Optical Imaging of Ovarian Carcinogenesis in a Rat Menopause Model

卵巢癌是所有妇科癌症中死亡率最高的，70%的卵巢癌患者是男性。 癌症患者在5年内死于癌症。早期疾病的生存率很高，但卵巢癌不是| 通常比III期或IV期更早发现，因为其表现模糊，卵巢难以进入， 而对浸润前病变知之甚少。努力了解卵巢癌的病因和发展 对这种疾病的有效检测和治疗受到缺乏适当和良好的 特征动物模型。最近，将啮齿动物卵巢直接暴露于低剂量的 致癌物质7，12 <$二甲基苯并[a]蒽（DMBA）已被报道开发类人类 （前）肿瘤病变。我们正在改进这种致癌物模型，将其与卵泡耗竭， 卵巢完整大鼠绝经模型。这一改进的模型将有助于确定差异 绝经后妇女对卵巢癌的易感性。 这项研究的总体目标是开发两种战斗中急需的能力 针对卵巢癌：1）与人类疾病非常相似的卵巢癌大鼠模型，和2） 对早期肿瘤变化敏感的微创成像方式。我们希望我们的研究能帮助 在识别早期肿瘤变化预测癌症。该提案有四个具体目标： 1.建立绝经期和绝经后大鼠卵巢癌模型。最佳剂量，给药 并将确定使用4- 乙烯基环己烯二环氧化物（VCD）和DMBA。将评价解剖学和生化变化。 2.开发光学成像技术，以实现高分辨率的体外和体内时间序列 大鼠卵巢成像。微型光学相干断层扫描（OCT），激光诱导荧光（LIF）， 和高分辨率光学相干显微镜（OCM）将被开发， 在我们改进的动物模型中成像。 3.确定造影剂在正常卵巢组织、卵泡缺失卵巢组织和癌性卵巢组织中的作用机制。 我们将进行一项全面的体外研究，以阐明三种成像中的对比机制。 在具体目标2中制定的模式。 4.进行卵巢癌发生的体内连续成像研究。我们会尽可能地- 侵入性、时间序列成像旨在跟踪我们的大鼠模型中的致癌作用。本研究的目的是 确定OCT、OCM或LIF上可见的早期解剖学或生化变化， 肿瘤的发展，并确定病变的时间顺序是否与循环不同， 没有卵泡的动物

Ovarian cancer has the highest mortality of all gynecologic cancers, and 70% of women with ovarian cancer die of their disease within 5 years. Survival is high with early stage disease, yet ovarian cancer is not| usually detected earlier than Stage III or IV because its presentation is vague, the ovary is difficult to access, and little is known about preinvasive lesions. Efforts to understand ovarian cancer etiology and to develop effective detection and treatments for this disease have been hampered by lack of appropriate and well- characterized animal models. Recently, models that directly expose the rodent ovary to low doses of the carcinogen 7, 12¿Dimethylbenz[a]anthracene (DMBA) have been reported to develop human-like (pre)neoplastic lesions. We are improving upon this carcinogen model by combining it with a follicle-deplete, ovary-intact rat model of menopause. This improved model will be useful for determining the differential susceptibility of post-menopausal women to ovarian cancer. The overall goal of this research is to develop two capabilities critically needed in the fight against ovarian cancer: 1) a rat model of ovarian cancer that closely resembles the human disease, and 2) minimally-invasive imaging modalities sensitive to early neoplastic changes. We expect our research to aid in identification of early neoplastic changes that predict cancer. This proposal has four specific aims: 1. Develop a peri- and post-menopausal rat ovarian cancer model. Optimum dosing, administration and timing will be determined for the creation of a novel ovary-intact rat model of menopause using 4- Vinylcyclohexene Diepoxide (VCD) and DMBA. Anatomical and biochemical changes will be evaluated. 2. Develop optical imaging technologies to permit high resolution ex vivo and time-serial in vivo imaging of rat ovary. Miniaturized optical coherence tomography (OCT), laser induced fluorescence (LIF), and high resolution optical coherence microscopy (OCM) will be developed to enable minimally invasive imaging in our improved animal model. 3. Determine mechanisms of contrast in normal, follicle deplete, and cancerous ovarian tissues. We will undertake a comprehensive ex vivo study to elucidate mechanisms of contrast in the three imaging modalities developed in specific aim 2. 4. Perform in vivo, serial imaging studies of ovarian carcinogenesis. We will perform minimally- invasive, time-serial imaging order to follow carcinogenesis in our rat models. The goal of this study is to determine early anatomical or biochemical changes visible on OCT, OCM, or LIF that predict future development of neoplasms, and to determine if the time sequence of lesions is different for cycling and follicle-deplete animals.