• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1497-1500
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• 2014

Cervical cancer continues to be an important public health problem in Thailand. While the high risk human papillomavirus (HPV) types have been established as the principle causative agent of both malignancies and the precursor lesions, cervical intraepithelial neoplasia (CIN), other factors may also be involved like other sexually transmitted diseases, as well as smoking. Chlamydia trachomatis is an obligate intracellular Gramnegative bacterium which has a tendency to cause chronic infection featuring inflammation and therefore might be expected to increase the risk of cervical cancer. In the present nested case-control study, 61 cases of cervical cancer and 288 matched controls with original serum samples were identified from the Khon Kaen Cohort, established in the North-East of Thailand, by linkage to the Khon Kaen population based cancer registry. C. trachomatis specific IgG antibodies at recruitment were measured by microimmunofluorescence and assessed for association with cervical cancer using STATA release10. No significant link was noted either with all cancers or after removal of adenocarcinomas. The results suggest no association between Chlamydia infection and cervical cancer development in North-East Thailand, but possible influencing factors must be considered in any future research on this topic.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4149-4154
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• 2016

Background: Cervical carcinoma is one of the main causes of mortality in women worldwide as well as in India. It occurs as a result of various molecular events that develop from the combined influences of an individual's genetic predisposition and external agents such as smoking and menstrual hygiene, for example. However, infection with human papillomavirus (HPV) is the established major risk factor. The aim of the current study was to investigate p16 CpG island methylation and establish any correlation with mRNA expression in north Indian population. Materials and Methods: We analyzed 196 woman volunteer out of which 98 were cases and 98 healthy controls. For the analysis of methylation pattern, DNA extracted from blood samples was modified with a bisulfate kit and used as template for methylation specific PCR (MSP). Quantitative real-time PCR (QRT-PCR) was performed to check mRNA expression. Results: Correlation between methylation status of p16 gene and poor menstrual hygiene was significant (p=0.006), high parity cases showed methylation of p16 gene (p=0.031) with increased risk up to 1.86 times for cervical cancer and smoking was a strong risk factor associated with cervical cancer. We analyzed methylation pattern and found 60.3% methylation in cases with low mRNA expression level (0.014) as compare to controls (1.24). It was also observed that promoter methylation of p16 gene was significantly greater in FIGO stage III. Conclusions: We conclude that p16 methylation plays an important role in cervical cancer in the north Indian population and its methylation decreases mRNA expression. It can be used as an important and consistent blood biomarker in cervical cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7357-7362
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• 2014

Interleukin-6 (IL-6), a central proinflammatory cytokine, maintains immune homeostasis and also plays important roles in cervical cancer. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms at positions -174 and -572 with predisposition to cervical cancer in a Chinese population. The present hospital-based case-control study comprised 518 patients with cervical cancer and 518 healthy controls. Polymorphisms of the IL-6 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients with cervical cancer had a significantly higher frequency of the IL-6 -174 CC genotype [odds ratio (OR) =1.52, 95% confidence interval (CI) = 1.06-2.19; p=0.02], IL-6 -572 CC genotype (OR =1.91, 95% CI = 1.16-3.13; p=0.01) and IL-6 -174 C allele (OR =1.21, 95% CI = 1.02-1.44; p=0.03) compared to healthy controls. When stratifying by the FIGO stage, patients with III-IV cervical cancer had a significantly higher frequency of IL-6 -174 CC genotype (OR =1.64, 95% CI =1.04-2.61; p=0.04). The CC genotypes of the IL-6 gene polymorphisms at positions -174 and -572 may confer a high risk of cervical cancer. Additional studies with detailed human papillomavirus (HPV) infection data are warranted to validate our findings.

• Toxicological Research
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• 제18권1호
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• pp.23-29
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• 2002

Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.589-594
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• 2013

Background: Prospective cohort studies to determine cofactors with oncogenic HPV-infections for cervical cancer are very rare from developing countries and such data are limited to the few screening trials. Large screening trials provide such data as a by product. Some of the cases are prevented by screening and do not surface as invasive cancers at all. Also, pre-invasive lesions are detected almost entirely by screening. Screening causes selection bias if attendance in or effectiveness of screening is correlated with the risk factors. The aim of this study was to quantify the influence of screening on risk factors for cervical cancer. Materials and Methods: Our material stems from a rural cohort of 80,000 women subjected to a randomised screening trial. The effect of screening on the incidence of cervix cancer was estimated with reference to socio-demographic and reproductive risk factors of cervical cancer. We compared these risks with the incidence of cancer in the randomised control population by the same determinants of risk. Results: The results in the screening arm compared to the control arm showed that the women of low SES and young age were benefitting more than those of high SES and old age. The relative risk by age (30-39 vs 50-59) was 0.33 in the control arm and 0.24 in the screening arm. The relative risk by education (not educated vs educated) was 2.8 in the control arm and 1.8 in the screening arm. The previously married women did not benefit (incidence 113 and 115 per 100,000 women years in control vs screening arms) whereas the effect was substantial in those married (86 vs 54). Conclusions: The results in controls were consistent with the general evidence, but results in attenders and nonattenders of the screening arm showed that screening itself and self-selection in attendance and effectiveness can influence the effect estimates of risk factors. The effect of cervical cancer screening programmes on the estimates of incidence of cervical cancer causes bias in the studies on etiology and, therefore, they should be interpreted with caution.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6639-6641
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• 2014

Background: To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. Materials and Methods: A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Results: Mean age of the patients was $54.6{\pm}6.5$ years in group 1 and $38{\pm}6.6$ years in group 2. Some 14 (8.5%) of post-menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). Conclusions: In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post-menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4429-4434
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• 2015

Background: Public awareness/knowledge on oral and pharyngeal cancer (OPC), potentially malignant disorders (PMODs) and their risk factors is crucial for prevention and early detection of OPC and PMODs. Yet, there are no published data available on the awareness and knowledge of OPC and PMODs among people living in Far North Queensland, Australia. Materials and Methods: This study was conducted as a cross sectional survey. A self-administered questionnaire was designed and consisted of relevant questions to ascertain socio-demographic information, awareness and knowledge of OPC, PMODs and risk factors and questions on participant's exposure to risk factors and dietary history were also included. Survey was carried out at the Dental Clinic of the James Cook University School of Dentistry (JCU Dental), Cairns, Australia. Subjects above the age of 20 years (n=366) were randomly selected during the period from 31st July to 6th September 2013 and questionnaire was distributed to complete while they are waiting for treatment. Data analysis was carried out using SPSS version 21 and the chi -squared test was employed to compare groups. P<0.05 was considered statistically significant. Results: The study revealed that 52.3% of the respondents were aware of the existence of OPC but only 19.0% were aware of PMODs. Of those who were aware of oral cancer, 92% agreed or strongly agreed that smoking is a strong risk factor for OPC. Similarly a relatively high proportion of the respondents agreed or strongly agreed that tobacco chewing (84%), tobacco chewing with areca nut (68%), chewing areca nut alone (51%) and exposure to actinic radiation (71%) as risk factors. However, the results for alcohol intake, age, and HPV infection were found to be relatively poor with proportions 33%, 34%, and 23% respectively. Conclusions: This study revealed an alarming lack of awareness and knowledge of OPC and PMODs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6557-6559
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• 2015

Background: Cervical human papillomavirus (HPV) infection among young women (20-25 years of age) is common and normally transient. There are growing concerns that referral to a colposcopy clinic may lead to unnecessary treatment with an increased risk of obstetric complications. Therefore, the purpose of this study was to determine the level of intervention for cervical abnormalities in this age group of the Northern Ireland population. Materials and Methods: A review of all serial new patients under 25 years of age, who were referred to colposcopy clinics in Northern Ireland between January 1, 2009 to June 30, 2009 formed the basis of this study. Results: During the study period, a total of 4,767 women under 25 years of age were screened. Two-hundred-and-thirty-four (4.9%) cases were referred to the colposcopy clinics. The cervical cytology results were: high-grade abnormality in 35%, and low-grade abnormality in 31% of these cases. One-hundred-and-seventy-eight (76%) of the referred women received at least one treatment. One-hundred-and-twenty-one of 234 (51.5%) women underwent an excisional treatment with histology showing the presence of high-grade abnormalities (CIN2-3) in 52%, CIN1 in 28%, and Koilocytosis or normal tissue in 20% of this sub-group of cases. Conclusions: Screening women under the age of 25 years cause unnecessary referral for colposcopy. This may also result in considerable anxiety and psychosexual morbidity. It leads to an over-treatment with a potential of negative impact on the future pregnancy outcomes (including pre-term delivery, low birth weight, and pre-term premature rupture of membranes).

• 한국치위생학회지
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• 제15권3호
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• pp.523-529
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• 2015

Objectives: Oropharynx tumors(oral cancer), are caused by tobacco, alcohol consumption, and high-risk human papillomavirus(HPV) infection. Oral squamous cell carcinoma(OSCC) is the most common type of oral cancer and frequently arises from the mucosa of the oropharynx and oral cavity. Despite advances in the diagnosis and treatment(chemotherapy, radiotherapy, and surgery) of oral cancer, over the past two decades, the overall survival rates remains at about 60%. Methods: We pretreated HSC-2 cells with various doses of exposed the cells to eugenol and then we measured cell viability by MTT assay. Results: Cell proliferation was markedly inhibited after eugenol treatment compared to the control. The majority of HSC-2 cells in the control groups showed normal morphology with round regular nuclei. In contrast, apoptotic bodies were seen in the 0.5 mM, 1 mM, 2 mM group. However, the pretreatment with eugenol increased HSC-2 cells apoptosis according to dose-dependency. PI staining quantitatively confirmed the anti-apoptotic effects of propofol. The expression levels of cleaved caspase 3, and Bak significantly increased in HSC-2 cells. Conclusions: These findings indicate that eugenol could be a potential anti-cancer agent for human OSCC and provide valuable data for the development of a novel anticancer strategy.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.296-307
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• 2017

In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced block-age of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs. We also observed their robust responsiveness to various exogenous stimuli, which was evidenced by increased mRNA expression of epithelial differentiation markers and pro-inflammatory genes in response to three reactive chemicals. In addition, their applicability to cytotoxicity assessment turned out to be comparable to that of HaCaT cells. Finally, we confirmed their differentiation capacity by construction of well-stratified three dimensional skin cultures. These newly established immortalized HFKs will be valuable tools not only for generation of in vitro skin disease models but also for prediction of potential toxicities of various cosmetic chemicals.