• Biomolecules & Therapeutics
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• 제30권6호
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• pp.593-602
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• 2022

The human papillomavirus (HPV)-18 E7 (E7) oncoprotein is a major transforming protein that is thought to be involved in the development of cervical cancer. It is well-known that E7 stimulates tumour development by inactivating pRb. However, this alone cannot explain the various characteristics acquired by HPV infection. Therefore, we examined other molecules that could help explain the acquired cancer properties during E7-induced cancer development. Using the yeast two-hybrid (Y2H) method, we found that the Elk-1 factor, which is crucial for cell proliferation, invasion, cell survival, anti-apoptotic activity, and cancer development, binds to the E7. By determining which part of E7 binds to which domain of Elk-1 using the Y2H method, it was found that CR2 and CR3 of the E7 and parts 1-206, including the ETS-DNA domain of Elk-1, interact with each other. As a result of their interaction, the transcriptional activity of Elk-1 was increased, thereby increasing the expression of target genes EGR-1, c-fos, and E2F. Additionally, the colony forming assay revealed that overexpression of Elk-1 and E7 promotes C33A cell proliferation. We expect that the discovery of a novel E7 function as an Elk-1 activator could help explain whether the E7 has novel oncogenic activities in addition to p53 inactivation. We also expect that it will offer new methods for developing improved strategies for cervical cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8239-8245
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• 2016

The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor ${\beta}$, showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower ${\beta}$-tubulin levels and comparatively higher p53/${\beta}$-tubulin or CAR/${\beta}$-tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6693-6696
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• 2013

Background: Cold knife conization is a surgical procedure that allows both diagnosis and treatment of cervical lesions at the same time. It is mainly performed for indications of high-grade cervical intraepithelial neoplasia (CIN). In this study, we aimed to investigate the clinical outcome of cases without CIN in cold knife conization specimen, following a high-grade lesion (CIN2/3) in cervical biopsy. Materials and Methods: We performed a retrospective cohort study at a tertiary referral hospital between January $1^{st}$ 2008 and August $1^{st}$ 2012. Cases that underwent cold knife conization for CIN2/3 within the study period were included. Cone-negative (Group 1) and cone-positive (Group 2) cases were analyzed for various clinical parameters, and were compared in the 1-year post-conization period for histological recurrence and human papillomavirus (HPV) DNA status. Results: A total of 173 women underwent cold knife conization for CIN2/3 within the study period. Twenty-two cases (12.7%) were included in Group 1 and 151 cases (87.3%) in Group 2. There were no significant differences between the two groups in terms of age, gravidity, parity, menopausal status and HPV-DNA status (pre-conization and 1 year post-conization) (p>0.05). Recurrence rates were also similar between the groups (9.1% vs 9.9%, p>0.05). Conclusions: Clinical outcomes were similar in terms of histological recurrence and HPV persistence after 1 year of follow-up between cone-negative and cone-positive cases. Clinical follow-up of cone-negative cases should therefore be performed similar to cone-positive cases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2545-2549
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• 2013

Cervical cancer is one of the most frequent cancers in women worldwide. Persistent infection with a human papillomavirus (HPV) is the main cause for cervical cancer. Vaccination and Pap smear screening are the best methods for prevention of the disease. The objective of this cross-sectional study was to assess the knowledge and views of upper secondary school female students in Kuala Lumpur, Malaysia, toward prevention of cervical cancer. This study was conducted from April 2009 to September 2009 in 8 schools in Kuala Lumpur area using pre-tested and validated questionnaires. Results indicated that the respondents had low knowledge of cervical cancer and its prevention although the majority of students (80.4%) had heard about the disease. The level of knowledge of cervical cancr and its prevention was significantly higher among students from the science stream (p<0.001) compared to students from the art stream. Most students (69.3%) agreed to take the vaccination if the service was available in schools. A high percentage of students (82.2%) agreed that the vaccination should be compulsory to the students. In conclusion, most students had low knowledge of cervical cancer and its prevention but they had positive attitude toward vaccination and agreed that vaccination should be compulsory. Therefore, suitable educational programmes should be developed to improve the knowledge of secondary school students on the prevention of cervical cancer.

• Advances in pediatric surgery
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• 제5권1호
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• pp.69-74
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• 1999

Condyloma acuminata, an uncommon disease m the pediatric patients, is being reported with increasing frequency in both adults and children. During the last 10 years, we managed 11 children with condyloma acuminata of the anogenital area. The patients' age at presentation varied from 9 months to 11 years, and boys outnumbered girls by a ratio of 2 : 1. The lesions were found in the perianal area in 9 patients and the genital area in 2. No history of sexual contact or abuse could be elicited. Although the exact mode of transmission of human papillomavirus(HPV) couldn't be defined, maternal-infant transmission at birth and close nonsexual family contact were the main possible causes of HPV infection in our patients. Our experience suggest that fulguration of the warts and concomitant excision with scissors of the larger lesions are the most satisfactory method of treatment in children. However, condyloma acuminata have high recurrence rate despite these treatments. Viral typing and careful epidemiological investigation on a larger series of patients may clarify the causative factors and effective modalities of treatment in childhood anogenital condyloma acuminata.

• 한방안이비인후피부과학회지
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• 제29권2호
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• pp.180-186
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• 2016

Anal and perianal condyloma acuminatum(CA), which is a large cauliflower-like tumor, is a manifestation of human papillomavirus (HPV) infection. HPV may be acquired via sexual transmission, vertical transmission or nonsexual contact. It is an uncommon condition in children but the incidence in children has been increasing recently. There are many therapies for CA including chemical or physical destruction, immunological therapy, or a surgical excision. All these procedures have some degree of limitations such as limited clearance rate, high recurrence rate, pain, bleeding, release of potentially infectious aerosols and scar. It may be traumatic mentally to the children as well as physically. Korean Medicine included herbal treatment and herbal ointment for CA is no pain, and it doesn't need an anesthesia. We present a case of anal and perianal CA in a 2 years old boy that was treated successfully with Korean Medicine, with no recurrence during the follow up 3 months.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.16.1-16.5
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• 2018

Background: Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder, characterized by multifocal expression, progressive clinical evolution, and a high rate of malignant transformation. Evidence-based information regarding optimal PVL management is lacking, due to the paucity of data. The present report describes a case of PVL associated with HPV-16 infection and epithelial dysplasia treated by diode laser surgery, and the outcome of disease clinical remission over a 2-year follow-up period. Case report: A 61-year-old Caucasian male with oral verrucous hyperkeratosis presented for diagnosis. The lesions were localized on the maxillary gingiva and palatal alveolar ridge. Multiple biopsy specimens have been taken by mapping the keratotic lesion area. Microscopic examination was compatible with a diagnosis of PVL with focal mild dysplasia, localized in the right maxillary gingiva. Polymerase chain reaction (PCR) was done for human papillomavirus (HPV) detection which revealed presence of HPV DNA, and the genotype revealed HPV 16 in the sample. The PVL in the right gingival area was treated on an outpatient basis by excision with a diode laser. This approach resulted in good clinical response and decreased morbidity over a 2-year follow-up period. Conclusions: This case illustrates the benefit of a conservative approach by diode laser treatment than wide surgical excision for management of the PVL lesions associated with mild dysplasia and HPV-16 infection.

• 대한의용생체공학회:학술대회논문집
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• 대한의용생체공학회 1995년도 추계학술대회
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• pp.14-17
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• 1995

An in vitro construct of three dimensional artificial skin equivalent has been engineered using human cervical epithelial cells and human foreskin fibroblasts with a matrix of bovine type I collagen. Two cell lines were established from cervical uteri cancer tissues which have the HPV(human papillomavirus)18 genome. These two cell lines came from the same origin but have slight differencies in growth rate and tumorigenicity. The organotypic raft culturing of epithelial cells were accomplished at air-liquid interface. The differentiation related characteristics were examined by immunohistochemistry using monoclonal antibodies against EGFreceptor, cytokeratin 5/6/18 as proliferation markers and against filaggrin, involucrin, and cytokeratin 10/13 as differentiation marker. We have obtained the stratification and the differentiation in the artificial skin equivalent, and differentiation-related proteins were expressed more in the C3-artificial skin, and proteins of proliferation were expressed more in the C3N-artificial skin, relatively. We found that reconstituted artificial skin have the same characteristics of differentiation proteins of original tissue or cells of human body.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4977-4980
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• 2015

Background: ASC-US cases are managed according to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guideline in which a human papillomavirus (HPV) test and repeat Pap smear are performed in the next 1 year. Colposcopy in cases of positive high risk HPV and persistent ASC-US or more in subsequent Pap smear is recommended. The HPV test is more expensive and still not currently a routine practice in Thailand. Objective: To identify the risk factors of persisted abnormal Pap smear and the colposcopic requirement rate in women with ASC-US. Materials and Methods: During 2008-2013, this study was conducted in Prapokklao Hospital, Chanthaburi, Thailand. Participants were women who attended gynaecology clinic for cervical cancer screening. Women who had cytological reports with ASC-US were recruited. During the study period, 503 cases were enrolled. Colposcopic requirement was defined as those who were detected with an ASC-US or more in subsequent Pap smears up to 1 year follow-up. Results: The colposcopic referral rate was 23.2 (85/365) percent at 12 months. Prevalence of cervical intraepithelial neoplasia (CIN) 2/3 was 3.3 (12/365) percent. Loss follow-up rate of subsequent Pap smear and colposcopic appointment were 27.4 (138/503) and 48.2 (41/85) percent, respectively. There was no invasive cancer. High risk factors for persisted abnormal Pap smears in subsequent test were premenopausal status, HIV infected patients and non-oral contraceptive pills (COC) users. Conclusions: Referral rate for colposcopy in women with ASC-US reports was rather high. Loss to follow-up rate was the major limitation. Immediate colposcopy should be offered for women who had high risk for silent CIN.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.253-258
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• 2015

Background: Development of squamous cell cancer of head and neck (SCCHN) is associated with human papillomavirus (HPV) infection, which in turn is closely related with expression of $p16^{INK4A}$. Loss of $p16^{INK4A}$ expression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated $p16^{INK4A}$ as a prognostic marker of treatment response and survival in our SCCHN patients with laryngeal, hypopharyngeal or nasopharyngeal cancers. Materials and Methods: 131 patients diagnosed with SCCHN between January 2,2006 and July 17, 2010 were examined for $p16^{INK4A}$. The median age was 60 years (15-82 years). Fifty one patients were stage I-II and 80 were stage III-IV. Immunohistochemical expression of $p16^{INK4A}$ was analyzed in pretreatment paraffin-embedded tumor blocks. The influence of $p16^{INK4A}$ status on disease-free survival, and overall survival after treatment was evaluated. Results: $p16^{INK4A}$ positivity was found in 58 patients (44%). Tumor-positivity for$ p16^{INK4A}$ was correlated with improved disease free survival (70.1 months vs 59 months) and improved overall survival (2, 3 and 5-year values; 77% vs 72%, 70% vs 63% and, 63% vs 55%; respectively). On multivariate analysis, stage was determined as independent prognostic factor for disease-free survival. Conclusions: Stage was the major prognostic factor on treatment response and survival in our patients. $p16^{INK4A}$ status predicts better outcome in laryngeal, hypopharyngeal or nasopharyngeal cancer cases treated with surgery plus adjuvant radiochemotherapy as well as with definitive radiation therapy and/or chemotherapy.