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通过光学分子成像对恩度抗肝癌血管生成及抗肿瘤作用的综合评价

Comprehensive evaluation of the anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer through optical molecular imaging.

作者信息

Zhang Qian, Du Yang, Xue Zhenwen, Chi Chongwei, Jia Xiaohua, Tian Jie

机构信息

School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi, China ; Institute of Automation, Chinese Academy of Sciences, Beijing, China.

Institute of Automation, Chinese Academy of Sciences, Beijing, China.

出版信息

PLoS One. 2014 Jan 8;9(1):e85559. doi: 10.1371/journal.pone.0085559. eCollection 2014.

Abstract

Molecular imaging enables non-invasive monitoring of tumor growth, progression, and drug treatment response, and it has become an important tool to promote biological studies in recent years. In this study, we comprehensively evaluated the in vivo anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer based on the optical molecular imaging systems including micro-computer tomography (Micro-CT), bioluminescence molecular imaging (BLI) and fluorescence molecular tomography (FMT). Firefly luciferase (fLuc) and green fluorescent protein (GFP) dual labeled human hepatocellular carcinoma cells (HCC-LM3-fLuc-GFP cells) were used to establish the subcutaneous and orthotopic liver tumor model. After the tumor cells were implanted 14∼18 days, Endostar (5 mg/kg/day) was administered through an intravenous tail vein injection for continuous 14 days. The computer tomography angiography (CTA) and BLI were carried out for the subcutaneous tumor model. FMT was executed for the orthotopic tumor model. The CTA data showed that tumor vessel formation and the peritumoral vasculature of subcutaneous tumor in the Endostar treatment group was significantly inhibited compared to the control group. The BLI data exhibited the obvious tumor inhibition day 8 post-treatment. The FMT detected the tumor suppression effects of Endostar as early as day 4 post-treatment and measured the tumor location. The above data confirmed the effects of Endostar on anti-angiogenesis and tumor suppression on liver cancer. Our system combined CTA, BLI, and FMT to offer more comprehensive information about the effects of Endostar on the suppression of vessel and tumor formation. Optical molecular imaging system enabled the non-invasive and reliable assessment of anti-tumor drug efficacy on liver cancer.

摘要

分子成像能够对肿瘤生长、进展及药物治疗反应进行非侵入性监测,近年来已成为促进生物学研究的重要工具。在本研究中,我们基于包括微型计算机断层扫描(Micro-CT)、生物发光分子成像(BLI)和荧光分子断层扫描(FMT)在内的光学分子成像系统,全面评估了恩度对肝癌的体内抗血管生成和抗肿瘤作用。采用萤火虫荧光素酶(fLuc)和绿色荧光蛋白(GFP)双标记的人肝癌细胞(HCC-LM3-fLuc-GFP细胞)建立皮下和原位肝肿瘤模型。肿瘤细胞植入14至18天后,通过尾静脉注射给予恩度(5mg/kg/天),持续14天。对皮下肿瘤模型进行计算机断层血管造影(CTA)和BLI检查。对原位肿瘤模型进行FMT检查。CTA数据显示,与对照组相比,恩度治疗组皮下肿瘤的肿瘤血管形成和瘤周血管系统受到显著抑制。BLI数据显示治疗后第8天肿瘤有明显抑制。FMT早在治疗后第4天就检测到了恩度的肿瘤抑制作用,并测量了肿瘤位置。上述数据证实了恩度对肝癌的抗血管生成和肿瘤抑制作用。我们的系统结合了CTA、BLI和FMT,以提供关于恩度对血管和肿瘤形成抑制作用的更全面信息。光学分子成像系统能够对肝癌的抗肿瘤药物疗效进行非侵入性和可靠的评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/511c/3885728/2469c537fe0d/pone.0085559.g001.jpg

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