Optical Imaging of Ovarian Carcinogenesis in a Rat Menopause Model

大鼠更年期模型中卵巢癌发生的光学成像

• 批准号: 7208181
• 负责人: Jennifer Kehlet Barton
• 金额: $ 27.33万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-11 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208181
• 关键词: 4-vinyl-1-cyclohexene dioxide; Age; Anatomy; Animal Model; Animals; Anthracenes; Architecture; Bilateral oophorectomy; Biochemical; Biochemical Pathway; Biochemistry; Biological Assay; Biological Factors; CA-125 Antigen; Cancer Etiology; Cancer Model; Cancerous; Carcinogens; Chemopreventive Agent; Clinical; Collagen; Detection; Development; Disease; Dose; Early Diagnosis; Early identification; Endoscopes; Epithelial; Epithelium; Euthanasia; Face; Fluorescence; Future; Goals; Gonadotropins; Growing Follicle; Harvest; Hormone replacement therapy; Hormones; Human; Human Development; Image; Imaging technology; Incidence; Individual; Intraperitoneal Injections; Invasive; Laser Microscopy; Lasers; Lead; Lesion; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Maps; Menopause; Methods; Microscopy; Modality; Modeling; Morbidity - disease rate; NADH; Neoplasms; Optical Coherence Tomography; Optics; Organ; Ovarian; Ovarian Tissue; Ovariectomy; Ovary; Oxidation-Reduction; Performance; Physiological; Postmenopause; Predisposition; Premalignant; Premenopause; Prevention; Procedures; Rattus; Reporting; Research; Resolution; Risk; Rodent; Screening procedure; Sensitivity and Specificity; Severities; Speed; Staging; Standards of Weights and Measures; Surface; System; Testing; Therapeutic Agents; Time; Tissues; Ultrasonography; Woman; anthracene; cancer cell; carcinogenesis; design; desire; fight against; fluorophore; human disease; improved; in vivo; instrument; miniaturize; model development; mortality; neoplastic; novel; optical imaging; prophylactic; software development; tomography

DESCRIPTION (provided by applicant): 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 wellcharacterized 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 2 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 aid in identification of early neoplastic changes that predict cancer. This proposal has 4 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 3 imaging modalities developed.in specific aim 2. 4. Perform in vivo, serial imaging studies of ovarian carcinogenesis. We will perform minimallyinvasive, 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.

描述（由申请人提供）：卵巢癌在所有妇科癌症中的死亡率最高，并且有70％的卵巢癌女性在5年内死于其疾病。生存率很高，患有早期疾病，但由于其表现模糊，卵巢很难进入，通常不早于第三阶段检测到卵巢癌，并且对侵染前病变知之甚少。缺乏适当且表现良好的动物模型，阻碍了了解卵巢癌病因并为这种疾病开发有效检测和治疗的努力。最近，据报道，直接将啮齿动物卵巢暴露于低剂量的致癌物7,12--二甲基苯甲[A]蒽（DMBA）的模型已形成类似人类的（前）肿瘤病变。我们通过将这种致癌模型与更年期的卵泡 - 卵巢独立大鼠模型相结合，从而改善了这种致癌模型。这种改进的模型将有助于确定绝经后妇女对卵巢癌的差异敏感性。这项研究的总体目标是在与卵巢癌作斗争中建立2种至关重要的能力：1）与人类疾病相似的大鼠卵巢癌模型，以及2）对早期肿瘤变化敏感的微创成像模式。我们期望我们的研究有助于鉴定预测癌症的早期肿瘤变化。该提案具有4个具体目标：1。开发杂期和绝经后大鼠卵巢癌模型。最佳剂量，给药和时机将用于使用4-乙烯基环己烯二氧化碳（VCD）和DMBA创建新型的卵巢直大大鼠模型。将评估解剖学和生化变化。 2。开发光学成像技术，以允许体内高分辨率和时间序列 大鼠卵巢的成像。微型光学相干断层扫描（OCT），激光诱导的荧光（LIF）和高分辨率光学相干显微镜（OCM）将开发以在我们改善的动物模型中启用微创成像。 3。确定正常，卵泡耗尽和癌性卵巢组织中对比度的机制。我们将进行一项全面的离体研究，以阐明开发的3种成像模式中的对比机制。在特定目标中2。4。进行卵巢致癌的体内，串行成像研究。我们将执行微型渗透性的时间播放成像顺序，以遵循大鼠模型中的癌变。这项研究的目的是确定在OCT，OCM或LIF上可见的早期解剖学或生化变化，以预测肿瘤的未来发展，并确定病变的时间顺序在循环和卵泡动物中是否有所不同。