Steroids and Stem Cell in Carcinogenesis

描述（由申请人提供）： 器官型培养物是通过操纵细胞外基质内和细胞外基质上的上皮细胞和基质细胞来模拟体内组织结构的组织培养模型。这些模型结合了细胞-基质和上皮-基质相互作用的方面，这些方面不能在单层培养中进行评价。它们可用于评估单克隆集落，而动物中的单个异种移植肿瘤是由数百万个细胞建立的。因此，器官型培养中的集落比动物异种移植物更准确地模拟肿瘤发生。器官型培养比动物模型更容易进行遗传和化学操作，从而增加了实验数量，降低了成本。然而，它们不能取代动物模型，因为它们不包括代谢、生理和免疫作用。因此，器官型培养物可以潜在地用于在动物模型中测试之前筛选和改进化学预防剂。此外，他们提供了机会，以评估假设驱动的研究致癌和化学预防。 我们开发了正常人子宫内膜、良性人卵巢组织和低度恶性潜能的人卵巢交界性肿瘤（LMP）的器官型模型。该项目的目标是进一步发展这些器官型模型，使其成为可用于研究致癌和化学预防过程的致癌模型。实验将评估芳烃，雌激素，孕激素，他莫昔芬，分化和成体干细胞在子宫内膜和卵巢癌发生的相互作用。我们未来的目标将是验证这些模型，并将其用于我们开发低毒性类维生素A，heteroarotinoids，用于化学预防。 这项研究将提高我们对致癌过程和化学预防的理解，最终转化为预防癌症的策略和药物。

DESCRIPTION (provided by applicant): Organotypic cultures are tissue culture models that mimic in vivo tissue architecture through manipulation of epithelial and stromal cells within and on top of an extracellular matrix. These models incorporate aspects of cell-matrix and epithelial-stromal interactions that cannot be evaluated in monolayer cultures. They can be used to evaluate monoclonal colonies, whereas individual xenograft tumors in animals are established from millions of cells. Colonies in organotypic culture therefore, more accurately mimic tumorigenesis than animal xenografts. Organotypic cultures can be more readily genetically and chemically manipulated than animal models, allowing increased numbers of experiments and less cost. They cannot replace animal models however, because they do not incorporate metabolic, physiologic and immunologic effects. Thus organotypic cultures can potentially be used to screen and improve chemoprevention agents prior to testing in animal models. In addition, they provide opportunities to evaluated hypothesis driven research on carcinogenesis and chemoprevention. We developed organotypic models of normal human endometrium, benign human ovarian tissue, and human borderline ovarian tumors of low malignant potential (LMP). The objective of this project is to further develop these organotypic models into models of carcinogenesis that can be used to study the processes of carcinogenesis and chemoprevention. The experiments proposed will evaluate the interaction of aromatic hydrocarbons, estrogen, progesterone, tamoxifen, differentiation and adult stem cells in endometrial and ovarian carcinogenesis. Our future goals will be to validate these models and to use them in our efforts to develop low-toxicity retinoids, heteroarotinoids, for chemoprevention. This research will enhance our understanding of the process of carcinogenesis and chemoprevention, which could ultimately translate into strategies and pharmaceuticals for prevention of cancer.