目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome At...目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。展开更多
Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell p...Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.展开更多
AIM： To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS： Between January 2003 and December 2004, twenty patients who were diagnosed ...AIM： To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS： Between January 2003 and December 2004, twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism, underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalinfixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours （00：00, 06：00, 12：00, 18：00 and 24：00）, we studied the expression of G1 phase cyclins （D1 and E） as well as the expression of the G1 phase cyclin-dependent kinase （CDK） inhibitors p16 and p21 as indicators of cell cycle progres- sion in colonic epithelial cells using immunohistochemical methods. RESULTS： The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00：00 and 18：00, respectively （P〈 0.001）. A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12：00 and 18：00 （P〈0.001）, respectively. When the complexes cyclins D1-p21 and E-p21 were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D1-p16 and E-p16 were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00：00, 06：00 and 24：00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18：00. CONCLUSION： Colonic epithelial cells seem to enter the G1 phase of the cell cycle during afternoon （between 12：00 and 18：00） with the highest rates obtained at 18：00. From a clinical point of view, the present results suggest that G1-phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.展开更多
BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are incr...BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.展开更多
文摘目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。
基金National Nature Science Foundation for Distinguished Young Scholar of China (No.39525022)National Basic Research Program(No.2004CB518703) National Nature Science Foundation of China (No.30570085).
文摘Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
文摘AIM： To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS： Between January 2003 and December 2004, twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism, underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalinfixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours （00：00, 06：00, 12：00, 18：00 and 24：00）, we studied the expression of G1 phase cyclins （D1 and E） as well as the expression of the G1 phase cyclin-dependent kinase （CDK） inhibitors p16 and p21 as indicators of cell cycle progres- sion in colonic epithelial cells using immunohistochemical methods. RESULTS： The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00：00 and 18：00, respectively （P〈 0.001）. A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12：00 and 18：00 （P〈0.001）, respectively. When the complexes cyclins D1-p21 and E-p21 were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D1-p16 and E-p16 were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00：00, 06：00 and 24：00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18：00. CONCLUSION： Colonic epithelial cells seem to enter the G1 phase of the cell cycle during afternoon （between 12：00 and 18：00） with the highest rates obtained at 18：00. From a clinical point of view, the present results suggest that G1-phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.
文摘BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.
