Magnetic resonance and fluorescence-protein imaging of the anti-angiogenic and anti-tumor efficacy of selenium in an orthotopic model of human colon cancer.

Magnetic resonance and fluorescence-protein imaging of the anti-angiogenic and anti-tumor efficacy of selenium in an orthotopic model of human colon cancer.
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发表时间:
2011-02
影响因子:
2
通讯作者:
Arup Bhattacharya;Steven G. Turowski;I. San Martín;A. Rajput;Y. Rustum;R. Hoffman;M. Seshadri
Arup Bhattacharya;Steven G. Turowski;I. San Martín;A. Rajput;Y. Rustum;R. Hoffman;M. Seshadri
中科院分区:
医学4区
文献类型:
--
作者:
Arup Bhattacharya;Steven G. Turowski;I. San Martín;A. Rajput;Y. Rustum;R. Hoffman;M. Seshadri

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肿瘤进展和血管生成密切相关。为了理解这两个过程之间的相互关系,实时成像可以做出重大贡献。在这份报告中,荧光蛋白成像(FPI)和磁共振成像(MRI)被用来证明硒对肿瘤的进展和血管生成的人结肠癌原位模型的影响。将转染有绿色荧光蛋白(GFP)的GEO(高分化人结肠癌)细胞原位植入无胸腺裸鼠的结肠中。从植入后5天开始,进行全身FPI以监测体内肿瘤生长。在通过FPI成功可视化肿瘤生长后,将动物随机分配至对照组或治疗组。治疗包括每日口服有机硒化合物甲基硒代半胱氨酸(MSC; 0.2 mg/天× 5周)。动态增强MRI检查治疗后肿瘤血容量的变化。还对肿瘤切片进行CD 31免疫染色以定量微血管密度(MVD)。虽然T1和T2加权MRI提供了足够的对比度和GEO肿瘤生长的体积评估,GFP成像允许体内肿瘤进展的高通量可视化。硒治疗导致GEO肿瘤的血容量和微血管密度显著降低。与未处理的对照动物相比,在硒处理的动物中也观察到肿瘤生长的显著抑制。总之,这些结果突出了多模式成像方法的有用性,以证明抗肿瘤和抗血管生成的功效和硒治疗结肠癌的前景。
Tumor progression and angiogenesis are intimately related. To understand the interrelationship between these two processes, real-time imaging can make a major contribution. In this report, fluorescent protein imaging (FPI) and magnetic resonance imaging (MRI) were utilized to demonstrate the effects of selenium on tumor progression and angiogenesis in an orthotopic model of human colon cancer. GEO (well-differentiated human colon carcinoma) cells transfected with green fluorescent protein (GFP) were implanted orthotopically into the colon of athymic nude mice. Beginning at five days post implantation, whole-body FPI was performed to monitor tumor growth in vivo. Upon successful visualization of tumor growth by FPI, animals were randomly assigned to either a control group or a treatment group. Treatment consisted of daily oral administration of the organoselenium compound, methyl-selenocysteine (MSC; 0.2 mg/day × five weeks). Dynamic contrast-enhanced MRI was performed to examine the change in tumor blood volume following treatment. CD31 immunostaining of tumor sections was also performed to quantify microvessel density (MVD). While T1- and T2-weighted MRI provided adequate contrast and volumetric assessment of GEO tumor growth, GFP imaging allowed for high-throughput visualization of tumor progression in vivo. Selenium treatment resulted in a significant reduction in blood volume and microvessel density of GEO tumors. A significant inhibition of tumor growth was also observed in selenium-treated animals compared to untreated control animals. Together, these results highlight the usefulness of multimodal imaging approaches to demonstrate antitumor and anti-angiogenesis efficacy and the promise of selenium treatment of colon cancer.