MRI & MRS OF HORMONAL INDUCED CHANGES IN BREAST CANCER

描述（改编自申请人的摘要）： 该提案旨在为早期发展非侵入性MRI和MRS方法， 评估乳腺癌对激素治疗的反应，并帮助 改善乳腺癌内分泌治疗。拟议的实验是 设计来检验假设， 血管内皮生长因子（VEGF）是受血管调节的， 反过来，以特定的方式改变肿瘤血管分布和灌注， 决定了治疗的效果。分子生物学与磁共振成像的整合 研究将涉及在人体乳腺癌细胞和肿瘤中进行的裸 小鼠在不同的激素操纵与雌激素，他莫昔芬和新的 他莫昔芬的衍生物-他莫昔芬甲碘化物（TMI）。具体目标是 设计用于测试上述假设并在分子上表征， 细胞和整个肿瘤水平的抗雌激素的作用，特别是 他莫昔芬和TMI，对各种VEGF亚型和密度的影响， 乳腺癌脉管系统的渗透性和灌注能力。这些目标 包括使用分子生物学方法， mRNA水平和蛋白质水平的VEGF亚型在体外，并映射 VEGF在体内的表达，在不同的激素治疗。此外，本发明还提供了一种方法， 他们计划继续开发和应用MRI和MRS方法， 在体内监测激素诱导的血管系统和其他 病理生理特征最后，该提案还旨在 对TMI的药代动力学、药效及作用机制进行了研究。这项工作 将增加对乳腺癌血管生成的基本理解， 帮助设计和改进新抗雌激素和抗乳腺血管生成疗法 癌动物模型的MRI研究结果将作为基础 用于开发非侵入性和早期监测的临床方案， 对激素治疗的反应。

DESCRIPTION (Adapted from applicant's abstract): The long range objectives of this proposal are to develop non-invasive MRI and MRS methods for the early evaluation of the response of breast cancer to hormonal therapy and to help improve endocrine therapy of breast cancer. The proposed experiments were designed to test out hypothesis that the expressions of the isoforms of vascular endothelial growth factor (VEGF) are hormonally regulated and this, in turn, modifies tumor vascularity and perfusion in a specific manner which determines the results of therapy. The integration of molecular Biology and MRI studies will involve studies in human breast cancer cells and tumors in nude mice under varying hormonal manipulations with estrogen, tamoxifen and the new derivative of tamoxifen-tamoxifen methiodide (TMI). The specific aims are designed to test the above hypothesis and to characterize at the molecular, cellular and whole tumor levels the effects of anti-estrogens, particularly tamoxifen and TMI, on the various VEGF isoforms and on the density, permeability and perfusion capacity of breast cancer vasculature. These aims include the use of molecular biology methods that will be used to establish the mRNA levels and protein levels of VEGF isoforms in vitro and to map the expression of VEGF in vivo, under varying hormonal treatments. In addition, they plan to continue the development and application of MRI and MRS methods to monitor in vivo the hormonal induced changes in the vasculature and other pathophysiologic characteristics. Finally, this proposal is also designed to test the pharmacokinetics, potency and mechanism of activity of TMI. This work will add to the basic understanding of breast cancer angiogenesis and may also help design and improve new anti-estrogen and anti-angiogenic therapy of breast cancer. The results of the MRI studies in animal models will serve as a basis for developing clinical protocols for non-invasive and early monitoring of response to hormonal therapy.