• Title/Summary/Keyword: Oral cancers

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ACRYLAMIDE-INDUCED NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (Acrylamide가 인체상피세포의 발암화에 미치는 영향)

  • Kim, Sang-Kyu;Kim, Jin-Wook;Kim, Chin-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.34 no.6
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    • pp.602-610
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    • 2008
  • Purpose Acrylamide is present in significant quantities in a wide range of commonly consumed human foods. Carcinogenic risk of acrylamide through the consumption of food is a great public concern and in controversy, but it is not properly addressed due to the lack of evidence in humans. While a plenty of data is available on the carcinogenicity in animal models, the studies in humans are limited. Thus, the present study attempted to examine the carcinogenic potentials of acrylamide on the human epithelial cell, which is the target cell origin of the most cancers. Material and method & Result 1. Acrylamide was not cytotoxic up to $100{\mu}M$ as measured by MTT and LDH assays, indicating a relatively low toxicity of this substance in human epithelial cells. 2. The parameters of neoplastic cellular transformation such as cell saturation density, soft-agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of acrylamide. 3. The neoplastic transformation was further increased with the co-treatment of TPA 4. Antioxidants blocked the generation of Reactive Oxygen Species(ROS) and the GSH depleting agent dramatically increased the ROS production. 5. mRNA levels of fibronectin following acrylamide exposure was increased in a dose-dependent manner, indicating a possible biomarker of acrylamide-induced cellular transformation. Conclusion The present study will provide a valuable basis to compare the interspecies differences in response to carcinogenic potentials of acrylamide. The data on the interspecies differences are essential element in human risk assessment. Thus, our results obtained from the human epithelial cells will contribute to improving the risk assessment of human neoplasm including oral cancer.

Lack of Mutations in Protein Tyrosine Kinase Domain Coding Exons 19 and 21 of the EGFR Gene in Oral Squamous Cell Carcinomas

  • Mehta, Dhaval Tushar;Annamalai, Thangavelu;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4623-4627
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    • 2014
  • Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

CHEMOPREVENTIVE EFFECT OF GENISTEIN IN HAMSTER BUCCAL POUCH CARCINOGENESIS (Genistein이 햄스터 협낭 구강암 모델에 미치는 암예방 효과)

  • Kim, Young-Youn;Myoung, Hoon;Kim, Myung-Jin
    • 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.

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New formulated "DOX-MTX-loaded Nanoparticles" Down-regulate HER2 Gene Expression and Improve the Clinical Outcome in OSCCs Model in Rat: the Effect of IV and Oral Modalities

  • Abbasi, Mehran Mesgari;Monfaredan, Amir;Hamishehkar, Hamed;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9355-9360
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    • 2014
  • Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. Results: DOX-MTX- nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0.05) and this finding was more pronounced with the IV mode (p<0.000). Surprisingly, HER2 mRNA was not affected in DOX treated as compared to the control group (p>0.05). On the other hand, in the DOX-MTX NP treated group, fewer tumors characterized with advanced stage and decreased HER2 paralleled improved clinical outcome (P<0.05). Moreover, the effectiveness of the oral route in the group treated with nanodrug accounted for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Furthermore, there was no significant difference in mRNA level of HER2 (p>0.05). Conclusions: Influence of HER2 gene expression is a new feature and mechanism of action observed only in dual action DOX-MTX-NPs treated groups. Down-regulation of HER2 mRNA as a promising marker and prognosticator of OSCC adds to the cytotoxic benefits of DOX in its new formulation. Both oral and IV application of this nanodrug could be used, with no preferences in term of their safety or toxicity. As HER2 is expressed abundantly by a wide spectrum of tumors, i DOX-MTX NPs may be useful for a wide-spectrum of lesions. However, molecular mechanisms underlying HER2 down regulation induced by DOX-MTX NPs remain to be addressed.

Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma

  • Khor, Goot Heah;Froemming, Gabrielle Ruth Anisah;Zain, Rosnah Binti;Abraham, Thomas Mannil;Lin, Thong Kwai
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.219-223
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    • 2016
  • Background: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers. Objectives: The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters. Materials and Methods: Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM. Results: MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001). Conclusions: CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication.

A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia

  • Govindarajan, Giri Valanthan Veda;Bhanumurthy, Lokesh;Balasubramanian, Anandh;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3627-3629
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    • 2016
  • Background: Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation. Materials and Methods: Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample. Conclusions: The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.

Anticancer effect of methanol extract of Erigeron bonariensis on oral cancer cells (구강암 세포주에서 실망초 추출물의 항암효능)

  • Jang, Boon-Sil;Lim, Sun-A
    • Journal of Korean society of Dental Hygiene
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    • v.20 no.5
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    • pp.763-771
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    • 2020
  • Objectives: Erigeron bonariensis is a type of Erigeron found throughout the tropical and subtropical areas as one of the perennial plants or pioneer plants. It is known to show detoxifying, antipyretic, and anticancer effects for various cancers. However, there are no reports on the anticancer effect of E. bonariensis on oral cancer cells. In the present study, we investigated the effects of the methanol extract of Erigeron bonariensis (MEEB) on the inhibition of cell growth and induction of apoptosis in mucoepidermoid carcinoma (MEC) cell lines, including the MC3 and YD15 oral cancer cells. Methods: MC3 Cells were treated by dimethyl sulfoxide (DMSO) or methanol extracts of 20 various natural products 20 ㎍/mL for 48 hours and cell viability were analyzed as Trypan blue exclusion assay. The effects of MEEB treatment on the cell viability of MC3 and YD15 cells, for 48 h, were analyzed by Trypan blue exclusion assay. The anticancer efficacy and apoptosis of oral cancer cell lines were analyzed by western blot analysis. The statistical significance of differences between groups was analyzed by Student's two-tailed t-test. A value of P<0.05 compared to the vehicle control was considered statistically significant. Results: Among 20 different naturally derived products, MEEB significantly inhibited cell viability and increased cleaved poly [ADP-ribose] polymerase 1 (PARP) protein in the MC3 and YD15 cells in a concentration-dependent manner. Conclusions: These results suggest that MEEB can be used as a natural anticancer drug for the treatment of human oral cancer.

ANALYSIS OF PROSTHODONTIC AND SURGICAL TREATMENT OF ACQUIRED PALATAL DEFECT AFTER MAXILLECTOMY (상악절제술 후 외과적 재건과 보철적 치료의 비교)

  • Kwon, Ho-Beom;Hong, Jong-Rak
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.2
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    • pp.143-151
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    • 2007
  • One of the treatment methods for maxillary cancers or infections in maxilla is maxillectomy. Palatal defect can be resulted from this operation and it may cause functional problems with swallowing and speech, and psychological problems of patients. After maxillectomy, as rehabilitation, there can be two options. One is a prosthodontic treatment using obturator and the other is surgical reconstruction of defect with graft. As both methods have advantages and disadvantages, in determining treatment method after maxillectomy, various factors have to be considered. The purpose of this study is to compare the prosthodontic group to surgical group after maxillectomy with elapsed days prior to commencement of postoperative oral feeding, and to analyze the results of prosthodontic treatment and surgical treatment. During the period from March of 2000 to June of 2006, 74 patients were treatment by prosthodontic methods for maxillary defect. Among these patients, patients who had only velopharyngeal deficiency after surgery, whose data were incomplete, whose causes of palatal defect were not the treatment of diseases in maxilla, and who already had palatal defect due to previous surgery were excluded in this study. The patients who underwent maxillectomy for the treatment of diseases in the maxilla and were treated immediately after operation using surgical reconstruction or prosthodontic rehabilitation were included in this study. The records of 43 patients were reviewed to compare and to analyze the prosthodontic treatment and surgical reconstruction after maxillectomy. The median of days elapsed prior to commencement of postoperative oral feeding in the prosthodontic group was compared with data of surgical group. The data was analyzed using the Mann-Whitney test (${\alpha}$=.05). Days elapsed prior to postoperative oral feeding commencement in the prosthodontic group were less than those in the surgical group.

Incidence of Head and Neck Lymphoma in Guilan Province, Iran

  • Basirat, Maryam;Rabiei, Maryam;Bashardoust, Nazanin
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.1-4
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    • 2016
  • The aim of this research was to describe the incidence and histopathological subtypes of head and neck lymphoma in Guilan province, Iran. In this retrospective study, all cases of head and neck cancers registered in Iranian Cancer Registry Program in Guilan province of Iran from 2004 to 2009 were obtained and included in the analysis. Out of 1,510 cases, 169 (11.2%) were reported as lymphomas (87 cases of non-Hodgkin, 67 cases of Hodgkin, and 13 cases of unknown type). The mean ages of males and females diagnosed with Hodgkin's lymphoma were 30.4 and 28.7 years, respectively. For non-Hodgkin's lymphoma the respective figures were 50.5 and 49.3 years old. Among various histological subtypes of non-Hodgkin's lymphoma, the diffuse large B-cell type (74.2%) was the most frequent while immunoblastic lymphoma (1.1%) was the least frequent. Nodular sclerosis (58.2%) and mixed cellularity (18.0%) types were most frequent among Hodgkin's lymphomas.

Prevalence of Human Papillomavirus Infection in the Korean Oral Cancer Patients (한국인 구강암 환자에서 인유두종 바이러스의 발현율 분석)

  • Kim, Hyun Soo;Seo, Mi Hyun;Kim, Soung Min;Cho, Young Ah;Lee, Suk Keun;Lee, Jong Ho;Myoung, Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.35 no.4
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    • pp.227-235
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    • 2013
  • Purpose: High risk human papillomavirus (HPV) is the main source of cervical cancer, nearly up to 100%. Because there are no affordable data regarding the incidence of HPV in different sites of oral cavity, the purpose of this study is to review the previous article and to find out about the incidence and types of HPV in specific areas of oral cavity. Methods: We examined a total of 106 patients with oral cavity cancer for HPV detection. Available DNA chip (MY-HPV chip kit$^{(R)}$, Mygene Co., Korea) was used for the detection of low risk HPV types (6, 11, 34, 40, 42, 43, 44) and high risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58). Patients were previously diagnosed as invasive cancer of oral cavity. Specimen used for HPV detection was extracted from the main mass during resection and were tested for HPV type, performed by a DNA chip method. Results: Histologic results showed that there were squamous cell carcinomas, mucoepidermoid carcinomas, cystadenocarcinomas, leiomyosarcoma and etc. Among HPV positive cancer, 2 patients showed positive for high risk HPV type 16, 3 patients showed positive for low risk HPV type 6 and the other 2 patients were positive for other types of HPV. Of the 7 patients with HPV positive, 4 patients were on the tongue, 3 on the lower gingiva. Conclusion: Most of the HPV positive cancers were on the tongue in our study. Cervical cancer of HPV infection is reported to be increasing in our society and because HPV infection largely spreads by sexual contact, the incidence of oral cancer with HPV infection is greatly assumed to be on the increase, simultaneously. Because the incidence of HPV on specific areas of oral cavity among oral cancer patients is not identified, more studies are ongoing.