Publications by authors named "Huageng Liang"

22 Publications

  • Page 1 of 1

Development of a four-gene prognostic model for clear cell renal cell carcinoma based on transcriptome analysis.

Genomics 2021 Apr 7;113(4):1816-1827. Epub 2021 Apr 7.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China. Electronic address:

This study aimed to develop a prognostic model for clear cell renal cell carcinoma (ccRCC) based on transcriptome analysis. We screened Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database for gene expression data and clinical characteristics of ccRCC. After differentially expression analysis, we identified 533 key genes of the development of ccRCC. Next, a weighted gene co-expression network analysis (WGCNA) was executed to investigate the association between differentially expressed genes and clinical characteristics. Then, based on protein-protein interaction (PPI) network, least absolute shrinkage and selection operator (LASSO) regression and Cox regression, a four-gene (COL4A5, ABCB1, NR3C2 and PLG) prognostic model has been constructed in TCGA training cohort. Finally, we examined the predictive power of this model with survival analysis and receiver operating characteristic (ROC) curve both in training cohort and in validation cohorts. And we found this model was significantly correlated with infiltrating immune cells. The four-gene prognosis model could be a potential prediction tool with high accuracy and reliability for ccRCC patients.
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http://dx.doi.org/10.1016/j.ygeno.2021.04.005DOI Listing
April 2021

The Identification of Critical mA RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma.

Front Genet 2020 4;11:602485. Epub 2020 Dec 4.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

RNA methylation accounts for over 60% of all RNA modifications, and N-methyladenosine (mA) is the most common modification on mRNA and lncRNA of human beings. It has been found that mA modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The mA modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of mA RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 mA RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed mA RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of mA RNA methylation regulators in prostate cancer and determined a mA gene expression classifier that well predicted the prognosis of prostate cancer.
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http://dx.doi.org/10.3389/fgene.2020.602485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746824PMC
December 2020

Folic acid-modified Exosome-PH20 enhances the efficiency of therapy via modulation of the tumor microenvironment and directly inhibits tumor cell metastasis.

Bioact Mater 2021 Apr 9;6(4):963-974. Epub 2020 Oct 9.

Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

High accumulation of hyaluronan (HA) in the tumor microenvironment leads to an increase in the interstitial pressure and reduction perfusion of drugs. Furthermore, high molecular-weight (HMW)-HA suppresses M1 macrophage polarization, enhances M2 polarization, and induces immunosuppression. Hyaluronidase treatment have attempted to decrease the quantity of HA in tumors. However, hyaluronidase-driven HA degradation driven accelerates tumor cell metastasis, which is a major cause of mortality in cancer patients. Thus, we designed a novel exosome-based drug delivery system (DDS), named Exos-PH20-FA, using genetic engineering to express human hyaluronidase (PH20) and self-assembly techniques to modify the exosomes with folic acid (FA). Our results show that Exos-PH20-FA degraded HMW-HA to low-molecular-weight (LMW)-HA. Moreover, LMW-HA polarized macrophages to the M1 phenotype and reduced the number of relevant immunosuppressive immunocytes which changed the immune microenvironment from an immunosuppressive to immunosupportive phenotype. Furthermore, we demonstrated Exos-PH20-FA directly reduced hyaluronidase-induced metastasis of tumor cells. This tumor treatment also allowed an enhanced delivery of chemotherapy by tumor-targeting effect with FA modification. Our findings indicate that Exos-PH20-FA improves tumor treatment efficiency and reduces the side effects of hyaluronidase treatment, namely tumor cell metastasis. This all-in-one exosome-based HA targeting DDS maybe a promising treatment that yields more efficient and safer results.
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http://dx.doi.org/10.1016/j.bioactmat.2020.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560580PMC
April 2021

LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation.

Aging (Albany NY) 2020 Sep 13;12(17):17459-17479. Epub 2020 Sep 13.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Patients with advanced renal cell carcinoma who are resistant to sunitinib currently have limited clinical options for treatment. Therefore, it is necessary to explore the biological basis of sunitinib resistance and to uncover new targets for the intervention of sunitinib resistance. In this study, we identified that LINC00160 was associated with sunitinib resistance in renal cell carcinoma. Resistant tumor cells highly expressed LINC00160 to recruit transcriptional factor TFAP2A, which bound to SAA1 promoter regions and activated its expression. On one hand, SAA1 linked to ABCB1 protein, which facilitated sunitinib cellular efflux and diminished drug accumulation. On the other hand, SAA1 stimulated JAK-STAT signaling pathways, which countered cellular survival inhibition from drug. All these regulatory networks were well organized and collaborated, thus promoting sunitinib resistance in renal cell carcinoma. LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation, which offers an opportunity for targeted intervention and molecular therapies in the future.
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http://dx.doi.org/10.18632/aging.103755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521490PMC
September 2020

Miniature Hollow Gold Nanorods with Enhanced Effect for In Vivo Photoacoustic Imaging in the NIR-II Window.

Small 2020 09 11;16(37):e2002748. Epub 2020 Aug 11.

Department of Urology, Union Hospital, Tongji Medical College, School of Materials Science and Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, P. R. China.

The miniaturization of gold nanorods exhibits a bright prospect for intravital photoacoustic imaging (PAI) and the hollow structure possesses a better plasmonic property. Herein, miniature hollow gold nanorods (M-AuHNRs) (≈46 nm in length) possessing strong plasmonic absorbance in the second near-infrared (NIR-II) window (1000-1350 nm) are developed, which are considered as the most suitable range for the intravital PAI. The as-prepared M-AuHNRs exhibit 3.5 times stronger photoacoustic signal intensity than the large hollow Au nanorods (≈105 nm in length) at 0.2 optical density under 1064 nm laser irradiation. The in vivo biodistribution measurement shows that the accumulation in tumor of miniature nanorods is twofold as high as that of the large counterpart. After modifying with a tumor-targeting molecule and fluorochrome, in living tumor-bearing mice, the M-AuHNRs group gives a high fluorescence intensity in tumors, which is 3.6-fold that of the large ones with the same functionalization. Moreover, in the intravital PAI of living tumor-bearing mice, the M-AuHNRs generate longer-lasting and stronger photoacoustic signal than the large counterpart in the NIR-II window. Overall, this study presents the fabrication of M-AuHNRs as a promising contrast agent for intravital PAI.
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http://dx.doi.org/10.1002/smll.202002748DOI Listing
September 2020

Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells.

Sci Rep 2020 05 7;10(1):7714. Epub 2020 May 7.

Department of Biology, College of Life Science and Technology, Huazhong University of Science and Technology, 430074, Wuhan, China.

Vitamin K2 has been shown to exert remarkable anticancer activity. However, the detailed mechanism remains unclear. Here, our study was the first to show that Vitamin K2 significantly promoted the glycolysis in bladder cancer cells by upregulating glucose consumption and lactate production, whereas inhibited TCA cycle by reducing the amounts of Acetyl-CoA. Moreover, suppression of PI3K/AKT and HIF-1α attenuated Vitamin K2-increased glucose consumption and lactate generation, indicating that Vitamin K2 promotes PI3K/AKT and HIF-1α-mediated glycolysis in bladder cancer cells. Importantly, upon glucose limitation, Vitamin K2-upregulated glycolysis markedly induced metabolic stress, along with AMPK activation and mTORC1 pathway suppression, which subsequently triggered AMPK-dependent autophagic cell death. Intriguingly, glucose supplementation profoundly abrogated AMPK activation and rescued bladder cancer cells from Vitamin K2-triggered autophagic cell death. Furthermore, both inhibition of PI3K/AKT/HIF-1α and attenuation of glycolysis significantly blocked Vitamin K2-induced AMPK activation and subsequently prevented autophagic cell death. Collectively, these findings reveal that Vitamin K2 could induce metabolic stress and trigger AMPK-dependent autophagic cell death in bladder cancer cells by PI3K/AKT/HIF-1α-mediated glycolysis promotion.
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http://dx.doi.org/10.1038/s41598-020-64880-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206016PMC
May 2020

IMPDH1/YB-1 Positive Feedback Loop Assembles Cytoophidia and Represents a Therapeutic Target in Metastatic Tumors.

Mol Ther 2020 05 10;28(5):1299-1313. Epub 2020 Mar 10.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Recently, cytoophidium, a nonmembrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene Y-box binding protein 1 (YB-1) and served as an independent prognostic factor in ccRCC. Kaplan-Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.
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http://dx.doi.org/10.1016/j.ymthe.2020.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210706PMC
May 2020

ISG20 serves as a potential biomarker and drives tumor progression in clear cell renal cell carcinoma.

Aging (Albany NY) 2020 01 30;12(2):1808-1827. Epub 2020 Jan 30.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies and lacks reliable biomarkers for diagnosis and prognosis, which results in high incidence and mortality rates of ccRCC. In this study, ISG20, HJURP, and FOXM1 were identified as hub genes via weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Samples validation showed that only ISG20 was up-regulated in ccRCC. Therefore, ISG20 was selected for further study. High ISG20 expression was associated with poor overall survival and disease-free survival. Furthermore, the expression of ISG20 could effectively differentiate ccRCC from normal tissues and was positively correlated to clinical stages. Functional experiments proved that knockdown of ISG20 expression could obviously inhibit cell growth, migration, and invasion in ccRCC cells. To find the potential mechanisms of ISG20, gene set enrichment analysis (GSEA) was performed and revealed that high expression of ISG20 was significantly involved in metastasis and cell cycle pathways. In addition, we found that ISG20 could regulate the expression of MMP9 and CCND1. In conclusion, these findings suggested that ISG20 promoted cell proliferation and metastasis via regulating MMP9/CCND1 expression and might serve as a potential biomarker and therapeutic target in ccRCC.
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http://dx.doi.org/10.18632/aging.102714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053611PMC
January 2020

Paclitaxel-Potentiated Photodynamic Theranostics for Synergistic Tumor Ablation and Precise Anticancer Efficacy Monitoring.

ACS Appl Mater Interfaces 2020 Feb 22;12(5):5476-5487. Epub 2020 Jan 22.

National Engineering Research Center for Nanomedicine, College of Life Science and Technology , Huazhong University of Science and Technology , Wuhan 430074 , China.

Photodynamic theranostics that allows for concurrent photodynamic therapy (PDT) and precise therapeutic response report has emerged as an intriguing direction in the development of precision medicine. An ultra-efficient photodynamic theranostics platform was developed here based on combining and potentiating a theranostic photosensitizer, TPCI, with other therapies for synergistic anticancer effect and synchronous self-reporting of therapeutic response. In this study, TPCI and a chemotherapy agent paclitaxel (PTX) were co-encapsulated in liposomes, which exhibited a superb synergistic anticancer effect against a series of tumor cell lines. The potency of both drugs had been boosted for up to 30-fold compared with sole PDT or chemotherapy. More strikingly, the released TPCI lighted up the nuclei of dead cells, triggered either by PDT or chemotherapy, through binding with the chromatin and activating its aggregation-induced emission, therefore self-reporting the anticancer effect of the combined therapy in real time. The in vivo study using a mouse model bearing PC3 prostate tumor cells demonstrated the effective ablation of tumors with initial sizes of 200 mm and the precise early tumor response monitoring by TPCI/PTX@Lipo. This PTX-potentiated photodynamic theranostics strategy herein represented a new prototype of self-reporting nanomedicine for precise tumor therapy.
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http://dx.doi.org/10.1021/acsami.9b19073DOI Listing
February 2020

A cluster of long non-coding RNAs exhibit diagnostic and prognostic values in renal cell carcinoma.

Aging (Albany NY) 2019 11 14;11(21):9597-9615. Epub 2019 Nov 14.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Kidney cancer ranked in the top 10 for both men and women in the estimated numbers of new cancer cases in the United States in 2018. Targeted therapies have recently been administered to patients with clear cell renal cell carcinoma (ccRCC), but the overall survival of patients at the terminal stage of the disease has not been as good as expected. It is therefore necessary to uncover efficient biomarkers for early diagnosis, and to clarify the molecular mechanisms underlying ccRCC progression and metastasis. Increased evidence has shown that long non-coding RNAs (lncRNAs) play important roles during tumor progression. In this study, 10 candidate lncRNAs with diagnostic and prognostic values in ccRCC were identified: IGFL2-AS1, AC023043.1, AP000439.2, AC124854.1, AL355102.4, TMEM246-AS1, AL133467.3, ZNF582-AS1, LINC01510 and PSMG3-AS1. Enrichment analysis revealed metabolic and functional pathways, which may be closely associated with kidney cancer tumorigenesis. Six representative processes were summarized, namely glycolysis, amino acid metabolism, lipid synthesis, reductive carboxylation, nucleotide metabolism, transmembrane transport and signal transduction. In combination, the present results provided prognostic and diagnostic biomarkers for ccRCC and might pave the way for targeted intervention and molecular therapies in the future.
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http://dx.doi.org/10.18632/aging.102407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874440PMC
November 2019

LXRα promotes cell metastasis by regulating the NLRP3 inflammasome in renal cell carcinoma.

Cell Death Dis 2019 02 15;10(3):159. Epub 2019 Feb 15.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Notwithstanding the researches on biomarkers and targeted therapies in renal cell carcinomas (RCC) have made progress in the last decades, the application of the biomarkers and targeted therapy agents for RCC in clinic are restricted because of their limitation or side effects. Liver X receptors (LXRs) and the NLRP3 inflammasome have been the research hotspots in recent years. In our study, we integrated bioinformatics analysis, molecular biology experiments and biological function experiments to study the roles of LXRα and the NLRP3 inflammasome in RCC. The study demonstrated that the elevated LXRα expression is correlated with a poor prognosis in RCC. Furthermore, our study revealed the expression levels and roles of the NLRP3 inflammasome in RCC for the first time. This research demonstrated that LXRα could promote the metastasis of RCC cells by suppressing the expression of the NLRP3 inflammasome. In Brief, LXRα had the possibility to be a novel diagnostic and prognostic biomarker and therapeutic target in renal cell cancer and LXRα could regulate the metastasis of renal cell cancer via NLRP3 inflammamsome.
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http://dx.doi.org/10.1038/s41419-019-1345-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377709PMC
February 2019

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras.

Cell Death Dis 2018 12 5;9(12):1170. Epub 2018 Dec 5.

Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation of bladder cancer cells. In addition, GGPP was required to maintain the function of UBIAD1 in regulating the Ras/ERK signaling pathway. A Drosophila model was employed to confirm the function of UBIAD1/HEIX in vivo. The activation of Ras/ERK signaling at the plasma membrane induced melanotic masses in Drosophila larvae. Our study suggests that UBIAD1 serves as a tumor suppressor in cancer and tentatively reveals the underlying mechanism of melanotic mass formation in Drosophila.
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http://dx.doi.org/10.1038/s41419-018-1215-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281600PMC
December 2018

Prostate lesion delineation from multiparametric magnetic resonance imaging based on locality alignment discriminant analysis.

Med Phys 2018 Oct 19;45(10):4607-4618. Epub 2018 Sep 19.

Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China.

Purpose: Multiparametric MRI (mpMRI) has shown promise in the detection and localization of prostate cancer foci. Although techniques have been previously introduced to delineate lesions from mpMRI, these techniques were evaluated in datasets with T2 maps available. The generation of T2 map is not included in the clinical prostate mpMRI consensus guidelines; the acquisition of which requires repeated T2-weighted (T2W) scans and would significantly lengthen the scan time currently required for the clinically recommended acquisition protocol, which includes T2W, diffusion-weighted (DW), and dynamic contrast-enhanced (DCE) imaging. The goal of this study is to develop and evaluate an algorithm that provides pixel-accurate lesion delineation from images acquired based on the clinical protocol.

Methods: Twenty-five pixel-based features were extracted from the T2-weighted (T2W), apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) images. The pixel-wise classification was performed on the reduced space generated by locality alignment discriminant analysis (LADA), a version of linear discriminant analysis (LDA) localized to patches in the feature space. Postprocessing procedures, including the removal of isolated points identified and filling of holes inside detected regions, were performed to improve delineation accuracy. The segmentation result was evaluated against the lesions manually delineated by four expert observers according to the Prostate Imaging-Reporting and Data System (PI-RADS) detection guideline.

Results: The LADA-based classifier (60 ± 11%) achieved a higher sensitivity than the LDA-based classifier (51 ± 10%), thereby demonstrating, for the first time, that higher classification performance was attained on the reduced space generated by LADA than by LDA. Further sensitivity improvement (75 ± 14%) was obtained after postprocessing, approaching the sensitivities attained by previous mpMRI lesion delineation studies in which nonclinical T2 maps were available.

Conclusion: The proposed algorithm delineated lesions accurately and efficiently from images acquired following the clinical protocol. The development of this framework may potentially accelerate the clinical uses of mpMRI in prostate cancer diagnosis and treatment planning.
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http://dx.doi.org/10.1002/mp.13155DOI Listing
October 2018

Usefulness of real-time three-dimensional ultrasonography in percutaneous nephrostomy: an animal study.

BJU Int 2018 10 13;122(4):639-643. Epub 2018 Jun 13.

Department of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Objectives: To evaluate the effect of real-time three-dimensional (3D) ultrasonography (US) in guiding percutaneous nephrostomy (PCN).

Materials And Methods: A hydronephrosis model was devised in which the ureters of 16 beagles were obstructed. The beagles were divided equally into groups 1 and 2. In group 1, the PCN was performed using real-time 3D US guidance, while in group 2 the PCN was guided using two-dimensional (2D) US. Visualization of the needle tract, length of puncture time and number of puncture times were recorded for the two groups.

Results: In group 1, score for visualization of the needle tract, length of puncture time and number of puncture times were 3, 7.3 ± 3.1 s and one time, respectively. In group 2, the respective results were 1.4 ± 0.5, 21.4 ± 5.8 s and 2.1 ± 0.6 times. The visualization of needle tract in group 1 was superior to that in group 2, and length of puncture time and number of puncture times were both lower in group 1 than in group 2.

Conclusions: Real-time 3D US-guided PCN is superior to 2D US-guided PCN in terms of visualization of needle tract and the targeted pelvicalyceal system, leading to quick puncture. Real-time 3D US-guided puncture of the kidney holds great promise for clinical implementation in PCN.
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http://dx.doi.org/10.1111/bju.14403DOI Listing
October 2018

A self-tuned graph-based framework for localization and grading prostate cancer lesions: An initial evaluation based on multiparametric magnetic resonance imaging.

Comput Biol Med 2018 05 3;96:252-265. Epub 2018 Apr 3.

Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China. Electronic address:

Multiparametric magnetic resonance imaging (mpMRI) has been established as the state-of-the-art examination for the detection and localization of prostate cancer lesions. Prostate Imaging-Reporting and Data System (PI-RADS) has been established as a scheme to standardize the reporting of mpMRI findings. Although lesion delineation and PI-RADS ratings could be performed manually, human delineation and ratings are subjective and time-consuming. In this article, we developed and validated a self-tuned graph-based model for PI-RADS rating prediction. 34 features were obtained at the pixel level from T2-weighted (T2W), apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) images, from which PI-RADS scores were predicted. Two major innovations were involved in this self-tuned graph-based model. First, graph-based approaches are sensitive to the choice of the edge weight. The proposed model tuned the edge weights automatically based on the structure of the data, thereby obviating empirical edge weight selection. Second, the feature weights were tuned automatically to give heavier weights to features important for PI-RADS rating estimation. The proposed framework was evaluated for its lesion localization performance in mpMRI datasets of 12 patients. In the evaluation, the PI-RADS score distribution map generated by the algorithm and from the observers' ratings were binarized by thresholds of 3 and 4. The sensitivity, specificity and accuracy obtained in these two threshold settings ranged from 65 to 77%, 86 to 93% and 85 to 88% respectively, which are comparable to results obtained in previous studies in which non-clinical T2 maps were available. The proposed algorithm took 10s to estimate the PI-RADS score distribution in an axial image. The efficiency achievable suggests that this technique can be developed into a prostate MR analysis system suitable for clinical use after a thorough validation involving more patients.
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http://dx.doi.org/10.1016/j.compbiomed.2018.03.017DOI Listing
May 2018

Combining Protein and miRNA Quantification for Bladder Cancer Analysis.

ACS Appl Mater Interfaces 2017 Jul 6;9(28):23420-23427. Epub 2017 Jul 6.

Department of Urology, Union Hospital, Tongji Medical College, Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology (HUST) , Wuhan 430074, China.

We combine the telomerase extension reaction and microRNA (miRNA)-induced rolling circle amplification, followed by graphene oxide (GO) and nicking enzyme-assisted signal amplification as a method to analyze telomerase and miRNA-21 in urine samples with the following merits. First, it is a binary assay and can simultaneously output double signals that correspond to the quantities of telomerase and miRNA, respectively. Second, telomerase activity is enhanced by using a DNA molecular beacon probe to inhibit the formation of G-quadruplex. Third, background noise is decreased significantly via introduction of GO. Fourth, performance tests on about 258 urine samples demonstrate that this binary assay can distinguish between urine from bladder cancer patients, those with cystitis, and normal individuals. Finally, this strategy also shows great potential in distinguishing between muscle-invasive bladder cancers and non-muscle-invasive bladder cancers. The proposed strategy will greatly contribute to clinical decision-making and individualized treatments.
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http://dx.doi.org/10.1021/acsami.7b05639DOI Listing
July 2017

Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways.

PLoS One 2016 29;11(8):e0161886. Epub 2016 Aug 29.

Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.

The effects of vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003392PMC
August 2017

Antibody-Modified Reduced Graphene Oxide Films with Extreme Sensitivity to Circulating Tumor Cells.

Adv Mater 2015 Nov 1;27(43):6848-54. Epub 2015 Oct 1.

Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

An antibody-modified reduced graphene oxide (rGO) film with unexpected -extreme sensitivity to circulating tumor cells (CTCs) is reported. The antibody--modified rGO films efficiently capture CTCs from billions of blood cells and minimize the background of white blood cells, without complex microfluidic operations.
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http://dx.doi.org/10.1002/adma.201502615DOI Listing
November 2015

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging.

Int J Nanomedicine 2015 16;10:5805-17. Epub 2015 Sep 16.

College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China ; National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of -12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0-20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue(®) microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging.
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http://dx.doi.org/10.2147/IJN.S83582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577262PMC
August 2016

ELL Protein-associated Factor 2 (EAF2) Inhibits Transforming Growth Factor β Signaling through a Direct Interaction with Smad3.

J Biol Chem 2015 Oct 14;290(43):25933-45. Epub 2015 Sep 14.

From the Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China,

A series of in vitro and in vivo studies has shown that EAF2 can affect multiple signaling pathways involved in cellular processes. However, the molecular mechanisms underlying its effects have remained elusive. Here we report the discovery of a new functional link between EAF2 and TGF-β signaling. Promoter reporter assays indicated that EAF2 suppresses Smad3 transcriptional activity, resulting in inhibition of TGF-β signaling. Coimmunoprecipitation assays showed that EAF2 specifically interacts with Smad3 in vitro and in vivo but not with other Smad proteins. In addition, we observed that EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation. Furthermore, we demonstrated that EAF2 suppresses both TGF-β-induced G1 cell cycle arrest and TGF-β-induced cell migration. This study identifies and characterizes a novel repressor of TGF-β signaling.
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http://dx.doi.org/10.1074/jbc.M115.663542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646248PMC
October 2015

Quencher group induced high specificity detection of telomerase in clear and bloody urines by AIEgens.

Anal Chem 2015 Sep 25;87(18):9487-93. Epub 2015 Aug 25.

Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.

Telomerase is a widely used tumor biomarker for early cancer diagnosis. On the basis of the combined use of aggregation-induced emission (AIE) fluorogens and quencher, a quencher group induced high specificity strategy for detection of telomerase activity from cell extracts and cancer patients' urine specimens was creatively developed. In the absence of telomerase, fluorescence background is extremely low due to the short distance between quencher and AIE dye. In the addition of telomerase, fluorescence enhances significantly. The telomerase activity in the E-J, MCF-7, and HeLa extracts equivalent to 5-10 000 cells can be detected by this method in ∼1 h. Furthermore, the distinguishing of telomerase extracted from 38 cancer and 15 normal urine specimens confirms the reliability and practicality of this protocol. In contrast to our previous results (Anal. Chem. 2015, 87, 6822-6827), these advanced experiments obtain more remarkable specificity.
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http://dx.doi.org/10.1021/acs.analchem.5b02699DOI Listing
September 2015

[An integrated segmentation method for 3D ultrasound carotid artery].

Zhongguo Yi Liao Qi Xie Za Zhi 2013 Jul;37(4):235-9

Institute for Pattern Recognition and Artificial Intelligence (IPRAI), Huazhong University of Science and Technology, State Key Laboratory for Multi-spectral Information Processing Technologies, Wuhan 430074.

An integrated segmentation method for 3D ultrasound carotid artery was proposed. 3D ultrasound image was sliced into transverse, coronal and sagittal 2D images on the carotid bifurcation point. Then, the three images were processed respectively, and the carotid artery contours and thickness were obtained finally. This paper tries to overcome the disadvantages of current computer aided diagnosis method, such as high computational complexity, easily introduced subjective errors et al. The proposed method could get the carotid artery overall information rapidly, accurately and completely. It could be transplanted into clinical usage for atherosclerosis diagnosis and prevention.
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July 2013