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Tumor-specific design of PEGylated gadolinium-based nanoscale particles: Facile synthesis, characterization, and improved magnetic resonance imaging of metastasis lung cancer.

基于聚乙二醇化钆的纳米级颗粒的肿瘤特异性设计: 转移肺癌的简易合成、表征和改进的磁共振成像。

  • 影响因子:3.92
  • DOI:10.1016/j.jphotobiol.2019.111669
  • 作者列表:"Sui Y","Li Y","Li Y","Jin H","Zheng Y","Huang W","Chen S
  • 发表时间:2020-01-01

:Herein we report the synthesis and characterization of the antifouling Gadolinium oxide (Gd2O3) nanoparticles (NPs) modified with PEG with improved biocompatibility for MR imaging purposes. In this report, using the solvothermal decomposition of Gadolinium (III) in the presence of Na3cit, monitored by surface modification with PEG and L-Cys. The synthesized nanoparticles were confirmed by the TEM, DLS and UV-Visible spectroscopy. The morphological results show normal distance across of the flawless Gd2O3-PEG-Cys-NPs show 7.9 ± 0.4 nm, discretely, with a thin size exchange. This infers the surface adjustment does not obviously alteration the center size of the Gd2O3-NPs when contrasted with the perfect sodium citrate-balanced out Gd2O3-NPs. The Gd2O3-PEG-L-Cys-NPs are highly stable at room temperature, water dispersible and importantly less cytotoxic at high concentration of the NPs. The T1-weighted MR phantasm readings evidentially displayed that the formed PEG coated Gd2O3-PEG and Gd2O3-PEG-Cys-NPs with and without Cys may be performed as the promising T1-weighted MR imaging. The NPs displays no signs of toxicity against the human blood, which represents the biocompatibility for the human medicine applications. The Gd2O3-PEG-Cys-NPs shows relatively, high r1 acceptable cytocompatibility, target specific cancer cells and activate the dual mode MR imaging of lung metastasis cancer model in vitro. The development of versatile zwitterion functionalized Gd2O3 may be promising as an active nanoparticle probe for improved multi-model of MR imaging agents for various cancer diseases.


: 在这里,我们报道了用PEG修饰的防污氧化钆 (Gd2O3) 纳米颗粒 (NPs) 的合成和表征,其具有用于MR成像目的的改进的生物相容性。在本报告中,在Na3cit存在下使用钆 (III) 的溶剂热分解,通过用PEG和L-Cys进行表面改性来监测。通过TEM、DLS和紫外-可见光谱对合成的纳米粒子进行了表征。形态学结果显示无瑕疵Gd2O3-PEG-Cys-NPs的正常距离显示 7.9   ± 0.4 nm nm,离散,具有薄尺寸交换。当与完美的柠檬酸钠平衡Gd2O3-NPs形成对比时,这推断表面调整不会明显改变Gd2O3-NPs的中心尺寸。Gd2O3-PEG-L-Cys-NPs在室温下是高度稳定的,水可分散的,并且重要的是在高浓度的NPs下细胞毒性较小。T1-weighted的MR幻像读数有证据表明,形成的PEG涂覆的Gd2O3-PEG和有和没有Cys的Gd2O3-PEG-Cys-NPs可以作为MR成像有前途T1-weighted进行。NPs没有显示出对人类血液的毒性迹象,这代表了人类医学应用的生物相容性。Gd2O3-PEG-Cys-NPs显示相对较高的r1 可接受的细胞相容性,靶向特异性癌细胞并激活体外肺转移癌模型的双模式MR成像。多功能两性离子官能化Gd2O3 的开发可能有希望作为用于各种癌症疾病的改进的MR显像剂的多模型的活性纳米颗粒探针。



作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

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作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

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作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

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