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Rosiglitazone enhances 5-fluorouracil-induced cell growth inhibition in hepatocellular carcinoma cell line Hep3B

Chinese Journal of Cancer 2010年第8期29卷 741-746页

作者： Liang-Qi Cao Zi-Li Shao He-Ping Peng Jian-Bin Xiao Ting Xia Department of Hepatobiliary Surgery the Second Affiliated Hospital of Guangzhou Medical College Guangzhou Guangdong 510260 P. R. China

Background and Objective: Rosiglitazone is a peroxisome proliferators-activated receptor γ (PPARγ) ligand, which inhibits tumor growth by activating PPARγ signaling pathways. Fluorouracil (5-FU) is one of the commonly used chemotherapeutic drugs. However, patients develop drug resistance of 5-FU over time. The aim of this study was to investigate whether rosiglitazone can enhance 5-FU-induced cell growth inhibition and to explore its potential ***: Cell viability was measured using MTT assay. Protein expression levels were detected by Western blot analysis. Small interference RNA was utilized to knockout PPARγ and PTEN in Hep3B cells. Results: After 48 h of treatment with 10, 20, and 40 μmol/L rosiglitazone, the viability of Hep3B cells was (78.0 ± 2.7)%, (37.3 ± 8.1)%, and (19.8 ± 2.2)%, respectively (compared with control group, P values were all < 0.001). After 48 h of treatment with 10 μmol/L 5-FU, the viability of Hep3B cells was about (82.6 ± 3.9)%. When cells were treated with 10 μmol/L 5-FU in combination with either 10, 20 or 40 μmol/L rosiglitazone, the cell viability was (51.6 ± 5.4)%, (14.8 ± 4.2)%, and (8.5 ± 0.9)%, with corresponding q value of 1.36, 1.23, and 1.19, respectively. These data suggested that the two drugs had synergic effect in inhibiting Hep3B cell growth, which was further confirmed in an in vivo mice model. Subsequent investigations showed that rosiglitazone activated PPARγ signaling pathways and increased the expression of PTEN. Conclusions: Rosiglitazone enhances 5-FU-induced cell growth inhibition of Hep3B cells.

关键词：罗格列酮生长抑制过氧化物酶体增殖物激活受体细胞株诱导氟尿嘧啶细胞存活率 PTEN基因

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Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma cells

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World Journal of Gastroenterology 2012年第7期18卷 646-653页

作者： Xiang-Liang Zhang An-Bin Hu Shu-Zhong Cui Hong-Bo Wei Department of Gastroin-testinal Surgery The Third Affiliated Hospital of Sun Yat-SenUniversity Guangzhou 510630 Guangdong Province China Department of General Surgery The First AffiliatedHospital of Sun Yat-Sen University Guangzhou 510080 Guang-dong Province China Department of Abdominal Surgery AffiliatedTumor Hospital of Guangzhou Medical College Guangzhou510095 Guangdong Province China

AIM： To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells.

关键词： Colorectal cancer Oxaliplatin Thermoche-motherapy Mitochondrial apoptotic pathway

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MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

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World Journal of Gastroenterology 2014年第32期20卷 11347-11355页

作者： Xiang-Liang Zhang Hui-Juan Shi Ji-Ping Wang Hong-Sheng Tang Yin-Bing Wu Zhi-Yuan Fang Shu-Zhong Cui Lian-Tang Wang Department of Abdominal Surgery (Section 2) Affiliated Tumor Hospital of Guangzhou Medical College Department of Pathology The First Affiliated Hospital of Sun Yat-Sen University Department of Surgery Brigham and Women’s Hospital and Harvard Medical School Massachusetts General Hospital and Harvard medical School Boston MA 02114 United States

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

关键词： Advanced gastric cancer Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy miR-218 Multi-drug resistance MicroRNA

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Identification of Risk Pathways and Functional Modules for Coronary Artery Disease Based on Genome-wide SNP Data

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Genomics, Proteomics & Bioinformatics 2016年第6期14卷 349-356页

作者： Xiang Zhao Yi-Zhao Luan Xiaoyu Zuo Ye-Da Chen Jiheng Qin Lv Jin Yiqing Tan Meihua Lin Naizun Zhang Yan Liang Shao-Qi Rao Institute for medical Systems Biology and Department of medical Statistics and Epidemiology School of Public HealthGuangdong Medical CollegeDongguan 523808China School of Life Sciences Sun Yat-sen UniversityGuangzhou 510080China Department of medical Statistics and Epidemiology School of Public HealthSun Yat-sen UniversityGuangzhou 510080China Maoming People's Hospital Maoming 525000China

Coronary artery disease （CAD） is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism （SNP） profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium （WTCCC） SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein protein interaction （PPI） knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer＇s disease, non-alcoholic fatty liver disease, and Huntington＇s disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer＇s disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer＇s disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.

关键词： Coronary artery disease Genome-wide SNP profiling Risk pathway Functional module Genetic network

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Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

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World Journal of Gastroenterology 2004年第16期10卷 2397-2401页

作者： Yu-YuanLi Yu-QiangNie Wei-HongSha ZhengZeng Fu-YingYang LiPing LinJia DepartmentofGastroenterology FirstMunicipalPeople'sHospitalofGuangzhou510180GuangdongProvinceChina DepartmentofNeurology FirstMunicipalPeople'sHospitalofGuangzhou510180GuangdongProvinceChina DepartmentofGastroenterology FirstMunicipalPeople'sHospitalofGuangzhou510180GuangdongProvinceChina

AIM: Subclinical hepatic encephalopathy (SHE) is a common complication of liver diseases. The aim of this study was to find out the normal value of psychometric test and to investigate the prevalence of SHE in Chinese patients with stabilized hepatic ***: Four hundred and nine consecutive cirrhotic patients without overt clinical encephalopathy were screened for SHE by using number connection test part A (NCT-A) and symbol digit test (SDT). SHE was defined as presence of at least one abnormal psychometric test. The age-corrected normal values were defined as the mean±2times standard deviation (2SD), and developed in 356 healthypersons as normal controls. Four hundred and sixteen patients with chronic viral hepatitis were tested as negative controls to assess the diagnostic validity of this test ***: There was no significant difference in NCT scores and SDT quotients between healthy controls and chronic hepatitis group (P>0.05). In all age subgroups,the NCT and SDT measurements of cirrhotic patients differed significantly from those of the controls (P<0.05).When mean±2SD of SDT and NCT measurements from healthy control group was set as the normal range, 119 cirrhotic patients (29.1%) were found to have abnormal NCT-A and SDT tests, 53 (13.0%) were abnormal only in SDT and 36 (8.8%) only in NCT-A. Taken together, SHE was diagnosed in 208 (50.9%) cirrhotic patients by this test battery. The prevalence of SHE increased from 39.9% and 55.2% in Child-Pugh's grade A and B groups to 71.8% in Child-Pugh's grade C group (P<0.05). After the adjustment of age and residential areas required from the tests, no correlation was found in the rate of SHE and causes of cirrhosis, education level and smoking ***: Psychometric tests are simple and reliable indicators for screening SHE among Chinese cirrhotic patients. By using a NCT and SDT battery, SHE could be found in 50.9% of cirrhotic patients without overt clinical encephalopathy. The prevale

关键词：流行病临床症状肝性脑病肝硬化症中国 NCT-A

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Pathway-based Analysis Tools for Complex Diseases: A Review

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Genomics, Proteomics & Bioinformatics 2014年第5期12卷 210-220页

作者： Lv Jin Xiao-Yu Zuo Wei-Yang Su Xiao-Lei Zhao Man-Qiong Yuan Li-Zhen Han Xiang Zhao Ye-Da Chen Shao-Qi Rao Institute for medical Systems Biology and Department of Medical Statistics and Epidemiology School of Public HealthGuangdong Medical College Department of medical Statistics and Epidemiology School of Public Health Sun Yat-Sen University Community Health Service Management Center of Panyu District Department of Statistical Sciences School of Mathematics and Computational Science Sun Yat-Sen University

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehen- sive understanding of the molecular mechanisms underlying complex diseases. Extensive studies uti- lizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available path- way-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are dis- cussed. This review will provide a useful guide to dissect complex diseases.

关键词： Complex disease Pathway-based analysisAlgorithms Software and databases

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铁死亡参与油酸诱导的小鼠急性肺损伤（英文）

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生理学报 2019年第5期71卷 689-697页

作者：周航李凤牛建一钟伟勇汤敏誉林栋崔洪珲黄学涵陈莹莹王红艳涂永生广州医科大学基础医学院生理教研室广州511436 广州医科大学第一临床学院广州511436 广州医科大学第六临床学院广州511436 广州医科大学基础医学院病理教研室广州511436

本研究旨在探讨铁死亡在油酸(oleic acid, OA)致急性肺损伤(acute lung injury, ALI)小鼠模型中的作用。小鼠尾静脉注射纯OA制备ALI模型,以肺组织病理学评分、肺湿干重比、支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)蛋白含... 详细信息

本研究旨在探讨铁死亡在油酸(oleic acid, OA)致急性肺损伤(acute lung injury, ALI)小鼠模型中的作用。小鼠尾静脉注射纯OA制备ALI模型,以肺组织病理学评分、肺湿干重比、支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)蛋白含量作为ALI的评价指标,用试剂盒检测肺组织的铁浓度、谷胱甘肽(glutathione, GSH)和丙二醛(malondialdehyde, MDA)含量,用透射电子显微镜观察肺细胞的超微结构,用定量PCR (q-PCR)检测肺组织中前列腺素内过氧化物合酶2 (prostaglandin-endoperoxide synthase 2, PTGS2) mRNA表达,用Western blot测定肺组织谷胱甘肽过氧化物酶4 (glutathione peroxidase 4, GPX4)、铁蛋白和转铁蛋白受体1 (transferrin receptor 1, TfR1)的蛋白表达水平。结果表明,OA组小鼠肺组织病理评分、肺湿干重比和BALF中蛋白均高于对照组。OA组小鼠肺细胞线粒体缩小,线粒体膜破裂。与对照组相比,OA组PTGS2 mRNA表达增加7倍。OA组小鼠肺组织出现铁过载、GSH含量减少和MDA累积。与对照组相比,OA组小鼠肺组织GPX4和铁蛋白表达水平下调。以上结果提示,铁死亡可能在ALI发病机制中发挥作用,这为治疗ALI的新药开发提供了新的角度。

关键词：铁死亡油酸急性肺损伤谷胱甘肽谷胱甘肽过氧化物酶4 铁

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Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

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Genomics, Proteomics & Bioinformatics 2014年第1期12卷 31-38页

作者： Xiaolei Zhao Shouqiang Zhong Xiaoyu Zuo Meihua Lin Jiheng Qin Yizhao Luan Naizun Zhang Yan Liang Shaoqi Rao Institute for medical Systems Biology and Department of medical Statistics and Epidemiology School of Public HealthGuangdong Medical College Maoming People’s Hospital Department of medical Statistics and Epidemiology School of Public HealthSun Yat-Sen University

Many cancers apparently showing similar phenotypes are actually distinct at the molecular level,leading to very different responses to the same *** has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of ***,it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in ***,we aimed to test this possibility in the present ***,we used a NCI60 dataset to validate the ability of pathways to correctly partition ***,we applied the proposed method to identify the hidden subtypes in diffuse large B-cell lymphoma （DLBCL）.Finally,the clinical significance of the identified subtypes was verified using survival *** the NCI60 dataset,we achieved highly accurate partitions that best fit the clinical cancer ***,for a DLBCL dataset,we identified three hidden subtypes that showed very different 10-year overall survival rates （90％,46％ and 20％） and were highly significantly （P =0.008） correlated with the clinical survival *** study demonstrated that the pathwaybased approach is promising for unveiling genetic heterogeneities in complex human diseases.

关键词： Genetic heterogeneity Pathway-based approach Sample partitioning Enrichment analysis Survival analysis Cancer

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Curcumin ameliorates hippocampal neuron damage induced by human immunodeficiency virus-1

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Neural Regeneration Research 2013年第15期8卷 1368-1375页

作者： Hongmei Tang Rui Pan Wenli Fang Yanyan Xing Dexi Chen Xiaobao Chen Yuanyuan Yu Junbing Wang Zheng Gong Guoyin Xiong Jun Dong Department of Pathophysiology Key Laboratory of State Administration of Traditional Chinese Medicine Medical College of Jinan University Institute of Brain Research Medical College of Jinan University Joint Laboratory for Brain Function and Health of Jinan University and the University of Hong Kong Department of Orthopedics First Affiliated Hospital Medical College of Jinan University STD/AIDS Research Lab Beijing Youan Hospital Capital Medical University

Our previous studies have shown that infection with the gp120 V3 loop can cause human immunodeficiency virus-1 associated neurocognitive disorders. Curcumin has been shown to improve these effects to some degree, but the precise mechanisms remain unknown. The present study analyzed the neuroprotective effect and mechanism of curcumin in relation to hippocampal neurons. Results showed that 1 nmol/L gp120 V3 loop suppressed the growth of synapses. After administration of 1 !umol/L curcumin, synaptic growth improved. Curcumin is neuroprotective against gp120 V3 loop-induced neuronal damage by inhibiting the activation of L-type calcium currents, relieving intracellular Ca^2＋ overload, promoting Bcl-2 expression, and inhibiting Bax activation. The effect of curcumin was identical to nimodipine, suggesting that curcumin has the same neuroprotective effects against gp120 V3 loop-induced neuronal damage.

关键词： neural regeneration traditional Chinese medicine curcumin gp120 V3 loop humanimmunodeficiency virus-1 associated neurocognitive disorders Ca^2+ synapse apoptosis grants-supported paper neuroregeneration

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丝裂霉素C诱导小鼠NIH-3T3细胞出现衰老相关分泌表型

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生理学报 2017年第1期69卷 33-40页

作者：黄炜幸郭晓璇彭忠智翁春亮黄春燕石本艳杨杰廖小欣李晓毅郑慧玲刘新光孙雪荣广东医科大学东莞科研中心衰老研究所广东医科大学第二临床学院广东省医学分子诊断重点实验室东莞523808 广东医科大学医学检验学院生物化学与分子生物学研究所湛江524023

衰老相关分泌表型(senescence-associated secretory phenotype,SASP)是指随细胞衰老而出现的分泌功能亢进,其分泌的因子参与细胞衰老、免疫调节、血管生成、细胞增殖及肿瘤侵袭等过程。与人类细胞相比,目前小鼠细胞的体外SASP模型尚十... 详细信息

衰老相关分泌表型(senescence-associated secretory phenotype,SASP)是指随细胞衰老而出现的分泌功能亢进,其分泌的因子参与细胞衰老、免疫调节、血管生成、细胞增殖及肿瘤侵袭等过程。与人类细胞相比,目前小鼠细胞的体外SASP模型尚十分缺乏,而建立该模型将为研究SASP的发生机制及生物学作用提供便利。为此,本文以INK4a基因座缺失(编码p16INK4a蛋白)的小鼠NIH-3T3细胞系及野生型小鼠胚胎成纤维细胞(mouse embryonic fibroblasts,MEF)为研究对象,用丝裂霉素C(mitomycin C,MMC)诱导细胞DNA损伤,并通过细胞形态、衰老相关β-半乳糖苷酶(β-gal)活性染色、Ed U整合率、Western blot、定量RT-PCR及ELISA等检测方法,观察细胞的衰老情况及SASP因子的表达和分泌水平。结果显示,MMC(1μg/m L)处理12 h或24 h,并继续培养到第8天后,NIH-3T3细胞体积变大,β-gal染色阳性(蓝染)细胞的百分率明显升高,分别达到77.4%和90.4%,并伴有P21蛋白表达上调及Ed U整合率下降(P<0.01)。同时,IL-6、TNF-α、IL-1α和IL-1β等常见SASP基因的m RNA表达水平显著上调,ELISA检测证明IL-6的分泌量亦显著升高(P<0.01)。相反,尽管MMC处理12 h或24 h也能诱导野生型MEF出现细胞体积增大、β-gal染色阳性率升高(分别达71.7%和80.2%)及P21表达上调,但其IL-6的分泌量无显著上升。本研究表明,MMC能诱导NIH-3T3和野生型MEF出现细胞衰老,但只有NIH-3T3细胞出现了典型的SASP现象。衰老NIH-3T3细胞可能是研究小鼠SASP的合适模型。

关键词：细胞衰老小鼠衰老相关分泌表型 p16INK4a 成纤维细胞

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