徐顺清
进行环境污染对人体健康危害的生物标志物研究
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- 姓名:徐顺清
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学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
- 职称:-
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学科领域:
劳动卫生学
- 研究兴趣:进行环境污染对人体健康危害的生物标志物研究
徐顺清教授,1966年3月出生,1993年毕业于同济医科大学,1993年获博士学位,1999年被破格晋升为同济医科大学教授,2000年被聘为博士生导师,现任国家环境保护总局武汉环境医学研究所副所长。1999年和2002年分别赴德国Max-Planck生物化学研究所和Tuebingen大学进行访问研究,与德国有良好的国际合作关系。主要进行环境污染对人体健康危害的生物标志物研究。先后承担国家863项目1项、国家自然科学基金重大项目子课题1项、面上项目8项、海外青年合作基金1项,“九五”国家科技攻关计划专题1项,“十五”国家科技攻关计划专题1项,此外还承担了数项省部级课题。先后发表论文100多篇,其中SCI论文20余篇,ISTP收录7篇。获湖北省科技进步二等奖1项,获国家专利一项,1998年获霍英东教育基金会全国高等院校优秀青年教师奖,1999年获卫生部优秀青年科技人才奖,2004年入选教育部跨世纪优秀人才支持计划。代表性成果有:⑴ 酶切保护分析检测痕量二恶英化合物,在国际上率先建立了一种全新的超痕量二恶英生物分析方法,其检测灵敏度可达10-15g/L,申请了国家专利,该成果以快报的形式发表于国际毒理学学权威期刊Toxicological Science(影响因子3.3)。该方法在二恶英的生物检测方法方面有较大的突破,灵敏度提高了2-3个数量级,引起了国际同行的广泛关注,并具有广阔的应用前景和商业价值;⑵ 利用aptamer建立了一种高灵敏度的蛋白质检测新方法,具有广泛的应用价值,该成果发表与国际分析化学顶级杂志Analytical Chemistry(影响因子5.3);⑶ 在国际上率先利用生物发光技术建立了一种不依赖于TRAP的端粒酶活性定量检测方法,该方法被 国际权威期刊Clinical Chemistry(影响因子4.8)作为封面标题论文发表;⑷ 水污染对人群健康危害的预警研究,获得湖北省科技进步二等奖。
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【期刊论文】DNA repair gene XRCC1 polymorphisms, smoking, and esophageal cancer risk
徐顺清, Hong-Ping Yu, MD, Ph.D a, Xiao-Yong Zhang, MD b, Xiao-Li Wang, MD a, Lu-Yuan Shi, BS c, Yuan-Yuan Li, Fang Li, Yan-Hua Su, You-Jie Wang, Bin Lu, Xi Sun, Wen-Hong Lu, BS a, Shun-Qing Xu, *
Cancer Detection and Prevention 28(2004)194-199,-0001,():
-1年11月30日
To investigate the effect of X-ray repair cross complementing 1 (XRCC1) genetic polymorphisms on esophageal cancer risk, we determined XRCC1 polymorphisms at codon 194 (Arg→Trp) and codon 399 (Arg→Gln) in 135 patients with esophageal squamous cell carcinoma (ESCC) and 152 normal controls from hospitals. Although polymorphism at codon 194 was not associated with risk for ESCC, we found that the frequency of XRCC1 399 Gln/Gln genotype in ESCC patients (14.1%) was significantly higher than that in normal controls (3.3%), and that XRCC1 399 Gln/Gln genotype was associated with an increased risk of ESCC (odds ratio (OR)=5.15, 95% confidence interval (CI): 2.42-0.93). In addition, we found that the risk for smoker increased 4.2-fold than non-smokers in the 399 Gln/Gln genotype (OR=4.20, 95% CI: 2.37-7.44). These results suggest that XRCC1 399 Gln/Gln genotype may contribute to the risk of ESCC and modify risk associated with smoking.
Esophageal cancer, Genetic polymorphism, Susceptibility, XRCC1 gene, Molecular epidemiology
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【期刊论文】Ultrasensitive Detection of Protein Using an Aptamer-Based Exonuclease Protection Assay
徐顺清, Xiao-Li Wang, † Fang Li, † Yan-Hua Su, † Xi Sun, † Xiao-Bo Li, † Hermann J. Schluesener, ‡ Fei Tang, † and Shun-Qing Xu*, †
Anal. Chem. 2004, 76, 5605-5610,-0001,():
-1年11月30日
Currently, methods for protein detection are not as sensitive and specific as methods for detection of specific nucleic acid sequences. Here, we present an analogous technique for detection of proteins using aptamers as ligands for target binding. We have named this method the aptamer-based exonuclease protection assay. We applied a special oligonucleotide probe containing a thrombin aptamer, which has the capacity to recognize thrombin with high affinity and specificity. The aptamer probe is a 22-base-long single-strand oligonucleotide with the thrombin aptamer sequence at the 3
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【期刊论文】Cyclooxygenase-2 expression in squamous dysplasia and squamous cell carcinoma of the esophagus
徐顺清, Hong-Ping Yu a, Shun-Qing Xu a, *, Li Liu b, Lu-Yuan Shi c, Xiao-Kun Cai a, Wen-Hong Lu a, Bin Lu a, Yan-Hua Su a, Yuan-Yuan Li a
Cancer Letters 198(2003)193-201,-0001,():
-1年11月30日
Cyclooxygenase-2 (cox-2) overexpression has been observed in several types of human cancers and has been implicated in carcinogenesis. To elucidate the role of cox-2 in esophageal carcinogenesis, we evaluated the expression of cox-2 in normal squamous epithelium squamous epithelial dysplasia
Cyclooxygenase-2, Esophagus, Squamous epithelial dysplasia, Squamous cell carcinoma, Immunohistochemistry
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徐顺清, HONG-PING YU, * LU-YUAN SHI, † WEN-HONG LU, * YAN-HUA SU, * YUAN-YUAN LI * AND SHUN-QING XU *
Journal of Gastroenterology and Hepatology (2004) 19, 638-642,-0001,():
-1年11月30日
Background: The purpose of the present paper was to study the expression of cyclooxygenase-2 (COX-2) in normal squamous epithelium, squamous dysplasia and squamous cell carcinoma (SCC) of the esophagus, to elucidate the role of COX-2 in esophageal carcinogenesis, and to evaluate the in vitro effect and mechanism of a COX-2 inhibitor, NS-398, in inducing growth inhibition and apoptosis of human esophageal cancer cells. Methods: Biopsy specimens of esophageal dysplasia (n=21), and surgical resections of SCC (n=37) were compared with normal esophagus (n=37) and analyzed by RT-PCR. Human esophageal cells were used for the study. Anti-proliferative effect was measured by MTT, apoptosis was determined by DNA fragmentation assay. Results: Marked COX-2 expression was shown in SCC and esophageal squamous dysplasia, and no marked COX-2 expression was observed in the normal squamous epithelium, respectively. NS-398 could inhibit esophageal cells growth in a dose-dependent manner, induce apoptosis, and elevate caspase-3 activity in vitro. Conclusions: This study provides evidence that COX-2 is upregulated in the majority of cases of squamous dysplasia and SCC of esophagus, and that NS-398 can inhibit growth and induce apoptosis via activating caspase-3 activity in vitro. These results suggest that selective inhibitors of COX-2 may be an effective preventive and therapeutic option for esophageal carcinoma.
apoptosis,, cyclooxygenase-2,, esophageal squamous cell carcinoma,, inhibitor,, NS-398.,
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徐顺清, Zhi-Ren Zhang, Shun-Qing Xu, Xi Sun, Yong-Jun Xu, Xiao-Kun Cai, Zhi-Wei Liu, Xiang-Lin Tan, Yi-Kai Zhou, Jun-Yue Zhang, Hong Yan, Zhi-Ren Zhang
World J Gastroenterol 2003; 9 (7): 1460-1464,-0001,():
-1年11月30日
AIM: To establish a luciferase reporter cell line that responds dioxin-like chemicals (DLCs) and on this basis to evaluate its characteristics and application in the determination of DLCs. METHODS: A recombinant luciferase reporter plasmid was constructed by inserting dioxin-responsive element (DREs) and MMTV promoter segments into the pGL3-promoter plasmid immediately upstream of the luciferase gene, which was structurally demonstrated by fragment mapping analysis in gel electrophoresis and transfected into the human hepatoma cell line HepG2, both transiently and stably, to identify the inducible expression of luciferase by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). The time course, responsive period, sensitivity, structure-inducibility and doseeffect relationships of inducible luciferase expression to DLCs was dynamically observed in HepG2 cells stably transfected by the recombinant vector (HepG2-Luc) and compared with that assayed by ethoxyresorufin-O-deethylase (EROD) in non-transfected HepG2 cells (HepG2-wt). RESULTS: The inducible luciferase expression of HepG2-Luc cells was noted in a time-, dose-, and AhR-dependent manner, which peaked at 4 h and then decreased to a stable level at 14 h after TCDD treatment. The responsiveness of HepG2-Luc cells to TCDD induction was decreased with culture time and became undetectable at 10th month of HepG2-Luc cell formation. The fact that luciferase activity induced by 3, 3', 4, 4'-PCB in HepG2-Luc cells was much less than that induced by TCDD suggests a structureinducibility relationship existing among DLCs. Within the concentrations from 3.5
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【期刊论文】Bioluminescent Method for Detecting Telomerase Activity
徐顺清, Shun-Qing Xu, * Min He, Hong-Ping Yu, Xiao-Yang Wang, Xiang-Lin Tan, Bin Lu, , Xi Sun, Yi-Kai Zhou, Qun-Feng Yao, Yong-Jun Xu, and Zhi-Ren Zhang
Clinical Chemistry 48: 7 1016-1020 (2002),-0001,():
-1年11月30日
Background: Telomerase is a promising biomarker in cancer diagnosis and therapy. The elongation of telomeric repeats catalyzed by telomerase is accompanied by release of six PPi for each TTAGGG repeat (1 pmol PPi/310 pg telomeric repeats). We developed a novel method to measure telomerase activity by use of an enzymatic luminometric PPi assay (ELIPA). Methods: Extracts of cell lines and tissues were incubated with primer at 30℃ for 30min. Released PPi was converted to ATP by sulfurylase, and ATP was detected by a luciferase bioluminescence system. The ELIPA results were compared with results obtained with the conventional telomeric repeat amplification (TRAP)-ELISA in 42 lung carcinoma tissues and 27 control tissues without malignancy. Results: The lower detection limits of ELIPA and TRAP-ELISA were 5 and 10 cells, respectively. The within-run imprecision (CV) of ELIPA was <12%. When compared with TRAP-ELISA, the correlation coefficient (r) was 0.79. When we used the cutoff value from ROC analysis to distinguish malignant and nonmalignant tissues, the sensitivity and specificity of ELIPA were 83% and 96%, respectively, whereas the sensitivity and specificity of TRAP-ELISA were 71% and 96%, respectively. Conclusion: ELIPA is a simple and sensitive homogeneous method to quantify telomerase activity.
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徐顺清, Xi Sun, Fang Li, You-jie Wang, Yi-rong Li, Yan-hua Su, Yuan-yuan Li, Hong Yan, and Shun-qing Xu
TOXICOLOGICAL SCIENCES 80, 49-53 (2004),-0001,():
-1年11月30日
The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biological and toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. Here we developed a novel method to detect the presence of AhR ligands using Exonuclease Protection Mediated PCR bioassay (EPM-PCR). This assay measures the ability of a chemical to activate AhR DNA binding in vitro. In the presence of AhR ligand, an expected length PCR product was observed on electrophoresis, but no signal was detected in the absence of ligand. Real-time quantitative PCR was performed to quantifyDNA bound to ligand:AhR complex. We obtained a standard curve with TCDD concentration to bound DNA copies in the range of 0.01pM-10nM of TCDD. Minimal detection limit of the assay was below 0.01pM TCDD, and the whole detection time was less than 5h. In comparison to the chemical-activated luciferase gene expression (CALUX) bioassay, EPM-PCR bioassay is more sensitive and easier to perform. These results suggest that this assay is useful for detection and quantification of TCDD and related AhR ligands in a cell-free system without the use of radioactivity.
Ah receptor, 2,, 3,, 7,, 8- TCDD, exonuclease Ⅲ, S1 nuclase, real-time PCR.,
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徐顺清, HONG-PING YU, SHUN-QING XU, * WEN-HONG LU, YUAN-YUAN LI, FANG LI, XIAO-LI WANG, AND YAN-HUA SU
Journal of Surgical Oncology 2004; 86: 99-104,-0001,():
-1年11月30日
Background: Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Activation of telomerase plays a key role in the malignant transformation process. The aim of this study was to study the regulation of telomerase, and to explore the possibility of telomerase as a biomarker in squamous carcinogenesis of the esophagus. Methods: Twenty-nine esophageal squamous cell carcinomas (ESCC) and its corresponding adjacent normal tissues, and 47 epithelial squamous dysplasia tissues were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique for the mRNA expression of three major telomerase subunits: human telomerase RNA (hTR), telomerase protein component 1 (TP1), and human telomerase reverse transcriptase (hTERT) and by telomeric repeat amplification protocol assay (TRAP) for telomerase activity. Results: For the expression of hTR and TP1 mRNA, there were no significant differences among ESCC, dysplasia and normal tissues (P>0.05). In contrast, hTERT mRNA expression was detected in 28 of 29 ESCC (96.6%), in 23 of 47 dysplasia (48.9%), and only in two of 29 normal tissues (7.5%). Telomerase activity was positive in 25 of 29 ESCC (86.2%), in 21 of 47 (44.7%) epithelial dysplasia tissues, and in none of normal tissue. All together, 95 of 105 cases (90.48%) were concordant for both results, i.e., telomerase activity positive and hTERT positive or telomerase activity negative and hTERT negative tissues, and telomerase activity correlated with hTERT mRNA expression (P<0.001). Conclusions: Higher telomerase activity and hTERT mRNA expression were shown during an early stage in the esophageal carcinogenesis. Activation of telomerase activity was strongly correlated with hTERT mRNA expression, suggesting hTERT is a major regulator of telomerase activity, and telomerase activation may play a critical role in esophageal carcinogenesis. Therefore, telomerase, especially hTERT can be used as a potential molecular biomarker of ESCC.
telomerase, esophagus, squamous cell carcinoma, carcinogenesis
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徐顺清, Shunqing Xu, Min He, Hongping Yu, Xiaokun Cai, Xianglin Tan, Bin Lu, and Baihua Shu
Analytical Biochemistry 299, 188-193 (2001),-0001,():
-1年11月30日
Telomerase is expected to be a new biomarker for cancer diagnosis. The telomeric repeat amplification protocol (TRAP) is a sensitive method to detect telomerase activity. However, TRAP and its modified protocols are not always suitable for measuring telomerase activity of a large number of clinical samples to diagnosis cancer because these methods generally require a time-consuming detection step such as gel electrophoresis. To improve the procedure for mass diagnosis, we applied bioluminescence to replace the detection step. Telomerase activity is measured by evaluating the amount of inorganic pyrophosphate generated in PCR amplification of telomerase elongation product, with use of the sensitive enzymatic luminometric inorganic pyrophosphate detection assay (ELIDA). TRAP connected with ELIDA (TRAP-ELIDA) can quantitatively detect telomerase activity within linearity from 2 to 1000 cell equivalents. The ELIDA signals accorded with results of TRAP-SYBR green staining, and the results of ELIDA were significantly correlated to those of TRAP connected with an enzymelinked immunosorbent assay (TRAP-ELISA) (250.992, P<0.001). TRAP-ELIDA is a simple and sensitive method to quantify telomerase activity without time-consuming gel electrophoresis. Because TRAP-ELIDA measures telomerase activity with a luminometer, it could be applied to a large number of clinical samples at the same time.
telomerase, TRAP assay, bioluminescence, pyrophosphate.,
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徐顺清, Hong-Ping Yu a, Xiao-Li Wang a, Xi Sun a, Yan-Hua Su a, You-Jie Wang a, Bin Lu a, Lu-Yuan Shi b, Chun-lan Xiong c, Yuan-Yuan Li a, Fang Lia, Shun-Qing Xu a, *
Cancer Genetics and Cytogenetics 154(2004)10-15,-0001,():
-1年11月30日
Polymorphisms of the nucleotide excision repair gene XPD are candidates for influencing cancer susceptibility. To determine the effect of XPD genetic polymorphisms on the risk of esophageal squamous cell carcinoma (ESCC) and its interaction with carcinogen exposure, XPD polymorphisms at codon 312 (Asp→Asn) and codon 751 (Lys→Gln) were determined in 135 ESCC patients and 152 normal controls. Polymorphism at codon 312 made no contribution to genetic risk for ESCC. Our results showed that there was a significant difference between frequencies for XPD 751 Gln/Gln genotype in ESCC patients (8.9%) and normal cases (1.3%), and that Gln/Gln genotype was associated with an increased risk of ESCC (odds ratio [OR]=6.71; 95% confidence interval [CI]: 1.90-23.73). The results of the logistic regression model showed that XPD 751 Gln/Gln genotype and drinking were candidates for influencing the risk of ESCC. Among smokers, the risk of ESCC in XPD 751 Gln/Gln genotype increased 8-fold than that XPD 751 Lys/Lys genotype (OR=8.42, 95% CI: 1.02-69.58). The results indicated that XPD 751 Gln/Gln genotype may be contributing factors in the risk of ESCC and may modify risk attributable to environmental exposures.
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