46 results on '"Zhao, You"'
Search Results
2. Construction and validation of a nomogram for blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures in the elderly: a cross-sectional study
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Chen, Lu-ying, Wang, Ji-qi, Zhao, You-ming, and Feng, Yong-zeng
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- 2024
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3. Physical activity improves outcomes of combined lenvatinib plus anti-PD-1 therapy in unresectable hepatocellular carcinoma: a retrospective study and mouse model
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Liu, Xue-Feng, Zhu, Xiao-Dong, Feng, Long-Hai, Li, Xiao-Long, Xu, Bin, Li, Kang-Shuai, Xiao, Nan, Lei, Ming, Sun, Hui-Chuan, and Tang, Zhao-You
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- 2022
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4. Development of a nomogram to predict surgical site infection after closed comminuted calcaneal fracture
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Hu, Jia-sen, Huang, Cheng-bin, Mao, Shu-ming, Fang, Kang-hao, Wu, Zong-yi, and Zhao, You-ming
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- 2022
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5. PCSK9 promotes tumor growth by inhibiting tumor cell apoptosis in hepatocellular carcinoma
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Zhang, Shi-Zhe, Zhu, Xiao-Dong, Feng, Long-Hai, Li, Xiao-Long, Liu, Xue-Feng, Sun, Hui-Chuan, and Tang, Zhao-You
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- 2021
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6. Comparison between minimally invasive deltoid-split and extended deltoid-split approach for proximal humeral fractures: a case-control study
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Wang, Ji-Qi, Lin, Chui-cong, Zhao, You-Ming, Jiang, Bing-Jie, and Huang, Xiao-Jing
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- 2020
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7. Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis
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Huang, Xiu-Yan, Huang, Zi-Li, Huang, Jin, Xu, Bin, Huang, Xin-Yu, Xu, Yong-Hua, Zhou, Jian, and Tang, Zhao-You
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- 2020
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8. Comparative genomics and transcriptomics analysis reveals evolution patterns of selection in the Salix phylogeny
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Zhao, You-jie, Liu, Xin-yi, Guo, Ran, Hu, Kun-rong, Cao, Yong, and Dai, Fei
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- 2019
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9. Serial changes in the head-shaft angle of proximal humeral fractures treated by placing locking plates: a retrospective study
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Wang, Ji-Qi, Jiang, Bing-Jie, Guo, Wei-Jun, and Zhao, You-Ming
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- 2018
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10. Transcriptome sequencing of Pinus kesiya var. langbianensis and comparative analysis in the Pinus phylogeny
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Zhao, You-jie, Cao, Yong, Wang, Juan, and Xiong, Zhi
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- 2018
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11. Clinical significance of hyaluronan levels and its pro-osteogenic effect on mesenchymal stromal cells in myelodysplastic syndromes
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Fei, Cheng-Ming, Guo, Juan, Zhao, You-Shan, Zhao, Si-Da, Zhen, Qing-Qing, Shi, Lei, Li, Xiao, and Chang, Chun-Kang
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- 2018
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12. Correction to: miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a
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Cao, Man-Qing, You, A-Bin, Zhu, Xiao-Dong, Zhang, Wei, Zhang, Yuan-Yuan, Zhang, Shi-Zhe, Zhang, Kei-wei, Cai, Hao, Shi, Wen-Kai, Li, Xiao-Long, Li, Kang-Shuai, Gao, Dong-Mei, Ma, De-Ning, Ye, Bo-Gen, Wang, Cheng-Hao, Qin, Cheng-Dong, Sun, Hui-Chan, Zhang, Ti, and Tang, Zhao-You
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- 2018
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13. miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a
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Cao, Man-Qing, You, A-Bin, Zhu, Xiao-Dong, Zhang, Wei, Zhang, Yuan-Yuan, Zhang, Shi-Zhe, Zhang, Ke-wei, Cai, Hao, Shi, Wen-Kai, Li, Xiao-Long, Li, Kang-Shuai, Gao, Dong-Mei, Ma, De-Ning, Ye, Bo-Gen, Wang, Cheng-Hao, Qin, Cheng-Dong, Sun, Hui-Chuan, Zhang, Ti, and Tang, Zhao-You
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- 2018
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14. An observation of the peer-assisted learning (PAL) method in the clinical teaching of vertigo/dizziness-related diseases for standardized residency training (SRT) students in China: a randomized, controlled, multicenter study
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Xiaojun Liang, Shu Liu, Rui Xu, Qingwu Yang, Yang Bai, Gong Wang, Meng Guo, Qian He, Chun-Mei Duan, Qin Zhang, Wei Duan, Zhao-You Meng, Xiaoyan Chen, and Yue Wang
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Medical education ,China ,Students, Medical ,media_common.quotation_subject ,Internship and residency ,education ,Burnout ,Dizziness ,Education ,Rating scale ,Statistical significance ,Medicine ,Humans ,Clinical teaching ,media_common ,Teamwork ,LC8-6691 ,business.industry ,Research ,Teaching ,Peer group ,General Medicine ,Special aspects of education ,humanities ,Multicenter study ,Vertigo ,business ,Residency training ,Education, Medical, Undergraduate - Abstract
Background Vertigo and dizziness (VD) are among the most frequently seen symptoms in clinics and are important for medical students, especially for those in Chinese standardized residency training (SRT). The aim of our study was to examine the PAL method’s feasibility in the clinical teaching of VD-related diseases for SRT students in China. Methods This is a randomized, controlled, multicenter study. A total of 228 residents were invited to participate in this study, of which 198 completed the program. The students were randomized into two groups, and VD-related diseases were taught using lecture-based learning (control group) or peer-assisted learning (PAL). An examination paper and a rating scale were used to evaluate students’ performance in the mastery of VD-related theoretical knowledge and clinical skills, meanwhile students’ perceptions, satisfaction, and risk of burnout were also analyzed using a questionnaire. Independent-samples t-test and chi-square analysis were performed to evaluate statistical significance for continuous variables and categorical variables, respectively, using SPSS 18.0 software. Results The PAL group performed better in mastering theoretical knowledge and clinical skills than the control group. And more students believed that PAL could help improve their personal qualities such as teamwork skills. However, more students reported that PAL increased the risk of burnout. Conclusions PAL was a suitable and effective method in the clinical teaching of some specialized diseases, especially it was recommended for students who had gained initial knowledge and skills, such as Chinese SRT students. However, we should draw attention to the increased risk of burnout if PAL is intended to be widely used in clinical teaching. Trial registration ISRCTN registry, ISRCTN53773239, 05/07/2021, retrospectively registered.
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- 2021
15. Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis
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Xiu-Yan Huang, Zhao-You Tang, Jin Huang, Yong-Hua Xu, Bin Xu, Jian Zhou, Xinyu Huang, and Zi-Li Huang
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0301 basic medicine ,Male ,Cancer Research ,Carcinoma, Hepatocellular ,Angiogenesis ,Mice, Nude ,Transfection ,lcsh:RC254-282 ,Exosome ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Gentamicin protection assay ,Medicine ,Animals ,Humans ,Vasculogenic mimicry ,Neoplasm Invasiveness ,Hepatocellular carcinoma (HCC) ,Neoplasm Metastasis ,Tumor microenvironment ,Neovascularization, Pathologic ,business.industry ,Research ,Liver Neoplasms ,RNA, Circular ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Microvesicles ,Disease Models, Animal ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,business ,Tumor metastasis ,CircRNA-100,338 - Abstract
Background Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules. Methods We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks. Results We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival. Conclusions Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.
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- 2020
16. miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a
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Wei Zhang, Cheng-Dong Qin, Zhao-You Tang, Ti Zhang, Man-Qing Cao, De-Ning Ma, Kang-Shuai Li, Dong-Mei Gao, Cheng-Hao Wang, Yuan-Yuan Zhang, A-Bin You, Wen-Kai Shi, Xiao-Dong Zhu, Bo-Gen Ye, Shi-Zhe Zhang, Xiao-Long Li, Hui-Chuan Sun, Ke‑Wei Zhang, and Hao Cai
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Carcinoma, Hepatocellular ,miR-182-5p ,In situ hybridization ,lcsh:RC254-282 ,Flow cytometry ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,HCC ,FOXO3a ,Molecular Biology ,Protein kinase B ,Wnt Signaling Pathway ,Cell Proliferation ,medicine.diagnostic_test ,business.industry ,lcsh:RC633-647.5 ,Research ,Forkhead Box Protein O3 ,Liver Neoplasms ,Wnt signaling pathway ,Correction ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Wnt signaling ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,HEK293 Cells ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,Disease Progression ,Immunohistochemistry ,Female ,business - Abstract
Background High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown. Methods Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression. Results We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a. Conclusions Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
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- 2018
17. Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma
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Bin Xu, Qi Zheng, Zi Chen, Xin-Yu Huang, Thomas J. Re, Zi-Li Huang, Xiu-Yan Huang, and Zhao-You Tang
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,MMP2 ,Lung Neoplasms ,Hepatocellular carcinoma ,medicine.medical_treatment ,Metastasis ,Mice ,0302 clinical medicine ,Invasion ,Neoplasm Metastasis ,Liver Neoplasms ,Microfilament Proteins ,Hepatitis B ,Prognosis ,Neoplasm Proteins ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,030220 oncology & carcinogenesis ,Matrix Metalloproteinase 2 ,Female ,Metastasis suppressor 1 ,Erratum ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Mice, Nude ,03 medical and health sciences ,In vivo ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Survival analysis ,Hepatitis ,business.industry ,Research ,medicine.disease ,Survival Analysis ,digestive system diseases ,030104 developmental biology ,Hepatectomy ,business ,Neoplasm Transplantation - Abstract
Background Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. Methods An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed. Results Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo. Conclusions The poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0361-8) contains supplementary material, which is available to authorized users.
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- 2016
18. Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma.
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Xiu-Yan Huang, Zi-Li Huang, Bin Xu, Zi Chen, Joseph Re, Thomas, Qi Zheng, Zhao-You Tang, and Xin-Yu Huang
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METASTASIS ,LIVER cancer ,HEPATITIS B ,HEPATECTOMY ,GENE expression ,MATRIX metalloproteinases ,CANCER cells - Abstract
Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed. Results: Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo. Conclusions: The poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. [ABSTRACT FROM AUTHOR]
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- 2016
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19. MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2.
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De-Ning Ma, Zong-Tao Chai, Xiao-Dong Zhu, Ning Zhang, Di-Hua Zhan, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Yi-Ming Zhao, Wei-Ping Zhu, Man-Qing Cao, Dong-Mei Gao, Hui-Chuan Sun, and Zhao-You Tang
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MICRORNA ,LIVER cancer ,MACROPHAGES ,CANCER cells ,CANCER cell migration ,GENETIC overexpression ,GENETICS - Abstract
Background: Our previous study reported that microRNA-26a (miR-26a) inhibited tumor progression by inhibiting tumor angiogenesis and intratumoral macrophage infiltration in hepatocellular carcinoma (HCC). The direct roles of miR-26a on tumor cell invasion remain poorly understood. In this study, we aim to explore the mechanism of miR- 26a in modulating epithelial-mesenchymal transition (EMT) in HCC. Methods: In vitro cell morphology and cell migration were compared between the hepatoma cell lines HCCLM3 and HepG2, which were established in the previous study. Overexpression and down-regulation of miR-26a were induced in these cell lines, and Western blot and immunofluorescence assays were used to detect the expression of EMT markers. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Immunohistochemical assays were conducted to study the relationships between miR-26a expression and enhancer of zeste homolog 2 (EZH2) and E-cadherin expression in human HCC samples. Results: Down-regulation of miR-26a in HCCLM3 and HepG2 cells resulted in an EMT-like cell morphology and high motility in vitro and increased in tumor growth and pulmonary metastasis in vivo. Through down-regulation of EZH2 expression and up-regulation of E-cadherin expression, miR-26a inhibited the EMT process in vitro and in vivo. Luciferase reporter assay showed that miR-26a directly interacted with EZH2 messenger RNA (mRNA). Furthermore, the expression of miR-26a was positively correlated with E-cadherin expression and inversely correlated with EZH2 expression in human HCC tissue. Conclusions: miR-26a inhibited the EMT process in HCC by down-regulating EZH2 expression. [ABSTRACT FROM AUTHOR]
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- 2016
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20. Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin
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Zhenggang Ren, Zhao-You Tang, Lu Wang, Wen-Quan Wang, Qi-Song Li, Wei Zhang, Xiao-Dong Zhu, Bin-bin Liu, Wei Xiong, Liang Liu, Hui-Chuan Sun, and Shuang-Jian Qiu
- Subjects
Male ,Cancer Research ,Pathology ,Lung Neoplasms ,Neoplasm, Residual ,Time Factors ,Organoplatinum Compounds ,medicine.medical_treatment ,Fluorescent Antibody Technique ,Metastasis ,Mice ,Nude mouse ,Cell Movement ,Mice, Inbred BALB C ,biology ,Liver Neoplasms ,Hep G2 Cells ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunohistochemistry ,Tumor Burden ,Oxaliplatin ,Oncology ,Hepatocellular carcinoma ,medicine.drug ,Research Article ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cell Survival ,Blotting, Western ,Mice, Nude ,Antineoplastic Agents ,lcsh:RC254-282 ,In vivo ,Genetics ,Carcinoma ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Cell Proliferation ,Chemotherapy ,business.industry ,medicine.disease ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,digestive system diseases ,Cancer cell ,Cell Transdifferentiation ,business ,Drugs, Chinese Herbal - Abstract
Background The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Methods Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. Results MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). Conclusions The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.
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- 2010
21. Chemokine receptor CXCR4 expression in hepatocellular carcinoma patients increases the risk of bone metastases and poor survival
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Jian He, Zhao-You Tang, Jia Fan, Peng-Yuan Zhuang, Zhao-Chong Zeng, Ying Liang, Yunshan Tan, and Zuo-Lin Xiang
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Pathology ,Cancer Research ,Receptors, CXCR4 ,Carcinoma, Hepatocellular ,Adolescent ,Bone Neoplasms ,CXCR4 ,lcsh:RC254-282 ,Young Adult ,Surgical oncology ,Risk Factors ,Internal medicine ,medicine ,Carcinoma ,Genetics ,Humans ,Risk factor ,Child ,Aged ,Aged, 80 and over ,Tissue microarray ,business.industry ,Liver Neoplasms ,Bone metastasis ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Microarray Analysis ,Immunohistochemistry ,Hepatocellular carcinoma ,Female ,business ,Research Article - Abstract
Background The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers. This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival. Methods Tumor tissue from HCC patients with (n = 43) and without (n = 138) bone metastasis was subjected to immunohistochemical staining for CXCR4 using tissue microarrays. Immunoreactivity was evaluated semi-quantitatively. A receiver-operating characteristic-based approach and logistical regression analysis were used to determine the predictive value of clinicopathologic factors, including CXCR4 expression, in bone metastasis. Patient survival was analyzed by Kaplan-Meier curves and log-rank tests. Results CXCR4 overexpression was detected in 34 of 43 (79.1%) patients with bone metastases and in 57 of 138 (41.3%) without bone metastases. CXCR4 expression correlated with (correlation coefficient: 0.551, P < 0.001) and was predictive of HCC bone metastases (AUC: 0.689; 95%CI: 0.601 – 0.776; P < 0.001). CXCR4 staining intensity correlated with the bone metastasis-free survival (correlation coefficient: -0.359; P = 0.018). CXCR4 overexpression in primary tumors (n = 91) decreased overall median survival (18.0 months vs. 36.0 months, P <0.001). Multivariable analysis identified CXCR4 as a strong, independent risk factor for reduced disease-free survival (relative risk [RR]: 5.440; P = 0.023) and overall survival (RR: 7.082; P = 0.001). Conclusion CXCR4 expression in primary HCCs may be an independent risk factor for bone metastasis and may be associated with poor clinical outcome.
- Published
- 2009
22. Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse model.
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Ke-Zhi Zhang, Qiang-Bo Zhang, Quan-Bao Zhang, Hui-Chuan Sun, Jian-Yang Ao, Zong-Tao Chai, Xiao-Dong Zhu, Lu Lu, Yuan-Yuan Zhang, Yang Bu, Ling-Qun Kong, and Zhao-You Tang
- Abstract
Background: Cancer stem cells (CSCs) play a key role in the posthepatectomy recurrence of hepatocellular carcinoma (HCC). CD133
+ HCC cells exhibit liver CSC–like properties, and CSC differentiation–inducing therapy may lead these cells to lose their self-renewal ability and may induce terminal differentiation, which may in turn allow their malignant potential to be controlled. Because arsenic trioxide (As2 O3 ) increases remission rates and prolongs survival among patients with acute promyelocytic leukemia by inducing differentiation and apoptosis of leukemic cells, we hypothesized that As2 O3 might also inhibit HCC recurrence and prolong survival time after hepatectomy by inducing differentiation of HCC CSCs. Methods: We evaluated the As2 O3 induced differentiation of human HCC CSCs and its mechanism in vitro, and we investigated the effects of treatment with As2 O3 on recurrence rates and median survival in a mouse xenograft model. Results: We found that As2 O3 induced HCC CSC differentiation by down-regulating the expression of CD133 and some stemness genes, thus inhibiting the cells’ self-renewal ability and tumorigenic capacity without inhibiting their proliferation in vitro. In vivo experiments indicated that As2 O3 decreased recurrence rates after radical resection and prolonged survival in a mouse model. As2 O3 , which shows no apparent toxicity, may induce HCC CSC differentiation by down-regulating the expression of GLI1. Conclusions: We found that As2 O3 induced HCC CSC differentiation, inhibited recurrence, and prolonged survival after hepatectomy by targeting GLI1expression. Our results suggest that the clinical safety and utility of As2 O3 should be further evaluated. [ABSTRACT FROM AUTHOR]- Published
- 2014
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23. Erratum to: Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma
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Huang, Xiu-Yan, Huang, Zi-Li, Xu, Bin, Chen, Zi, Re, Thomas Joseph, Zheng, Qi, Tang, Zhao-You, and Huang, Xin-Yu
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- 2016
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24. Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma
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Huang, Xiu-Yan, Huang, Zi-Li, Xu, Bin, Chen, Zi, Re, Thomas Joseph, Zheng, Qi, Tang, Zhao-You, and Huang, Xin-Yu
- Subjects
Metastasis suppressor 1 ,Hepatocellular carcinoma ,Invasion ,Metastasis - Abstract
Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed. Results: Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo. Conclusions: The poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0361-8) contains supplementary material, which is available to authorized users.
- Published
- 2016
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25. Herbal compound 'Songyou Yin' attenuates hepatoma cell invasiveness and metastasis through downregulation of cytokines secreted by activated hepatic stellate cells.
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Qing-An Jia, Zhi-Ming Wang, Zheng-Gang Ren, Yang Bu, Xiao-Ying Xie, Yan-Hong Wang, Lan Zhang, Qiang-Bo Zhang, Tong-Chun Xue, Li-Fen Deng, and Zhao-You Tang
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- 2013
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26. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization.
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Wen-Quan Wang, Liang Liu, Hui-Chuan Sun, Yan-Ling Fu, Hua-Xiang Xu, Zong-Tao Chai, Qiang-Bo Zhang, Ling-Qun Kong, Xiao-Dong Zhu, Lu Lu, Zheng-Gang Ren, and Zhao-You Tang
- Subjects
METASTASIS ,CANCER cells ,HYPEROXIA ,HYPOXEMIA ,CYTOKINES ,LIVER tumors - Abstract
Background: Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR) of hepatocellular carcinoma (HCC). Methods: A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential) and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs) treated with tanshinone IIA. Results: PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT) in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α) or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR) upregulation. Although the microvessel density (MVD) of residual tumor tissue increased after PR, the microvessel integrity (MVI) was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions: Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical benefit of preventing postsurgical recurrence. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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- View/download PDF
27. Up-regulation of platelet-derived growth factor-A is responsible for the failure of re-initiated interferon alpha treatment in hepatocellular carcinoma.
- Author
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Zhang, Ju-Bo, Sun, Hui-Chuan, Jia, Wei-Dong, Zhuang, Peng-Yuan, Qian, Yong-Bing, Zhu, Xiao-Dong, Kong, Ling-Qun, Wang, Lu, Wu, Wei-Zhong, and Tang, Zhao-You
- Subjects
LIVER cancer ,ADJUVANT treatment of cancer ,VASCULAR endothelial growth factors ,TUMORS ,APOPTOSIS ,NEOVASCULARIZATION - Abstract
Background: Postoperative interferon-α(IFN-α) treatment delays hepatocellular carcinoma(HCC) recurrence and prolongs patient survival, and may thus be an effective form of adjuvant therapy. However, clinical observations found that HCC recurs in some patients within 8 months of IFN-α treatment being discontinued. We investigated whether HCC regrowth appears after IFN-α is discontinued, whether re-initiated IFN-α is effective, and the underlying mechanisms of IFN-α treatment. Methods: The human HCC nude mouse model LCI-D20 was used to study the effects of IFN-α treatment, discontinued IFN-α treatment, and re-initiated IFN-α treatment on tumor growth. Tumor weight, microvessel density(MVD), serum vascular endothelial growth factor (VEGF), and tumor cell apoptosis were analyzed. Angiogenesis-related factors were studied using cDNA microarray in different tumor samples and confirmed using reverse transcription–polymerase chain reaction(RT-PCR) and Western blotting assays. Finally, imatinib was added with re-initiated IFN-α treatment to improve efficacy. Results: IFN-α (1.5×10
7 U/kg/day for 20 days) suppressed HCC growth by 60.3% and decreased MVD by 52.2% compared with the control. However, tumor regrowth occurred after IFN-α was discontinued, and re-initiated IFN-αtreatment was not effective for inhibiting tumor growth or reducing MVD compared with a saline-treated group. cDNA microarray showed VEGF was down-regulated while platelet-derived growth factor-A (PDGF-A) was up-regulated when IFN-α treatment was re-initiated. These findings were further confirmed with RT-PCR and Western blotting assay. The combination of imatinib with re-initiated IFN-α reduced HCC weight by 30.7% and decreased MVD by 31.1% compared with IFN-α treatment only (P=0.003 and 0.015, respectively). Conclusion: Tumor regrowth occurred after IFN-α treatment was discontinued. Re-initiated IFN-α treatment was not effective and was associated with up-regulation of PDGF-A, while the VEGF remained suppressed. The combination of a PDGF-receptor inhibitor with IFN-α improved the effect of the re-initiated treatment. [ABSTRACT FROM AUTHOR]- Published
- 2012
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- View/download PDF
28. Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice.
- Author
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Chun-Li Xiao, Zhong-Hua Tao, Lin Guo, Wei-Wei Li, Jin-Liang Wan, Hui-Chuan Sun, Lu Wang, Zhao-You Tang, Jia Fan, and Wei-Zhong Wu
- Subjects
LIVER cancer ,OLIGOSACCHARIDES ,LABORATORY mice ,XENOGRAFTS ,GENES - Abstract
Background: Hepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model. Methods: The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells. Results: IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS. Conclusions: IMOS is a potential anti-HCC candidate through inhibition of ERK and JNK signaling independent of p53 and worth studying further in patients with HCC, especially at advanced stages. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
29. Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography.
- Author
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Xiao-Dong Zhu, Ju-Bo Zhang, Pei-Li Fan, Yu-Quan Xiong, Peng-Yuan Zhuang, Wei Zhang, Hua-Xiang Xu, Dong-Mei Gao, Ling-Qun Kong, Lu Wang, Wei-Zhong Wu, Zhao-You Tang, Hong Ding, and Hui-Chuan Sun
- Subjects
XENOGRAFTS ,LIVER cancer ,ULTRASONIC imaging ,CELL lines ,LABORATORY mice - Abstract
Background: Antiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC), but the effects are difficult to be evaluated. Pazopanib (GW786034B) is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC. Methods: In vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS), and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms. Results: In vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density. Conclusions: Antitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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- View/download PDF
30. Herbal compound Songyou Yin reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice.
- Author
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Xiu-Yan Huang, Zi-Li Huang, Lu Wang, Yong-Hua Xu, Xin-Yu Huang, Kai-Xing Ai, Qi Zheng, and Zhao-You Tang
- Subjects
METASTASIS ,PALLIATIVE treatment ,LIVER cancer ,LABORATORY mice ,TUMOR growth - Abstract
Background: Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches. Methods: Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound "Songyou Yin," interferon-alfa-1b (IFN-α), or their combination to assess their effects. Results: In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and downregulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm
3 , 724.9 ± 337.6 mm3 , 507.6 ± 367.0 mm3 , and 245.3 ± 181.2 mm3 in the control, "Songyou Yin," IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively. Conclusion: Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. "Songyou Yin" reinforced the ability of IFN-α to inhibit the metastasis-enhancing potential induced by palliative resection, which indicated its potential postoperative use in patients with HCC. [ABSTRACT FROM AUTHOR]- Published
- 2010
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- View/download PDF
31. Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients.
- Author
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Yi-Xing Chen, Zhao-Chong Zeng, Zhao-You Tang, Jia Fan, Jian Zhou, Wei Jiang, Meng-Su Zeng, and Yun-Shan Tan
- Subjects
RADIOTHERAPY ,CHOLANGIOCARCINOMA ,LIVER cancer ,JAUNDICE ,LYMPH nodes ,METASTASIS - Abstract
Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary liver cancer. Only few studies have focused on palliative radiotherapy used for patients who weren't suitable for resection by surgery. This study was conducted to investigate the effect of external beam radiotherapy (EBRT) for patients with unresectable ICC. Methods: We identified 84 patients with ICC from December 1998 through December 2008 for retrospective analysis. Thirty-five of 84 patients received EBRT therapy five times a week (median dose, 50 Gy; dose range, 30-60 Gy, in fractions of 1.8-2.0 Gy daily; EBRT group); the remaining 49 patients comprised the non-EBRT group. Tumor response, jaundice relief, and survival rates were compared by Kaplan-Meier analysis. Patient records were reviewed and compared using Cox proportional hazard analysis to determine factors that affect survival time in ICC. Results: After EBRT, complete response (CR) and partial response (PR) of primary tumors were observed in 8.6% and 28.5% of patients, respectively, and CR and PR of lymph node metastases were observed in 20% and 40% of patients. In 19 patients with jaundice, complete and partial relief was observed in 36.8% and 31.6% of patients, respectively. Median survival times were 5.1 months for the non-EBRT group and 9.5 months for the EBRT group (P = 0.003). One-and two-year survival rates for EBRT versus non-EBRT group were 38.5% versus 16.4%, and 9.6% versus 4.9%, respectively. Multivariate analysis revealed that clinical symptoms, larger tumor size, no EBRT, multiple nodules and synchronous lymph node metastases were associated with poorer prognosis. Conclusions: EBRT as palliative care appears to improve prognosis and relieve the symptom of jaundice in patients with unresectable ICC. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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32. Residual hepatocellular carcinoma after oxaliplatintreatment has increased metastatic potential in anude mouse model and is attenuated by SongyouYin.
- Author
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Wei Xiong, Zheng-Gang Ren, Shuang-Jian Qiu, Hui-Chuan Sun, Lu Wang, Bin-Bin Liu, Qi-Song Li, Wei Zhang, Xiao-Dong Zhu, Liang Liu, Wen-Quan Wang, and Zhao-You Tang
- Subjects
LIVER cancer ,CANCER cells ,LABORATORY animals ,DRUG therapy ,CELLULAR pathology - Abstract
Background: The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Methods: Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. Results: MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelialmesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). Conclusions: The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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- View/download PDF
33. Indirect 3D printing technology for the fabrication of customised β-TCP/chitosan scaffold with the shape of rabbit radial head—an in vitro study.
- Author
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Wang, Ji-Qi, Jiang, Bing-Jie, Guo, Wei-Jun, and Zhao, You-Ming
- Subjects
CELL proliferation ,ALKALINE phosphatase ,ANIMAL experimentation ,BIOLOGICAL assay ,BONE growth ,CELL differentiation ,ELBOW fractures ,MATERIALS testing ,PHOSPHATES ,POLYSACCHARIDES ,PROSTHETICS ,RABBITS ,SCANNING electron microscopy ,STAINS & staining (Microscopy) ,STEM cells ,TISSUE engineering ,THREE-dimensional printing ,TISSUE scaffolds ,IN vitro studies - Abstract
Background: With the development of indirect three-dimensional (3D) printing technology, it is possible to customise individual scaffolds to be used in bone transplantation and regeneration. In addition, materials previously limited to the 3D printing (3DP) process due to their own characteristics can also be used well in indirect 3DP. In this study, customised β-TCP/chitosan scaffolds with the shape of rabbit radial head were produced by indirect 3D printing technology. Methods: Swelling ability, porosity, mechanical characterisation, and degradation rate analysis were performed, and in vitro studies were also implemented to evaluate the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) on the scaffolds. CCK8 cell proliferation assay kit and alkaline phosphatase (ALP) staining solution were used to study cell proliferation and early ALP content at the scaffold surface. Moreover, the osteogenic differentiation of MSCs on scaffolds was also evaluated through the scanning electron microscopy analysis. Results: β-TCP/chitosan scaffold has good performance and degradation rate, and in vitro cell experiments also confirm that the scaffold has adequate cytocompatibility and bioactivity. Conclusion: This study provides a promising new strategy for the design of customised scaffolds for the repair of complex damaged tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
34. Correction to: miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a.
- Author
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Zhu, Xiao-Dong, Zhang, Yuan-Yuan, Zhang, Shi-Zhe, Cai, Hao, Shi, Wen-Kai, Li, Xiao-Long, Li, Kang-Shuai, Gao, Dong-Mei, Sun, Hui-Chan, Tang, Zhao-You, Cao, Man-Qing, Zhang, Wei, Zhang, Ti, You, A-Bin, Zhang, Kei-wei, Ma, De-Ning, Ye, Bo-Gen, Wang, Cheng-Hao, and Qin, Cheng-Dong
- Subjects
CARCINOMA ,LIVER cancer - Abstract
The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
35. Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma.
- Author
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Wu, Jiao, Hao, Zhi-Wei, Zhao, You-Xu, Yang, Xiang-Min, Tang, Hao, Zhang, Xin, Song, Fei, Sun, Xiu-Xuan, Wang, Bin, Nan, Gang, Chen, Zhi-Nan, and Bian, Huijie
- Abstract
Background: As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection.Methods: We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed.Results: Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P < 0.001). Soluble CD147 levels were found to be associated with HCC tumor size (P = 0.007) and Child-Pugh grade (P = 0.007). Moreover, soluble CD147 showed a better performance in distinguishing HCC compared with alpha-fetoprotein.Conclusions: The extracellular domain of soluble CD147 enhances the secretion of MMP-2 from HCC cells, requiring the cooperation of membrane CD147 and activation of ERK, FAK, and PI3K/Akt signaling. The measurement of soluble CD147 may offer a useful approach in diagnosis of HCC. [ABSTRACT FROM AUTHOR]- Published
- 2014
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- View/download PDF
36. Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice.
- Author
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Xiao, Chun-Li, Tao, Zhong-Hua, Guo, Lin, Li, Wei-Wei, Wan, Jin-Liang, Sun, Hui-Chuan, Wang, Lu, Tang, Zhao-You, Fan, Jia, and Wu, Wei-Zhong
- Abstract
Background: Hepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model.Methods: The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells.Results: IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS.Conclusions: IMOS is a potential anti-HCC candidate through inhibition of ERK and JNK signaling independent of p53 and worth studying further in patients with HCC, especially at advanced stages. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
37. Herbal compound "Songyou Yin" reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice.
- Author
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Huang, Xiu-Yan, Huang, Zi-Li, Wang, Lu, Xu, Yong-Hua, Huang, Xin-Yu, Ai, Kai-Xing, Zheng, Qi, and Tang, Zhao-You
- Abstract
Background: Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches.Methods: Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound "Songyou Yin," interferon-alfa-1b (IFN-α), or their combination to assess their effects.Results: In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and down-regulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, "Songyou Yin," IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively.Conclusion: Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. "Songyou Yin" reinforced the ability of IFN-α to inhibit the metastasis-enhancing potential induced by palliative resection, which indicated its potential postoperative use in patients with HCC. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
38. MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2.
- Author
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Ma DN, Chai ZT, Zhu XD, Zhang N, Zhan DH, Ye BG, Wang CH, Qin CD, Zhao YM, Zhu WP, Cao MQ, Gao DM, Sun HC, and Tang ZY
- Subjects
- Animals, Blotting, Western, Cadherins genetics, Cadherins metabolism, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Enhancer of Zeste Homolog 2 Protein, HEK293 Cells, Hep G2 Cells, Humans, Immunohistochemistry, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Mice, Inbred BALB C, Mice, Nude, Polycomb Repressive Complex 2 metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transplantation, Heterologous, Carcinoma, Hepatocellular genetics, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic, Liver Neoplasms genetics, MicroRNAs genetics, Polycomb Repressive Complex 2 genetics
- Abstract
Background: Our previous study reported that microRNA-26a (miR-26a) inhibited tumor progression by inhibiting tumor angiogenesis and intratumoral macrophage infiltration in hepatocellular carcinoma (HCC). The direct roles of miR-26a on tumor cell invasion remain poorly understood. In this study, we aim to explore the mechanism of miR-26a in modulating epithelial-mesenchymal transition (EMT) in HCC., Methods: In vitro cell morphology and cell migration were compared between the hepatoma cell lines HCCLM3 and HepG2, which were established in the previous study. Overexpression and down-regulation of miR-26a were induced in these cell lines, and Western blot and immunofluorescence assays were used to detect the expression of EMT markers. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Immunohistochemical assays were conducted to study the relationships between miR-26a expression and enhancer of zeste homolog 2 (EZH2) and E-cadherin expression in human HCC samples., Results: Down-regulation of miR-26a in HCCLM3 and HepG2 cells resulted in an EMT-like cell morphology and high motility in vitro and increased in tumor growth and pulmonary metastasis in vivo. Through down-regulation of EZH2 expression and up-regulation of E-cadherin expression, miR-26a inhibited the EMT process in vitro and in vivo. Luciferase reporter assay showed that miR-26a directly interacted with EZH2 messenger RNA (mRNA). Furthermore, the expression of miR-26a was positively correlated with E-cadherin expression and inversely correlated with EZH2 expression in human HCC tissue., Conclusions: miR-26a inhibited the EMT process in HCC by down-regulating EZH2 expression.
- Published
- 2016
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39. Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse model.
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Zhang KZ, Zhang QB, Zhang QB, Sun HC, Ao JY, Chai ZT, Zhu XD, Lu L, Zhang YY, Bu Y, Kong LQ, and Tang ZY
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- AC133 Antigen, Animals, Arsenic Trioxide, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Cell Differentiation drug effects, Cell Line, Tumor, Disease Models, Animal, Down-Regulation, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Liver Neoplasms surgery, Male, Mice, Mice, Inbred NOD, Mice, SCID, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Neoplastic Stem Cells pathology, Random Allocation, Signal Transduction, Survival Analysis, Transcription Factors genetics, Xenograft Model Antitumor Assays, Zinc Finger Protein GLI1, Antigens, CD metabolism, Arsenicals pharmacology, Carcinoma, Hepatocellular drug therapy, Glycoproteins metabolism, Liver Neoplasms drug therapy, Oxides pharmacology, Peptides metabolism, Transcription Factors biosynthesis
- Abstract
Background: Cancer stem cells (CSCs) play a key role in the posthepatectomy recurrence of hepatocellular carcinoma (HCC). CD133+ HCC cells exhibit liver CSC-like properties, and CSC differentiation-inducing therapy may lead these cells to lose their self-renewal ability and may induce terminal differentiation, which may in turn allow their malignant potential to be controlled. Because arsenic trioxide (As₂O₃) increases remission rates and prolongs survival among patients with acute promyelocytic leukemia by inducing differentiation and apoptosis of leukemic cells, we hypothesized that As₂O₃ might also inhibit HCC recurrence and prolong survival time after hepatectomy by inducing differentiation of HCC CSCs., Methods: We evaluated the As₂O₃ induced differentiation of human HCC CSCs and its mechanism in vitro, and we investigated the effects of treatment with As₂O₃ on recurrence rates and median survival in a mouse xenograft model., Results: We found that As₂O₃ induced HCC CSC differentiation by down-regulating the expression of CD133 and some stemness genes, thus inhibiting the cells' self-renewal ability and tumorigenic capacity without inhibiting their proliferation in vitro. In vivo experiments indicated that As₂O₃ decreased recurrence rates after radical resection and prolonged survival in a mouse model. As₂O₃, which shows no apparent toxicity, may induce HCC CSC differentiation by down-regulating the expression of GLI1., Conclusions: We found that As₂O₃ induced HCC CSC differentiation, inhibited recurrence, and prolonged survival after hepatectomy by targeting GLI1expression. Our results suggest that the clinical safety and utility of As₂O₃ should be further evaluated.
- Published
- 2014
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40. Herbal compound "Songyou Yin" attenuates hepatoma cell invasiveness and metastasis through downregulation of cytokines secreted by activated hepatic stellate cells.
- Author
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Jia QA, Wang ZM, Ren ZG, Bu Y, Xie XY, Wang YH, Zhang L, Zhang QB, Xue TC, Deng LF, and Tang ZY
- Subjects
- Animals, Cadherins metabolism, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cells, Cultured, Humans, Liver Neoplasms genetics, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Neoplasm Invasiveness, Neoplasm Metastasis, Rats, Rats, Inbred BUF, Transforming Growth Factor beta1 metabolism, Carcinoma, Hepatocellular drug therapy, Cytokines metabolism, Down-Regulation drug effects, Drugs, Chinese Herbal pharmacology, Hepatic Stellate Cells metabolism, Liver Neoplasms drug therapy
- Abstract
Background: Activated hepatic stellate cells (aHSCs) play an important role in the progression of hepatocellular carcinoma (HCC). Here, we determined if cytokines secreted in response to the herbal compound "Songyou Yin" (SYY) treatment of aHSCs could influence invasiveness and metastatic capabilities of hepatoma cells., Methods: Primary rat hepatic stellate cells (HSCs) were isolated, activated, divided into SYY treated and untreated (nSYY) groups, and conditioned media (CM-SYY and CM-nSYY, respectively) were collected. The hepatoma cell line, McA-RH7777 was cultured for 4 weeks with SYY, CM-SYY, and CM-nSYY, designated McA-SYY, McA-SYYCM and McA-nSYYCM. The invasiveness and metastatic capabilities were evaluated using Matrigel invasion assay in vitro and pulmonary metastasis in vivo. Matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, N-cadherin, and vimentin protein levels in McA-SYYCM and McA-nSYYCM were evaluated by Western blot. Cytokine levels in conditioned media were tested using enzyme-linked immunosorbent assay (ELISA)., Results: Matrigel invasion assay indicated that the number of McA-SYYCM cells passing through the basement membrane was less than in McA-nSYYCM cells (P < 0.01). Similar results were also observed in vivo for lung metastasis. McA-SYYCM cells showed less pulmonary metastasis capabilities than McA-nSYYCM cells (P < 0.001). The reduced expression of MMP-2 and reversed epithelial to mesenchymal transition with E-cadherin upregulation, and N-cadherin and vimentin downregulation were also found in McA-SYYCM compared to McA-nSYYCM. Metastasis-promoting cytokines hepatocyte growth factor, interleukin-6, transforming growth factor-β1, and vascular endothelial growth factor were markedly decreased in CM-SYY compared to CM-nSYY., Conclusions: SYY attenuates hepatoma cell invasiveness and metastasis capabilities through downregulating cytokines secreted by activated hepatic stellate cells.
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- 2013
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41. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization.
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Wang WQ, Liu L, Sun HC, Fu YL, Xu HX, Chai ZT, Zhang QB, Kong LQ, Zhu XD, Lu L, Ren ZG, and Tang ZY
- Subjects
- Animals, Antineoplastic Agents, Phytogenic administration & dosage, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Cell Growth Processes drug effects, Cell Line, Tumor, Humans, Liver Neoplasms pathology, Liver Neoplasms surgery, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Random Allocation, Xenograft Model Antitumor Assays, Abietanes pharmacology, Antineoplastic Agents, Phytogenic therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background: Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR) of hepatocellular carcinoma (HCC)., Methods: A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential) and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs) treated with tanshinone IIA., Results: PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT) in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α) or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR) upregulation. Although the microvessel density (MVD) of residual tumor tissue increased after PR, the microvessel integrity (MVI) was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization., Conclusions: Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical benefit of preventing postsurgical recurrence.
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- 2012
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42. Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography.
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Zhu XD, Zhang JB, Fan PL, Xiong YQ, Zhuang PY, Zhang W, Xu HX, Gao DM, Kong LQ, Wang L, Wu WZ, Tang ZY, Ding H, and Sun HC
- Subjects
- Animals, Apoptosis drug effects, Blood Vessels drug effects, Blood Vessels pathology, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular pathology, Cell Line, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Hep G2 Cells, Humans, Image Enhancement, Indazoles, Liver Neoplasms, Experimental diagnostic imaging, Liver Neoplasms, Experimental pathology, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Tumor Burden drug effects, Ultrasonography methods, Angiogenesis Inhibitors pharmacology, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms, Experimental drug therapy, Pyrimidines pharmacology, Sulfonamides pharmacology, Xenograft Model Antitumor Assays
- Abstract
Background: Antiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC), but the effects are difficult to be evaluated. Pazopanib (GW786034B) is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC., Methods: In vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS), and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms., Results: In vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density., Conclusions: Antitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS.
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- 2011
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43. Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients.
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Chen YX, Zeng ZC, Tang ZY, Fan J, Zhou J, Jiang W, Zeng MS, and Tan YS
- Subjects
- Bile Duct Neoplasms pathology, Bile Duct Neoplasms surgery, Bile Ducts, Intrahepatic pathology, Bile Ducts, Intrahepatic surgery, Cholangiocarcinoma pathology, Cholangiocarcinoma surgery, Female, Follow-Up Studies, Gastrointestinal Neoplasms pathology, Gastrointestinal Neoplasms surgery, Humans, Liver Neoplasms secondary, Liver Neoplasms surgery, Lymphatic Metastasis, Male, Middle Aged, Retrospective Studies, Survival Rate, Treatment Outcome, Bile Duct Neoplasms radiotherapy, Bile Ducts, Intrahepatic radiation effects, Cholangiocarcinoma radiotherapy, Gastrointestinal Neoplasms radiotherapy, Liver Neoplasms radiotherapy
- Abstract
Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary liver cancer. Only few studies have focused on palliative radiotherapy used for patients who weren't suitable for resection by surgery. This study was conducted to investigate the effect of external beam radiotherapy (EBRT) for patients with unresectable ICC., Methods: We identified 84 patients with ICC from December 1998 through December 2008 for retrospective analysis. Thirty-five of 84 patients received EBRT therapy five times a week (median dose, 50 Gy; dose range, 30-60 Gy, in fractions of 1.8-2.0 Gy daily; EBRT group); the remaining 49 patients comprised the non-EBRT group. Tumor response, jaundice relief, and survival rates were compared by Kaplan-Meier analysis. Patient records were reviewed and compared using Cox proportional hazard analysis to determine factors that affect survival time in ICC., Results: After EBRT, complete response (CR) and partial response (PR) of primary tumors were observed in 8.6% and 28.5% of patients, respectively, and CR and PR of lymph node metastases were observed in 20% and 40% of patients. In 19 patients with jaundice, complete and partial relief was observed in 36.8% and 31.6% of patients, respectively. Median survival times were 5.1 months for the non-EBRT group and 9.5 months for the EBRT group (P = 0.003). One-and two-year survival rates for EBRT versus non-EBRT group were 38.5% versus 16.4%, and 9.6% versus 4.9%, respectively. Multivariate analysis revealed that clinical symptoms, larger tumor size, no EBRT, multiple nodules and synchronous lymph node metastases were associated with poorer prognosis., Conclusions: EBRT as palliative care appears to improve prognosis and relieve the symptom of jaundice in patients with unresectable ICC.
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- 2010
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44. Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin.
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Xiong W, Ren ZG, Qiu SJ, Sun HC, Wang L, Liu BB, Li QS, Zhang W, Zhu XD, Liu L, Wang WQ, and Tang ZY
- Subjects
- Animals, Blotting, Western, Carcinoma, Hepatocellular secondary, Cell Movement drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Cell Transdifferentiation drug effects, Fluorescent Antibody Technique, Hep G2 Cells, Humans, Immunohistochemistry, Liver Neoplasms pathology, Lung Neoplasms secondary, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Neoplasm, Residual secondary, Oxaliplatin, Time Factors, Tumor Burden, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Carcinoma, Hepatocellular drug therapy, Drugs, Chinese Herbal pharmacology, Liver Neoplasms drug therapy, Lung Neoplasms drug therapy, Neoplasm, Residual drug therapy, Organoplatinum Compounds pharmacology
- Abstract
Background: The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC., Methods: Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells., Results: MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively)., Conclusions: The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.
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- 2010
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45. Chemokine receptor CXCR4 expression in hepatocellular carcinoma patients increases the risk of bone metastases and poor survival.
- Author
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Xiang ZL, Zeng ZC, Tang ZY, Fan J, Zhuang PY, Liang Y, Tan YS, and He J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bone Neoplasms secondary, Carcinoma, Hepatocellular secondary, Child, Female, Humans, Immunohistochemistry, Liver Neoplasms pathology, Male, Microarray Analysis methods, Middle Aged, Risk Factors, Young Adult, Bone Neoplasms metabolism, Carcinoma, Hepatocellular metabolism, Liver Neoplasms metabolism, Receptors, CXCR4 biosynthesis
- Abstract
Background: The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers. This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival., Methods: Tumor tissue from HCC patients with (n = 43) and without (n = 138) bone metastasis was subjected to immunohistochemical staining for CXCR4 using tissue microarrays. Immunoreactivity was evaluated semi-quantitatively. A receiver-operating characteristic-based approach and logistical regression analysis were used to determine the predictive value of clinicopathologic factors, including CXCR4 expression, in bone metastasis. Patient survival was analyzed by Kaplan-Meier curves and log-rank tests., Results: CXCR4 overexpression was detected in 34 of 43 (79.1%) patients with bone metastases and in 57 of 138 (41.3%) without bone metastases. CXCR4 expression correlated with (correlation coefficient: 0.551, P < 0.001) and was predictive of HCC bone metastases (AUC: 0.689; 95%CI: 0.601 - 0.776; P < 0.001). CXCR4 staining intensity correlated with the bone metastasis-free survival (correlation coefficient: -0.359; P = 0.018). CXCR4 overexpression in primary tumors (n = 91) decreased overall median survival (18.0 months vs. 36.0 months, P <0.001). Multivariable analysis identified CXCR4 as a strong, independent risk factor for reduced disease-free survival (relative risk [RR]: 5.440; P = 0.023) and overall survival (RR: 7.082; P = 0.001)., Conclusion: CXCR4 expression in primary HCCs may be an independent risk factor for bone metastasis and may be associated with poor clinical outcome.
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- 2009
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46. Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma.
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Lei KF, Wang YF, Zhu XQ, Lu PC, Sun BS, Jia HL, Ren N, Ye QH, Sun HC, Wang L, Tang ZY, and Qin LX
- Subjects
- Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular secondary, Carcinoma, Hepatocellular virology, Cell Line, Tumor, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms pathology, Liver Neoplasms virology, Male, Methionine Sulfoxide Reductases, Middle Aged, Neoplasm Invasiveness, Oxidoreductases physiology, Carcinoma, Hepatocellular genetics, Chromosomes, Human, Pair 8, Genes, Tumor Suppressor, Hepatitis B virus isolation & purification, Liver Neoplasms genetics, Neoplasm Metastasis prevention & control, Oxidoreductases genetics
- Abstract
Background: The prognosis of patients with hepatocellular carcinoma (HCC) still remains very dismal, which is mainly due to metastasis. In our previous studies, we found that chromosome 8p deletions might contribute to metastasis of HCC. In this study, we aimed to identify the candidate metastatic suppressor gene on chromosome 8p., Methods: Oligo-nucleotide microarrays which included 322 genes on human chromosome 8p were constructed to analyze the difference in gene expression profiles between HCC tissues with and without metastasis. The leading differentially expressed genes were identified and selected for further analysis by real-time PCR and Western blotting. Recombinant expression plasmid vectors for each target gene were constructed and transfected into HCC cells and its in vitro effects on proliferation and invasion of HCC cells were also investigated., Results: Sixteen leading differentially expressed genes were identified from the HCC tissues with metastasis compared with those without metastasis (p < 0.01, q < 16 %). Among of the 10 significantly down-regulated genes in HCC with metastasis, methionine sulfoxide reductase A (MSRA) had the lowest p value and false discovery rate (FDR), and was considered as a potential candidate for metastasis suppressor gene. Real-time PCR and Western blotting confirmed that the mRNA and protein expression levels of MSRA were significantly decreased in HCC with metastasis compared with those without metastasis (p < 0.001), and MSRA mRNA level in HCCLM6 cells (with high metastatic potential) was also much lower than that of other HCC cell lines. Transfection of a recombinant expression plasmid vector and overexpression of MSRA gene could obviously inhibit cell colony formation (4.33 +/- 2.92 vs. 9.17 +/- 3.38, p = 0.008) and invasion (7.40 +/- 1.67 vs. 17.20 +/- 2.59, p= 0.0001) of HCCLM6 cell line., Conclusion: MSRA gene on chromosome 8p might possess metastasis suppressor activity in HCC.
- Published
- 2007
- Full Text
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