• International Journal of Oral Biology
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• 제47권1호
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• pp.9-15
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• 2022

Humulus japonicus (HJ) is a widely used herbal medicine for pulmonary tuberculosis, hypertension, leprosy, and venomous wounds in Asia, particularly in China. Although HJ has certain physiological activities, such as longitudinal bone growth, antioxidation and alleviation of rheumatism, its anticancer activities, other than in colorectal and ovarian cancer, are yet to be studied. In this study, we investigated the anti-cancer activity and mechanism of methanol extracts of HJ (MeHJ) against human FaDu hypopharyngeal squamous carcinoma cells. MeHJ suppressed FaDu cell viability without affecting normal cells (L929), which was demonstrated using the MTT and Live & Dead assays. Furthermore, MeHJ effectively inhibited colony formation of FaDu cells, even at non-cytotoxic concentrations, and significantly induced apoptosis through the proteolytic cleavage of caspase-9, -3, -7, poly (ADP-ribose) polymerase and through the downregulation of BCL-2 and upregulation of BAX in FaDu cells, as determined by DAPI staining, flow cytometry, and western blot analyses. Collectively, these findings suggest that the inhibitory effects of MeHJ on the growth and colony formation of oral cancer cells may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeHJ has the potential to be used as a natural chemotherapeutic drug against human oral cancer.

• International Journal of Oral Biology
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• 제46권4호
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• pp.160-167
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• 2021

Nypa fruticans Wurmb (NFW) contains a large amount of phenolic acid and flavonoids, and is popular as a superfood in Myanmar. NFW has various biological activities, such as anti-inflammatory, anti-oxidant, and neuroprotective properties; however, the anti-cancer effect of NFW have not been reported. In this study, we investigated the anticancer activity of water extracts of NFW (WeNFW) and the underlying mechanism in human FaDu hypopharyngeal squamous carcinoma cells. The WeNFW inhibited FaDu cell growth in a dose-dependent manner without affecting normal cells (L929), as determined by an MTT assay and Live and Dead assay. In addition, the concentrations of WeNFW without cytotoxicity (0.025, 0.05, and 0.1 mg/mL) inhibited wound healing and colony formation. Furthermore, WeNFW significantly induced apoptosis through the proteolytic cleavage of caspase-3 and -9, poly (ADP-ribose) polymerase, and downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by DAPI staining, FACS analysis, and western blot analysis. Taken together, these results suggest that WeNFW exhibits potent anti-cancer effects by suppressing the growth of oral cancer cells, wound healing and colony formation activity. Via mitrochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, WeNFW can provide a natural chemotherapeutic drug for oral cancer in humans.

• 한국컴퓨터정보학회논문지
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• 제27권6호
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• pp.87-93
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• 2022

본 연구는 암환자의 구강검진 수검여부와 미수검에 영향을 미치는 요인을 분석함으로써 구강검진 수검률을 높이기 위한 기초자료로 활용하고자 시행되었다. 자료 수집은 제7기(2016-2018) 국민건강영양조사의 자료를 이용하여 40세 이상 성인 중 암환자로 진단받고, 현재 유병 여부 질문에 "있음"이라고 응답한 376명을 최종대상자로 선정하였고, SPSS/WIN 26.0 프로그램을 이용하여 복합표본 분석을 하였다. 연구 결과 암 환자 중 구강검진 수검이 있는 경우 38%, 없는 경우는 62%이었다. 구강검진 미수검에 영향을 미치는 요인은 연령이 70세 이상일 경우 3.641배, 교육수준이 초등학교 이하일 경우 3.928배, 소득분위(가구)가 낮을 경우 3.740배, 하루 칫솔질 횟수가 2회 이하일 경우 2.050배, 최근 1년간 치과병·의원 이용이 없을 경우 2.533배, 저작불편을 호소할 경우 2.533배, 말하기 문제가 있을 경우 2.746배 통계적으로 유의하게 증가하는 것으로 나타났다(p<0.05). 이상의 결과를 통해 암환자의 치료과정 중 발생되는 구강내 합병증을 고려한 구강관리와 구강검진의 중요성에 대한 교육 확대가 요구되었고, 암환자를 위한 맞춤형 구강건강관리 프로그램 운영의 적극적인 도입이 필요할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.1913-1918
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• 2014

Background: The study is the first of its kind to be conducted in Saudi Arabia (KSA), aiming to analyze the effectiveness of an intervention program in improving the knowledge of oral cancer among the youth. Materials and Methods: A total of 1,051 young Saudis (57% males and 43% females with a mean age of $20.4{\pm}1.98$) were selected using multi-stage cluster sampling. Knowledge assessment was accomplished using a closed-ended questionnaire which was subjected to reliability tests. Prevalence of risk factors in relation to gender was analyzed using the chi-squared test. Effectiveness was calculated by comparing the pre- and post-intervention means, using the two-tailed paired t-test. Multiple logistic regression was employed in order to determine factors associated with awareness of risk habits, signs/symptoms and prevention of oral cancer. The significance level in this study was set at 0.05. Results: Females were seen to be more into the habit of sheesha smoking (3.3% rather than the use of other forms of risk factors. Prevalence of diverse risk factors such as cigarette smoking (20%), sheesha (15.3%), khat (27%) and shamma (9%) was seen among males. Gender and the use of modifiable risk factors among the study sample were significantly (p<0.001) associated with effectiveness of the intervention. The intervention program was highly effective (p<0.001) in improving the knowledge of oral cancer among the youth in Jazan, KSA. Multivariate analysis revealed that age and gender are the most significant factors affecting knowledge. Conclusions: The study gives a direction for further public health initiatives in this oral cancer prone region.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2225-2229
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• 2014

Background: Carcinoma of the tongue is the most common intra-oral malignancy in Western countries. Incidence and mortality rates have increased in recent years, and survival has not improved. This study aimed to determine etiologic factors for tongue cancer with age-sex matched case-control data. Materials and Methods: 47 patients with carcinoma of the tongue referred to our oral medicine clinic between years 2005-2006 were analyzed and compared with control group data. The medical records, including family history of cancer, dental trauma, and history of abuse of alcohol and tobacco products was recorded for all subjects. Chi square comparison tests and linear regression analysis were performed using the SPSS program for statistics. Results: Patient and randomly selected control groups each consisted of 30 male and 17 female subjects with mean ages 53.2 (${\pm}12.6$) and 52.6 (${\pm}11.5$) years respectively. Smoking and alcohol abuse proportions were significantly higher in the patient group (p=0.0001, p<0.0001 respectively). Chronic mechanical trauma was observed in 44.7% of the patients and 17.0% of the control group (p=0.004). Similarly, family history of cancer of any type (for the first degree relatives) was found to be more common in the patient group (p=0.009). On regression analysis, alcohol abuse, family history of cancer, smoking, chronic mechanical traumas appeared as significant etiologic factors (p=0.0001). Conclusions: We believe that field cancerization may become evident in oral and oropharyngeal mucosa with multiple steps of molecular changes starting from the first sign of dysplasia with chronic exposure to etiological factors. Chronic trauma cases need particular attention to search for very early signs of cancer.

• 한국융합학회논문지
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• 제10권8호
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• pp.59-65
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• 2019

암 조직에는 다양한 형태의 세포가 존재하지만, 이들의 조성을 실험적으로 확인하기는 매우 어렵다. 본 연구에서는 유전자 발현 데이터에 통계적 기계학습 모델을 적용하여 각 샘플의 세포 조성을 추론하고, 이러한 세포 조성이 암조직과 정상 조직간에 차이가 있는지를 확인하였다. 두 가지 서로 다른 회귀 모델을 이용하여 세포 조성을 예측한 결과 CD8 T cell과 Neutrophil이 구강암 조직에서 정상 조직에 비해 증가함을 확인할 수 있었다. 또한 비지도학습 중 하나인 t-SNE를 적용하여, 유추된 세포 조성에 의해 정상 조직과 구강암 조직이 서로 군집을 이루고 있음을 확인하였고, 지도 학습 기반의 다양한 분류 알고리즘들을 이용하여 세포 조성 정보를 이용하여 구강암과 정상 조직을 예측하는 것이 가능함을 보였다. 이 연구는 구강암의 면역 세포 침투에 대한 이해도를 증진하는데에 도움을 줄 수 있을 것이다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권4호
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• pp.199-204
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• 2009

Purpose: The purpose of this study is to investigate the epithelial-mesenchymal transition (EMT) induced by Snail transcription factor and Snail-transfected in vivo tumors with histopathological features. Materials and methods: We induced in vivo xenografted tumorigenesis in the oral vestibules of nude mice by a Snail transfected HaCaT cell line and investigated morphological and immunohistochemical features in Snail expressive tumors. Results: We identified tumor masses in 14 out of 15 nude mice in the HaCaT-Snail cell inoculation group, but no tumors were present in any of the HaCaT cell inoculation group. Induced tumors showed features of poorly differentiated carcinoma with invasion to neighboring muscles and bones. The HaCaT-Snail tumors showed decreased expressions of E-cadherin and cytokeratin, but showed increased expressions of vimentin and N-cadherin. Discussion: The Snail transfected xenograft can improve productivity of malignant tumors, show various histopathological features including invasive growth, and aid in the investigation of tumor progression and the interaction with surrounding tissues.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1421-1426
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• 2016

Background: There is a considerable lack of understanding of oral cancer incidence, especially its time trend in Iran. In this study, the authors aimed to analyze time trend of oral cancer incidence with a focus on differences by gender in a period of six years - from 2005 to 2010. Materials and Methods: Both population-based cancer registry and national cancer registry (NCR) data based on pathologic reports from 2005 to 2010 were obtained from the Ministry of Health and Medical Education (MOHME). Population data were also received from Statistical Centre of Iran. Age-standardized incidence rates (ASRs) based on the World Standard Population were then calculated. Finally, Negative Binomial regression was run for time trend analysis. Results: The maximum ASR for males was calculated as 2.5 per 100,000 person-years in 2008 and the minimum was observed as 1.9 per 100,000 person-years in 2005 and 2006. Meanwhile, the maximum ASR for females was estimated as 1.8 per 100,000 person-years in 2009 and the minimum was calculated as 1.6 per 100,000 person-years in 2005 and 2006. Additionally, in females, incidence risk ratio (IRR) did not show a clear decreasing or increasing trend during the six years. Nevertheless, in males an increasing trend was observed. The maximum IRR adjusted for age group and province, for females was reported in 2009 (IRR=1.05 95% CI: 0.90-1.23), and for males was estimated in 2010 (IRR=1/2 95% CI: 1.04 - 1.38). Conclusions: Our findings highlight disparities between oral cancer incidence trends in males and females over the six years from 2005 to 2010.

• International Journal of Oral Biology
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• 제32권3호
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• pp.93-101
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• 2007

Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1599-1603
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• 2015

Background: Epigenetic silencing of tumor suppressor genes due to promoter hypermethylation is one of the frequent mechanisms observed in cancers. Hypermethylation of several tumor suppressor genes involved in cell cycle regulation has been reported in many types of tumors including oral squamous cell carcinomas. LATS1 (Large Tumor Suppressor, isoform 1) is a novel tumor suppressor gene that regulates cell cycle progression by forming complexes with the cyclin dependent kinase, CDK1. Promoter hypermethylation of the LATS1 gene has been observed in several carcinomas and also has been linked with prognosis. However, the methylation status of LATS1 in oral squamous cell carcinomas is not known. As oral cancer is one of the most prevalent forms of cancer in India, the present study was designed to investigate the methylation status of LATS1 promoter and associate it with histopathological findings in order to determine any associations of the genetic status with stage of differentiation. Materials and Methods: Tumor chromosomal DNA isolated from biopsy tissues of thirteen oral squamous cell carcinoma biopsy tissues were subjected to digestion with methylation sensitive HpaII enzyme followed by amplification with primers flanking CCGG motifs in promoter region of LATS1 gene. The PCR amplicons were subsequently subjected to agarose gel electrophoresis along with undigested amplification control. Results: HpaII enzyme based methylation sensitive PCR identified LATS1 promoter hypermethylation in seven out of thirteen oral squamous cell carcinoma samples. Conclusions: The identification of LATS1 promoter hypermethylation in seven oral squamous cell carcinoma samples (54%), which included one sample with epithelial dysplasia, two early invasive and one moderately differentiated lesions indicates that the hypermethylation of this gene may be one of the early event during carcinogenesis. To the best of our knowledge, this is the first study to have explored and identified positive association between LATS1 promoter hypermethylation with histopathological features in oral squamous cell carcinomas.