Ultrasound Monitoring of Rat Metastatic Uveal Melanoma

大鼠转移性葡萄膜黑色素瘤的超声监测

• 批准号: 7120035
• 负责人: RODNEY D BRAUN
• 金额: $ 14.7万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120035
• 关键词: bioimaging /biomedical imaging; biomarker; choroid uvea; disease /disorder model; histology; immunocytochemistry; laboratory rat; liver; melanoma; metastasis; model design /development; neoplasm /cancer blood supply; neoplastic growth; portable biomedical equipment; statistics /biometry; technology /technique development; tissue /cell preparation; ultrasound; uvea disorder; xenotransplantation

DESCRIPTION (provided by applicant): About 30% of uveal melanoma patients die from metastatic disease within 5 years. The primary target of metastasis is the liver, and the median survival after a diagnosis is 4 to 7 months. There is current no standard treatment, and better therapies are needed to improve patient survival. It will be necessary to rigorously test new treatments in clinically relevant animal models that mimic the human disease. Ideally these primary and metastatic uveal melanoma models should allow tumor size to be measured over time. This would permit treatment to begin at a standard tumor size and allow tumor growth to be monitored during therapy. In current models of orthotopic human uveal melanoma, it is not possible to continuously monitor tumor growth, because immunocompromised animals cannot be readily moved to standard imaging equipment. The development of a hand-held, high-resolution, high-frequency ultrasound (HF-US) system has made it feasible to attempt to image tumor growth in the eye and liver of nude rats. In this study, the following overall hypothesis will be tested: Using HF-US and a new model of primary choroidal melanoma, differences in tumor progression can be correlated to the presence of periodic acid-Schiff base (PAS)-positive loops in the primary tumor. It will be addressed in 2 specific aims (SA) which hypothesize that: 1) HF-US imaging can be repeatedly used to monitor primary tumor growth and the extent of metastatic disease in nude rat models of primary and metastatic human choroidal melanoma and 2) nude rat survival, levels of plasma tumor markers, and the number of metastatic lesions will be related to the presence of PAS-positive loops, networks, and cross-linked parallel channels in the primary human choroidal melanoma at the time of enucleation. In SA1 HF-US will be innovatively used to noninvasively image primary tumor growth and hepatic metastatic disease in nude rat models of primary and metastatic human uveal melanoma. In SA2 the HF-US system will be used to image primary melanomas in nude rats that reliably reproduce the PAS-positive vascular patterns associated with patient survival. After the tumor-bearing eyes have been enucleated, biweekly HF-US images of the liver will be obtained to track metastatic progression. If rats with primary tumors that show PAS-positive loops have a higher liver metastatic burden as determined by HF-US, this model could be used to study the importance of these patterns in tumor growth and in treatment response. In summary, this project should reveal the applicability of powerful new techniques to study the growth and treatment response of primary and metastatic uveal melanoma in models that mimic the human disease.

描述（由申请人提供）：约 30% 的葡萄膜黑色素瘤患者在 5 年内死于转移性疾病。转移的主要目标是肝脏，诊断后的中位生存期为4至7个月。目前尚无标准治疗方法，需要更好的治疗方法来提高患者的生存率。有必要在模拟人类疾病的临床相关动物模型中严格测试新疗法。理想情况下，这些原发性和转移性葡萄膜黑色素瘤模型应该允许随着时间的推移测量肿瘤大小。这将允许治疗从标准肿瘤大小开始，并允许在治疗期间监测肿瘤生长。在当前的原位人类葡萄膜黑色素瘤模型中，不可能连续监测肿瘤生长，因为免疫功能低下的动物无法轻易转移到标准成像设备。手持式高分辨率高频超声（HF-US）系统的开发使得对裸鼠眼睛和肝脏中的肿瘤生长进行成像成为可能。在本研究中，将测试以下总体假设：使用 HF-US 和原发性脉络膜黑色素瘤的新模型， 肿瘤进展的差异可能与原发肿瘤中高碘酸希夫碱（PAS）阳性环的存在相关。它将在 2 个具体目标 (SA) 中得到解决，假设：1) HF-US 成像可重复用于监测原发性和转移性人脉络膜黑色素瘤裸鼠模型中的原发性肿瘤生长和转移性疾病的程度，2)裸鼠的存活率、血浆肿瘤标志物水平和转​​移病灶的数量将与原发性人脉络膜黑色素瘤中 PAS 阳性环、网络和交联平行通道的存在有关。去核。在 SA1 中，HF-US 将创新地用于对原发性和转移性人类葡萄膜黑色素瘤裸鼠模型中的原发性肿瘤生长和肝转移性疾病进行无创成像。在 SA2 中，HF-US 系统将用于对裸鼠的原发性黑色素瘤进行成像，可靠地再现与患者生存相关的 PAS 阳性血管模式。在携带肿瘤的眼睛被摘除后，将获得每两周一次的肝脏 HF-US 图像以跟踪转移进展。如果经 HF-US 测定，患有显示 PAS 阳性环的原发性肿瘤的大鼠具有较高的肝脏转移负担，则该模型可用于研究这些模式在肿瘤生长和治疗反应中的重要性。总之，该项目应揭示强大的新技术在模拟人类疾病模型中研究原发性和转移性葡萄膜黑色素瘤的生长和治疗反应的适用性。