy

卵巢癌化疗后转移的高分辨率动态成像

基本信息

批准号：
10314067
负责人：
Marcin Iwanicki
金额：
$ 18.21万
依托单位：
STEVENS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-08 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10314067
关键词：
3-Dimensional Abdomen Address Biological Biological Assay Breast cancer metastasis Cancer cell line Carcinoma Cell Culture Techniques Cell Survival Cells Clinical Clinical Treatment Cytotoxic Chemotherapy Deposition Development Dorsal Environment Event Evolution Exposure to Greater sac of peritoneum Growth Human Image Imaging Device In Vitro Individual Label Link Malignant Epithelial Cell Malignant neoplasm of ovary Measurable Measurement Mesothelial Cell Mesothelial Neoplasms Mesothelium Metastatic Malignant Neoplasm to the Ovary Methods Modeling Molecular Morbidity - disease rate Morphology Mus Neoplasm Metastasis Optical Coherence Tomography Organ Organoids Ovary Paclitaxel Peritoneal Phenotype Population Primary Neoplasm Process Qualitative Evaluations Recovery Reproductive system Resolution Rosaniline Dyes Structure System Testing Three-Dimensional Imaging Time Tissue Engineering Tissues Transgenic Organisms Tumor Burden Tumor Tissue Visualization Woman Xenograft procedure base cancer cell cell motility chemotherapeutic agent chemotherapy design imaging approach imaging modality improved in vivo in vivo imaging insight intercalation interest intravital imaging live cell microscopy member millimeter mouse model multidisciplinary novel peritoneal cancer prevent quantitative imaging reproductive response spatiotemporal treatment effect treatment strategy tumor tumor microenvironment

项目摘要

Project Summary/Abstract Women undergoing chemotherapy treatment for ovarian cancer (OC) can develop new peritoneal metastases during recovery time, indicating a possibility that therapy promotes the evolution of metastatic cell populations. Therefore, it is of the highest clinical interest to study the effects of chemotherapy on peritoneal dissemination. A hallmark of OC peritoneal dissemination is a disruption of tumor tissue that leads to the formation of carcinoma outgrowths that subsequently detach, transit into the peritoneal cavity, and intercalate into mesothelium that covers vital organs. In this application, we hypothesize that chemotherapy disrupts tumor tissue, promotes outgrowths, cell detachment, and tumor mesothelial intercalation. To test our hypothesis, we propose two Aims that center on the development of in vitro and in vivo imaging approaches that will enable visualization and quantification of OC dissemination post-chemotherapy. In Aim 1 of this project, we will establish an organoid-based imaging assay to determine the effects of chemotherapy on OC organoid structure, outgrowth formation, cell detachment, and mesothelial intercalation. Aim 2 of this proposal focuses on developing an in vivo imaging assay in a mouse model to study the dynamic activities of OC in response to chemotherapy. To complete these aims, we have assembled an interinstitutional team with members that bring unique expertise in tissue engineering of OC dissemination, 3D in vivo imaging of the mouse reproductive system, and genetically modified models of ovarian cancer. This multi-PI combined efforts will provide much-needed information about the effects of chemotherapy on the dynamics of OC peritoneal dissemination.

项目摘要/摘要接受卵巢癌化疗的妇女可能会出现新的腹膜转移在恢复期，表明治疗可能促进了转移细胞群体的进化。因此，研究化疗对腹膜播散的影响具有重要的临床意义。 OC腹膜扩散的一个特征是肿瘤组织的破坏导致癌症的形成突起，随后分离，进入腹膜腔，并插入间皮细胞，覆盖了重要的器官。在这个应用中，我们假设化疗破坏肿瘤组织，促进突起、细胞脱落和肿瘤间皮细胞嵌入。为了验证我们的假设，我们提出了两个目标其核心是体外和体内成像方法的开发，这将使可视化和化疗后OC播散的量化研究。在本项目的目标1中，我们将建立一种基于有机物的成像分析方法来确定化疗对OC类器官结构、突起形成、细胞脱落和间皮嵌入的影响。这项建议的目的2集中在建立一种在小鼠模型上的体内成像分析来研究动态 OC对化疗的反应。为了实现这些目标，我们组建了一个跨机构的团队成员带来了OC传播的组织工程、3D活体成像等方面的独特专业知识小鼠的生殖系统，以及卵巢癌的转基因模型。这个多PI组合努力将提供关于化疗对卵巢癌动态影响的迫切需要的信息腹膜扩散。