66 results on '"Zhao, Yongfu"'
Search Results
2. Effect of Boron Content in LiOH Solutions on the Corrosion Behavior of Zr-Sn-Nb Alloy.
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Zhao Y, Wu Z, Chen Z, Yin Z, Tang M, Xiong J, and Deng P
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In pressurized water reactors, LiOH may be concentrated in some areas, leading to the accelerated corrosion of fuel claddings. Injecting boric acid into primary coolants can mitigate the accelerated corrosion effect of LiOH on Zircaloys, but the effects of boron content on the corrosion behavior of the Zr-Sn-Nb alloy are still unknown. This work focused on the corrosion and hydrogen absorption behavior at 360 °C/18.6 MPa in 100 mg/kg LiOH solutions with 0 mg/kg, 50 mg/kg, and 200 mg/kg boron contents for up to 510 days, aiming to study the effect of boron content on corrosion resistance in LiOH solutions. Corrosion kinetics, microstructures of oxide films, hydrogen absorption concentrations and hydride morphology were obtained after the test. The results show that injecting boron in LiOH solutions can significantly reduce the corrosion weight gain, hydrogen concentration, and hydrogen length of Zr-Sn-Nb alloys, that is, improving corrosion resistance effectively. During the oxidation of the Zr-Sn-Nb alloy, B
3+ and Li+ incorporate in oxide films. The incorporation of Li+ may lead to the generation of oxygen vacancies, which can carry oxygen from the solutions to O/M interface, accelerating corrosion. The incorporation of B3+ in oxide films will slow down the oxidation of Zr-Sn-Nb alloys by reducing the oxygen vacancies caused by Li+ aggregation.- Published
- 2024
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3. ATN-Res2Unet: an advanced deep learning network for the elimination of saturation artifacts in endoscopy optical coherence tomography.
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Zhao Y, Kong R, Ma F, Qi S, Dai C, and Meng J
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- Humans, Image Processing, Computer-Assisted methods, Tomography, Optical Coherence methods, Deep Learning, Artifacts, Endoscopy methods
- Abstract
Endoscopic optical coherence tomography (OCT) possesses the capability to non-invasively image internal lumens; however, it is susceptible to saturation artifacts arising from robust reflective structures. In this study, we introduce an innovative deep learning network, ATN-Res2Unet, designed to mitigate saturation artifacts in endoscopic OCT images. This is achieved through the integration of multi-scale perception, multi-attention mechanisms, and frequency domain filters. To address the challenge of obtaining ground truth in endoscopic OCT, we propose a method for constructing training data pairs. Experimental in vivo data substantiates the effectiveness of ATN-Res2Unet in reducing diverse artifacts while preserving structural information. Comparative analysis with prior studies reveals a notable enhancement, with average quantitative indicators increasing by 45.4-83.8%. Significantly, this study marks the inaugural exploration of leveraging deep learning to eradicate artifacts from endoscopic OCT images, presenting considerable potential for clinical applications.
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- 2024
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4. Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study.
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Huang J, Wang J, Xv J, Wang J, Wang G, and Zhao Y
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- Humans, Thyroid Cancer, Papillary genetics, Retrospective Studies, Proto-Oncogene Proteins B-raf genetics, Mutation, Gene Frequency, Thyroid Neoplasms genetics, Telomerase genetics
- Abstract
The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis., (© 2024. The Author(s).)
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- 2024
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5. High-precision retinal blood vessel segmentation based on a multi-stage and dual-channel deep learning network.
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Guo H, Meng J, Zhao Y, Zhang H, and Dai C
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- Retinal Vessels diagnostic imaging, Image Enhancement, Image Processing, Computer-Assisted methods, Algorithms, Deep Learning, Spiro Compounds
- Abstract
Objective. The high-precision segmentation of retinal vessels in fundus images is important for the early diagnosis of ophthalmic diseases. However, the extraction for microvessels is challenging due to their characteristics of low contrast and high structural complexity. Although some works have been developed to improve the segmentation ability in thin vessels, they have only been successful in recognizing small vessels with relatively high contrast. Approach. Therefore, we develop a deep learning (DL) framework with a multi-stage and dual-channel network model (MSDC_NET) to further improve the thin-vessel segmentation with low contrast. Specifically, an adaptive image enhancement strategy combining multiple preprocessing and the DL method is firstly proposed to elevate the contrast of thin vessels; then, a two-channel model with multi-scale perception is developed to implement whole- and thin-vessel segmentation; and finally, a series of post-processing operations are designed to extract more small vessels in the predicted maps from thin-vessel channels. Main results. Experiments on DRIVE, STARE and CHASE_DB1 demonstrate the superiorities of the proposed MSDC_NET in extracting more thin vessels in fundus images, and quantitative evaluations on several parameters based on the advanced ground truth further verify the advantages of our proposed DL model. Compared with the previous multi-branch method, the specificity and F
1 score are improved by about 2.18%, 0.68%, 1.73% and 2.91%, 0.24%, 8.38% on the three datasets, respectively. Significance. This work may provide richer information to ophthalmologists for the diagnosis and treatment of vascular-related ophthalmic diseases., (© 2024 Institute of Physics and Engineering in Medicine.)- Published
- 2024
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6. Pathogenesis and signaling pathways related to iodine-refractory differentiated thyroid cancer.
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Zhao S, Zhao Y, Zhao Y, and Wang G
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- Humans, Iodine Radioisotopes therapeutic use, Signal Transduction, Iodine therapeutic use, Thyroid Neoplasms pathology, Adenocarcinoma drug therapy
- Abstract
Thyroid cancer is the most common malignant neoplasm within the endocrine system and the field of head and neck surgery. Although the majority of thyroid cancers, more than 90%, are well-differentiated thyroid carcinomas with a favourable prognosis, the escalating incidence of this disease has contributed to an increasing number of patients with a propensity for recurrent disease, rapid disease progression, and poor or no response to conventional treatments. These clinical challenges are commonly attributed to alterations in key thyroid oncogenes or signaling pathways, thereby initiating tumour cell dedifferentiation events, accompanied by reduced or virtually absent expression of the sodium/iodine symporter (NIS). As a result, the disease evolves into iodine-refractory differentiated thyroid cancer (RAIR-DTC), an entity that is insensitive to conventional radioiodine therapy. Despite being classified as a differentiated thyroid cancer, RAIR-DTC has an extremely poor clinical prognosis, with a 10-year survival rate of less than 10%. Therefore, it is of paramount importance to comprehensively elucidate the underlying pathogenesis of RAIR-DTC and provide specific targeted interventions. As the pathogenic mechanisms of RAIR-DTC remain elusive, here we aim to review recent advances in understanding the pathogenesis of RAIR-DTC and provide valuable insights for the development of future molecularly targeted therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhao, Zhao and Wang.)
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- 2024
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7. DPHL v.2: An updated and comprehensive DIA pan-human assay library for quantifying more than 14,000 proteins.
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Xue Z, Zhu T, Zhang F, Zhang C, Xiang N, Qian L, Yi X, Sun Y, Liu W, Cai X, Wang L, Dai X, Yue L, Li L, Pham TV, Piersma SR, Xiao Q, Luo M, Lu C, Zhu J, Zhao Y, Wang G, Xiao J, Liu T, Liu Z, He Y, Wu Q, Gong T, Zhu J, Zheng Z, Ye J, Li Y, Jimenez CR, A J, and Guo T
- Abstract
A comprehensive pan-human spectral library is critical for biomarker discovery using mass spectrometry (MS)-based proteomics. DPHL v.1, a previous pan-human library built from 1,096 data-dependent acquisition (DDA) MS data of 16 human tissue types, allows quantifying of 10,943 proteins. Here, we generated DPHL v.2 from 1,608 DDA-MS data. The data included 586 DDA-MS data acquired from 18 tissue types, while 1,022 files were derived from DPHL v.1. DPHL v.2 thus comprises data from 24 sample types, including several cancer types (lung, breast, kidney, and prostate cancer, among others). We generated four variants of DPHL v.2 to include semi-tryptic peptides and protein isoforms. DPHL v.2 was then applied to two colorectal cancer cohorts. The numbers of identified and significantly dysregulated proteins increased by at least 21.7% and 14.2%, respectively, compared with DPHL v.1. Our findings show that the increased human proteome coverage of DPHL v.2 provides larger pools of potential protein biomarkers., Competing Interests: T.G. is shareholder of Westlake Omics, Inc. N.X., X.Y., and W.L. were employees of Westlake Omics, Inc., when they participated in this project., (© 2023 The Author(s).)
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- 2023
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8. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition).
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Zhou J, Sun H, Wang Z, Cong W, Zeng M, Zhou W, Bie P, Liu L, Wen T, Kuang M, Han G, Yan Z, Wang M, Liu R, Lu L, Ren Z, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Hou J, Ji Y, Yun J, Bai X, Cai D, Chen W, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Guo Y, Hua B, Huang X, Jia W, Li Q, Li T, Li X, Li Y, Li Y, Liang J, Ling C, Liu T, Liu X, Lu S, Lv G, Mao Y, Meng Z, Peng T, Ren W, Shi H, Shi G, Shi M, Song T, Tao K, Wang J, Wang K, Wang L, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zeng Y, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhang Y, Zhao M, Zhao Y, Zheng H, Zhou L, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Zhang L, Yang C, Wu Z, Dai Z, Chen M, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Teng G, Dong J, and Fan J
- Abstract
Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people., Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer., Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint.", Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
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9. Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression.
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Chen H, Li Z, Xu J, Zhang N, Chen J, Wang G, and Zhao Y
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- Humans, Carcinogenesis, Heme Oxygenase-1, Adenocarcinoma, Follicular pathology, Curcumin pharmacology, Ferroptosis, Thyroid Neoplasms pathology
- Abstract
Follicular thyroid cancer (FTC) is a highly aggressive type of endocrine malignancy. It is necessary to investigate the mechanisms of tumorigenesis and therapeutic pathways in patients with FTC. Haem oxygenase-1 (HO-1) can regulate oxidative stress and the occurrence of tumors and diseases. In this study, we discovered that HO-1 was abnormally overexpressed in FTC compared with adjacent tissues. However, the HO-1 overexpression was demonstrated to decrease cell viability and to potentially activate the ferroptosis signalling pathway. Ferroptosis is a newly identified form of oxidative cell death and is currently being targeted as a new cancer treatment. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Huanjie Chen et al.)
- Published
- 2023
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10. Increased expression of GPX4 promotes the tumorigenesis of thyroid cancer by inhibiting ferroptosis and predicts poor clinical outcomes.
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Chen H, Peng F, Xu J, Wang G, and Zhao Y
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- Humans, Phospholipid Hydroperoxide Glutathione Peroxidase genetics, Carcinogenesis genetics, Cell Transformation, Neoplastic, Ferroptosis genetics, Thyroid Neoplasms genetics
- Abstract
Background: Ferroptosis plays a critical role in suppressing cancer progression, and its essential regulator is glutathione peroxidase 4 (GPX4). High GPX4 expression can inhibit accumulation of iron, thus suppressing ferroptosis. However, its function in thyroid cancer has not been fully illuminated. Here, we explore the effect of GPX4 on thyroid cancer tumorigenesis and prognosis., Methods: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, GPX4 expression was investigated in cancer tissues and adjacent tissues. We determined the biological functions of GPX4-associated differentially expressed genes (DEGs) by using the "clusterProfiler" R package. In addition, the predictive value of GPX4 in thyroid cancer was assessed by using Cox regression analysis and nomograms. Finally, we conducted several in vitro experiments to determine the influence of GPX4 expression on proliferation and ferroptosis in thyroid cancer cells., Results: GPX4 expression was obviously elevated in thyroid cancer tissues compared with normal tissues. Biological function analysis indicated enrichment in muscle contraction, contractile fiber, metal ion transmembrane transporter activity, and complement and coagulation cascades. GPX4 overexpression was associated with stage T3-T4 and pathologic stage III-IV in thyroid cancer patients. Cox regression analysis indicated that GPX4 may be a risk factor for the overall survival of thyroid cancer patients. In vitro research showed that knockdown of GPX4 suppressed proliferation and induced ferroptosis in thyroid cancer cells., Conclusions: GPX4 overexpression in thyroid cancer might play an essential role in tumorigenesis and may have prognostic value for thyroid cancer patients.
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- 2023
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11. Author Correction: Artificial intelligence defines protein-based classification of thyroid nodules.
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Sun Y, Selvarajan S, Zang Z, Liu W, Zhu Y, Zhang H, Chen W, Chen H, Li L, Cai X, Gao H, Wu Z, Zhao Y, Chen L, Teng X, Mantoo S, Lim TK, Hariraman B, Yeow S, Alkaff SMF, Lee SS, Ruan G, Zhang Q, Zhu T, Hu Y, Dong Z, Ge W, Xiao Q, Wang W, Wang G, Xiao J, He Y, Wang Z, Sun W, Qin Y, Zhu J, Zheng X, Wang L, Zheng X, Xu K, Shao Y, Zheng S, Liu K, Aebersold R, Guan H, Wu X, Luo D, Tian W, Li SZ, Kon OL, Iyer NG, and Guo T
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- 2022
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12. Mitoxantrone hydrochloride injection for tracing helps to decrease parathyroid gland resection and increase lymph node yield in thyroid cancer surgery: a randomized clinical trial.
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Chen S, Hou X, Hua S, Liu Z, Li B, Li X, Cong L, Liao Q, Fang J, Hou L, Jing S, Zhao Z, Qin J, Zhang S, Li Z, Huang D, Zhang N, Zhao Y, Liu J, Wang S, Chen G, and Zhao Y
- Abstract
The identification and preservation of parathyroid glands (PGs) during thyroid surgery can be challenging. Many techniques have been developed to help surgeons find PGs. We have developed a novel mitoxantrone hydrochloride injection that can be used for lymphatic targeting. After local application during surgery, mitoxantrone hydrochloride injection for tracing (MHI) helps surgeons better identify and preserve PGs and helps pathologists find more lymph nodes. We conducted an open-label, multicenter, randomized clinical trial (CTR20171137) in six centers in China from 08/2017 to 12/2018. Patients with thyroid carcinoma were randomized to the MHI group or the control group. All patients received total thyroidectomy and bilateral central compartment lymph node dissection. The primary outcomes were the PG resection rate and lymph node staining rate. The full analysis set (FAS) included 461 patients, of which 228 were assigned to the MHI group, and 233 were assigned to the control group. The PG resection rates of the MHI group and the control group were 6.6% (15/228) and 26.6% (62/233), respectively, with a significant difference (P < 0.001). No PGs were stained blue with MHI. The central lymph nodes were stained blue with MHI, and the staining rate was 90.5%±12.0%. More lymph nodes were detected in the MHI group than in the control group (13.0±7.3 vs. 10.1±6.4 nodes/patient, P < 0.001). No adverse events related to MHI were observed. MHI is a safe and effective tracer that may help to preserve PGs and identify more central lymph nodes in patients with thyroid cancer., Competing Interests: None., (AJCR Copyright © 2022.)
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- 2022
13. Artificial intelligence defines protein-based classification of thyroid nodules.
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Sun Y, Selvarajan S, Zang Z, Liu W, Zhu Y, Zhang H, Chen W, Chen H, Li L, Cai X, Gao H, Wu Z, Zhao Y, Chen L, Teng X, Mantoo S, Lim TK, Hariraman B, Yeow S, Alkaff SMF, Lee SS, Ruan G, Zhang Q, Zhu T, Hu Y, Dong Z, Ge W, Xiao Q, Wang W, Wang G, Xiao J, He Y, Wang Z, Sun W, Qin Y, Zhu J, Zheng X, Wang L, Zheng X, Xu K, Shao Y, Zheng S, Liu K, Aebersold R, Guan H, Wu X, Luo D, Tian W, Li SZ, Kon OL, Iyer NG, and Guo T
- Abstract
Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods., (© 2022. The Author(s).)
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- 2022
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14. Stratification of follicular thyroid tumours using data-independent acquisition proteomics and a comprehensive thyroid tissue spectral library.
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Sun Y, Li L, Zhou Y, Ge W, Wang H, Wu R, Liu W, Chen H, Xiao Q, Cai X, Dong Z, Zhang F, Xiao J, Wang G, He Y, Gao J, Kon OL, Iyer NG, Guan H, Teng X, Zhu Y, Zhao Y, and Guo T
- Subjects
- Humans, Proteomics, Adenocarcinoma, Follicular diagnosis, Adenocarcinoma, Follicular metabolism, Adenocarcinoma, Follicular pathology, Adenoma diagnosis, Carcinoma, Thyroid Neoplasms metabolism
- Abstract
Thyroid nodules occur in about 60% of the population. A major challenge in thyroid nodule diagnosis is to distinguish between follicular adenoma (FA) and carcinoma (FTC). Here, we present a comprehensive thyroid spectral library covering five types of thyroid tissues. This library includes 121 960 peptides and 9941 protein groups. This spectral library can be used to quantify up to 7863 proteins from thyroid tissues, and can also be used to develop parallel reaction monitoring (PRM) assays for targeted protein quantification. Next, to stratify follicular thyroid tumours, we compared the proteomes of 24 FA and 22 FTC samples, and identified 204 differentially expressed proteins (DEPs). Our data suggest altered ferroptosis pathways in malignant follicular carcinoma. In all, 31 selected proteins effectively distinguished follicular tumours. Of those DEPs, nine proteins were further verified by PRM in an independent cohort of 18 FA and 19 FTC. Together, we present a comprehensive spectral library for DIA and targeted proteomics analysis of thyroid tissue specimens, and identified nine proteins that could potentially distinguish FA and FTC., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2022
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15. Case Report and Systematic Review: Sarcomatoid Parathyroid Carcinoma-A Rare, Highly Malignant Subtype.
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Yu Y, Wang Y, Wu Q, Zhao X, Liu D, Zhao Y, Li Y, Wang G, Xu J, Chen J, Zhang N, and Tian X
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- Female, Humans, Middle Aged, Adenoma diagnostic imaging, Adenoma surgery, Neoplasm Recurrence, Local diagnostic imaging, Parathyroid Neoplasms diagnostic imaging, Parathyroid Neoplasms surgery
- Abstract
Background: Parathyroid carcinoma (PC) is a rare malignancy, the incidence of which is less than 1/1 million per year. Sarcomatoid parathyroid carcinoma (SaPC) is an extremely peculiar subtype; only three cases have been reported internationally. It consists of both malignant epithelial components and sarcomatoid components (mesenchymal origin) simultaneously. This "confusing" cancer exhibits higher invasiveness, and traditional surgery does not appear to achieve the expectation, which differs significantly from that of general PC., Objective: To characterize the clinicopathologic features of SaPC and explore similarities and differences between SaPC and general PC., Materials and Methods: We collected clinical data of SaPC cases from our center and literature. The SaPC case in our center was presented. To better understand the characteristics of SaPC, we also reviewed clinical information in general PC cases from our center and literature within the last 5 years, and a systematic review was performed for further comparison., Results: A 60-year-old woman was admitted for a neck mass and hoarseness. After the surgery, she was confirmed as SaPC and ultimately developed local recurrence at 3 months. Together with the reported cases from literature, four cases of SaPC (three cases from literature) and 203 cases of general PC (200 cases from literature) were reviewed. Both tumors showed obvious abnormalities in parathormone (PTH) level and gland size. Compared to general PC, SaPC has a later age of onset (60.50 ± 7.42 vs. 51.50 ± 8.29), relatively low levels of PTH (110.28 ± 59.32 vs. 1,156.07 ± 858.18), and a larger tumor size (6.00 ± 1.63 vs. 3.14 ± 0.70). For SaPC, all four cases were initially misdiagnosed as thyroid tumors (4/4). Spindle cell areas or transitional zones were common pathological features in SaPC cases (3/4)., Conclusion: SaPC is a very rare pathologic subtype of PC and appears to be much more easily misdiagnosed as a thyroid tumor. Spindle cell areas or transitional zones are highly possible to be pathological features in its sarcomatoid components. Despite many similarities, there are some differences between SaPC and general PC-SaPC does not show the obvious endocrine feature but stronger aggressiveness. Surgical treatment of SaPC does relieve life-threatening symptoms and improve quality of life even with recurrence in the short term., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Wang, Wu, Zhao, Liu, Zhao, Li, Wang, Xu, Chen, Zhang and Tian.)
- Published
- 2021
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16. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition).
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Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, and Fan J
- Abstract
Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people., Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years., Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)
- Published
- 2020
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17. Phenotype Classification using Proteome Data in a Data-Independent Acquisition Tensor Format.
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Zhang F, Yu S, Wu L, Zang Z, Yi X, Zhu J, Lu C, Sun P, Sun Y, Selvarajan S, Chen L, Teng X, Zhao Y, Wang G, Xiao J, Huang S, Kon OL, Iyer NG, Li SZ, Luan Z, and Guo T
- Subjects
- Carcinoma, Hepatocellular chemistry, Carcinoma, Hepatocellular diagnosis, Deep Learning, Humans, Liver Neoplasms chemistry, Liver Neoplasms diagnosis, Peptides analysis, Software, Thyroid Gland chemistry, Mass Spectrometry methods, Proteome analysis, Proteomics methods
- Abstract
A novel approach for phenotype prediction is developed for data-independent acquisition (DIA) mass spectrometric (MS) data without the need for peptide precursor identification using existing DIA software tools. The first step converts the DIA-MS data file into a new file format called DIA tensor (DIAT), which can be used for the convenient visualization of all the ions from peptide precursors and fragments. DIAT files can be fed directly into a deep neural network to predict phenotypes such as appearances of cats, dogs, and microscopic images. As a proof of principle, we applied this approach to 102 hepatocellular carcinoma samples and achieved an accuracy of 96.8% in distinguishing malignant from benign samples. We further applied a refined model to classify thyroid nodules. Deep learning based on 492 training samples achieved an accuracy of 91.7% in an independent cohort of 216 test samples. This approach surpassed the deep-learning model based on peptide and protein matrices generated by OpenSWATH. In summary, we present a new strategy for DIA data analysis based on a novel data format called DIAT, which enables facile two-dimensional visualization of DIA proteomics data. DIAT files can be directly used for deep learning for biological and clinical phenotype classification. Future research will interpret the deep-learning models emerged from DIAT analysis.
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- 2020
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18. Role of noncoding RNAs in cholangiocarcinoma (Review).
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Lv Y, Wang Z, Zhao K, Zhang G, Huang S, and Zhao Y
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- Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Bile Duct Neoplasms diagnosis, Bile Duct Neoplasms drug therapy, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Carcinogenesis drug effects, Carcinogenesis genetics, Cholangiocarcinoma diagnosis, Cholangiocarcinoma drug therapy, Epigenesis, Genetic drug effects, Gene Expression Regulation, Neoplastic drug effects, High-Throughput Nucleotide Sequencing, Humans, RNA, Untranslated analysis, RNA, Untranslated genetics, Sequence Analysis, RNA, Bile Duct Neoplasms genetics, Cholangiocarcinoma genetics, Gene Expression Regulation, Neoplastic genetics, RNA, Untranslated metabolism
- Abstract
Cholangiocarcinoma (CCA) is a malignant tumour originating from biliary epithelial cells, and is increasing in incidence. Radical surgery is the main treatment. However, the pathogenesis of CCA is unclear. Noncoding RNAs (ncRNAs) are non‑protein‑coding RNAs produced by genomic transcription that include microRNAs (miRNAs), circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs). They play important roles in gene expression, epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also serve key roles in cancer development. Numerous studies have been carried out on ncRNAs, and associated publications have shown that ncRNAs are closely associated with the physiological and pathological mechanisms of CCA. The findings of these studies can provide new insights into the diagnosis, treatment and prognosis of CCA. The present review summarizes the pathophysiological mechanisms of different types of ncRNAs, including miRNAs, circRNAs and lncRNAs in CCA, and their applications in the diagnosis and treatment of CCA.
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- 2020
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19. Resveratrol Inhibits the Tumorigenesis of Follicular Thyroid Cancer via ST6GAL2-Regulated Activation of the Hippo Signaling Pathway.
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Xu G, Chen J, Wang G, Xiao J, Zhang N, Chen Y, Yu H, Wang G, and Zhao Y
- Abstract
Follicular thyroid carcinoma (FTC) is a common endocrine malignancy with highly aggressive features. In this study, next-generation sequencing technology was used to identify aberrant expression of sialyltransferase (ST) family members in FTC. Aberrant high expression of alpha-2,6-sialyltransferase 2 (ST6GAL2) was demonstrated to promote tumorigenesis of FTC in vitro and in vivo . Furthermore, ST6GAL2 promoted tumorigenesis by inactivating the Hippo signaling pathway. Resveratrol is a native compound extracted from Vitis species, and many studies have confirmed its protective cardiovascular and antineoplastic effects. Here we found that resveratrol can inhibit the tumorigenesis of FTC by suppressing the expression of ST6GAL2, further activating the Hippo pathway. In summary, this study revealed the role of the ST6GAL2-Hippo signaling pathway in FTC tumorigenesis and indicated that resveratrol, a commonly found antineoplastic compound, could inhibit tumorigenesis of FTC by regulating the abovementioned pathways., (© 2020 The Authors.)
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- 2020
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20. Low density lipoprotein receptor (LDLR)-targeted lipid nanoparticles for the delivery of sorafenib and Dihydroartemisinin in liver cancers.
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Wang Z, Duan X, Lv Y, and Zhao Y
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Artemisinins administration & dosage, Cell Survival drug effects, Drug Delivery Systems, Hep G2 Cells, Humans, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Reactive Oxygen Species metabolism, Sorafenib administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lipids pharmacology, Liver Neoplasms drug therapy, Nanoparticles, Receptors, LDL drug effects
- Abstract
Aims: Liver cancer is one of the leading causes of cancer mortality worldwide. Inspired by the biological structure and function of low-density lipoprotein (LDL), in this study, an ApopB-100 based targeted lipid nanoparticles was synthesized to improve the therapeutic efficacy in liver cancer treatment., Main Methods: The biological composition of ApopB is similar to LDL which can effectively increase the targeting efficiency of nanoparticles in LDL receptor (LDLR)-overexpressed liver tumors., Keyfindings: We have demonstrated that the co-administration of sorafenib (SRF) and Dihydroartemisinin (DHA) could exhibit synergistic anticancer effect in HepG2 liver cancer cells. DHA produced excessive cellular reactive oxygen species (ROS) and induced greater apoptosis of cancer cells. LDL-based SRF/DHA-loaded lipid nanoparticles (LD-SDN) showed remarkable decrease in the cell viability compared to that of either of single drug treated cancer cells. Combination of SRF+DHA resulted in predominant SubG1 proportion of cells. LD-SDN exhibited the highest SubG1 (%) of cells compared to that of any of the individual drugs. Most importantly, robust antitumor response and delayed tumor growth was observed for LD-SDN treated xenograft tumor model. Ki67 proliferation index of LD-SDN (22.1 ± 5.6%) is significantly lesser compared to that of either control (86.2 ± 6.9%) or SRF (75.4 ± 4.89%) or DHA (69.4 ± 6.9%)., Significances: These data provide strong evidence that LDL-mimetic lipid nanoformulations could be utilized as a biocompatible and tumor targeted platform for the delivery of multiple anticancer drugs in cancer treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
21. Correction: LncRNA HCP5A promotes follicular thyroid carcinoma progression via miRNAs sponge.
- Author
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Liang L, Xu J, Wang M, Xu G, Zhang N, Wang G, and Zhao Y
- Abstract
Following the publication of this article, the authors realized there was an error in Figure 3a wherein the migration panel of pcDNA3.3 was replicated in the invasion panel for HCP5. This error did not impact the conclusions of the article.
- Published
- 2019
- Full Text
- View/download PDF
22. Anti-GPC3 Antibody Tagged Cationic Switchable Lipid-Based Nanoparticles for the Co-Delivery of Anti-miRNA27a And Sorafenib in Liver Cancers.
- Author
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Wang Z, Zhao K, Zhang Y, Duan X, and Zhao Y
- Subjects
- Animals, Apoptosis drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Cholesterol chemistry, Drug Synergism, Forkhead Box Protein O1 metabolism, Hep G2 Cells, Humans, Hydrogen-Ion Concentration, Mice, Inbred BALB C, Mice, Nude, PPAR gamma metabolism, Phosphorylcholine chemistry, Polyethylene Glycols chemistry, Antagomirs administration & dosage, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Glypicans immunology, Lipids chemistry, Liver Neoplasms drug therapy, MicroRNAs immunology, Nanoparticles chemistry, Sorafenib administration & dosage
- Abstract
Purpose: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy., Methods: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system., Results: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation., Conclusion: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers.
- Published
- 2019
- Full Text
- View/download PDF
23. Withdrawal: Modification of sialylation mediates the invasive properties and chemosensitivity of human hepatocellular carcinoma.
- Author
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Zhao Y, Li Y, Ma H, Dong W, Zhou H, Song X, Zhang J, and Jia L
- Published
- 2019
- Full Text
- View/download PDF
24. Activation of CXCL5-CXCR2 axis promotes proliferation and accelerates G1 to S phase transition of papillary thyroid carcinoma cells and activates JNK and p38 pathways.
- Author
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Cui D, Zhao Y, and Xu J
- Subjects
- Animals, Anthracenes pharmacology, Anthracenes therapeutic use, Cell Line, Tumor, Cell Proliferation drug effects, Chemokine CXCL5 genetics, G1 Phase Cell Cycle Checkpoints drug effects, G1 Phase Cell Cycle Checkpoints physiology, Humans, Imidazoles pharmacology, Imidazoles therapeutic use, MAP Kinase Signaling System drug effects, MAP Kinase Signaling System physiology, Mice, Mice, Nude, Phenylurea Compounds pharmacology, Phenylurea Compounds therapeutic use, Phosphorylation drug effects, Pyridines pharmacology, Pyridines therapeutic use, Receptors, Interleukin-8B antagonists & inhibitors, Recombinant Proteins genetics, Recombinant Proteins metabolism, Thyroid Cancer, Papillary drug therapy, Thyroid Neoplasms drug therapy, Xenograft Model Antitumor Assays, Chemokine CXCL5 metabolism, Receptors, Interleukin-8B metabolism, Thyroid Cancer, Papillary pathology, Thyroid Neoplasms pathology
- Abstract
C-X-C motif chemokine ligand 5 (CXCL5) is initially identified to recruit neutrophils by interacting with its receptor, C-X-C motif chemokine receptor 2 (CXCR2). Our prior work demonstrated that the expression levels of CXCL5 and CXCR2 were higher in the papillary thyroid carcinoma (PTC) tumors than that in the non-tumors. This study was performed to further investigate how this axis regulates the growth of PTC cells. B-CPAP cells (BRAF
V600E ) and TPC-1 cells (RET/PTC rearrangement) expressing CXCR-2 were used as in vitro cell models. Our results showed that the recombinant human CXCL5 (rhCXCL5) promoted the proliferation of PTC cells. rhCXCL5 accelerated the G1/S transition, upregulated the expression of a group of S (DNA synthesis) or M (mitosis)-promoting cyclins and cyclin-dependent kinases (CDKs), and downregulated CDK inhibitors in PTC cells. The CDS region of homo sapiens CXCL5 gene was inserted into an eukaryotic expression vector to mediate the overexpression of CXCL5 in PTC cells. The phosphorylation of c-Jun N-terminal kinases (JNK) and p38, and the nuclear translocation of c-Jun were enhanced by CXCL5 overexpression, whereas attenuated by CXCR2 antagonist SB225002. Additionally, CXCL5/CXCR2 axis, JNK and p38 pathway inhibitors, SB225002, SP600125 and SB203580, suppressed the growth of PTC cells overexpressing CXCL5 in nude mice, respectively. Collectively, our study demonstrates a growth-promoting effect of CXCL5-CXCR2 axis in PTC cells in vitro and in vivo.- Published
- 2019
- Full Text
- View/download PDF
25. Development and characterization of irradiated-corn-starch films.
- Author
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Li L, Chen H, Wang M, Lv X, Zhao Y, and Xia L
- Abstract
The effect of
60 Co gamma ray irradiation on the physicochemical and crystalline properties of native corn starch were investigated. Fourier transform infrared spectroscopy and X-ray diffraction showed that irradiation had a slight effect on the molecular structure of corn starch with crystallinity decreasing with increasing irradiation dose. Particle size analysis showed that 59.1% of native corn starch granules had sizes of ≥8 μm, which decreased to only 24.1% after treatment with an irradiation dose of 40 kGy. Irradiated-corn-starch films were prepared by casting gelatinized irradiated-corn-starch solutions. An increased irradiation dose was found to increase the tensile strength of the resultant films, but caused a significant decrease in water vapor permeability. The irradiated-corn-starch films showed potential for the development of biodegradable starch films with improved properties., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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- View/download PDF
26. Activated CXCL5-CXCR2 axis promotes the migration, invasion and EMT of papillary thyroid carcinoma cells via modulation of β-catenin pathway.
- Author
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Cui D, Zhao Y, and Xu J
- Subjects
- Carcinoma, Papillary metabolism, Humans, Neoplasm Invasiveness, Thyroid Neoplasms metabolism, Carcinoma, Papillary pathology, Cell Movement, Chemokine CXCL5 metabolism, Epithelial-Mesenchymal Transition, Receptors, Interleukin-8B metabolism, Thyroid Neoplasms pathology, Wnt Signaling Pathway
- Abstract
Initiation of epithelial-to-mesenchymal transition (EMT) is common in papillary thyroid carcinoma (PTC) and may contribute to its metastasis. Aims of the present study are to investigate whether and how the C-X-C motif chemokine ligand (CXCL)-5/C-X-C motif receptor 2 (CXCR2) axis affects PTC metastasis, with a focus on the EMT process. Herein, two PTC cell lines, KTC-1 and B-CPAP cells, identified as CXCR2-positive cells were used as the cell model. We found that a 24-h stimulation of 1 or 10 nM recombinant human CXCL5 (rhCXCL5) enhanced the migration and invasion of both KTC-1 and B-CPAP cells without affecting their proliferation. The migration- and invasion-promoting effects of rhCXCL5 were attenuated if CXCR2 was silenced by its specific short hairpin RNAs (shRNAs). EMT initiation is defined as downregulation of epithelial-cadherin (E-cadherin) and upregulation of N-cadherin, Vimentin and Snail. Our data showed that rhCXCL5-induced EMT in PTC cells was suppressed by CXCR2 shRNA. Furthermore, the active CXCL5-CXCR2 axis enhanced the phosphorylation of Akt at Ser 473 residue and that of glycogen synthase kinase-3 (GSK-3β) at Ser 9 residue, and accelerated the nuclear accumulation of β-catenin in PTC cells. Re-expression of the active form of β-catenin in PTC cells rescued their impaired invasiveness caused by the blockade of CXCL5-CXCR2 axis. In addition, CXCL5 and CXCR2 were overexpressed in the metastatic lymph nodes obtained from 18 patients with PTC. In summary, our study demonstrates that the activated CXCL5-CXCR2 axis contributes to the metastatic phenotype of PTC cells by modulating Akt/GSK-3β/β-catenin pathway., (Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
27. LncRNA HCP5 promotes follicular thyroid carcinoma progression via miRNAs sponge.
- Author
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Liang L, Xu J, Wang M, Xu G, Zhang N, Wang G, and Zhao Y
- Subjects
- Adenocarcinoma, Follicular genetics, Animals, Cell Line, Tumor, Cell Movement genetics, Cell Movement physiology, Cell Proliferation genetics, Cell Proliferation physiology, Gene Expression Regulation, Neoplastic genetics, Gene Expression Regulation, Neoplastic physiology, High-Throughput Nucleotide Sequencing, Humans, Mice, Nude, Polymerase Chain Reaction, RNA, Long Noncoding genetics, Adenocarcinoma, Follicular metabolism, Adenocarcinoma, Follicular pathology, MicroRNAs metabolism, RNA, Long Noncoding metabolism
- Abstract
Long non-coding RNAs (lncRNAs), which are important functional regulators in cancer, have received increased attention in recent years. In this study, next-generation sequencing technology was used to identify aberrantly expressed lncRNAs in follicular thyroid carcinoma (FTC). The long non-coding RNA-HLA complex P5 (HCP5) was found to be overexpressed in FTC. The results of the qPCR analysis were consistent with the sequencing results. In addition, functional experiments showed that overexpression of HCP5 can promote the proliferation, migration, invasiveness and angiogenic ability of FTC cells. Furthermore, according to the sequencing results, HCP5 and alpha-2, 6-sialyltransferase 2 (ST6GAL2) were co-expressed in FTC. We hypothesised that ST6GAL2 may be regulated by HCP5, which would in turn mediate the activity of FTC cells. Through qPCR, immunostaining analyses and functional experiments, we determined that the expression of HCP5 was elevated and was correlated with the levels of ST6GAL2 in FTC tissues and cells. Mechanistic experiments showed that HCP5 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-22-3p, miR-186-5p and miR-216a-5p, which activates ST6GAL2. In summary, our study revealed that HCP5 is a tumour regulator in the development of FTC and that it may contribute to improvement of FTC diagnosis and therapy.
- Published
- 2018
- Full Text
- View/download PDF
28. Paper-based immune-affinity arrays for detection of multiple mycotoxins in cereals.
- Author
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Li L, Chen H, Lv X, Wang M, Jiang X, Jiang Y, Wang H, Zhao Y, and Xia L
- Subjects
- Animals, Equipment Design, Food Analysis instrumentation, Humans, Immunoassay instrumentation, Limit of Detection, Luminescent Measurements instrumentation, Luminescent Measurements methods, Polymerization, Reproducibility of Results, T-2 Toxin analogs & derivatives, T-2 Toxin analysis, Trichothecenes analysis, Zearalenone analysis, Antibodies, Immobilized chemistry, Edible Grain chemistry, Food Analysis methods, Food Contamination analysis, Immunoassay methods, Mycotoxins analysis, Paper
- Abstract
Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 μg·kg
-1 , respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods. Graphical abstract Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone.- Published
- 2018
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- View/download PDF
29. Microarray Analysis of Differentially Expressed Profiles of Circular RNAs in a Mouse Model of Intestinal Ischemia/Reperfusion Injury with and Without Ischemic Postconditioning.
- Author
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Feng D, Li Z, Wang G, Yao J, Li Y, Qasim W, Zhao Y, and Tian X
- Subjects
- Animals, Computational Biology, Disease Models, Animal, Down-Regulation, Ischemic Postconditioning, Male, Mice, Mice, Inbred C57BL, MicroRNAs metabolism, Oligonucleotide Array Sequence Analysis, RNA, Circular, RNA, Messenger metabolism, Reperfusion Injury genetics, Tumor Necrosis Factor-alpha blood, Up-Regulation, Intestines pathology, RNA metabolism, Reperfusion Injury pathology
- Abstract
Background/aims: Ischemic postconditioning (iPoC) represents a promising strategy to mitigate ischemia/reperfusion (I/R) injury of the intestine, yet the mechanisms of this treatment remain to be elucidated. Circular RNAs (circRNAs), a novel class of endogenous non-coding RNAs, have recently been recognized as important regulators of gene expression and pathological processes. Here, we aimed to investigate the expression patterns of circRNAs after intestinal I/R with and without iPoC and, furthermore, to explore the potential mechanisms of iPoC in relation to the differentially expressed circRNAs., Methods: The global circRNA and mRNA expression profiles in mouse intestinal mucosa were initially screened by microarray (n = 3 per group) and quantitative real-time PCR was used to validate the expression pattern of circRNAs and mRNAs. Bioinformatics analysis including Gene ontology, KEGG pathway analysis, microRNA binding sites identification and circRNA-miRNA-mRNA network construction were utilized for in-depth mechanism exploration., Results: There were 4 up- and 58 downregulated circRNAs as well as 322 up- and 199 downregulated mRNAs in the intestinal I/R group compared with the sham group, whereas compared with I/R, iPoC treatment significantly upregulated 12 circRNAs and 129 mRNAs and downregulated 21 circRNAs and 174 mRNAs. The expression levels of a randomly selected set of 6 circRNAs and 5 mRNAs were successfully validated by qRT-PCR. Through a systematic comparison of the direction of circRNA expression changes in all groups, we identified two circRNAs, circRNA_012412 and circRNA_016863, that may be closely associated with the protective mechanisms of iPoC. Finally, four possible circRNA_012412/circRNA_016863-miRNA-mRNA pathways were predicted, which may play important roles in endogenous protective signaling in iPoC., Conclusions: This study was the first to comprehensively delineate the expression profiles of circRNAs in a mouse model of intestinal I/R and iPoC and provides novel clues for understanding the mechanisms of iPoC against intestinal I/R injury., (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2018
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- View/download PDF
30. Gamma irradiation-induced decomposition of sulfamethoxazole in aqueous solution: the influence of additives, biological inhibitory, and degradation mechanisms.
- Author
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Wang J, Guo Z, Shen X, Guo Q, Zhao Y, Zhu S, and Guo Z
- Subjects
- Gamma Rays, Kinetics, Sulfamethoxazole chemistry, Water, Water Purification methods, 2-Propanol chemistry, Chromium chemistry, Sulfamethoxazole analysis
- Abstract
Sulfamethoxazole (SMX) was decomposed by using gamma irradiation in the presence of different additives such as NO
3 - , NO2 - , Cr(VI), 2-propanol, and tert-butanol. The results demonstrated that NO3 - , NO2 - , 2-propanol, and tert-butanol inhibited SMX radiolytic removal. However, there existed a synergetic effect for radiolytic removal of the mixture containing SMX and Cr(VI). At an absorbed dose of 150 Gy, the removal percentages of SMX and Cr(VI) in the mixture were 73.5 and 84.6%, respectively, which was higher than the removal percentages of 70.6 and 4.1% for the single component of SMX and Cr(VI). This provides us an insight into treating the combined pollution in micro-polluted water. The SMX radiolytic removal followed a pseudo first-order reaction kinetic model, and the rate constant ratios of ·OH, eaq - , and H· towards SMX radiolysis were 10.4:1:2.9. In addition, 24-h bio-inhibitory to the macroalgae of SMX solution during gamma irradiation reached the maximum of 0.85 at an adsorbed dose of 100 Gy, then gradually decreased with the increasing adsorbed dose. Based on LC-MS analysis and quantum chemical calculation, the degradation intermediates were determined and concluded that SMX radiolytic removal was mainly via ·OH radical attack and direct decomposition of SMX molecule by gamma ray.- Published
- 2017
- Full Text
- View/download PDF
31. miR-125a-3p/FUT5-FUT6 axis mediates colorectal cancer cell proliferation, migration, invasion and pathological angiogenesis via PI3K-Akt pathway.
- Author
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Liang L, Gao C, Li Y, Sun M, Xu J, Li H, Jia L, and Zhao Y
- Subjects
- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Female, Fucosyltransferases genetics, Humans, Male, MicroRNAs genetics, Middle Aged, Neoplasm Invasiveness, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins c-akt genetics, RNA, Neoplasm genetics, Tumor Cells, Cultured, Cell Movement, Cell Proliferation, Colorectal Neoplasms metabolism, Fucosyltransferases metabolism, MicroRNAs metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, RNA, Neoplasm metabolism, Signal Transduction
- Abstract
The fucosyltransferase (FUT) family produces glycans, a fundamental event in several cancers, including colorectal cancer (CRC). miR-125a-3p is a non-coding RNA that can reduce cell proliferation and migration in cancer. In this study, we explored the levels of miR-125a-3p and FUT expression in human CRC tissues and two human CRC cell lines by qPCR. The results showed that miR-125a-3p, FUT5 and FUT6 are differentially expressed in normal and tumour tissues. On the basis of our previous research, FUT can be regulated by miRNA, which influences the proliferation and invasion of breast and hepatocellular cancer cells. We hypothesised that FUT5 and FUT6 may be regulated by miR-125a-3p. Luciferase reporter analyses were applied to identify potential target genes of miR-125a-3p. A functional study showed that miR-125a-3p overexpression can inhibit the proliferation, migration, invasion and angiogenesis of CRC cells via down-regulating FUT5 and FUT6. In addition, regulating miR-125a-3p, FUT5 or FUT6 expression markedly modulated the activity of the PI3K/Akt signalling pathway, and this effect of FUT5 or FUT6 could be reversed by transfection with miR-125a-3p-mimics. Taken together, our data suggest that both FUT5 and FUT6 can promote the development of CRC via the PI3K/Akt signalling pathway, which is regulated by miR-125a-3p. miR-125a-3p may serve as a predictive biomarker and a potential therapeutic target in CRC treatment.
- Published
- 2017
- Full Text
- View/download PDF
32. Immune-affinity monolithic array with chemiluminescent detection for mycotoxins in barley.
- Author
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Li L, Xia L, Zhao Y, Wang M, and Jiang X
- Subjects
- Antibodies, Immobilized chemistry, Food Microbiology, Hordeum microbiology, Immunoassay methods, Food Contamination analysis, Hordeum chemistry, Luminescent Measurements methods, Mycotoxins analysis, Protein Array Analysis methods
- Abstract
Background: Mycotoxins are produced by fungi as secondary metabolites. They often multi-contaminate food and feed commodities posing a health risk to humans and animals. Fast and easy multiplex screening could be thought as a useful tool for detection of multi-contaminated food and feed commodities., Results: A highly sensitive immune-affinity monolithic arrays for detecting the mycotoxins zearalenone, deoxynivalenol, T-2 toxin, HT-2 toxin, aflatoxins, ochratoxin A, and fumonisin B
1 were fabricated using UV induced co-polymerisation. The mycotoxin antibodies firstly reacted with functional monomer to form antibody/functional monomer bio-conjugates. Subsequently, the antibody/functional monomer bio-conjugates co-polymerised with cross-linker to form mycotoxins immune-affinity arrays. With optimal fabrication conditions, all mycotoxin immune-affinity monolithic arrays exhibited a linear response spanning three orders of magnitude. And the immune-affinity monolithic array has a low detection limit and has a good uniformity (intra-assay CV, and inter-assay CV both <8%)., Conclusion: The fabricated mycotoxin immune-affinity monolithic arrays were proved as a sensitive, stable and economical tool in real food samples detection. Moreover, the mycotoxin immune-affinity monolithic arrays would be able to minimise manipulation steps: add samples and enzyme labelled mycotoxins, and detect CL signals. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)- Published
- 2017
- Full Text
- View/download PDF
33. miR-146a and miR-146b promote proliferation, migration and invasion of follicular thyroid carcinoma via inhibition of ST8SIA4.
- Author
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Ma W, Zhao X, Liang L, Wang G, Li Y, Miao X, and Zhao Y
- Subjects
- Adenocarcinoma, Follicular metabolism, Adenocarcinoma, Follicular pathology, Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Models, Animal, Heterografts, Humans, Mice, Multigene Family, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Adenocarcinoma, Follicular genetics, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, RNA Interference, Sialyltransferases genetics
- Abstract
Follicular thyroid carcinoma (FTC) is a more aggressive form of thyroid cancer than the common papillary type. Alpha-2,8-sialyltransferase (ST8SIA) family members are expressed in various cancers and may be associated with FTC progression. In this study, we measured ST8SIA family expression in two FTC cell lines with different invasive potentials (FTC-133 and FTC-238) and Nthy-ori 3-1 cell lines, as well as FTC and normal thyroid tissues. ST8SIA4 was downregulated in the highly invasive FTC-238 cells and FTC tissues. Additionally, ST8SIA4 inhibited proliferation, migration and invasion of FTC both in vitro and in vivo. miR-146a and miR-146b were previously shown to be upregulated in thyroid carcinoma, and bioinformatics analyses indicated that miR-146a and miR-146b inhibit ST8SIA4. We found that miR-146a and miR-146b were significantly upregulated in FTC and promoted tumour progression. Furthermore, ST8SIA4 restoration decreased the invasiveness of miR-146a/b-overexpressing FTC-133 cells, and ST8SIA4 suppression reversed the effects of miR-146a/b inhibition in FTC-238 cells. We showed that miR-146a/b activated the PI3K-AKT-mTOR signalling pathway at least partially via suppression of ST8SIA4. Thus, our results demonstrate that miR-146a and miR-146b promote proliferation, migration and invasion of FTC via inhibition of ST8SIA4.
- Published
- 2017
- Full Text
- View/download PDF
34. Sialyltransferase ST3GAL6 mediates the effect of microRNA-26a on cell growth, migration, and invasion in hepatocellular carcinoma through the protein kinase B/mammalian target of rapamycin pathway.
- Author
-
Sun M, Zhao X, Liang L, Pan X, Lv H, and Zhao Y
- Subjects
- Animals, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular secondary, Cell Line, Tumor, Cell Movement, Cell Proliferation, Humans, Liver Neoplasms metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Signal Transduction, Tumor Stem Cell Assay, Up-Regulation, beta-Galactoside alpha-2,3-Sialyltransferase, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, MicroRNAs physiology, Proto-Oncogene Proteins c-akt metabolism, Sialyltransferases physiology, TOR Serine-Threonine Kinases metabolism
- Abstract
Aberrant sialylation profiles on the cell surface have been recognized for their potential diagnostic value in identifying the regulation of tumor properties in several cancers, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that the deregulation of microRNA (miRNA) is a common feature in human cancers. In this study, we found obvious upregulation of sialyltransferase ST3GAL6 both in HCC cell lines and in tissue samples. The altered expression of ST3GAL6 was found to correlate with cell proliferation, migration, and invasion ability in HCC. Further investigation showed that miR-26a negatively regulated ST3GAL6, inducing the suppression of cell proliferation, migration, and invasion in vitro. Moreover, we identified the protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway as the target of ST3GAL6 based on Western blot analysis. Analysis of a xenograft mouse model showed that miR-26a significantly reduced tumor growth by suppressing activation of the Akt/mTOR pathway by directly targeting ST3GAL6. In conclusion, these data indicate that ST3GAL6 promotes cell growth, migration, and invasion and mediates the effect of miR-26a through the Akt/mTOR signaling pathway in HCC., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2017
- Full Text
- View/download PDF
35. Activated platelets inhibit hepatocellular carcinoma cell differentiation and promote tumor progression via platelet-tumor cell binding.
- Author
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Zhang R, Guo H, Xu J, Li B, Liu YJ, Cheng C, Zhou C, Zhao Y, and Liu Y
- Subjects
- Adenosine Diphosphate metabolism, Aged, Animals, Carcinogenesis, Cell Differentiation, Clopidogrel, Female, Hep G2 Cells, Humans, Male, Mice, Mice, SCID, Middle Aged, P-Selectin metabolism, Protein Binding, RNA, Small Interfering genetics, Ticlopidine analogs & derivatives, Ticlopidine therapeutic use, Transcription Factor 4 genetics, Transcription Factor 4 metabolism, Tumor Microenvironment, Xenograft Model Antitumor Assays, Blood Platelets immunology, Carcinoma, Hepatocellular immunology, Intercellular Junctions immunology, Liver Neoplasms immunology, Platelet Activation
- Abstract
Lack of differentiation in hepatocellular carcinoma (HCC) is associated with increased circulating platelet size. We measured platelet activation and plasma adenosine diphosphate (ADP) levels in HCC patients based on differentiation status. Local platelet accumulation and platelet-hepatoma cell binding were measured using immunohistochemistry (IHC) or flow cytometry. Using a xenograft assay in NON/SCID mice, we tested the effects of the anti-platelet drug clopidogrel on platelet activation, platelet infiltration, platelet-tumor cell binding and tumor cell differentiation. HCC patients with poor differentiation status displayed elevated platelet activation and higher ADP levels. Platelets accumulated within poorly differentiated tissues and localized at hepatoma cell membranes. Platelet-tumor cell binding was existed in carcinoma tissues, largely mediated by P-selectin on platelets. NOD/SCID mice with xenograft tumors also exhibited increased platelet activation and platelet-tumor cell binding. Clopidogrel therapy triggered hepatoma cell differentiation by attenuating platelet activation and platelet-tumor cell binding. TCF4 knockdown promoted HepG-2 cell differentiation and inhibited tumor formation, and TCF4 could be the potential downstream target for clopidogrel therapy.
- Published
- 2016
- Full Text
- View/download PDF
36. miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4.
- Author
-
Zhao L, Feng X, Song X, Zhou H, Zhao Y, Cheng L, and Jia L
- Subjects
- 3' Untranslated Regions genetics, Breast Neoplasms pathology, Cell Line, Tumor, Cell Proliferation genetics, Female, Gene Expression Regulation, Neoplastic genetics, Humans, MCF-7 Cells, Neoplasm Invasiveness pathology, RNA, Messenger genetics, Breast Neoplasms genetics, Carcinogenesis genetics, Fucosyltransferases genetics, Lewis X Antigen genetics, MicroRNAs genetics, Neoplasm Invasiveness genetics
- Abstract
Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR‑493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR‑493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer.
- Published
- 2016
- Full Text
- View/download PDF
37. CHST11/13 Regulate the Metastasis and Chemosensitivity of Human Hepatocellular Carcinoma Cells Via Mitogen-Activated Protein Kinase Pathway.
- Author
-
Zhou H, Li Y, Song X, Zhao Y, Cheng L, Zhao L, and Jia L
- Subjects
- Cell Line, Tumor, Female, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic physiology, Gene Knockdown Techniques, Humans, MAP Kinase Signaling System physiology, Male, Middle Aged, RNA, Small Interfering metabolism, Sulfotransferases genetics, Carcinoma, Hepatocellular metabolism, Liver Neoplasms metabolism, Neoplasm Metastasis physiopathology, Sulfotransferases metabolism
- Abstract
Background: Carbohydrate sulfotransferases 11-13 (CHST11-13), that catalyze the transfer of sulfate to position 4 of the GalNAc residue of chondroitin, have been implicated in various diseases., Aim: This study aimed to clarify the association of CHST11-13 expression with metastasis and drug sensitivity in hepatocellular carcinoma (HCC) cells., Methods: We measured the levels of CHST11 and CHST13 in a series of HCC cells using real-time PCR and Western blotting. After RNAi and forced expression treatment of CHST11 and CHST13 in MHCC97L and MHCC97H cells, metastatic potential and drug sensitivity of the two cells were investigated with ECM invasion assay, drug sensitivity assay, and in vivo antitumor activity assay. By real-time PCR and Western blotting, we explored the possible impacts of these two genes on mitogen-activated protein kinase (MAPK) signal pathway. MAPK pathway was blocked by PD98059 or SP600125 to elucidate the effects of MAPK pathway on metastasis and chemosensitivity., Results: Significantly reduced levels of CHST11 and CHST13 were observed in highly invasive MHCC97H cells compared with those of MHCC97L cell line with low metastatic potential. Decreased or forced expression of CHST11 and CHST13 altered metastatic potential and drug sensitivity of MHCC97L and MHCC97H cells. Remarkable alteration of MAPK activity was shown in two HCC cells with genetic manipulation. Conversely, pharmacologic inhibition of the MAPK pathway suppressed invasive potential and rescued drug sensitivity of MHCC97H cells., Conclusions: Our results have demonstrated that CHST11 and CHST13 negatively modulate metastasis and drug resistance of HCC cells probably via oncogenic MAPK signal pathway.
- Published
- 2016
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38. Myocardial protective effects of a c-Jun N-terminal kinase inhibitor in rats with brain death.
- Author
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Guo W, Cao S, Yan B, Zhang G, Li J, Zhao Y, and Zhang S
- Subjects
- Animals, Apoptosis drug effects, Apoptosis genetics, Caspase 3 metabolism, Cytochromes c metabolism, Gene Expression Regulation drug effects, JNK Mitogen-Activated Protein Kinases metabolism, Male, Mitochondria genetics, Myocardium metabolism, Phosphorylation drug effects, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Sprague-Dawley, bcl-2-Associated X Protein metabolism, Anthracenes pharmacology, Brain Death pathology, Cardiotonic Agents pharmacology, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Myocardium pathology, Protein Kinase Inhibitors pharmacology
- Abstract
To investigate whether the mitochondrial apoptotic pathway mediates myocardial cell injuries in rats under brain death (BD), and observe the effects and mechanisms of the c-Jun N-terminal kinase (JNK) inhibitor SP600125 on cell death in the heart. Forty healthy male Sprague-Dawley (SD) rats were randomized into four groups: sham group (dural external catheter with no BD); BD group (maintain the induced BD state for 6 hrs); BD + SP600125 group (intraperitoneal injection of SP600125 10 mg/kg 1 hr before inducing BD, and maintain BD for 6 hrs); and BD + Dimethyl Sulphoxide (DMSO) group (intraperitoneal injection of DMSO 1 hr before inducing BD, and maintain BD for 6 hrs). Real-time quantitative PCR was used to evaluate mRNA levels of Cyt-c and caspase-3. Western blot analysis was performed to examine the levels of mitochondrial apoptosis-related proteins p-JNK, Bcl-2, Bax, Cyt-c and Caspase-3. TUNEL assay was employed to evaluate myocardial apoptosis. Compared with the sham group, the BD group exhibited increased mitochondrial apoptosis-related gene expression, accompanied by the elevation of p-JNK expression and myocardial apoptosis. As the vehicle control, DMSO had no treatment effects. The BD + SP600125 group had decreased p-JNK expression, and reduced mitochondrial apoptosis-related gene expression. Furthermore, the apoptosis rate of myocardial cells was reduced. The JNK inhibitor SP600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis-related pathways., (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Published
- 2016
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39. miR-34a-5p Inhibition Alleviates Intestinal Ischemia/Reperfusion-Induced Reactive Oxygen Species Accumulation and Apoptosis via Activation of SIRT1 Signaling.
- Author
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Wang G, Yao J, Li Z, Zu G, Feng D, Shan W, Li Y, Hu Y, Zhao Y, and Tian X
- Subjects
- Animals, Caco-2 Cells, Gene Expression, Gene Expression Regulation, Enzymologic, Humans, Intestines blood supply, Intestines pathology, Male, Mesenteric Arteries pathology, Mice, Inbred C57BL, Oxidative Stress, RNA Interference, Signal Transduction, Apoptosis, Intestinal Mucosa metabolism, MicroRNAs physiology, Reactive Oxygen Species metabolism, Reperfusion Injury enzymology, Sirtuin 1 metabolism
- Abstract
Aims: Reactive oxygen species (ROS) generation and massive epithelial apoptosis are critical in the pathogenesis of intestinal ischemia/reperfusion (I/R) injury. We previously found that the Sirtuin 1 (SIRT1)-mediated antioxidant pathway was impaired in the intestine after I/R. Here, we investigate the potential role of SIRT1-targeting microRNAs (miRNAs) in regulating ROS accumulation and apoptosis in intestinal I/R, and the important role SIRT1 involved in., Results: C57BL/6 mice were subjected to intestinal I/R induced by occlusion of the superior mesenteric artery followed by reperfusion. Caco-2 cells were incubated under hypoxia/reoxygenation condition to mimic I/R in vivo. We find that SIRT1 is gradually repressed during the early reperfusion, and that this repression results in intestinal ROS accumulation and apoptosis. Using bioinformatics analysis and real-time PCR, we demonstrate that miR-34a-5p and miR-495-3p are significantly increased among the 41 putative miRNAs that can target SIRT1. Inhibition of miR-34a-5p, but not miR-495-3p, attenuates intestinal I/R injury, as demonstrated by repressing p66shc upregulation, manganese superoxide dismutase repression, and the caspase-3 activation in vitro and in vivo; it further alleviates systemic injury, as demonstrated by reducing inflammatory cytokine release, attenuating lung and liver lesions, and improving survival. Interestingly, SIRT1 plays an indispensable role in the protection afforded by miR-34a-5p inhibition., Innovation: This study provides the first evidence of miRNAs in regulating oxidative stress and apoptosis in intestinal I/R., Conclusion: miR-34a-5p knockdown attenuates intestinal I/R injury through promoting SIRT1-mediated suppression of epithelial ROS accumulation and apoptosis. This may represent a novel prophylactic approach to intestinal I/R injury. Antioxid. Redox Signal. 24, 961-973.
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- 2016
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40. Clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization on hepatocellular carcinoma.
- Author
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Liu C, Sun L, Xu J, and Zhao Y
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular therapy, Chemotherapy, Adjuvant, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Liver Neoplasms therapy, Male, Middle Aged, Neoplasm Recurrence, Local therapy, Neoplasm Staging, Postoperative Period, Prognosis, Retrospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Hepatocellular pathology, Chemoembolization, Therapeutic, Hepatectomy, Liver Neoplasms pathology, Neoplasm Recurrence, Local pathology
- Abstract
Background: The aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC)., Methods: Data from 117 patients with HCC who underwent hepatectomy between December 2010 and February 2014 were retrospectively reviewed. In total, 55 patients underwent surgical resection only (group A), and 62 patients underwent surgical resection with adjuvant TACE (group B). The perioperative clinical indicators, postoperative sequential treatment, and follow-up were compared between the two groups of patients. The Kaplan-Meier method was used to compare survival between the groups, and prognostic factors were evaluated by a Cox proportional hazard model., Results: The two groups showed no significant difference in age, gender, preoperative A-fetoprotein (AFP) values, preoperative Child-Pugh score, hepatitis B virus(HBV) DNA levels, duration of surgery, hepatectomy technique, albumin values 1-week postoperative, postoperative complications, duration of postoperative hospital stay, cirrhosis, tumor size, tumor differentiation, tumor encapsulation, satellite nodules, or microvascular infiltration. Cox regression analysis revealed that tumor size, satellite nodules, and microvascular infiltration were significantly independent prognostic factors (P = 0.001, 0.002, and 0.001). Of the 117 patients, the 1-, 2-, and 3-year disease-free survival rates were 64.5, 50.0, and 41.9%, respectively, for group B (62 patients) and 45.5, 36.4, and 30.9%, respectively, for group A (55 patients). Although improving trends of disease-free survival were observed in the adjuvant TACE group, there was a significant difference in postoperative 1-year survival between the two groups (P = 0.04) but no significant difference in postoperative 2- and 3-year survival. In patients with tumor size >5 cm, the 1-, 2-, and 3-year disease-free survival rates were 41.7, 25.0, and 12.5%, respectively, for group B and 11.8, 0, and 0%, respectively, for group A. There was a significant difference in postoperative 1- and 2-year survival between the two groups (P = 0.04 and 0.03, respectively) but no significant difference in postoperative 3-year survival. In patients with microvascular infiltration, the 1-, 2-, and 3-year disease-free survival rates were 42.3, 26.9, and 15.4%, respectively, for group B and 12.5, 4.2, and 0%, respectively, for group A. There was a significant difference between the two groups (P = 0.02, 0.03, and 0.045, respectively). In patients with satellite nodules, the 1-, 2-, and 3-year disease-free survival rates were 50.0, 50, and 40%, respectively, for group B and 17.6, 0, and 0%, respectively, for group A. There was a significant difference between the two groups (P = 0.04, 0.01, and 0.03, respectively). In patients with tumor size ≤5 cm, without satellite nodules, or without microvascular infiltration, there was no significant difference between the two groups in the 1-, 2-, or 3-year disease-free survival rates. Of 117 patients overall, 18 (15.4%) developed hepatitis B virus reactivation: 2 (3.6%) patients in group A and 16 (25.8%) patients in group B. There was a significant difference between the two groups (P = 0.000). Of these patients, one (1.8 %) patient in group A and five (8.1 %) patients in group B developed hepatitis due to hepatitis B virus reactivation. There was a significant difference between the two groups (P = 0.000)., Conclusions: Postoperative adjuvant TACE can improve the 1-year disease-free survival rate of HCC patients. Postoperative adjuvant TACE may improve 2- and 3-year disease-free survival rates, but no statistical significance was found. For patients with tumor size >5 cm, postoperative adjuvant TACE can improve 1- and 2-year disease-free survival rates, and postoperative adjuvant TACE may improve the 3-year disease-free survival rate. For HCC patients with tumor size ≤5 cm, postoperative adjuvant TACE may improve the 1-, 2-, and 3-year disease-free survival rates, but no statistical significance was found. For patients with microvascular infiltration or satellite nodules, postoperative adjuvant TACE can improve the 1-, 2-, and 3-year disease-free survival rates. For patients without microvascular infiltration or without satellite nodules, postoperative adjuvant TACE cannot improve 1-, 2-, or 3-year disease-free survival rates. For patients with tumor size >5 cm with microvascular infiltration or with satellite nodules, postoperative adjuvant TACE was suggested. Hepatitis B virus reactivation can occur in patients with postoperative adjuvant TACE; thus, antiviral treatment was suggested for these patients.
- Published
- 2016
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41. ST6GalNAcII mediates tumor invasion through PI3K/Akt/NF-κB signaling pathway in follicular thyroid carcinoma.
- Author
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Miao X and Zhao Y
- Subjects
- Adenocarcinoma, Follicular genetics, Adenocarcinoma, Follicular metabolism, Animals, Cell Line, Tumor, Chromones pharmacology, Gene Expression Regulation, Neoplastic, Humans, Mice, Morpholines pharmacology, NF-kappa B genetics, Neoplasm Invasiveness, Neoplasm Transplantation, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins c-akt genetics, Sialyltransferases genetics, Signal Transduction, Thyroid Neoplasms genetics, Thyroid Neoplasms metabolism, Adenocarcinoma, Follicular pathology, NF-kappa B metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Sialyltransferases metabolism, Thyroid Neoplasms pathology
- Abstract
Altered sialylation, closely associated with tumor progression and metastasis, has been implicated in human thyroid carcinoma. The present study investigated the alteration in expression of ST6GalNAcII involved in invasion and to clarify the possible mechanism of ST6GalNAcII in the metastasis process in human follicular thyroid carcinoma cell lines. Using real-time PCR, western blot and IHC analysis, ST6GalNAcII differed in three follicular thyroid cancer cell lines (FTC133, primary and FTC238, lung metastasis). It also showed differential expression in follicular thyroid carcinoma and tissue specimens. In addition, we analyzed the PI3K/Akt signaling pathway. The altered expression of ST6GalNAcII corresponded to changed invasive phenotype of FTC-238 and FTC-133 cells in vitro and in vivo. Further studies showed that regulating ST6GalNAcII expression markedly modulated the activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Targeting the PI3K/Akt pathway by its specific inhibitor LY294002, or by Akt small interfering RNA (siRNA) resulted in reduced capacity in invasion of FTC-238. In conclusion, taken together, our results imply that ST6GalNAcII activated the invasion in follicular thyroid cancer cells through regulating the activity of PI3K/Akt pathway.
- Published
- 2016
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42. Increased fucosylation has a pivotal role in multidrug resistance of breast cancer cells through miR-224-3p targeting FUT4.
- Author
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Feng X, Zhao L, Gao S, Song X, Dong W, Zhao Y, Zhou H, Cheng L, Miao X, and Jia L
- Subjects
- Animals, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Cell Proliferation drug effects, Doxorubicin administration & dosage, Female, Fucosyltransferases biosynthesis, Gene Expression Regulation, Neoplastic drug effects, Glycosylation drug effects, Humans, Lewis X Antigen biosynthesis, MCF-7 Cells, Mice, MicroRNAs biosynthesis, Polysaccharides genetics, RNA, Messenger biosynthesis, Xenograft Model Antitumor Assays, Breast Neoplasms genetics, Drug Resistance, Multiple genetics, Drug Resistance, Neoplasm genetics, Fucosyltransferases genetics, Lewis X Antigen genetics, MicroRNAs genetics
- Abstract
Fucosylation is the final step in the glycosylation machinery, which produces glycans involved in tumor multidrug resistance development. MicroRNAs (miRNAs) are endogenous negative regulators of gene expression and have been implicated in most cellular processes of tumors, including drug resistance. This study was undertaken to determine the roles of fucosylation and miR-224-3p in multidrug resistance of human breast cancer cell lines. Comparative analysis revealed differential modification patterns of fucosylation of the fucosylated N-glycans in drug-resistant T47D/ADR cells and sensitive line T47D cells. The expressional profiles of fucosyltransferase genes in two pairs of parental and chemoresistant human breast cancer cell lines showed that FUT4 was up-regulated highly in MDR cell lines. Altered level of FUT4 affected the drug-resistant phenotype of T47D and T47D/ADR cells both in vitro and in vivo. By bioinformatics analysis, we identified FUT4 as one of the miR-224-3p-targeted genes. Further studies showed an inverse relationship between of FUT4 and miR-224-3p in parental and ADR-resistant breast cancer cells, wherein miR-224-3p was downregulated in resistant cells. 3'-UTR dual-luciferase reporter assay confirmed that miR-224-3p directly targeted 3'-untranslation region (3'-UTR) of FUT4 mRNA. In addition, miR-224-3p overexpression sensitized T47D/ADR cells to chemotherapeutics and reduced the growth rate of breast cancer xenografts in vivo. Our results indicate that FUT4 and miR-224-3p are crucial regulators of cancer response to chemotherapy, and may serve as therapeutic targets to reverse chemotherapy resistance in breast cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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43. miR-4299 mediates the invasive properties and tumorigenicity of human follicular thyroid carcinoma by targeting ST6GALNAC4.
- Author
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Miao X, Jia L, Zhou H, Song X, Zhou M, Xu J, Zhao L, Feng X, and Zhao Y
- Subjects
- Adenocarcinoma, Follicular pathology, Animals, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, MicroRNAs genetics, Neoplasm Invasiveness genetics, Neoplasm Metastasis, Sialyltransferases genetics, Xenograft Model Antitumor Assays, Adenocarcinoma, Follicular genetics, Carcinogenesis genetics, MicroRNAs biosynthesis, Sialyltransferases biosynthesis
- Abstract
Altered sialylation is closely associated with tumor progression and invasiveness. Micro-RNAs endogenous regulators of gene expression have been implicated in human thyroid carcinoma invasiveness. The objective of this study is to examine the alterations of miR-4299 and ST6GALNAC family in human follicular thyroid carcinoma during metastatic process. qRT-PCR showed the differential expressional profiles of miR-4299 and ST6GALNAC family in three kinds of thyroid cell lines (FTC-133,FTC-238, Nthy-ori 3-1) and clinical tissue specimens(malignant and borderline). The altered expression levels of ST6GALNAC4 were corresponding to invasive phenotypes of FTC-133 and FTC-238 cells both in vitro and in vivo. Further date indicated that miR-4299 regulated tumor progression and invasiveness by directly targeting ST6GALNAC4. This study implies the potential therapeutic application of miR-4299 and ST6GALNAC4 in modulating the invasion and tumorigenicity of follicular thyroid carcinoma cell., (© 2015 International Union of Biochemistry and Molecular Biology.)
- Published
- 2016
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44. Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells.
- Author
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Li Z, Jiang K, Zhu X, Lin G, Song F, Zhao Y, Piao Y, Liu J, Cheng W, Bi X, Gong P, Song Z, and Meng S
- Subjects
- Cell Line, Tumor, Cellular Senescence drug effects, Cyclin D1 metabolism, Cyclin-Dependent Kinase Inhibitor p27 analysis, Glycogen Synthase Kinase 3 metabolism, Glycogen Synthase Kinase 3 beta, Humans, MAP Kinase Signaling System drug effects, Melanoma genetics, Melanoma pathology, Protein Serine-Threonine Kinases physiology, Protein-Tyrosine Kinases physiology, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Retinoblastoma Protein metabolism, TOR Serine-Threonine Kinases antagonists & inhibitors, Dyrk Kinases, Autophagy drug effects, Carbamates pharmacology, Melanoma drug therapy, Proto-Oncogene Proteins B-raf genetics, Sulfonamides pharmacology
- Abstract
Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials. However, the underlying mechanism remains to be elucidated. Here we show that LGX818 potently decreased ERK phosphorylation and inhibited proliferation in BRAFV600E melanoma cell lines. Moreover, LGX818 downregulated CyclinD1 in a glycogen synthase kinase 3β-independent manner and induced cell cycle arrest in the G1 phase, Surprisingly, LGX818 triggered cellular senescence in BRAFV600E melanoma cells, as evidenced by increased β-galactosidase staining, while no appreciable induction of apoptosis was detected, as determined by Annexin V and propidium iodide staining and immunoblot analysis of caspase-3 processing and poly (ADP-ribose) polymerase cleavage. Increased p27KIP1 expression and retinoblastoma protein activation were detected during LGX818-induced senescence. Additionally, inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 1B by AZ191 reversed LGX818-induced CyclinD1 turnover and senescence. Interestingly, autophagy is triggered through inhibition of the mTOR/70S6K pathway during LGX818-induced senescence. Moreover, autophagy inhibition by pharmacological and genetic regulation attenuates LGX818-induced senescence. Notably, combining LGX818 with autophagy modulators has anti-proliferative effect in LGX818-resistant BRAF mutant melanoma cells. Altogether, we uncovered a mechanism by which LGX818 exerts its anti-tumor activity in BRAFV600E melanoma cells., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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45. Radiolytic decomposition of ciprofloxacin using γ irradiation in aqueous solution.
- Author
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Guo Z, Zhu S, Zhao Y, Cao H, and Liu F
- Subjects
- Environmental Restoration and Remediation instrumentation, Gamma Rays, Oxidation-Reduction, Ciprofloxacin chemistry, Ciprofloxacin radiation effects, Environmental Restoration and Remediation methods, Water Pollutants, Chemical chemistry, Water Pollutants, Chemical radiation effects
- Abstract
Gamma irradiation-induced decomposition of ciprofloxacin (CIP) was elucidated with different additives, such as CO3 (2-), NO3 (-), NO2 (-), humic acid, methanol, 2-propanol, and tert-butanol. The results show that low initial concentration and acidic condition were favorable for CIP removal during γ irradiation. By contrast, radiolytic decomposition of CIP was inhibited with the addition of anions and organic additives. As a strong carcinogen, Cr(6+) was especially mixed with CIP to produce combined pollution. It is noteworthy that the removal of the mixture of CIP and Cr(6+) presented a synergistic effect; the degradation efficiency of the two pollutants was markedly improved compared to that of the single pollutant during γ irradiation. Based on the results of quantum chemical calculations and LC-MS analysis, we determined seven kinds of degradation intermediates and presented the CIP degradation pathways, which were mainly attributed to the oxidation process of hydroxyl radicals OH· and the direct decomposition of CIP molecules.
- Published
- 2015
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46. Increased cancer risk associated with the -607C/A polymorphism in interleukin-18 gene promoter: an updated meta-analysis including 12,502 subjects.
- Author
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Li X, Ren D, Li Y, Xu J, Liu C, and Zhao Y
- Subjects
- Case-Control Studies, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Neoplasms diagnosis, Neoplasms ethnology, Neoplasms immunology, Odds Ratio, Phenotype, Risk Assessment, Risk Factors, Interleukin-18 genetics, Neoplasms genetics, Polymorphism, Genetic, Promoter Regions, Genetic
- Abstract
Purpose: Increasing investigations have been performed on the association of -607C/A polymorphism in Interleukin-18 (IL-18) gene promoter with cancer risk and have yielded conflicting results. To derive a more precise estimation of the association, we performed an updated meta-analysis of all eligible studies., Methods: We searched all eligible studies by using PubMed, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) were pooled by the fixed-effects/random-effects model in STATA 12.0 software., Results: This meta-analysis included 29 studies with 6,026 cases and 6,476 controls. Overall, significantly increased cancer risk was observed (A vs C: OR=1.10, 95% CI: 1.01,1.19, Pheterogeneity=0.001; AA vs CC: OR=1.17, 95% CI: 1.01,1.37, Pheterogeneity=0.007; CA vs CC: OR=1.15, 95% CI: 1.05,1.25, Pheterogeneity=0.152; AA/CA vs CC: OR=1.17, 95% CI: 1.06,1.31, Pheterogeneity=0.042). In subgroup analyses based on ethnicity, the results suggested a significantly increased risk of cancer in Asian population (CA vs CC: OR=1.11, 95% CI: 1.00-1.24, Pheterogeneity=0.353; AA/CA vs CC: OR=1.14, 95% CI: 1.02-1.29, Pheterogeneity=0.081) and in Mixed population (A vs C: OR=1.72, 95% CI: 1.22-2.43, Pheterogeneity=NA; AA vs CC: OR=2.84, 95% CI: 1.43-5.64, Pheterogeneity=NA; AA vs CC/CA: OR=2.43, 95% CI: 1.34-4.42, Pheterogeneity=NA; AA/CA vs CC: OR=1.69, 95% CI: 1.00-2.85, Pheterogeneity=NA); however, no significant association was found in Caucasian or African populations. In the subgroup analysis by cancer type we found a significantly increased susceptibility to breast cancer (A vs C: OR=1.33, 95% CI: 1.00-1.75,Pheterogeneity=0.155; AA vs CC: OR=1.80, 95% CI: 1.02-3.21,Pheterogeneity=0.162; AA7sol;CA vs CC: OR=1.33, 95% CI: 1.00-1.78,Pheterogeneity=0.546), nasopharyngeal carcinoma (A vs C: OR=1.16, 95% CI: 1.01-1.32, Pheterogeneity=0.921; AA vs CC: OR=1.34, 95% CI: 1.02-1.75, Pheterogeneity=0.863; CA vs. CC: OR=1.36, 95% CI: 1.08-1.70, Pheterogeneity=0.824; AA/CA vs CC: OR=1.35, 95% CI: 1.09-1.68,Pheterogeneity=0.904), and esophageal cancer (CA vs CC: OR=1.37, 95% CI: 1.04-1.80, Pheterogeneity=0.528; AA/CA vs CC: OR =1.29, 95% CI: 1.00-1.66, Pheterogeneity=0.700)., Conclusions: The current meta-analysis suggests that the -607C/A polymorphism in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma and esophageal cancer and in Asian and Mixed populations. More studies with diverse ethnic groups, larger sample size, and well controlled confounding factors are warranted to further investigate the association.
- Published
- 2015
47. Combined cancer testis antigens enhanced prediction accuracy for prognosis of patients with hepatocellular carcinoma.
- Author
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Wang M, Li J, Wang L, Chen X, Zhang Z, Yue D, Ping Y, Shi X, Huang L, Zhang T, Yang L, Zhao Y, Ma X, Li D, Fan Z, Zhao L, Tang Z, Zhai W, Zhang B, and Zhang Y
- Subjects
- Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Middle Aged, Prognosis, ROC Curve, Testis immunology, Testis metabolism, Testis pathology, Antigens, Neoplasm immunology, Carcinoma, Hepatocellular immunology, Liver Neoplasms immunology, Testicular Neoplasms immunology
- Abstract
Cancer testis antigens (CTAs) are selectively expressed in malignant cells and can serve as ideal targets for immunotherapy. We investigated the expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 to determine if combinatorial expressions of CTAs might be as potential prognostic markers for patients with hepatocellular carcinoma (HCC). In tumor tissues of 142 HCC patients, the mRNA expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 were 78.9%, 33.8%, 74.6% and 14.1% respectively. Furthermore, the expressions of MAGE-A3, MAGE-A4 and combination of MAGE-A3, MAGE-A4 and NY-ESO-1 (CTAs-A3/A4/NY) showed positive correlations with serum AFP, tumor stages and Ki-67 (P < 0.05). In addition, mRNA expressions of CTAs were significantly consistent with protein expressions of CTAs by immunohistochemistry (P > 0.05). Receiver operating characteristic curves (ROC) analysis showed that CTAs-A3/A4/NY had larger areas under ROC curve (0.768), specificity (99.1%), Youden's index (44.6), positive predictive value (90.9%) and negative predictive value (89.9%) for predicting HCC recurrence than other CTAs. Moreover, the combinatorial expression of CTAs-A3/A4/NY was significantly associated with HCC recurrence by Kaplan-Meier analysis (HR = 69.36, P < 0.01) and multivariate Cox analysis (RR = 17.11, P < 0.01). The combinatorial expression of CTAs-A3/A4/NY mRNA promotes the predictive accuracy of HCC recurrence and itself may be a potential target for immunotherapy of HCC as well.
- Published
- 2015
48. A mass under parotid gland: a patient with Kimura disease.
- Author
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Gong Y and Zhao Y
- Published
- 2015
- Full Text
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49. Axl as a downstream effector of TGF-β1 via PI3K/Akt-PAK1 signaling pathway promotes tumor invasion and chemoresistance in breast carcinoma.
- Author
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Li Y, Jia L, Liu C, Gong Y, Ren D, Wang N, Zhang X, and Zhao Y
- Subjects
- Animals, Breast Neoplasms pathology, Drug Resistance, Neoplasm genetics, Female, Humans, MCF-7 Cells, Mice, Neoplasm Invasiveness genetics, Phosphatidylinositol 3-Kinases biosynthesis, Phosphatidylinositol 3-Kinases genetics, Signal Transduction, Transforming Growth Factor beta genetics, Axl Receptor Tyrosine Kinase, Breast Neoplasms genetics, Proto-Oncogene Proteins biosynthesis, Proto-Oncogene Proteins c-akt biosynthesis, Receptor Protein-Tyrosine Kinases biosynthesis, Transforming Growth Factor beta biosynthesis, p21-Activated Kinases biosynthesis
- Abstract
The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-β1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-β1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-β1 level, tumor differentiation, lymph node metastasis, and clinical stage (p < 0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.
- Published
- 2015
- Full Text
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50. Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors.
- Author
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Ren D, Li Y, Gong Y, Xu J, Miao X, Li X, Liu C, Jia L, and Zhao Y
- Subjects
- Adult, Aged, Animals, Blotting, Western, Breast Neoplasms pathology, Female, Heterografts, Humans, Immunohistochemistry, Mice, Middle Aged, Neoplasm Invasiveness, Phyllodes Tumor pathology, Real-Time Polymerase Chain Reaction, Tissue Array Analysis, Transcriptome, Axl Receptor Tyrosine Kinase, Breast Neoplasms metabolism, Phyllodes Tumor metabolism, Proto-Oncogene Proteins biosynthesis, Receptor Protein-Tyrosine Kinases biosynthesis, Sialyltransferases biosynthesis
- Abstract
Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.
- Published
- 2014
- Full Text
- View/download PDF
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