Ultrasound Monitoring of Rat Metastatic Uveal Melanoma

大鼠转移性葡萄膜黑色素瘤的超声监测

基本信息

批准号：
6962978
负责人：
RODNEY D BRAUN
金额：
$ 13.48万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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）：大约30％的紫veal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，诊断后的中位存活率为4至7个月。当前没有标准治疗方法，需要更好的疗法来改善患者的生存率。有必要在模仿人类疾病的临床相关动物模型中严格测试新的治疗方法。理想情况下，这些原发性和转移性卵子黑色素瘤模型应允许随着时间的推移测量肿瘤大小。这将允许治疗以标准的肿瘤大小开始，并允许在治疗期间监测肿瘤的生长。在当前的原位人紫紫色黑色素瘤的模型中，由于不容易移动到标准成像设备上，因此无法连续监测肿瘤的生长。手持，高分辨率，高频超声（HF-US）系统的发展使尝试在裸鼠眼睛和肝脏中成像肿瘤生长是可行的。在这项研究中，将测试以下总体假设：使用HF-US和新的原发性黑色素瘤模型，肿瘤进展的差异与原发性肿瘤中周期性酸 - chiff碱（PAS）阳性环的存在有关。 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摘除时，原发性人类脉络膜黑色素瘤中的平行通道。在SA1中，HF-US将在原发性和转移性人类紫veal黑色素瘤的裸大鼠模型中进行创新的原发性肿瘤生长和肝转移疾病。在SA2中，HF-US系统将用于成像裸鼠中的原发性黑色素瘤，这些黑色素瘤可靠地再现与患者生存相关的PAS阳性血管模式。持核肿瘤的眼睛被吸收后，将获得肝脏的双周hf-us图像以跟踪转移性进展。如果由HF-US确定的具有PAS阳性环的原发性肿瘤的大鼠具有较高的肝转移负担，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。总而言之，该项目应揭示强大的新技术在研究模仿人类疾病的模型中的原发性和转移性卵巢黑色素瘤的生长和治疗反应的适用性。