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Now showing items 1 - 16 of 17

  • DACH1 suppresses breast cancer as a negative regulator of CD44

    Xu, Hanxiao   Yu, Shengnan   Yuan, Xun   Xiong, Jing   Kuang, Dong   Pestell, Richard G.   Wu, Kongming  

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  • Recent advances of highly selective CDK4/6 inhibitors in breast cancer

    Xu, Hanxiao   Yu, Shengnan   Liu, Qian   Yuan, Xun   Mani, Sridhar   Pestell, Richard G.   Wu, Kongming  

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  • CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer

    Xu, Hanxiao   Wu, Kongju   Tian, Yijun   Liu, Qian   Han, Na   Yuan, Xun   Zhang, Lu   Wu, Gen   Wu, Kongming  

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  • Organoid technology in disease modelling, drug development, personalized treatment and regeneration medicine

    Xu, Hanxiao   Jiao, Ying   Qin, Shuang   Zhao, Weiheng   Chu, Qian   Wu, Kongming  

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  • Copper(II)-coated Fe3O4 nanoparticles as an efficient enzyme mimic for colorimetric detection of hydrogen peroxide

    Liu, Hongying   Zhu, Langlang   Ma, Huan   Wen, Jiajun   Xu, Hanxiao   Qiu, Yubing   Zhang, Linan   Li, Lihua   Gu, Chunchuan  

    The authors describe the preparation of Cu(II)-coated Fe3O4) nanoparticles (NPs) that possess excellent peroxidase-like activity. The NPs were formed by chelation between Cu(II) ions and the oxygen functional groups of sodium ligninsulfonate. The morphology and structure of the NPs were characterized by scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The NPs have an average diameter of 220 nm. They are shown to be viable peroxidase mimics that can catalyze the oxidation of 3,3', 5,5'tetramethylbenzidine by hydrogen peroxide to produce a blue coloration. The findings were used to design a colorimetric assay that has a linear response in the 2.5 to 100 mu MH2O2 concentration range and a 0.2 mu M detection limit. The assay excels by its selectivity, high sensitivity, good selectivity, portability and cost efficiency.
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  • Effects of the 5-HT2A and DRD3 genotypes on cortical morphology and functional connectivity density in drug-naive first episode schizophrenia

    Kang, Yafei   Zhang, Wei   Lv, Yahui   Cai, Suping   Xu, Hanxiao   Wang, Jijun   Huang, Liyu  

    The 5-hydroxytryptamine 2A receptor (5-HT2A) and dopamine D3 receptor (DRD3) have been extensively studied as promising candidate genes for schizophrenia. Magnetic resonance imaging studies have demonstrated that schizophrenia is associated with widespread structural and functional abnormalities in the brain. Serotonin and dopamine receptors play crucial roles in the development of the human cerebral cortex and brain activity. However, how the 5-HT2A and DRD3 genes impact brain structure and function in schizophrenia remains unknown. In the present study, we investigated the main effect of disease state and the interaction effect between disease state and genotype of these two genes on cortical volume, thickness, surface area and functional connectivity density (FCD) in fifty-five drug-naive first episode schizophrenia patients and fifty-three healthy controls. We found that the differences in local FCD (IFCD) and global FCD (gFCD) between patients and healthy controls were predominantly located in brain hub regions. The significant interaction effects of disease state and 5-HT2A and DRD3 genes on brain structure and function were mainly located in the temporal cortex. Our findings may help to improve the understanding of the relationship between 5-HT2A and DRD3 genotypes and schizophrenia pathogenesis. (C) 2019 Published by Elsevier B.V.
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  • Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application.

    Yuan, Xun   Wu, Hua   Han, Na   Xu, Hanxiao   Chu, Qian   Yu, Shiying   Chen, Yuan   Wu, Kongming  

    Through epithelial-mesenchymal transition (EMT), cancer cells acquire enhanced ability of migration and invasion, stem cell like characteristics and therapeutic resistance. Notch signaling regulates cell-cell connection, cell polarity and motility during organ development. Recent studies demonstrate that Notch signaling plays an important role in lung cancer initiation and cross-talks with several transcriptional factors to enhance EMT, contributing to the progression of non-small cell lung cancer (NSCLC). Correspondingly, blocking of Notch signaling inhibits NSCLC migration and tumor growth by reversing EMT. Clinical trials have showed promising effect in some cancer patients received treatment with Notch1 inhibitor. This review attempts to provide an overview of the Notch signal in NSCLC: its biological significance and therapeutic application. =20
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  • Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors.

    Yi, Ming   Jiao, Dechao   Xu, Hanxiao   Liu, Qian   Zhao, Weiheng   Han, Xinwei   Wu, Kongming  

    Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.=20
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  • EYA2 Correlates With Clinico-Pathological Features of Breast Cancer,Promotes Tumor Proliferation,and Predicts Poor Survival

    Xu, Hanxiao   Jiao, Ying   Yi, Ming   Zhao, Weiheng   Wu, Kongming  

    Eyes absent homolog 2 (EYA2), a transcriptional activator, is pivotal for organ development, but aberrant regulation of EYA2 has been reported in multiple human tumors. However, the role of EYA2 in breast cancer is still lack of full understanding. To explore the biological significance of EYA2 in breast cancer, we conducted data analysis on public breast cancer datasets, and performed immunohistochemistry (IHC) analysis, colony-forming unit assays, EdU assay, western blotting, and immunofluorescence (IF). Meta-analysis showed that EYA2 mRNA expression was correlated with tumor grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). IHC analysis displayed that EYA2 protein abundance was inversely associated with the status of ER and PR, and enriched in triple-negative breast cancer in comparison with luminal-type tumors. Additionally, correlation analysis reflected that EYA2 mRNA was negatively correlated with luminal markers, and positively associated with markers of basal cells, epithelial-mesenchymal transition and cancer stem cells. Clone-forming assay and EdU experiment showed that EYA2 overexpression enhanced proliferation of breast cancer cells. Results from western blotting and IF displayed that overexpression of EYA2 up-regulated the protein abundance of proliferation markers. Importantly, survival analysis indicated that higher EYA2 mRNA level predicted worse overall survival, relapse-free survival and metastasis-free survival among whole enrolled breast cancer patients. Collectively, EYA2 was closely correlated with clinico-pathological characteristics, and served as a proliferation stimulator for breast cancer cells and an unfavorable prognostic element for breast cancer patients, suggesting that EYA2 is involved in the progression of breast carcinoma.
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  • Protein-Protein Interactions Prediction Based on Graph Energy and Protein Sequence Information

    Xu, Da   Xu, Hanxiao   Zhang, Yusen   Chen, Wei   Gao, Rui  

    Identification of protein-protein interactions (PPIs) plays an essential role in the understanding of protein functions and cellular biological activities. However, the traditional experiment-based methods are time-consuming and laborious. Therefore, developing new reliable computational approaches has great practical significance for the identification of PPIs. In this paper, a novel prediction method is proposed for predicting PPIs using graph energy, named PPI-GE. Particularly, in the process of feature extraction, we designed two new feature extraction methods, the physicochemical graph energy based on the ionization equilibrium constant and isoelectric point and the contact graph energy based on the contact information of amino acids. The dipeptide composition method was used for order information of amino acids. After multi-information fusion, principal component analysis (PCA) was implemented for eliminating noise and a robust weighted sparse representation-based classification (WSRC) classifier was applied for sample classification. The prediction accuracies based on the five-fold cross-validation of the human, Helicobacter pylori (H. pylori), and yeast data sets were 99.49%, 97.15%, and 99.56%, respectively. In addition, in five independent data sets and two significant PPI networks, the comparative experimental results also demonstrate that PPI-GE obtained better performance than the compared methods.
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  • Non-invasive approaches to monitor EGFR-TKI treatment in non-small-cell lung cancer.

    Sun, Wei   Yuan, Xun   Tian, Yijun   Wu, Hua   Xu, Hanxiao   Hu, Guoqing   Wu, Kongming  

    Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. Nowadays, tumor tissues acquired by surgery or biopsy are the routine materials for EGFR mutation analysis. However, the accessibility of tumor tissues is not always satisfactory in advanced NSCLC. Moreover, a high proportion of NSCLC patients will eventually develop resistance to EGFR-TKIs. Invasive procedures, such as surgery or biopsy, are impractical to be performed repeatedly to assess the evolution of EGFR-TKI resistance. Thus, exploring some convenient and less invasive techniques to monitor EGFR-TKI treatment is urgently needed. Circulating cell-free tumor DNA (ctDNA) has a high degree of specificity to detect EGFR mutations in NSCLC. Besides, ctDNA is capable of monitoring the disease progression during EGFR-TKI treatment. Certain serum microRNAs that correlate with EGFR signaling pathway, such as miR-21 and miR-10b, have been demonstrated to be helpful in evaluating the efficiency of EGFR-TKI therapeutics. A commercialized serum-based proteomic test, named VeriStrat test, has shown an outstanding ability to predict the clinical outcome of NSCLC patients receiving EGFR-TKIs. Analysis of EGFR mutations in circulating tumor cells (CTCs) is feasible, and CTCs represent a promising material to predict EGFR-TKI-treatment efficacy and resistance. These evidences suggested that non-invasive techniques based on serum or plasma samples had a great potential for monitoring EGFR-TKI treatment in NSCLC. In this review, we summarized these non-invasive approaches and considered their possible applications in EGFR-TKI-treatment monitoring. =20
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  • Genetic polymorphism in catechol-O-methyltransferase associated with the functional connectivity of frontostriatal circuits in first episode schizophrenia patients

    Kang, Yafei   Zhang, Wei   Lv, Yahui   Xu, Hanxiao   Lin, Yanyan   Cai, Suping  

    Negative symptoms in schizophrenia have been associated with functional changes in frontostriatal pathways. Dysregulation of the dopamine signal in frontostriatal pathways leads to the symptomology observed in schizophrenia. Although the catechol-O-methyltransferase (COMT) gene, one of the susceptibility genes for schizophrenia, has been associated with dopamine activities in prefrontal and striatal regions, it is still unclear whether the disease state and COMT val(158)met genotype have an interaction effect on the functional connectivity of frontostriatal pathways. In this study, we evaluated the possible interactions between COMT val(158)met variations and the disease state on the resting-state functional connectivity (RSFC) of frontostriatal pathways in fifty-one first episode schizophrenia (FES) patients (val/val: 29, met +: 22) with prominent negative symptoms and forty-eight healthy controls (val/val: 31, met +: 17). Regions of interest were defined by the result of a meta-analysis of frontostriatal pathways using the Neurosynth database. We found a significant genotype x disease interaction effect on the RSFC between the bilateral anterior cingulate (ACC) and right caudate, which overlapped with the main effect of the disease state. Behavioural regression analysis suggested that RSFC between the right ACC and right caudate correlated with the severity of SANS avolition-apathy scores in patients who were met carriers but not in patients who were val homozygous. Our findings suggest that the RSFC of frontostriatal pathways may differentially affected by an individual's COMT val(158)met genotype.
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  • Hollow and porous nickel sulfide nanocubes prepared from a metal-organic framework as an efficient enzyme mimic for colorimetric detection of hydrogen peroxide

    Liu, Hongying   Ma, Huan   Xu, Hanxiao   Wen, Jiajun   Huang, Zhiheng   Qiu, Yubin   Fan, Kai   Li, Dujuan   Gu, Chunchuan  

    Hollow, porous NiS nanocubes were prepared by a hydrothermal method starting from Ni-Co Prussian blue analogue nanocubes as the template. The morphology and structure of the NiS nanocubes were tuned by adjustment of the ion-exchange rate and the degree of chemical etching, and they were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, and nitrogen sorption measurements. The NiS nanocubes are shown to act as a peroxidase mimic that can catalyze the oxidization of 3,3,5,5-tetramethylbenzidine by hydrogen peroxide (H2O2), producing a visible color change, for which the absorbance is best measured at 652 nm. The outstanding activity may result from the unique structure of the NiS nanocubes. The catalytic oxidation follows Michaelis-Menten kinetics and shows a ping-pong mechanism of enzyme action. The findings were used to develop a rapid, sensitive, and selective colorimetric H2O2 assay with a response that is linear in the 4-40 M range with a detection limit of 1.72 M (signal-to-noise ratio of 3).
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  • Meta-analysis reveals the correlation of Notch signaling with non-small cell lung cancer progression and prognosis.

    Yuan, Xun   Wu, Hua   Xu, Hanxiao   Han, Na   Chu, Qian   Yu, Shiying   Chen, Yuan   Wu, Kongming  

    Various studies have assessed the clinicopathological and prognostic value of Notch1 and Notch3 expression in Non-small cell lung cancer (NSCLC), but their results remain controversial. This meta-analysis was conducted to address the above issues by using a total of 19 studies involving 3663 patients. The correlations between Notch1 and Notch3 expression and clinicopathological features and NSCLC prognosis were analyzed. The meta-analysis indicated that higher expression of Notch1 was associated with greater possibility of lymph node metastasis and higher TNM stages. Moreover, patients with Notch1 overexpression and Notch3 overexpression showed significantly poor overall survival (Notch1: HR, 1.29; 95% CI, 1.06-1.57, p =3D 0.468 and I(2)=3D 0.0%; Notch3: HR, 1.57; 95%CI, 1.04-2.36, p =3D 0.445 and I(2)=3D 0.0%). Furthermore, there are statistically significant association between overall survival of NSCLC patients and the expression of Notch signaling ligand DLL3 and target gene HES1. Our meta-analysis supports that Notch signaling is a valuable bio-marker to predict progression and targeting Notch signaling could benefit subpopulation of NSCLC patients.=20
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  • MAT1 correlates with molecular subtypes and predicts poor survival in breast cancer

    Xu, Hanxiao   Bai, Xianguang   Yu, Shengnan   Liu, Qian   Pestell, Richard G.   Wu, Kongming  

    Objective: Menage a trois 1 (MAT1) is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase, which modulates cell cycle, transcription and DNA repair. Its dysregulation is responsible for diseases including cancers. To further explore the role of MAT1 in breast cancer, we investigated the pathways in which MAT1 might be involved, the association between MAT1 and molecular subtypes, and the role of MAT1 in clinical outcomes of breast cancer patients. Methods: We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells. Also, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis, correlation analysis and prognosis analysis on public databases. Results: MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling. Furthermore, MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor, and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both mRNA and protein levels. Correlation analysis revealed significant association between MAT1 mRNA amount and epithelial markers, mesenchymal markers, cancer stem cell markers, apoptosis markers, transcription markers and oncogenes. Consistently, the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor, vimentin, sex determining region Y-box 2 and sine oculis homeobox homolog 1. Importantly, Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival. Conclusions: MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.
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  • DACH1 suppresses breast cancer as a negative regulator of CD44

    Xu, Hanxiao   Yu, Shengnan   Yuan, Xun   Xiong, Jing   Kuang, Dong   Pestell, Richard G.   Wu, Kongming  

    Dachshund homolog 1 (DACH1), a key cell fate determination factor, contributes to tumorigenesis, invasion, metastasis of human breast neoplasm. However, the exact molecular mechanisms for the anti-tumor roles of DACH1 in breast carcinoma are still lack of extensive understanding. Herein, we utilized immunohistochemistry (IHC) staining and public microarray data analysis showing that DACH1 was higher in normal breast, low-grade and luminal-type cancer in comparison with breast carcinoma, high-grade and basal-like tumors respectively. Additionally, both correlation analysis of public databases of human breast carcinoma and IHC analysis of mice xenograft tumors demonstrated that DACH1 inversely related to cancer stem cells (CSCs) markers, epithelial-mesenchymal transition (EMT) inducers and basal-enriched molecules, while cluster of differentiation 44 (CD44) behaved in an opposite manner. Furthermore, mice transplanted tumor model indicated that breast cancer cells Met-1 with up-regulation of DACH1 were endowed with remarkably reduced potential of tumorigenesis. Importantly, meta-analysis of 19 Gene Expression Omnibus (GEO) databases of breast cancer implicated that patients with higher DACH1 expression had prolonged time to death, recurrence and metastasis, while CD44 was a promising biomarker predicting worse overall survival (OS) and metastasis-free survival (MFS). Collectively, our study indicated that CD44 might be a novel target of DACH1 in breast carcinoma.
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