AIM： To correlate the polymorphisms in the 5＇-untranslated region with thymidylate synthase （TS） protein expression in Han Chinese colonic neoplasms. METHODS： Adenocarcinoma samples were from 68 patients who rece...AIM： To correlate the polymorphisms in the 5＇-untranslated region with thymidylate synthase （TS） protein expression in Han Chinese colonic neoplasms. METHODS： Adenocarcinoma samples were from 68 patients who received no treatment before surgery. Tandem repeat length of TS gene was determined by PCR amplification of genomic DNA. Intratumoral TS protein expression was studied immunohistochemically in corresponding sections from paraffin-embedded primary loci. Immunoreactivity was semiquantitatively evaluated by immunoreactivity score （IRS）. RESULTS： Double-（2R） and triple-repeated （3R） sequences of the TS gene were found in the cancer tissues. Three genotypes of TS were found： 2R/2R （n = 6）, 2R/3R （n = 22） and 3R/3R （n = 40）. Patients who were homozygous for triple-repeated （3R/3R） sequences showed significantly higher IRS of TS than patients who were homozygous for double-repeated （2R/2R） sequences or heterozygous patients （2R/3R）： 5.73 ±3.25 vs 2.17 ± 1.47 or 3.77 ±2.64, P = 0.008 or P = 0.015. But no statistical significance of IRS in cancer tissues was observed between 2R/3R genotype and 2R/2R genotype. CONCLUSION： There is a relationship between TS genotype and TS protein expression in clinical specimens. The data might offer an advantage for selection of Chinese cancer patients to receive fluoropyrimidines treatment.展开更多
AIM: To assess the expression and prognostic value of nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) in gastric cancer, and its correlation with vascular endothelial growth factor(VEGF) and epidermal grow...AIM: To assess the expression and prognostic value of nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) in gastric cancer, and its correlation with vascular endothelial growth factor(VEGF) and epidermal growth factor receptor(EGFR).METHODS: Tumor and adjacent tissues were obtained from 123 patients who underwent radical surgery for gastric cancer at Renmin Hospital of Wuhan University from 2008-2009. The expression of NOX2, VEGF, EGFR and CD68 in tumor tissues was detected by immunohistochemistry. The expression of NOX2 in gastric cancer and adjacent tissues was detected by Western blot analysis. Spearman's correlation was performed to elucidate the relationship of NOX2 with VEGF and EGFR. The Kaplan-Meier method was used to calculate survival time, and the log-rank test was used to evaluate differences in survival. Cox‘s proportional hazards regression model was applied in a stepwise manner to analyze the independent prognostic factors.RESULTS: NOX2 exhibited positive expression in 47.2%(58/123) of the gastric cancer tissues. Western blot analysis revealed that NOX2 was up-regulated in tumor tissues compared to the adjacent tissue [39.0%(48/123)]. Immunohistochemistry staining revealed that CD68, which is a specific marker of macrophages, and NOX expression presented a similar localization and staining intensity. The expression of NOX2 was positively correlated with that of VEGF and EGFR. Comparison of the 5-year survival rates of the NOX2 positive and NOX2 negative groups showed that the NOX2 positive group presented a poor prognosis.CONCLUSION: NOX2 positively correlates with the levels of VEGF and EGFR. NOX2 may be used as a new biomarker and a potential therapeutic target for gastric cancer.展开更多
Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 pr...Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis.Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines.The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequeucing analysis.Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR.Results:HIC analysis indicated that HtrA1 was highly expressed in normal epithelium,but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues.HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to nontumorigenic counterparts.The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected.Total 14 CpGs in this region were all methylated in gastric cancer cells,whereas two normal cells.GES-1 and HFI-145,were having several unmethylated cytosines in this region.HtrA1 showed as^Mr 44,000,Expression of HtrA1 protein was not observed in any of the four gastric caucer cell lines.BGC-823.MKN-45.SGC-7901and MKN-28.HtrA1 expression was observed in the HF1-145and GES-1 cell lines.Conclusions:The epigenetic silencing for HtrA1gene expression could provide a possible strategy for re-activating Htrt1 gene expression in gastric cancer cells.thus facilitating further investigation of HtrA1's role in chemotherapy.展开更多
Micro RNAs（mi RNAs） are known to regulate post-transcriptional gene expression.They are involved in carcinogenesis and tumor progression.The aim of this study was to explore the micro RNA-m RNA regulatory network in...Micro RNAs（mi RNAs） are known to regulate post-transcriptional gene expression.They are involved in carcinogenesis and tumor progression.The aim of this study was to explore the micro RNA-m RNA regulatory network in esophageal squamous cell carcinoma（ESCC） using comprehensive computational approaches.In this study we have selected a total of 11 mi RNAs from one previously reported study in ESCC.The m RNA targets of these mi RNAs were predicted using various algorithms.The expression profiles of these m RNA targets were identified on DNA microarray experiment dataset across ESCC tissue samples.Based on the mi RNA-m RNA regulatory relationships,the network was inferred.A total of 23 mi RNA-m RNA regulatory interactions,with 11 mi RNAs and 13 m RNA targets,were inferred in ESCC.The mi RNA-m RNA regulatory network with increased confidence provides insights into the progression of ESCC and may serve as a biomarker for prognosis or the aggressiveness of ESCC.However,the results should be examined with further experimental validation.展开更多
文摘AIM： To correlate the polymorphisms in the 5＇-untranslated region with thymidylate synthase （TS） protein expression in Han Chinese colonic neoplasms. METHODS： Adenocarcinoma samples were from 68 patients who received no treatment before surgery. Tandem repeat length of TS gene was determined by PCR amplification of genomic DNA. Intratumoral TS protein expression was studied immunohistochemically in corresponding sections from paraffin-embedded primary loci. Immunoreactivity was semiquantitatively evaluated by immunoreactivity score （IRS）. RESULTS： Double-（2R） and triple-repeated （3R） sequences of the TS gene were found in the cancer tissues. Three genotypes of TS were found： 2R/2R （n = 6）, 2R/3R （n = 22） and 3R/3R （n = 40）. Patients who were homozygous for triple-repeated （3R/3R） sequences showed significantly higher IRS of TS than patients who were homozygous for double-repeated （2R/2R） sequences or heterozygous patients （2R/3R）： 5.73 ±3.25 vs 2.17 ± 1.47 or 3.77 ±2.64, P = 0.008 or P = 0.015. But no statistical significance of IRS in cancer tissues was observed between 2R/3R genotype and 2R/2R genotype. CONCLUSION： There is a relationship between TS genotype and TS protein expression in clinical specimens. The data might offer an advantage for selection of Chinese cancer patients to receive fluoropyrimidines treatment.
基金Supported by National Natural Science Foundation of China,No.81370562
文摘AIM: To assess the expression and prognostic value of nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) in gastric cancer, and its correlation with vascular endothelial growth factor(VEGF) and epidermal growth factor receptor(EGFR).METHODS: Tumor and adjacent tissues were obtained from 123 patients who underwent radical surgery for gastric cancer at Renmin Hospital of Wuhan University from 2008-2009. The expression of NOX2, VEGF, EGFR and CD68 in tumor tissues was detected by immunohistochemistry. The expression of NOX2 in gastric cancer and adjacent tissues was detected by Western blot analysis. Spearman's correlation was performed to elucidate the relationship of NOX2 with VEGF and EGFR. The Kaplan-Meier method was used to calculate survival time, and the log-rank test was used to evaluate differences in survival. Cox‘s proportional hazards regression model was applied in a stepwise manner to analyze the independent prognostic factors.RESULTS: NOX2 exhibited positive expression in 47.2%(58/123) of the gastric cancer tissues. Western blot analysis revealed that NOX2 was up-regulated in tumor tissues compared to the adjacent tissue [39.0%(48/123)]. Immunohistochemistry staining revealed that CD68, which is a specific marker of macrophages, and NOX expression presented a similar localization and staining intensity. The expression of NOX2 was positively correlated with that of VEGF and EGFR. Comparison of the 5-year survival rates of the NOX2 positive and NOX2 negative groups showed that the NOX2 positive group presented a poor prognosis.CONCLUSION: NOX2 positively correlates with the levels of VEGF and EGFR. NOX2 may be used as a new biomarker and a potential therapeutic target for gastric cancer.
基金supported by Natural Science and Technology Fund of Hubei Povince(012726334)
文摘Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis.Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines.The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequeucing analysis.Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR.Results:HIC analysis indicated that HtrA1 was highly expressed in normal epithelium,but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues.HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to nontumorigenic counterparts.The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected.Total 14 CpGs in this region were all methylated in gastric cancer cells,whereas two normal cells.GES-1 and HFI-145,were having several unmethylated cytosines in this region.HtrA1 showed as^Mr 44,000,Expression of HtrA1 protein was not observed in any of the four gastric caucer cell lines.BGC-823.MKN-45.SGC-7901and MKN-28.HtrA1 expression was observed in the HF1-145and GES-1 cell lines.Conclusions:The epigenetic silencing for HtrA1gene expression could provide a possible strategy for re-activating Htrt1 gene expression in gastric cancer cells.thus facilitating further investigation of HtrA1's role in chemotherapy.
基金supported by grants from Natural Science Foundation of Hubei Province,China(No.2010CDB09204)Youth Dawn Plan of Science and Technology in Wuhan,China(No.201150431137)
文摘Micro RNAs（mi RNAs） are known to regulate post-transcriptional gene expression.They are involved in carcinogenesis and tumor progression.The aim of this study was to explore the micro RNA-m RNA regulatory network in esophageal squamous cell carcinoma（ESCC） using comprehensive computational approaches.In this study we have selected a total of 11 mi RNAs from one previously reported study in ESCC.The m RNA targets of these mi RNAs were predicted using various algorithms.The expression profiles of these m RNA targets were identified on DNA microarray experiment dataset across ESCC tissue samples.Based on the mi RNA-m RNA regulatory relationships,the network was inferred.A total of 23 mi RNA-m RNA regulatory interactions,with 11 mi RNAs and 13 m RNA targets,were inferred in ESCC.The mi RNA-m RNA regulatory network with increased confidence provides insights into the progression of ESCC and may serve as a biomarker for prognosis or the aggressiveness of ESCC.However,the results should be examined with further experimental validation.
