Background: Nanog, nucleostemin (NS) and musashi1 (Msi1) are proteins that are highly expressed in undifferentiated embryonic stem (ES) cells and have been shown to be essential in maintaining the pluripotency and regulating the proliferation and asymmetric division of ES cells and several nervous system tumor cells. The roles of Nanog, NS and Msi1 in development and progression of cervical carcinoma have, until now, not been well documented. Methods: In this study, expression of Nanog, NS and Msi1 was detected by immunohistochemistry analysis in 235 patients with various degrees of cervical epithelial lesions, including 49 with normal cervical epithelia, 31 with mild dysplasia (CIN I), 77 with moderate-severe dysplasia (CIN II-III) and 78 with squamous cervical carcinomas (SCCs). Associations with various clinical pathological prognostic variables were analyzed in 50 early-stage SCC patients. Results: Nanog, NS and Msi1 expression levels were significantly higher in SCC patients compared with CIN patients, and were higher in CIN patients compared with those with normal cervical epithelia. Nanog expression levels showed significantly differences according to different tumor sizes (P < 0.05), whereas there were no differences in NS and Msi1 expression levels according to different clinical pathological parameters. Conclusion: Our findings indicate that Nanog, NS and Msi1 may be involved in carcinogenesis of the cervix and progression of cervical carcinoma.
Background: Benign or malignant lesions caused by Human papillomavirus (HPV) produce considerable health burden worldwide. Since limited cross-protection would be offered between HPV types, heterogeneity in HPV type-specific distribution should be taken into account when predicting the effect of current prophylactic vaccines and forming the basic for the second-generation vaccines targeted to specific regions. Here, we investigated the prevalence of cervical HPV infection, as well as predictors concerned, in Zhejiang Province, southeast China. Results: Totally 4987 cervical samples from five randomly chosen counties in Zhejiang Province were detected. The overall HPV prevalence was 13.3%. Established high-risk (HR) HPV prevalence was 10.2%. HPV-52 was the most prevalent type (3.1%), followed by HPV-16 (2.5%), -58 (2.1%), -68 (1.0%) and -81 (0.9%). HPV-16 or -18 were present in 3.1% of the detected samples, while 174 specimens (3.5%) were positive for any of HPV-6, -11, -16 and -18. The prevalence of HPV vaccine types was consistently low across age groups. Bimodal age distribution in HR-HPV, including established HR and probably HR-HPV, was observed, with a clear second peak in perimenopausal women. Multivariate unconditional logistic regression models revealed that partner's lifetime number of partners was the only common independent predictor of overall, established HR, established low-risk, single-type and multiple-type HPV infection in current study. Conclusions: We have observed low prevalence of HPV vaccine types and relatively high prevalence of HPV-52 and -58 in our population. Our findings support universal "catch-up" vaccination of sexual experienced young women in Zhejiang Province, as well as enhance the hypothesis that the second-generation HPV prophylactic vaccines including HPV-52 and -58 may offer higher protection for women in China and other Asian areas. Furthermore, our data support close surveillance of perimenopausal women with HR-HPV infection.
Background and Aims: Ovarian carcinoma (OC) is one of the most lethal malignant tumors with a high reoccurrence and chemoresistance. The key mechanism relationship with chemoresistance in ovarian carcinoma is still unclear. The existence of cancer stem cells involves in chemoresistance and reoccurrence in OC. The objective of this study was to investigate the expression, suppression of malignant properties and reversal of paclitaxel resistance inhibiting RNA-binding protein Musashi-1 with siRNA in ovarian cancer cells.
29 June 2009 in Journal of Experimental & Clinical Cancer Research
Background: Platinum-based neoadjuvant chemotherapy (NAC) is new therapeutic strategy for locally advanced cervical carcinoma, but the variables used to predict NAC response are still infrequently reported. The aim of our study was to investigate the association between XRCC1 gene single nucleotide polymorphisms (SNPs) and NAC response. Methods: Seventy patients with locally advanced cervical carcinoma who underwent NAC were collected. SNPs of XRCC1 (at codon 194 and 399) and XRCC1 protein expression were detected. The association of XRCC1 gene SNPs and protein expression with NAC response were analyzed. Results: Response to NAC was not statistically significant in three genotypes, Arg/Arg, Arg/Trp, Trp/Trp of XRCC1 at codon 194(X2 = 1.243, P = 0.07), while responses were significantly different in genotypes Arg/Arg, Arg/Gln, Gln/Gln of XRCC1 at codon 399 (X2 = 2.283, P = 0.020). The risk of failure to chemotherapy in the patients with a Gln allele(Arg/Gln+Gln/Gln) was significantly greater than that with Arg/Arg(OR = 3.254, 95%CI 1.708 ~ 14.951). The expression level of XRCC1 protein was significantly associated with response to NAC. Moreover, the genotype with the Gln allele(Arg/Gln+Gln/Gln) at codon 399, but not codon at 194, presented a significantly higher level of XRCC1 protein expression than that with Arg/Arg genotype (F = 2.699, p = 0.009). Conclusion: SNP of XRCC1 gene at codon 399 influences the response of cervical carcinoma to platinum-based NAC. This is probably due to changes in expression of XRCC1 protein, affecting response to chemotherapy.
18 June 2010 in Journal of Experimental & Clinical Cancer Research
Patients with cervical carcinoma (CC) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells. Using multicolor flow cytometry, the percentages of CD11c+ (DC1) and CD123+ (DC2) subsets, were determined in the peripheral blood of 37 patients with cervical carcinoma (CC), 54 patients with CIN, and 62 healthy individuals. A substantial reduction of circulating dendritic cells and accordingly immunodepression may be associated with increased IL-6 and TGF-β in serum. These findings could give expression to the immunosuppression of circulating dendritic cells in patients with CC and CIN, thus, may indicate novel aspects of cervical carcinoma immune evasion.
8 February 2019 in Genetic Testing and Molecular Biomarkers
Aim: This study investigated the association of the human 8-oxoguanine glycosylase 1 ( hOGG1 ) Ser326Cys polymorphism with risk of cervical squamous cell carcinoma (CSCC) and high-risk human papilloma virus (HR-HPV) infection. Background: The hOGG1 Ser326Cys polymorphism is reported to be correlated with the risk of several cancers. However, there are reports that have found no significant differences in the frequency of the hOGG1 Ser326Cys between cervical carcinoma patients and controls. Methods: hOGG1 Ser326Cys was genotyped through modified allele mismatch amplification polymerase chain reaction in 1200 healthy controls, 400 cervical intraepithelial neoplasia (CIN) grade III cases, and 400 CSCC cases. Results: The homozygous genotype of hOGG1 Cys326Cys (GG) was associated with increased risk of CIN III (odds ratio, OR = 1.81 [1.31-2.49], p < 0.001) and CSCC (OR = 3.05 [2.2-4.20], p < 0.001). The G allele or G carrier (GG + CG) genotype was a highly-significant risk factor for CSCC (OR = 1.49 [1.14-1.97], p = 0.004). In the HR-HPV-positive group, the homozygous genotype of hOGG1 GG was associated with increased risk of CSCC (OR = 3.66 [2.02-6.62], p < 0.001) and risk of CIN III (OR = 1.82 [1.08-3.06], p = 0.024). The proportion of G allele carriers was significantly increased in CIN III (51.9%, [322/620], OR = 1.33 [1.03-1.72], p = 0.028) and CSCC (62.1% [221/356], OR = 2.02 [1.51-2.71], p < 0.001). The GG and GC genotypes were consistently identified as significant risk factors for CSCC (OR = 1.73 [1.06-2.83], p = 0.029) in the HR-HPV infected group. We further observed enrichment of the hOGG1 Ser326Cys polymorphism in the CIN III ( p = 0.021) and CSCC ( p < 0.001) stratified by age at first intercourse, with more significant enrichment ( p = 0.036) in the HR-HPV infection group. Conclusions: Our findings support associations of the hOGG1 Ser326Cys polymorphism with CSCC carcinogenesis and susceptibility to HR-HPV infection. The hOGG1 Ser326Cys polymorphism may serve as a potential genetic biomarker of susceptibility to cervical cancer and HR-HPV infection.