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
Objective: To investigate the diagnostic value and prognostic value of HPV and P16 protein in patients with HSIL and to provide a reference for the clinical diagnosis and assessment of the prognosis of patients with H...Objective: To investigate the diagnostic value and prognostic value of HPV and P16 protein in patients with HSIL and to provide a reference for the clinical diagnosis and assessment of the prognosis of patients with HSIL. Methods: The surgical treatment of HSIL patients from January 2013 to January 2015 in our hospital were selected. All patients were routinely tested for HPV and P16 protein, All patients were followed up for 1 year. Patients were divided into progressive group and quiescent group according to whether the disease progressed one year after surgery. Preoperative HPV and P16 protein levels were compared between the two groups. Using receiver operating curve (ROC curve) Analysis of HPV diagnostic value of HSIL. The levels of HPV and P16 protein in the two groups were analyzed and compared. Results: The quantitative level of high-risk HPV-DNA after LEEP was significantly lower than that before operation. The level of P16 protein in preoperative patients was higher than that before operation, and the difference was statistically significant. There were 21 patients in the postoperative progression group, and the average HPV-DNA content in the patients in the progression group was higher than that in the control group within one year after operation. The difference was statistically significant. The P16 protein level in patients in advanced group was significantly higher than that in resting group. Preoperative HPV-DNA levels and P16 protein levels in patients with progressive disease were significantly higher than those in still group. ROC curve analysis showed that the cut-off value of 2.441, HPV-DNA prediction of HSIL patients one year after the recurrence of the sensitivity was 95.12%, the specificity was 76.16%, under the curve area of 0.878;7.4 cut-off value, P16 The predictive value of HSIL patients recurrence after 1 year was 71.95%, specificity was 66.67%, and the area under the curve was 0.753. The recurrence group HPV-DNA content and P16 protein level showed a significant positive correlation, with statistical significance. Conclusions: LEEP can reduce the postoperative levels of HPV and P16 protein in patients with HSIL. The HPV and P16 protein levels are of high value for the early diagnosis of HSIL and the prediction of postoperative disease progression.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。
基金Hainan Natural Science Foundation Surface Project(20168279).
文摘Objective: To investigate the diagnostic value and prognostic value of HPV and P16 protein in patients with HSIL and to provide a reference for the clinical diagnosis and assessment of the prognosis of patients with HSIL. Methods: The surgical treatment of HSIL patients from January 2013 to January 2015 in our hospital were selected. All patients were routinely tested for HPV and P16 protein, All patients were followed up for 1 year. Patients were divided into progressive group and quiescent group according to whether the disease progressed one year after surgery. Preoperative HPV and P16 protein levels were compared between the two groups. Using receiver operating curve (ROC curve) Analysis of HPV diagnostic value of HSIL. The levels of HPV and P16 protein in the two groups were analyzed and compared. Results: The quantitative level of high-risk HPV-DNA after LEEP was significantly lower than that before operation. The level of P16 protein in preoperative patients was higher than that before operation, and the difference was statistically significant. There were 21 patients in the postoperative progression group, and the average HPV-DNA content in the patients in the progression group was higher than that in the control group within one year after operation. The difference was statistically significant. The P16 protein level in patients in advanced group was significantly higher than that in resting group. Preoperative HPV-DNA levels and P16 protein levels in patients with progressive disease were significantly higher than those in still group. ROC curve analysis showed that the cut-off value of 2.441, HPV-DNA prediction of HSIL patients one year after the recurrence of the sensitivity was 95.12%, the specificity was 76.16%, under the curve area of 0.878;7.4 cut-off value, P16 The predictive value of HSIL patients recurrence after 1 year was 71.95%, specificity was 66.67%, and the area under the curve was 0.753. The recurrence group HPV-DNA content and P16 protein level showed a significant positive correlation, with statistical significance. Conclusions: LEEP can reduce the postoperative levels of HPV and P16 protein in patients with HSIL. The HPV and P16 protein levels are of high value for the early diagnosis of HSIL and the prediction of postoperative disease progression.
