High-Resolution Dynamic Imaging of Ovarian Cancer Metastasis Post Chemotherapy

项目总结/摘要 接受卵巢癌（OC）化疗的女性可能会发生新的腹膜转移 在恢复期间，表明治疗促进转移性细胞群进化的可能性。 因此，研究化疗对腹膜播散的影响具有最高的临床意义。 OC腹膜播散的一个标志是肿瘤组织的破坏，导致癌的形成 随后分离的副产物，转移到腹膜腔中，并插入间皮， 包括重要器官。在本申请中，我们假设化疗破坏肿瘤组织，促进肿瘤细胞增殖， 副产物、细胞脱离和肿瘤间皮嵌入。为了验证我们的假设，我们提出了两个目标 该中心致力于开发体外和体内成像方法， 化疗后OC播散的定量。 在本项目的目标1中，我们将建立一种基于类器官的成像分析，以确定 化疗对OC类器官结构、生长形成、细胞脱离和间皮嵌入的影响。 该提案的目的2集中于在小鼠模型中开发体内成像测定，以研究在小鼠模型中的动态变化。 OC对化疗反应的活性。为了实现这些目标，我们组建了一个机构间的 团队成员带来了独特的专业知识，组织工程的OC传播，3D在体内成像， 小鼠生殖系统和卵巢癌的基因修饰模型。这种多PI组合 这些努力将提供急需的关于化疗对OC动力学影响的信息， 腹膜播散

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.