Womens Reproductive Health Laboratory of Zhejiang Province

of Zhejiang Province, China

Womens Reproductive Health Laboratory of Zhejiang Province

of Zhejiang Province, China
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Zhou J.,Womens Reproductive Health Laboratory of Zhejiang Province | Zhou J.,Zhejiang Cancer Hospital | Li B.,Zhejiang University | Peng C.,Womens Reproductive Health Laboratory of Zhejiang Province | And 10 more authors.
Antiviral Research | Year: 2013

Deregulated expression of high-risk human papillomavirus oncogenes (E6and E7)is a pivotal event for pathogenesis and progression incervical cancer.Both viral oncogenes are therefore regarded a sideal therapeutic targets. Small interfering RNAs (siRNA)ordouble-str anded RNAs can knock down target genes effectively through siRNA-induced transcriptional gene silencing (TGS).Here,we established len- tiviral-vector mediated shRNA (LV-shRNA) targeting common promoter ofHPV16 E6/E7 and targeting E6 transcript, transduced the lentiviral construct into cervical HPV16-positive cell lines Siha and Caski,then selected and established stably transduced monoclonal cell lines.The results showed that LV-shRNA tar- geting promoter, as well a stargeting E6transcript,effectively knocked down E6and E7expression, resulted in accumulation of p53 and pRB protein and decrease ofMCM7 and p16 protein,and conse- quently remarkably reduced the abilities of proliferation and invasiveness of cervical cancers cells in vitro.Then we inoculated subcutaneously those monoclonal cells into nude mice to establish the trans- planted tumor animal models, and found dramatical lyinhibited tumorigenesis and growth,aswell as prolonged survival time of mice incubated bycells with LV-shRNA targeting promoter and E6transcript. Our results may provide evidence for application ofLV-shRNA targeting HR-HPV key oncogenes,asanew treatment strategy, incervical and other HPV-associated cancer therapy. © 2013 Elsevier B.V.


Li Y.,Womens Reproductive Health Laboratory of Zhejiang Province | Ye F.,Womens Reproductive Health Laboratory of Zhejiang Province | Ye F.,Zhejiang University | Lu W.-G.,Zhejiang University | And 3 more authors.
International Journal of Gynecological Cancer | Year: 2010

Objectives: The aims of this study were to compare the findings of fluorescence in situ hybridization (FISH) detection of human telomerase RNA gene (hTERC) amplification with that of cytological and human papillomavirus (HPV) DNA tests and explore the possibility to improve the accuracy of the diagnoses of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods: A total of 201 specimens of liquid-based thin-layer cytological examination findings were collected and detected by HPV DNA test and hTERC detected by FISH. All women underwent colposcopy and histological examination of biopsy specimen if needed. The 3 screening methods were compared based on histological examination of colposcopic biopsies. Results: The amplification of hTERC showed 6.06% in normal or inflammation cases, 10.00% in CIN 1, 66.67% in CIN 2, 72.50% in CIN 3, and 100.00% in carcinoma, with significant difference between the low- (≤CIN 1 or ≤low-grade squamous intraepithelial lesion) and high-grade (≥CIN 2 or ≥atypical squamous cells in which high-grade squamous intraepithelial lesion cannot be excluded) cervical lesions (P < 0.001). The hTERC amplification rate was consistent with abnormal rates of cytological and histological diagnoses. The detection of hTERC amplification had a much higher accuracy (87.56%) than the cytological (80.10%) and HPV DNA test (77.61%) findings. Conclusions: Using FISH to detect the amplification of hTERC had a much higher specificity and accuracy for the diagnoses of high-grade CIN and cervical cancer than cytological and HPV DNA test findings, suggesting that this detection might be a useful and specific screening method in cervical cancer and precancerous lesions.

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