An optimized recombinant HPV16 E6E7 fusion gene (HPV16 ofE6E7) was constructed according to codon usage for mammalian cell expression, and a mutant of HPV16 ofE6E7 fusion gene (HPV16 omfE6E7) was generated by site-dir...An optimized recombinant HPV16 E6E7 fusion gene (HPV16 ofE6E7) was constructed according to codon usage for mammalian cell expression, and a mutant of HPV16 ofE6E7 fusion gene (HPV16 omfE6E7) was generated by site-directed mutagenesis at L57G, C113R for the E6 protein and C24G, E26G for the E7 protein for HPV16 ofE6E7 [patent pending (CN 101100672)]. The HPV16 omfE6E7 gene constructed in this work not only lost the transformation capability to NIH 3T3 cells and tumorigenicity in SCID mice, but also maintained very good stability and antigenicity. These results suggests that the HPV16 omfE6E7 gene should undergo further study for application as a safe antigen-specific therapeutic vaccine for HPV16-associated tumors.展开更多
OBJECTIVE Notch1 signaling has been implicated intumorigenesis. The purpose of this study was to investigate theputative role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. Sinc...OBJECTIVE Notch1 signaling has been implicated intumorigenesis. The purpose of this study was to investigate theputative role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. Since human papillomavirus(HPV) is a causative agent in cervical carcinoma, the interactionbetween Notch1 and HPV infection was examined.METHODS Forty cervical cancer samples and 30 normalcervical tissue specimens were examined using Western blot andRT-PCR to detect Notch1 protein and mRNA levels. HPV16 DNAwas examined in all samples using PCR.RESULTS The level of Notch1 protein expression wassignificantly lower in cervical cancer tissue than in normal tissue.Levels of Notch1 mRNA were found to be substantially downregulatedin cancer tissue. Notch1 protein expression levelswere significantly higher in carcinomas without HPV DNAthan that in carcinomas with HPV infection (55.5% vs. 3.3%, P <0.05). Down-modulation of Notch1 mRNA levels in carcinomawas demonstrated to be associated with HPVE6 transcription.Moreover, levels of Notch1 expression were shown to besignificantly higher in early stage disease than in advanced stagedisease (P = 0.001).CONCLUSION Down-modulation of Notch1 expressionprobably plays an important role in the late stages of HPVinducedcervical cancer.展开更多
Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 （LSIL/CIN1） preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separat...Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 （LSIL/CIN1） preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus （HPV） 16/18 genotyping in 273 patients with LSIL/CINI. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV （hrHPV） were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases （69.6%） regressed, 37 （13.6%） persisted, and 46 （16.8%） progressed. HPV16/18 positivity （hazard ratio （HR）, 2.708; 95% confidence interval （CI）, 1.432-5.121; P=-0.002） is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.展开更多
基金National 863 Program(2007AA021107)Beijing Municipal Commission of Education Research Projects(KM201010005008)Doctoral Start-up Foundation of Beijing University of Technology
文摘An optimized recombinant HPV16 E6E7 fusion gene (HPV16 ofE6E7) was constructed according to codon usage for mammalian cell expression, and a mutant of HPV16 ofE6E7 fusion gene (HPV16 omfE6E7) was generated by site-directed mutagenesis at L57G, C113R for the E6 protein and C24G, E26G for the E7 protein for HPV16 ofE6E7 [patent pending (CN 101100672)]. The HPV16 omfE6E7 gene constructed in this work not only lost the transformation capability to NIH 3T3 cells and tumorigenicity in SCID mice, but also maintained very good stability and antigenicity. These results suggests that the HPV16 omfE6E7 gene should undergo further study for application as a safe antigen-specific therapeutic vaccine for HPV16-associated tumors.
文摘OBJECTIVE Notch1 signaling has been implicated intumorigenesis. The purpose of this study was to investigate theputative role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. Since human papillomavirus(HPV) is a causative agent in cervical carcinoma, the interactionbetween Notch1 and HPV infection was examined.METHODS Forty cervical cancer samples and 30 normalcervical tissue specimens were examined using Western blot andRT-PCR to detect Notch1 protein and mRNA levels. HPV16 DNAwas examined in all samples using PCR.RESULTS The level of Notch1 protein expression wassignificantly lower in cervical cancer tissue than in normal tissue.Levels of Notch1 mRNA were found to be substantially downregulatedin cancer tissue. Notch1 protein expression levelswere significantly higher in carcinomas without HPV DNAthan that in carcinomas with HPV infection (55.5% vs. 3.3%, P <0.05). Down-modulation of Notch1 mRNA levels in carcinomawas demonstrated to be associated with HPVE6 transcription.Moreover, levels of Notch1 expression were shown to besignificantly higher in early stage disease than in advanced stagedisease (P = 0.001).CONCLUSION Down-modulation of Notch1 expressionprobably plays an important role in the late stages of HPVinducedcervical cancer.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LQ14H160007)the National Natural Science Foundation of China(No.81402364)+2 种基金the Zhejiang Provincial Medical & Hygienic Science and Technology Project of China(No.2013KYA104)the Special Fund for Scientific Research in the Public Interest from the National Health and Family Planning Commission of the People’s Republic of China(No.2015SQ00243)the National Key Research and Development Program of China(No.2016YFC1302900)
文摘Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 （LSIL/CIN1） preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus （HPV） 16/18 genotyping in 273 patients with LSIL/CINI. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV （hrHPV） were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases （69.6%） regressed, 37 （13.6%） persisted, and 46 （16.8%） progressed. HPV16/18 positivity （hazard ratio （HR）, 2.708; 95% confidence interval （CI）, 1.432-5.121; P=-0.002） is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.
