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%的卵巢癌妇女 癌症在5年内死于他们的疾病。早期疾病的存活率很高，但卵巢癌不是 通常在III或IV期之前被发现，因为它的表现很模糊，卵巢很难进入， 而且对侵袭前病变知之甚少。努力了解卵巢癌的病因和发展 这种疾病的有效检测和治疗因缺乏适当和良好的治疗而受到阻碍。 典型的动物模型。最近，将啮齿动物卵巢直接暴露于低剂量的 据报道，致癌物7，12-二甲基苯并[a]菲(DMBA)可发展成类人 (前)肿瘤性病变。我们正在改进这一致癌模型，将其与卵泡去除剂相结合， 卵巢完整的绝经大鼠模型。这一改进的模型将有助于确定差值。 绝经后妇女对卵巢癌的易感性。 这项研究的总体目标是发展在战斗中至关重要的两种能力 抗卵巢癌：1)一种与人类疾病非常相似的卵巢癌大鼠模型，2) 对早期肿瘤性改变敏感的微创成像方式。我们希望我们的研究能帮助 以确定预测癌症的早期肿瘤性变化。这项建议有四个具体目标： 1.建立围绝经期和绝经后大鼠卵巢癌模型。最佳剂量、给药方式 并将确定创建一种新的卵巢完整的更年期大鼠模型的时机，使用4- 乙烯基环己烯二氧基醚(VCD)和DMBA。将对解剖和生化变化进行评估。 2.发展光学成像技术，实现高分辨率体外和体内时间序列 大鼠卵巢的成像。小型化光学相干层析成像(OCT)、激光诱导荧光(LIF)、 高分辨率光学相干显微镜(OCM)将被开发来实现微创 在我们改进的动物模型中进行成像。 3.确定正常卵巢组织、卵泡耗竭组织和卵巢癌组织的造影剂机制。 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.对卵巢癌的发生进行活体、系列的成像研究。我们将以最低限度的方式表演- 在我们的大鼠模型中，侵入性的、时间序列的成像顺序跟踪癌症的发生。这项研究的目标是 确定OCT、OCM或LIF上可见的预测未来的早期解剖或生化变化 肿瘤的发展，并确定病变的时间序列是否不同于周期和 耗尽卵泡的动物。

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.