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中华肝脏病杂志 2015年第10期23卷 797-800页

作者：潘刘翃姚敏姚登福南通大学附属医院临床医学研究中心 226001

肝细胞性肝癌（HCC）为我国常见恶性肿瘤之一，HCC发生、发展的机制十分复杂，主要与HBV和HCV的慢性持续性感染相关。Wnt信号通路是一条进化上相对保守的信号传导途径，具有调节细胞增殖、极性、

关键词：癌肝细胞 Wnt信号通路跨膜受体调节因子

High mucin 5AC expression predicts adverse postoperative recurrence and survival of patients with clear-cell renal cell carcinoma

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High mucin 5AC expression predicts adverse postoperative rec...

核因子-κB异常激活与肝炎病毒感染关系的研究进展

2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Haijian Zhang dengfu yao Jiejie Xu Jianxin Gu Research Center of Clinical Medicine Affiliated Hospital of Nantong University Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan University Department of Urology Fudan University Shanghai Cancer Center

Background: Mucin 5 AC(MUC5 AC), as a member of secreted/gel-forming mucin family, was frequently found to be abnormally expressed in inflammation or malignant diseases. However, the clinic pathologic features and prognostic values of MUC5 AC in clear cell renal cell carcinoma(ccRCC) have not been reported up to now. Methods: MUC5 AC expression was analyzed by immunohistochemistry on tissue microarrays. KaplanMeier survival curves, Univariate and Multivariate Cox analysis and newly-established nomogram model were performed to evaluate the prognostic value. Results: MUC5 AC expression was firstly found to be up-regulated in patients with ccRCC, positively associated with tumor size, pN stage, lymphovascular invasion, Fuhrman grade, rahbdoid differentiation, sarcomatoid features, tumor necrosis, ECOG-PS and recurrence. Furthermore, MUC5 AC expression might be contributed to risk stratification of ccRCC patients with TNM stage Ⅲ+Ⅳ or Fuhrman grade 3 or 4 for overall survival(OS) and recurrence-free survival(RFS) analysis, and it was demonstrated to be negatively correlated with OS and RFS of ccRCC patients. What’s more, MUC5 AC was identified as a potential independent adverse prognostic factor;prediction accuracy of MUC5 AC-based new nomogram model was drastically improved for OS and RFS of ccRCC patients. Conclusion: MUC5 AC is a promising independent adverse prognostic factor for ccRCC patients, it maybe conducive to postoperative risk stratification and guide treatment in the future.

关键词： mucin 5AC clear cell renal cell carcinoma overall survival recurrence-free survival prognostic biomarker

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中国实用内科杂志 2006年第12期26卷 1862-1864页

作者：姚登福苏小琴南通大学临床医学研究中心江苏南通226001

核因子-κB(NF-κB)是与免疫球蛋白κ轻链增强子B区结合,具有和某些基因上启动子区固定核苷酸序列结合而启动该基因转录的蛋白质.NF-κB是具有多向性调节作用的核转录因子,可调控多种基因(免疫、炎症反应、病毒和原癌基因)的转录表达[1]... 详细信息

核因子-κB(NF-κB)是与免疫球蛋白κ轻链增强子B区结合,具有和某些基因上启动子区固定核苷酸序列结合而启动该基因转录的蛋白质.NF-κB是具有多向性调节作用的核转录因子,可调控多种基因(免疫、炎症反应、病毒和原癌基因)的转录表达[1].激活的NF-κB参与癌症的启动、发生及发展过程,在炎症性相关的肝癌(HCC)发生发展中呈高表达,在肝细胞炎症与癌变间起桥梁作用,其中包括肝脏免疫炎症反应相关基因、肝炎病毒相关基因和原癌基因的转录表达.在肝癌组织中异常激活,可抑制细胞凋亡,促进肝细胞存活,与肝癌的发生发展密切相关[2].

关键词：肝炎病毒感染核因子-κB 激活免疫球蛋白κ轻链免疫炎症反应 NF-κB 基因转录肝癌组织

Clinicopathological features of hypoxia-inducible factor-1α and vascular endothelial growth factor expression in patients with lung cancer

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Oncology and Translational Medicine 2016年第6期2卷 261-267页

作者： Xuli Yang Li Wang Wenli Sai Yin Cai Juanjuan Gu Xin Chen dengfu yao Research Center of Clinical Medicine The Affiliated Hospital of Nantong University Center of Medical Informatics Medical School of Nantong University Department of Oncology The Affiliated Hospital of Nantong University School of Life Science Nantong University

Objective The aim of the study was to investigate the clinicopathological characteristics of hypoxiainducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) expression in patients with lung *** Cancerous and noncancerous tissues were collected post-operation from 115 patients with lung cancers by the self-control method. Total RNA was extracted from the lung tissues. The status of tissue HIF-1α expression and intercellular distribution was observed by immunochemistry using a tissue microarray. The expression levels of circulating HIF-1α and VEGF were detected by enzyme-linked immunosorbent assay(ELISA).Results The expression of serum HIF-1α [(138.3 ± 28.8) μg/L] in the group of patients with lung cancer was significantly higher(P < 0.01) than that in the group of patients with pneumonia [(58.8 ± 14.5) μg/L] and the control group of patients ((24.1 ± 3.3) μg/L)There was a strong positive correlation of serum HIF-1α levels(r = 0.937, P < 0.01) with serum VEGF levels. The specific concentration of total RNA [(1.52 ± 1.14) μg/mg wet lung tissues] in the cancerous tissues was significantly higher(t = 8.494, P < 0.001) than that in the noncancerous tissues ((0.58 ± 0.33) μg/mg)The clinicopathological features of HIF-1α expression in lung cancer tissues revealed a significant relationship between positive HIF-1α expression and patient sex(χ~2 = 4.494, P = 0.034), tumor size(χ~2 = 4.679, P = 0.031), differentiation degree(χ~2= 8.846, P = 0.012), and presence of lymphatic node metastasis(χ~2= 6.604, P = 0.037).Conclusion Abnormal HIF-1α expression in lung cancer is closely related with nucleic acid metabolism and angiogenesis, and it may be helpful in the diagnosis and identification of lung cancer.

关键词： lung cancer hypoxia-inducible factor-1α(HIF-1α) nucleic acid metabolism enzyme-linked immunosorbent assay(ELISA) diagnosis

Abnormal expression of VEGF and its gene transcription status as diagnostic indicators in patients with non-small cell lung cancer

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Oncology and Translational Medicine 2015年第5期1卷 201-207页

作者： Yun Shi Yang Shi Xuli Yang Jianrong Chen Qi Qian dengfu yao Guangzhou Wu Research Center of Clinical Medicine Affiliated Hospital of Nantong University Department of Cardiothoracic Surgery The Affiliated Yancheng Hospital of Nantong University Department of Respiration Medicine The 1st People's Hospital of Nantong City

Objective Angiogenesis is known to be essential for the survival,growth,invasion,and metastasis of lung cancer cells. Vascular endothelial growth factor(VEGF) is an important factor regulating angiogenesis of non-small cell lung cancer(NSCLC); however,its pathologic features and significance are unclear. In this study,the tissue VEGF expression levels and its gene transcriptional status,as well as circulating VEGF levels,were investigated in patients with lung disease. Methods VEGF protein and m RNA expression levels in 38 lung tissue samples were analyzed by immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR),respectively. Circulating VEGF levels were detected quantitatively by an enzyme linked immuno-sorbent assay. Results The level of VEGF expression was significantly higher in lung cancer tissue than in the corresponding paracancerous or non-cancerous tissues. The average level of VEGF-positive staining was 76% in tissue samples from NSCLC patients; the levels were 89% in tissue samples from stage III patients and 92% in stage IV patients. High VEGF expression was also evident in cases with lymph node metastasis(84%),distant metastasis(90%),and lower differentiation degree(89%). VEGF m RNA in cancerous tissues was represented predominantly by the VEGF121 and VEGF165 isoforms. Circulating VEGF levels were significantly higher in NSCLC patients [(840 ± 324) pg/m L] than in patients with benign lung diseases [(308 ± 96) pg/m L] or in healthy individuals serving as controls [(252 ± 108) pg/m L]. Conclusion The over-expression of lung VEGF and its gene transcription status should be useful molecular indicators for NSCLC diagnosis.

关键词： lung cancer vascular endothelial growth factor (VEGF) VEGF mRNA reverse transcription-polymerase chain reaction (RT-PCR) immunohistochemistry

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癌胚型特异标志物与肝癌免疫治疗

中华肝脏病杂志 2020年第6期28卷 466-470页

作者：姚敏杨君伶王理姚登福南通大学医学院免疫学教研室 226001 南通大学附属医院临床医学研究中心 226001 南通大学医学院医学信息教研室 226001

肝细胞肝癌(HCC)为源自于乙型肝炎病毒与丙型肝炎病毒感染背景、化学毒物摄入或非酒精性脂肪性肝病等慢性炎症。癌变肝细胞可表达和分泌多种相对特异性的标志物,如癌胚型的甲胎蛋白、磷脂酰肌醇蛋白多糖-3、Wnt/β-catenin通路关键信号... 详细信息

肝细胞肝癌(HCC)为源自于乙型肝炎病毒与丙型肝炎病毒感染背景、化学毒物摄入或非酒精性脂肪性肝病等慢性炎症。癌变肝细胞可表达和分泌多种相对特异性的标志物,如癌胚型的甲胎蛋白、磷脂酰肌醇蛋白多糖-3、Wnt/β-catenin通路关键信号分子Wnt3a和肝癌特异性GGT-II等,临床分析癌胚型标志物除有助于HCC诊断和预后判别外,也可能是HCC免疫治疗的靶目标,具有开发应用前景。现对有价值的癌胚型特异分子标志物与肝癌免疫治疗的最新进展进行评述。

关键词：肝细胞癌免疫治疗特异性标志物

Nonalcoholic Lipid Accumulation and Hepatocyte Malignant Transformation

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Journal of Clinical and Translational Hepatology 2016年第2期4卷 123-130页

作者： Juanjuan Gu Min yao Dengbing yao Li Wang Xuli Yang dengfu yao Research Center of Clinical Medicine and Department of Oncology Affiliated Hospital of Nantong UniversityNantongJiangsuChina Department of Immunology Medical School of Nantong UniversityNantongJiangsuChina School of Life Sciences Nantong UniversityNantongJiangsuChina Department of Medical Informatics Medical School of Nantong UniversityNantongJiangsuChina

Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing,highlighting its status as a public health concern,particularly due to its significant association with other comorbidities,such as ***,nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor,with its own prevalence increasing in recent years,and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus,exposure to aflatoxin,or alcohol liver *** deeply worrisome aspects of all of these high risk factors,however,are their remarkable presence within *** and genetic mechanisms involved in the malignant transformation of liver cells,as well as useful biomarkers of early stage HCC are being ***,the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely *** this review,some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation.(C) 2016 The Second Affiliated Hospital of Chongqing Medical *** by XIA & HE Publishing *** rights reserved.

关键词： Nonalcoholic fatty liver disease Hepatocellular carcinoma Metabolism

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Wnt通路关键信号分子与肝癌靶向治疗

中华肝脏病杂志 2018年第5期26卷 397-400页

作者：郑文杰姚登福南通大学附属医院临床医学研究中心 226001

肝细胞性肝癌（HCC）是常见的消化系统肿瘤，其发生和发展是多因素、多步骤共同作用的结果。近年来多项研究结果表明wnt通路在HCC进展中发挥重要作用，与肝细胞恶性转化、HCC转移与耐药、肝癌干细胞相关。该文分析了Wnt通路关键信号分子... 详细信息

肝细胞性肝癌（HCC）是常见的消化系统肿瘤，其发生和发展是多因素、多步骤共同作用的结果。近年来多项研究结果表明wnt通路在HCC进展中发挥重要作用，与肝细胞恶性转化、HCC转移与耐药、肝癌干细胞相关。该文分析了Wnt通路关键信号分子在HCC中的表达情况及其在诊断、预后和靶向治疗中的价值，并概述了Wnt通路靶向药物治疗HCC的研究进展，以期为HCC靶向治疗研究提供参考。

关键词：癌,肝细胞诊断预后 Wnt通路靶向治疗

Abnormal expression of vascular endothelial growth factor (VEGF) and its clinical features in tissues of human lung cancer

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Journal of Nanjing Medical University 2005年第4期19卷 194-198页

作者： Xinhua Wu dengfu yao Gongshen Shi Liwei Qiu Wei Wu Songshi Ni Xueguang Zhang Research Center of Clinical Molecular Biology Nantong 226001 China Department of Pathology Nantong 226001 China Departmennt of Respiration the Affiliated Hospital of Nantong University Nantong 226001 China The Academy of Life Science Suzhou University Suzhou 215000China

Objective： Angiogennesis, the formation of new blood vessels from the existing vascular bed, is essential step for growth and invasion of primary rumor. Vascular endothelial growth factor （VEGF） is known to play crucial role in tumor angiogenesis. In the present study, we investigate the expression of VEGF and VEGF-mRNA in the angiogennesis, metastasis and prognosis of lung cancer. Methods： The VEGF cellular distributions and expression in 38 specimens of patients with lung cancer were investigated with immunohistochemistry stain technology. The total RNAs in 38 tissues of lung cancer was measured, then the levels of VEGF-mRNA expression were analyzed by a reverse-transcription polymerase chain reaction （RT-PCR） assay. The levels of VEGF in sera of patients with lung cancer, benign lung diseases and healthy controls were detected through Enzyme linked immunosorbent assay （ELISA） method. Results： The VEGF positive stain was 76% in 38 cases of lung cancer specimens. The 89% rate of VEGF stain was found for clinical stage Ⅲ cases and 92% for stage Ⅳ lung cancers. The significantly higher expression of VEGF was evidenced in patients with lymph node metastasis （84%）, distant metastasis （90%）, and lung cancers with lower histological differentiation （89%）, respectively. The expression level of total RNA was significantly higher in patients with lung cancers than that in their paracancerons or distant lung tissues. The VEGF expressions were tightly correlated with total RNA concentration of lung carcinoma （ P 〈 0.01 ）. The predominant expressions of VEGF121 and VEGF165 gene fragments were found in lung cancer specimens by RT-PCR analysis. No significant difference of serum VEGF levels was detected between cases with lung cancer and patients with benign diseases. However, the VEGF level of cases with benign diseases was decreased significantly after patients with anti-inflammation medication. Conclusion： The present data suggested that the rumor tissue VEGF expression and V

关键词： vascular endothelial growth factor lung cancer gene amplification immuno-histochemlstry ELISA

环状RNA在非酒精性脂肪性肝病进展中的调控机制及潜在价值

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中华肝脏病杂志 2022年第11期30卷 1270-1275页

作者：谢群王玲玲王理姚登福姚敏南通大学附属医院临床医学研究中心南通226001 海安市人民医院感染性疾病科南通226600 南通大学医学免疫学系南通226001

非酒精性脂肪性肝病(NAFLD)或称代谢相关脂肪性肝病已成为全球最常见慢性肝病。NAFLD与非编码RNA(ncRNA)关系,已引起基础及临床研究的重视。在脂代谢相关ncRNA中,环状RNA(circRNA)在真核细胞中存在高度保守,异同于含5’’-末端和3’’-... 详细信息

非酒精性脂肪性肝病(NAFLD)或称代谢相关脂肪性肝病已成为全球最常见慢性肝病。NAFLD与非编码RNA(ncRNA)关系,已引起基础及临床研究的重视。在脂代谢相关ncRNA中,环状RNA(circRNA)在真核细胞中存在高度保守,异同于含5’’-末端和3’’-末端的线性ncRNAs,具有组织特异性且可稳定表达内源性ncRNA,在封闭、环状核苷链上含miRNA结合位点,形成circRNA-miR-mRNA轴或与蛋白质构成网络,以海绵样机制竞争内源RNA,发挥其抑制或促进相关靶基因表达,参与NAFLD进展。现综述circRNA在NAFLD调控机制、检测技术及其潜在临床价值。

关键词：非酒精性脂肪性肝病机制潜在价值环状RNA

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