目的构建和评价HPV16 E6、E7多表位DNA疫苗诱导的特异性CTL细胞应答及其对肿瘤生长的干预作用,从而揭示其作为候选HPV治疗性疫苗的潜能。方法首先通过IEDB网站中的MHC I Processing Predictions和MHC I Binding Predictions方法,分别预...目的构建和评价HPV16 E6、E7多表位DNA疫苗诱导的特异性CTL细胞应答及其对肿瘤生长的干预作用,从而揭示其作为候选HPV治疗性疫苗的潜能。方法首先通过IEDB网站中的MHC I Processing Predictions和MHC I Binding Predictions方法,分别预测人类HLA-A^(*)02:01、HLA-A^(*)11:01、HLA-A^(*)24:02和C57BL/6小鼠H-2b的限制性CTL表位,然后根据评分以及ELISPOT实验筛选出二者共同呈递的CTL表位,并将其构建成多表位DNA疫苗(pVAX1-10P)。从预防性和治疗性二个方面研究pVAX1-10P对小鼠移植TC-1异位癌的免疫干预作用,流式细胞术检测特异性CTL应答。结果获得10条可被人与鼠MHC分子共呈递的CTL表位,ELISPOT结果表明这10条CTL表位均能诱导小鼠淋巴细胞产生特异性免疫应答;由此构建的多表位DNA疫苗pVAX1-10P无论在预防性实验还是治疗性实验中,均能诱导特异性的细胞免疫并抑制肿瘤的生长。结论构建的HPV16 E6、E7多表位DNA疫苗pVAX1-10P能够诱导特异性CTL应答,显著抑制肿瘤生长,有望作为候选HPV治疗性DNA疫苗。展开更多
BACKGROUND The molecular mechanisms of colorectal cancer development and progression are far from being elucidated.AIM To investigate the role of microRNA-363-3p(miR-363-3p)in the progression of colorectal cancer.METH...BACKGROUND The molecular mechanisms of colorectal cancer development and progression are far from being elucidated.AIM To investigate the role of microRNA-363-3p(miR-363-3p)in the progression of colorectal cancer.METHODS Real-time polymerase chain reaction was performed to detect miRNA expression in human colorectal cancer tissues and paired normal colorectal tissues.PITA 6 was utilized to predict the targets of miR-363-3p.Dual-luciferase reporter system was used to validate the target of miR-363-3p.Plate colony formation assay and wound-healing assay were performed to evaluate cancer cells’clonogenic survival ability and migration ability,respectively.Cell proliferation was examined by cell counting kit-8 assay.Immunohistochemical staining was used to determine the expression level of interferon-induced transmembrane protein 1(IFITM1)in colorectal cancer tissues and adjacent tissues.The TCGA and GTEx databases were used to compare the expression levels of IFITM1 mRNA in colorectal cancer tissues and normal colorectal tissues and analyze the correlation between the expression levels of IFITM1 mRNA and overall survival and disease-free survival of patients.A colorectal cancer cell line with a deficiency of IFITM1 was constructed,and the regulation effect of IFITM1 on the clonogenic growth of colorectal cancer cells was clarified.RESULTS MiR-363-3p was decreased in colorectal cancer tissues compared to normal colorectal tissues.IFITM1 was characterized as a direct target of miR-363-3p.Overexpression of miR-363-3p led to decreased clonogenic survival,proliferation,and migration of colorectal cancer cells,which could be reversed by forced IFITM1 expression.CONCLUSION MiR-363-3p can constrain clonogenic survival,proliferation,and migration of colorectal cancer cells via targeting IFITM1.展开更多
干扰素诱导蛋白16(interferonγ-inducible protein 16,IFI16)是人类PYHIN(pyrin and HIN domain-containing protein)家族(也称干扰素诱导蛋白P200家族)成员之一,在人体器官组织中广泛存在,参与细胞周期调控、细胞衰老、细胞凋亡及免...干扰素诱导蛋白16(interferonγ-inducible protein 16,IFI16)是人类PYHIN(pyrin and HIN domain-containing protein)家族(也称干扰素诱导蛋白P200家族)成员之一,在人体器官组织中广泛存在,参与细胞周期调控、细胞衰老、细胞凋亡及免疫反应等多种生物过程。不同生理及病理状态下,IFI16的含量及定位均会发生改变,近年来研究发现,其在抗病毒、肿瘤、炎性疾病及其他多种疾病发生发展过程中可能发挥重要作用。该文对其机制及其在疾病中的研究现状进行综述,以期为深入研究IFI16提供参考。展开更多
Pneumoconiosis is a systemic occupational disease that commonly manifests as diffuse fibrosis of the lungs caused by long-term inhalation of silica dust in the production process. The development of pneumoconiosis is ...Pneumoconiosis is a systemic occupational disease that commonly manifests as diffuse fibrosis of the lungs caused by long-term inhalation of silica dust in the production process. The development of pneumoconiosis is a chronic and progressive process;once it occurs, it is irreversible, and gradually develops into lung injury and respiratory failure, and can cause death regardless of exposure to dust. The incidence of pneumoconiosis is the highest in China and the direct and indirect economic loss as a result of pneumoconiosis is approximately 9 billion yuan per year.展开更多
AIM:To investigate the expression of leukemia related protein 16 (LRP16), and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients.METHODS: Immunohistoch...AIM:To investigate the expression of leukemia related protein 16 (LRP16), and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients.METHODS: Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients' age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed.RESULTS: The expression of LRP16 was 58.6% (197/336) in gastric carcinoma and 31.7% (19/60) in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues (χ2=14.929, P=0.001). LRP16 protein expression was found in 44.1% (63/143) carcinomas at stage and,and 69.4%(134/193) carcinomas at stage and (χ2=21.804,P=0.001),and in 56.9%(182/320)of cancers without metastasis but 93.8%(15/16)of those with metastasis(χ2=8.543,P=0.003).The expression of LRP16 was correlated with tumor size,infiltrative depth,clinical stage,lymphatic invasion and distant metastasis(all P<0.05). Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 (27.0 mo) and those without (48.0 mo, Log rank=31.644, P=0.001).CONCLUSION: The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.展开更多
The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallb...The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line （Mz-ChA-1） were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.展开更多
文摘目的构建和评价HPV16 E6、E7多表位DNA疫苗诱导的特异性CTL细胞应答及其对肿瘤生长的干预作用,从而揭示其作为候选HPV治疗性疫苗的潜能。方法首先通过IEDB网站中的MHC I Processing Predictions和MHC I Binding Predictions方法,分别预测人类HLA-A^(*)02:01、HLA-A^(*)11:01、HLA-A^(*)24:02和C57BL/6小鼠H-2b的限制性CTL表位,然后根据评分以及ELISPOT实验筛选出二者共同呈递的CTL表位,并将其构建成多表位DNA疫苗(pVAX1-10P)。从预防性和治疗性二个方面研究pVAX1-10P对小鼠移植TC-1异位癌的免疫干预作用,流式细胞术检测特异性CTL应答。结果获得10条可被人与鼠MHC分子共呈递的CTL表位,ELISPOT结果表明这10条CTL表位均能诱导小鼠淋巴细胞产生特异性免疫应答;由此构建的多表位DNA疫苗pVAX1-10P无论在预防性实验还是治疗性实验中,均能诱导特异性的细胞免疫并抑制肿瘤的生长。结论构建的HPV16 E6、E7多表位DNA疫苗pVAX1-10P能够诱导特异性CTL应答,显著抑制肿瘤生长,有望作为候选HPV治疗性DNA疫苗。
文摘BACKGROUND The molecular mechanisms of colorectal cancer development and progression are far from being elucidated.AIM To investigate the role of microRNA-363-3p(miR-363-3p)in the progression of colorectal cancer.METHODS Real-time polymerase chain reaction was performed to detect miRNA expression in human colorectal cancer tissues and paired normal colorectal tissues.PITA 6 was utilized to predict the targets of miR-363-3p.Dual-luciferase reporter system was used to validate the target of miR-363-3p.Plate colony formation assay and wound-healing assay were performed to evaluate cancer cells’clonogenic survival ability and migration ability,respectively.Cell proliferation was examined by cell counting kit-8 assay.Immunohistochemical staining was used to determine the expression level of interferon-induced transmembrane protein 1(IFITM1)in colorectal cancer tissues and adjacent tissues.The TCGA and GTEx databases were used to compare the expression levels of IFITM1 mRNA in colorectal cancer tissues and normal colorectal tissues and analyze the correlation between the expression levels of IFITM1 mRNA and overall survival and disease-free survival of patients.A colorectal cancer cell line with a deficiency of IFITM1 was constructed,and the regulation effect of IFITM1 on the clonogenic growth of colorectal cancer cells was clarified.RESULTS MiR-363-3p was decreased in colorectal cancer tissues compared to normal colorectal tissues.IFITM1 was characterized as a direct target of miR-363-3p.Overexpression of miR-363-3p led to decreased clonogenic survival,proliferation,and migration of colorectal cancer cells,which could be reversed by forced IFITM1 expression.CONCLUSION MiR-363-3p can constrain clonogenic survival,proliferation,and migration of colorectal cancer cells via targeting IFITM1.
文摘干扰素诱导蛋白16(interferonγ-inducible protein 16,IFI16)是人类PYHIN(pyrin and HIN domain-containing protein)家族(也称干扰素诱导蛋白P200家族)成员之一,在人体器官组织中广泛存在,参与细胞周期调控、细胞衰老、细胞凋亡及免疫反应等多种生物过程。不同生理及病理状态下,IFI16的含量及定位均会发生改变,近年来研究发现,其在抗病毒、肿瘤、炎性疾病及其他多种疾病发生发展过程中可能发挥重要作用。该文对其机制及其在疾病中的研究现状进行综述,以期为深入研究IFI16提供参考。
基金supported by Nanjing Medical Technology Development Funds [YKK15188]Nanjing Medical Science and technique Development Foundation [QRX17197]
文摘Pneumoconiosis is a systemic occupational disease that commonly manifests as diffuse fibrosis of the lungs caused by long-term inhalation of silica dust in the production process. The development of pneumoconiosis is a chronic and progressive process;once it occurs, it is irreversible, and gradually develops into lung injury and respiratory failure, and can cause death regardless of exposure to dust. The incidence of pneumoconiosis is the highest in China and the direct and indirect economic loss as a result of pneumoconiosis is approximately 9 billion yuan per year.
基金Supported by Grant from the Ministry of Science and Technology of China,No.2010CB912802
文摘AIM:To investigate the expression of leukemia related protein 16 (LRP16), and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients.METHODS: Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients' age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed.RESULTS: The expression of LRP16 was 58.6% (197/336) in gastric carcinoma and 31.7% (19/60) in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues (χ2=14.929, P=0.001). LRP16 protein expression was found in 44.1% (63/143) carcinomas at stage and,and 69.4%(134/193) carcinomas at stage and (χ2=21.804,P=0.001),and in 56.9%(182/320)of cancers without metastasis but 93.8%(15/16)of those with metastasis(χ2=8.543,P=0.003).The expression of LRP16 was correlated with tumor size,infiltrative depth,clinical stage,lymphatic invasion and distant metastasis(all P<0.05). Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 (27.0 mo) and those without (48.0 mo, Log rank=31.644, P=0.001).CONCLUSION: The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.
文摘The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line （Mz-ChA-1） were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.
