• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.341-346
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• 2013

The risk of cervical cancer development in women infected with HPV varies in relation to the individual host's genetic makeup. Many studies on polymorphisms as genetic factors have been aimed at analyzing associations with cervical cancer. In this study, single nucleotide polymorphisms (SNPs) in 3 genes were investigated in relation to cervical cancer progression in HPV16 infected women with lesions. Two thousand cervical specimens were typed by PCR sequencing methods for TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566). Ninety two HPV16 positive cases and thirty two normal cases were randomly selected. Analysis of TP53 (rs1042522) showed a significantly higher frequency in cancer samples (OR=1.22, 95%CI=1.004-1.481, p-value=0.016) while differences in frequency were not significant within each group (p-value=0.070). The genotype distributions of p16 (rs11515 and rs3088440) and NQO1 (rs1800566) did not show any significantly higher frequency in cancer samples (p-value=0.106, 0.675 and 0.132, respectively) or within each group (p-value=0.347, 0.939 and 0.111, respectively). The results indicated that the polymorphism in TP53 (rs1042522) might be associated with risk of cervical cancer development in HPV16 infected women. Further studies of possible mechanisms of influence on cervical cancer development would be useful to manage HPV infected patients.

• Korean Journal of Clinical Laboratory Science
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• v.37 no.3
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• pp.197-206
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• 2005

To determine the correlation between mast cells(MCs) and neoangiogenesis in the growth and progression of cervical cancer, we investigated mast cell density(MCD), microvessel density(MVD) and the expression of vascular epithelial growth factor(VEGF) in cervical intraepithelial neoplasia and invasive suqamous cell carcinoma of the uterine cervix. Forty-five cervical intraepithelial neoplasia(CIN I, II and III), 15 microinvasive carcinomas, 15 invasive squamous cell carcinomas and 20 normal cervical epithelia were included in this study. MCs were stained with anti-c-Kit antibody and alcian blue, microvessels with anti-factor VIII antibody and VEGF with anti-VEGF antibody. The adjacent fields of both normal and neoplastic epithelium were used for counting MCs and microvessels. Computerized image analysis was used to evaluate MCD and MVD. MCD and MVD were the mean numbers per $1mm^2$ counted in 5-10 high and low power fields respectively. In both c-Kit and alcian blue stained sections, MCD progressively increased along the continuum from CIN I to invasive squamous cell carcinoma(p<0.001). MVD increased significantly with cervical neoplasia progression, from CIN to invasive squamous cell carcinoma (p<0.001). In double c-Kit and Factor VIII-stained sections, MCs were mainly present in the areas adjacent to newly formed blood vessels. However, there were no significant differences in MCD and MVD between normal epithelum and CIN I. A strong correlation was also observed between MCD and MVD. In double VEGF and alcian blue-stained sections, VEGF was expressed in only MCs. Strong VEGF-positive MCs were particularly abundant around the tumorous region. Our results suggest that MCs may upregulate neoangiogenesis by VGEF secretion in the development and progression of cervical neoplasia.

• The Korean Journal of Cytopathology
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• v.9 no.1
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• pp.29-35
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• 1998

In 1988, The Bethesda System for reporting cervical and vaginal cytologic diagnoses was introduced and this was revised in 1991. The new diagnostic category "atypical squamous cells of undetermined significance(ASCUS)" introduced by The Bethesda System is an area of controversy about the diagnostic category, clinical significance and appropriate treatment. A retrospective 2 years and 9 months study(April, 1994-December, 1996) was performed to evaluate the significance of reporting ASCUS on cervical smears. Sixtyseven(1.17%) of 5,730 smears were diagnosed as ASCUS and 21 cases were followed by cervical biopsies and/or endocervical curettages in 4 cases(19%), and repeat cervical smears in 17 cases(81%). Tissue diagnoses were benign in 2 cases and squamous cell carcinoma in situ in 2 cases. Cytologic diagnosis of follow up smear were negative in 14 cases(82.4%) and persistent ASCUS in 3 cases(17.6%).

• Korean Journal of Veterinary Research
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• v.53 no.3
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• pp.189-192
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• 2013

An adult beagle dog was presented with a cervical mass detected by palpation and computed tomography. Fine needle aspirates revealed numerous epithelial cells with plasmacytoid appearance and frequent naked nuclei. Histologically, the mass consists of multiple packets of neoplastic cells and extensive areas of necrosis and fibrosis. Neoplastic cells were also found in submandibular lymph nodes. Immunohistochemistry showed that neoplastic cells were positive for calcitonin and negative for thyroglobulin. Based on these findings, the cervical mass was diagnosed as thyroid C-cell carcinoma. Almost one year after the surgical excision, the dog remains healthy without any symptom of recurrence or metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.469-472
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• 2012

The present study was conducted to assess utility of $p16^{INK4a}$ immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for $p^{16INK4a}$ (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were $p^{16INK4a}$ immunopositive. All normal squamous epithelium did not express $p16^{INK4a}$. $p16^{INK4a}$ expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC. The increased $p16^{INK4a}$ immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.350-354
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• 2008

In order to investigate the prevalence of sexually transmitted viruses such as human papillomavirus (HPV) and herpes simplex virus (HSV) in Korean commercial sex workers (CSWs), we selected 188 CSWs (age range 20-44 years, median age 24 years) who regularly visited one public health center in Seoul, Korea. HPV genotypes were analyzed by using a HPV DNA Chip, and an enzyme-linked immunosorbent assay (ELISA) was used to detect type-specific IgG against HSV2 antibody identifying seropositivity for HSV2 infection. Polymerase chain reaction (PCR) was performed with specific primers to detect HPV and HSV1/2 in cervical swabs from the CSWs. The prevalence of HPV infection was 83.5% in 188 cervical swab specimens and the main high-risk HPV genotypes were HPV16, 18, 56, and 58. The principal low-risk HPV genotypes were HPV6 and 11. The prevalence of HSV1/2 DNA was 13.8% and HSV2 seroprevalence was 86.2%. These results suggest that high frequencies of HPV and HSV2 infection might contribute to the rapid spread of STD viruses in CSWs in Korea. Additionally, an understanding of why high-risk HPV genotypes are so prevalent could provide guidelines for prophylactic vaccine development in Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7749-7754
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• 2015

Background: Currently, cationic liposome has become the commonly used vehicles for gene transfection. Furthermore, one of the most significant steps in microRNAs expression studies is transferring microRNAs into cell cultures successfully. In this study we aim to approach the feasibility of transfection of cervical cancer cell lines mediated by liposome and to obtain the optimized transfection condition for cervical cancer cell lines. Materials and Methods: $Lipofectamine^{TM}2000$ as the carrier, miR-101 mimic was transfected into Hela cells and Siha cells. Using green fluorescent protein as reporter gene, to set different groups according to cell seeding density, the amount of miRNA, miRNA and the proportion of Liposomes, Whether to add serum into medium to study their impact on the liposomal transfection efficiency. Finally, MTT assay was used to analyze the relative minimal cell toxicity of liposome reagents. Results: The seeding density of Hela cell line and Siha are $1.5{\times}10^4$ (per well of 24 well plates), miRNA amount is 1ul of both, the ratio of miRNA and liposome is 1:0.5 of Hela cell line; 1:0.7 of Siha cell line respectively, after 24 hours we can get the highest transfection efficiency. Compared with serum medium, only Siha cells cultured with serum-free medium obtained higher transfection efficiency before transfection (P<0.01). MTT assay showed that according to the above conditions which has the lowest cytotoxicity. Conclusions: The method of Liposome to transfected is a suitable way and it can be an efficient reagent for miRNA delivery for Hela cells and Siha cells in vitro. It may serve as a reference for the further research or application.

• Biomedical Science Letters
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• v.21 no.2
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• pp.69-76
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• 2015

Cervical cancer is the third most common cancer in women worldwide and there is a significant association between human papillomavirus (HPV) infection and cervical cancer. Certain HPV groups, labeled high-risk (HR) HPV groups, are strongly associated with malignancies of the human cervix. HPV prevalence and genotype distribution were analyzed using the REBA $HPV-ID^{(R)}$ (YD Diagnostics, Yongin, Korea) assay based on the reverse blot hybridization assay (REBA) with a total of 324 liquid-based cytology samples from women in Western Shandong Province, East China and results were compared with cytological diagnosis. Most of the HPV genotypes that were detected in high-grade cervical lesions were HR-HPV genotypes such as HPV 16, 18, 33, 53, and 58. The prevalence of these HR-HPV genotypes increased in high-grade cervical lesions. However, from low- to high-grade cervical lesions, the ability to detect LR-HPV genotypes decreased. Additionally, in general, the single HPV genotype infection rate increases in proportion to the severity of the lesion. The study findings suggest that a currently available preventive vaccine against HPV 16 and 18 may have limited effectiveness for prevention of all HPV infection in this province. Finally, based on these findings, these data could guide national or regional vaccination programs in the Western Shandong Province of East China to substantially reduce the burden of cervical lesions.

• Biomedical Science Letters
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• v.7 no.3
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• pp.133-138
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• 2001

The recently proposed Bethesda system for cervical/vaginal cytology has made a standardization related to "atypia". In cellular change due to inflammation or repair, the word "benign cellular change" has been suggested as a substitute for atypia. Terminology related to atypia cells may become standardized, but the cytologic criteria has not been well defined yet Among 8113 cases screened, we evaluated 182 cases as atypia squamous cells undetermined significance (ASCUS) by the Bethesda system (TBS): 52 cases of ASCUS were cytologically diagnosed and 33 cases were histologically verified. ASCUS was diagnosed based on nuclear enlargement and nonclassical signs of condyloma. The results are as follows; Six cases (16.6%) turned out to have benign cellular change. Twenty five cases (69.1%) demonstrated squamous intraepthelial lesion, condyloma was 2 cases (6.0%) and mild dysplasia was not revealed. Moderate and severe dysplasia were 1 case (3.0%) and 16 cases (48.4%), squamous cell carcinoma and adenocarcinoma were 4 (12.1%) and 1 cases (3.0%), respectively. Our data suggested that patients with ASCUS are highly recommended to be examined colposcopic biosy to cornfim.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.599-606
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• 2012

The characterization of the whole genome of human papillomavirus type 16 (HPV16) from cervical cancer specimens with multiple infections in comparison with single infection samples as the oncogenic potential of the virus may differ. Cervical carcinoma specimens positive for HPV16 by PCR and INNO-LiPA were randomly selected for whole genome characterization. Two HPV16 single infection and six HPV16 multiple infection specimens were subjected to whole genome analysis by using conserved primers and subsequent sequencing. All HPV16 whole genomes from single infection samples clustered in the European (E) lineage while all multiple infection specimens belonged to the non-European lineage. The variations in nucleotide sequences in E6, E7, E2, L1 and Long control region (LCR) were evaluated. In the E6 region, amino acid changes at L83V were related to increased cancer progression. An amino acid variation N29S within the E7 oncoprotein significantly associated with severity of lesion was also discovered. In all three domains of the E2 gene non synonymous mutations were found. The L1 region showed various mutations which may be related to conformation changes of viral epitopes. Some transcription factor binding sites in the LCR region correlated to virulence were shown on GRE/1, TEF-1, YY14 and Oct-1. HPV16 European variant prone to single infection may harbor a major variation at L83V which significantly increases the risk for developing cervical carcinoma. HPV16 non-European variants prone to multiple infections may require many polymorphisms to enhance the risk of cervical cancer development.