• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.2
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• pp.135-141
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• 2001

Recently, the consumption of soy products has been associated with low rates of hormone-dependent and hormone-independent cancers. Asians, who consume $20{\sim}50times$ more soy per capita than Americans, have lower incidence and death rates from breast and prostate cancer. Because soy contains the isoflavones genistein and daidzein (present as their glycosidic conjugates) at mg/g concentrations, it has been suggested that isoflavones might be acting as natural chemopreventive agents. During the 1980s several groups of investigators carried out experiments to test the effectiveness of soy in the diet in animal models of cancer. These studies reported a protective effect of soy; none showed that soy increased cancer risk. Genistein was shown to inhibit the growth of a wide variety of tumor cell types in culture. The purpose of this study was to evaluate the effects of genistein on the carcinogenesis induced by topical application of 0.5% 9, 10-dimethyl 1,2-benzanthracene (DMBA) on the hamster buccal pouch. 48 syrian hamsters were employed in this study, divided into experimental group and control. 24 animals (DMBA topical application group) had the right buccal pouch painted 3times weekly with 0.5% DMBA in mineral oil, 24 animals (genistein group) were supplied with 0.1mg genistein with DMBA topical application. 3 animals in the experimental group and control were sacrificed at serially each other week after experiments. Their buccal pouches were removed and routinely processed for microscopic examination. The results were as follows: 1. In DMBA topical application and genistein group, they showed carcinogenesis as time goes by experimental stage. 2. Genistein group was retarded in carcinogenesis related to the acanthosis, hyperkeratosis, epithelial dysplasia. 3. p53 immunohistochemical study showed that the p53 protein of genistein group was less expressed than that of the control group. Thus, it seems that genistein has chemopreventive effect on the carcinogenesis in the oral cavity, but further study is required to elucidate the anticancer mechanism of genistein.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.2
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• pp.147-154
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• 2002

Genistein that is a component of soy has been reported to have a protective effect on the carcinogenesis of various tumors and to inhibit the growth of a wide variety of tumor cell in vitro. Angiogenesis is an essential process for the carcinogenesis, growth, invasion and metastasis of cancer and genistein has been suggested to act as natural anti-angiogenic agent. The purpose of this study was to evaluate the effects of genistein on the vascular endothelial growth factor (VEGF) expression in hamster buccal pouch oral carcinogenesis model induced by 9, 10-dimethyl 1,2-benzanthracene (DMBA). Experimental group that were supplied with 0.1mg/day genistein were sacrificed by time schedules and routinely processed for immunohistochemical examination of VEGF. In genistein treated group, carcinogenesis was retarded with respect to the acanthosis, hyperkeratosis, and epithelial dysplasia. Immunohistochemical study showed that the VEGF protein of genistein group was less expressed than that of the control group. (p<0.05) Thus, it is postulated that genistein has chemopreventive effect on the oral carcinogenesis, and this chemopreventive effect, at least partly, is originated from the anti-angiogenic effect of genistein

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.1
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• pp.1-8
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• 1991

In attempts to evaluate carcinogenic chemical effect on $Na^+,K^+$-ATPase activity in the rat submandibular gland tumor induced by DMBA, pellet from DMBA powder was inserted into the right submandibular gland. Both right and left submandibular gland were excised and weighed following the period of experiment. Excised glands were observed microscopically and estimated biochemically. The results were obtained as follows. 1. Swelling and nodular mass in the right submandibular gland region ould be found at 11th week post-implantation with DMBA. 2. The weight and size of the right submandibular gland was markedly increased following the period of the experiment. 3. Epithelial dysplasia and invasive epidermoid carcinoma could be observed at 7th and 11th week after implantation of DMBA, respectively. 4. The rate of tumor induction in the right submandibular gland was about 76% at 17th week following implantation of DMBA. 5. DMBA caused markedly depressed $Na^+,K^+$-ATPase activity as well as the activity ratio in the rgiht submandibular gland following the period of experiment.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.257-263
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• 2018

Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. Tff1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated Tff1-knockout (KO) mice, without a neomycin resistant ($Neo^R$) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our Tff1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established Tff1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that Tff1 expression influences gender differences.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.69-84
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• 1997

Background : Although the overall prognosis of patients with lung cancer is poor, highly effective treatment exists for the small subset of patients with early lung cancer(carcinoma in situ/micro- invasive cancer). But very few patients have benefit from them because these lesions are difficult to detect and localize with conventional white-light bronchoscopy. To overcome this problem, a Lung Imaging Fluorescence Endoscopic device(LIFE) was developed to detect and clearly delineate the exact location and extent of premalignant and early lung cancer lesions using differences in tissue autofluorescence. Purpose : The purpose of this study was to determine the difference of sensitivity and specificity in detecting dysplasia and carcinoma between fluorescence imaging and conventional white light bronchoscopy. Material and Methods : 35 patients (16 with abnormal chest X-ray, 2 with positive sputum study, 2 with undiagnosed pleural effusion, 15 with respiratory symptom) have been examined by LIFE imaging system. After a white light bronchoscopy, the patients were submitted to fluorescence bronchoscopy and the findings of both examinations have been classified in 3 categories(class I, II, III). From of all class n and III sites, 79 biopsy specimens have been collected for histologic examination: a comparison between histologic results and white light or fluorescence bronchoscopy has been performed for assessing sensitivity and specificity of the two methods. Results : 1) Total 79 sires in 35 patients were examined. Histology demonstrated 8 normal mucosa, 21 hyperplasia, 23 dysplasia, and 27 microinvasive and invasive carcinoma. 2) The sensitivity of white light or fluorescence bronchoscopy in detecting dysplasia was 60.9% and 82.6%, respectively. 3) The results of this study showed 70.3 % sensitivity for microinvasive or invasive carcinoma with LIFE system, versus 100% sensitivity for white light in 27 cases of carcinoma. The false negative study of LIFE system was 8 cases(3 adenocarcinoma and 5 small cell carcinoma), which were infiltrated in submucosal area and had normal epithelium. Conclusion : To improve the ability 10 diagnose and stage more accurately, fluorescence imaging may become an important adjunct to conventional bronchoscopic examination because of its high detection rate of premalignant and malignant epithelial lesion. But. it has limitation to detect in submucosal infiltrating carcinoma.

• Journal of the korean academy of Pediatric Dentistry
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• v.31 no.4
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• pp.651-658
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• 2004

Runx2 is a transcription factor in homologous with Drosophila runt gene and it is essential for bone formation during embryogenesis and a critical gene for osteoblast differentiation and osteoblast function. Runx2-haploinsufficency causes cleidocranial dysplasia (CCD). CCD is an autosomal-dominant inherited disorder characterized by hypoplastic clevicle and delayed ossification in fontanelles and wormian bones. Dental defects are possibly shown to CCD patients : multiple supernumerary teeth, irregular and compressed permanent tooth crowns, hypoplastic and hypomineralized defects in enamel and dentin, an excess of epithelial root remnants, the absence of cellular cementum, and abnormally shaped roots. In addition, delayed eruption of the secondary dentition is a constant finding. The aim of this study is to evaluate the role of Runx2 in the tooth development and eruption through analyzing the expression pattern of Runx2 by in situ hybridization during crown (late bell stage) and root formation of tooth, using postnatal day 1, 4, 7, 14 and 21 mice mandibular molar teeth. mRNA of Runx2-full length is expressed in dental follicle and surrounding tissue at postnatal day1 and 4. At postnatal day 7, it is expressed in ameloblasts of occlusal surface of enamel and bone area surrounding the tooth. In comparison with previous stage, at postnatal day 14, it is expressed in ameloblasts of proximal surface of enamel. At postnatal day 21 it's expression is observed only in bone area. mRNA of Runx2-typeII is not expressed. At postnatal day 1 and 7. At postnatal day 14 and 21, it's expression is observed in the bone area. In this study, we suggest that Runx2 have a relation of ameloblasts differentiation and an important role to tooth eruption made by dental follicle during intraosseous eruption stage. Also we can confirm that Runx2 has a role to bone formation.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.4 no.1
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• pp.33-41
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• 1991

The clinical entity referred to as epithelial hyperplasia has been called by various terms : keratosis, hyperkeratosis, pachydermia, acanthosis, leukoplakia, hyperkeratotic laryngitis. The metaplasia and keratinization of the layngeal mucosa are associated with the subsequent appearance of invasive epidermoid carcinoma. Therefore. frequent and prolonged periods of observation and histologic study on keratosis of the larynx are essential. A retrospective review of 18 patients with laryngeal hyperkeratosis seen at Department of Otolaryngology Yondong Severance Hospital during the 7 years period was completed. The results are summarized as follows : 1) The incidence was much higher in males(22 patients) than in females(4 patients) 2) The peak age of male was 4th decades and the peak age of female was 4th. 5th decades. 3) The chief complaint of the patients was hoarseness in all cases. 4) The average duration of symptoms was less than 24 months for 19 cases(73.1%). 5) 17 patients(65.4%) was smokers and duration of smoking was 10~20 years for 10 cases(38.8%). 6) On histological examination. the lesions were classified into three types: simple hyperplasia(61.5%). dysplasia(26.9%) and carcinoma in situ(2 cases). 7) The recurrence rates was 9 cases(34.6%) and transformation rate into invasive carcinoma was 1 case(3.8%).

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.1
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• pp.19-26
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• 2006

Objective: In order to elucidate the retrogressive degeneration of orofacial cleft, the fissured tissues of prenatal and postnatal cleft lip and palate were examined by histological and immunohistochemical methods. Design: Totally 42 cases of prenatal (n=17) and postnatal (n=25) cleft lip and/or palate were examined in comparison with 10 cases of normal lip and oral mucosa using immunohistochemical stainings of MMP-3, MMP-9, MMP-10, cathepsin G, PCNA, E-cadherin, TGase 2, HSP-70, vWF, and VEGF. Main Outcome Measures: In the fissured tissue the sebaceous glands were strongly positive for PCNA and grew into the underlying fibromuscular tissue (24/42). Some hyperplastic sebaceous glands of prenatal cleft lip produced infundibular follicular cyst (9/17). The skin and mucosal epithelia from the postnatal cleft lip and palate (10/25) showed severe basal hyperplasia (11/25) and melanocyte infiltration (7/25). Results: The immunostaining of MMP-3 and HSP-70 were strongly positive in the hyperplastic sebaceous glands and nearby atrophying muscle bundles of the fissured tissue, while MMP-9, MMP-10, and cathepsin G were almost negative. The immunoreactions of the other antibodies used in this study were similar between in the fissured tissues and in the normal controls. Conclusions: These data suggest that the over-expression of MMP-3 is closely related to the sebaceous gland hyperplasia, epithelial dysplasia, and the muscle degeneration, and that the over-expression of MMP-3 in the fissured tissue may continuously aggravate the cleft condition in the later life.