目的:基于TCGA和GTEx数据库探讨人免疫球蛋白γ-1重链恒定区(immunoglobulin γ-1 heavy chain constantreg ion,IGHG1)基因在皮肤黑色素瘤中的表达及其临床价值。方法:应用Wilcox检验和logistic回归分析IGHG1与临床病理特征之间的关系...目的:基于TCGA和GTEx数据库探讨人免疫球蛋白γ-1重链恒定区(immunoglobulin γ-1 heavy chain constantreg ion,IGHG1)基因在皮肤黑色素瘤中的表达及其临床价值。方法:应用Wilcox检验和logistic回归分析IGHG1与临床病理特征之间的关系。应用Cox回归和Kaplan-Meier法分析皮肤黑色素瘤患者的临床病理特征与总生存率的关系。使用基因集富集分析(gene set enrichment analysis,GSEA)探索IGHG1基因在皮肤黑色素瘤进展中的潜在机制。结果:与正常皮肤组织相比,皮肤黑色素瘤组织中IGHG1基因呈现高表达。皮肤黑色素瘤患者IGHG1表达量与T分期及临床分期有统计学意义(P<0.001);Kaplan-Meier生存分析表明IGHG1高表达明显优于低表达患者(P<0.001);单因素Cox分析显示IGHG1高表达能改善患者预后(P=0.002);多因素Cox回归分析显示IGHG1表达情况可作为皮肤黑色素瘤患者预后的独立指标(P=0.014)。GSEA显示T细胞受体信号通路、JAK-STAT信号通路等表型和信号通路在IGHG1高表达组发生不同程度的富集。结论:IGHG1表达量与皮肤黑色素瘤患者预后有显著相关性,并参与调节多种免疫学通路,影响肿瘤的发生、发展。展开更多
AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathologica...AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, α-catenin, β-catenin, γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS：The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression ratewas 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x^2=4.183 and x^2=5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (x^2=5.769, P<0.05). Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and inreduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.展开更多
Recent studies have revealed that the γ-chain of theIL-2 receptor is shared by the receptors for IL-4, IL7, IL-9, IL-13, and IL-15, and it is therefore also referred toas the common γ-chain (γc). Mutations of γc r...Recent studies have revealed that the γ-chain of theIL-2 receptor is shared by the receptors for IL-4, IL7, IL-9, IL-13, and IL-15, and it is therefore also referred toas the common γ-chain (γc). Mutations of γc result inX-linked severe combined immunodeficiency syndrome inhumans, indicating that rye is essential for normal development and function of the immune system. We demonstratethat human hematopoietic cells express two γc transcriptsdiffering in their carboxyl terminal coding region. Onetranscript is the previously reported sequence (γc-long),whereas the newly identified sequence exhibits a deletion of72 nucleotides close to the 3’-end of the open reading frame(γc-short). This alteration predicts a loss of 24 amino acidsincluding a conserved tyrosine residue which is shared byseveral members of the cytokine receptor family. Thepresence of these two distinct forms of rye transcripts wasdemonstrated by sequencing of reversely transcribed andpolymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines andhuman peripheral blood lymphocytes. Furthermore, thetwo variants were present in peripheral blood lymphocytesfrom both female and male donors, which rules out allelicvariants since rye is a single copy gene located on the Xchromosome. A truncation mutant at a site near the observed changes in γc-short has been reported by othersto alter biochemical events activated by cytokines. Thiscombined with the loss of a potential SH2 "docking" sitein γc-short suggests that γc-long and γc-short may link todifferent signaling pathways and may play an importantrole in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.展开更多
Objective To investigate the roles of the y-aminobutyric acid （GABA） in the metastasis of hepatocellular carcinoma （HCC） and to explore the potential of a novel therapeutic approach for the treatment of HCC. Metho...Objective To investigate the roles of the y-aminobutyric acid （GABA） in the metastasis of hepatocellular carcinoma （HCC） and to explore the potential of a novel therapeutic approach for the treatment of HCC. Methods The expression levels of GABA receptor subunit genes in various HCC cell lines and patients＇ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. Results The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABAA receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. Conclusions These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.展开更多
文摘目的:基于TCGA和GTEx数据库探讨人免疫球蛋白γ-1重链恒定区(immunoglobulin γ-1 heavy chain constantreg ion,IGHG1)基因在皮肤黑色素瘤中的表达及其临床价值。方法:应用Wilcox检验和logistic回归分析IGHG1与临床病理特征之间的关系。应用Cox回归和Kaplan-Meier法分析皮肤黑色素瘤患者的临床病理特征与总生存率的关系。使用基因集富集分析(gene set enrichment analysis,GSEA)探索IGHG1基因在皮肤黑色素瘤进展中的潜在机制。结果:与正常皮肤组织相比,皮肤黑色素瘤组织中IGHG1基因呈现高表达。皮肤黑色素瘤患者IGHG1表达量与T分期及临床分期有统计学意义(P<0.001);Kaplan-Meier生存分析表明IGHG1高表达明显优于低表达患者(P<0.001);单因素Cox分析显示IGHG1高表达能改善患者预后(P=0.002);多因素Cox回归分析显示IGHG1表达情况可作为皮肤黑色素瘤患者预后的独立指标(P=0.014)。GSEA显示T细胞受体信号通路、JAK-STAT信号通路等表型和信号通路在IGHG1高表达组发生不同程度的富集。结论:IGHG1表达量与皮肤黑色素瘤患者预后有显著相关性,并参与调节多种免疫学通路,影响肿瘤的发生、发展。
基金Supported by a grant of Shantou University Research & Development Fund,No.L03002
文摘AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, α-catenin, β-catenin, γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS：The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression ratewas 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x^2=4.183 and x^2=5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (x^2=5.769, P<0.05). Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and inreduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.
文摘Recent studies have revealed that the γ-chain of theIL-2 receptor is shared by the receptors for IL-4, IL7, IL-9, IL-13, and IL-15, and it is therefore also referred toas the common γ-chain (γc). Mutations of γc result inX-linked severe combined immunodeficiency syndrome inhumans, indicating that rye is essential for normal development and function of the immune system. We demonstratethat human hematopoietic cells express two γc transcriptsdiffering in their carboxyl terminal coding region. Onetranscript is the previously reported sequence (γc-long),whereas the newly identified sequence exhibits a deletion of72 nucleotides close to the 3’-end of the open reading frame(γc-short). This alteration predicts a loss of 24 amino acidsincluding a conserved tyrosine residue which is shared byseveral members of the cytokine receptor family. Thepresence of these two distinct forms of rye transcripts wasdemonstrated by sequencing of reversely transcribed andpolymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines andhuman peripheral blood lymphocytes. Furthermore, thetwo variants were present in peripheral blood lymphocytesfrom both female and male donors, which rules out allelicvariants since rye is a single copy gene located on the Xchromosome. A truncation mutant at a site near the observed changes in γc-short has been reported by othersto alter biochemical events activated by cytokines. Thiscombined with the loss of a potential SH2 "docking" sitein γc-short suggests that γc-long and γc-short may link todifferent signaling pathways and may play an importantrole in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.
基金supported by the Ministry of Health of China (No.2008ZX10002-022)the Doctoral Innovation Fund of Shanghai Cancer Institute(No.SB-09-02)
文摘Objective To investigate the roles of the y-aminobutyric acid （GABA） in the metastasis of hepatocellular carcinoma （HCC） and to explore the potential of a novel therapeutic approach for the treatment of HCC. Methods The expression levels of GABA receptor subunit genes in various HCC cell lines and patients＇ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. Results The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABAA receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. Conclusions These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.
