In vivo molecular mapping of the tumor microenvironment in an azoxymethane-treated mouse model of colon carcinogenesis.

In vivo molecular mapping of the tumor microenvironment in an azoxymethane-treated mouse model of colon carcinogenesis.
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DOI:
10.1002/lsm.22309
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发表时间:
2015-01
影响因子:
2.4
通讯作者:
Barton, Jennifer K.
Barton, Jennifer K.
中科院分区:
医学3区
文献类型:
--
作者:
Leung, Sarah J.;Rice, Photini S.;Barton, Jennifer K.

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在偶氮氧甲烷(AOM)诱导的结直肠癌小鼠模型中,使用分子探针的小型化成像系统的开发能够检查导致结直肠癌发生和进展的分子变化。通过对动物疾病模型的改进和新颖的研究,可以为临床转化开发更有效的诊断和治疗策略。我们介绍了使用小型多模态内窥镜和灌洗荧光探针来检查aom处理小鼠模型的动态微环境变化。内窥镜配备光学相干断层扫描(OCT)和激光诱导荧光(LIF)成像模式。它与cy5.5结合抗体一起用于创建结肠癌发生的时间分辨分子图谱。我们在5个月的时间里监测了四种生物标志物的体内分子表达变化:上皮生长因子受体(EGFR)、转铁蛋白受体(TfR)、转化生长因子β1 (TGFβ1)和趋化因子(C-X-C基序)受体2 (CXCR2)。在多个时间点比较体内OCT和LIF图像,以确定生物标志物表达增加与腺瘤发展的相关性。该系统具有追踪体内分子表达随时间变化的独特能力。生物标志物组的表达增加与疾病部位相对应,并在可检测的结构变化之前提供预测效用,以突出疾病部位。在结肠中,随着肿瘤负荷和生长速度的增加,生物标志物的表达也趋于增加。我们可以使用带有荧光探针的小型双模内窥镜来研究癌症动物模型的肿瘤微环境,并补充活检和组织采集的结果。
Development of miniaturized imaging systems with molecular probes enables examination of molecular changes leading to initiation and progression of colorectal cancer in an azoxymethane (AOM)-induced mouse model of the disease. Through improved and novel studies of animal disease models, more effective diagnostic and treatment strategies may be developed for clinical translation. We introduce use of a miniaturized multimodal endoscope with lavage-delivered fluorescent probes to examine dynamic microenvironment changes in an AOM-treated mouse model. The endoscope is equipped with optical coherence tomography (OCT) and laser induced fluorescence (LIF) imaging modalities. It is used with Cy5.5-conjugated antibodies to create time-resolved molecular maps of colon carcinogenesis. We monitored in vivo changes in molecular expression over a five month period for four biomarkers: epithelial growth factor receptor (EGFR), transferrin receptor (TfR), transforming growth factor beta 1 (TGFβ1), and chemokine (C-X-C motif) receptor 2 (CXCR2). In vivo OCT and LIF images were compared over multiple time points to correlate increases in biomarker expression with adenoma development. This system is uniquely capable of tracking in vivo changes in molecular expression over time. Increased expression of the biomarker panel corresponded to sites of disease and offered predictive utility in highlighting sites of disease prior to detectable structural changes. Biomarker expression also tended to increase with higher tumor burden and growth rate in the colon. We can use miniaturized dual modality endoscopes with fluorescent probes to study the tumor microenvironment in developmental animal models of cancer and supplement findings from biopsy and tissue harvesting.
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DOI: 10.1016/j.ccr.2012.08.013
发表时间: 2012-11-13
期刊: Cancer cell
影响因子: 50.3
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癌症的分子起源:结直肠癌的分子基础。
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发表时间: 2009-12-17
期刊: The New England journal of medicine
影响因子: --
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