High-Resolution Dynamic Imaging of Ovarian Cancer Metastasis Post Chemotherapy

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。

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.