• 제목/요약/키워드: Human oral cancer

검색결과 322건 처리시간 0.024초

구강암 유전자 치료를 위한 재조합 HSCC-1 아데노바이러스의 개발 (CONSTRUCTION OF RECOMBINANT HSCC-1 ADENOVIRUS VECTOR FOR ORAL CANCER GENE THERAPY)

  • 김창현;김진우;김명진;표성운
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제27권2호
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    • pp.103-109
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    • 2005
  • In spite of the ongoing advances, standard therapies for oral cancer still has some limitations in efficacy and in ability to prolong survival rate of advanced disease and result in significant functional defect and severe cosmetic deformity. Currently gene therapy using tumor suppressor gene is considered as a potent candidate for new therapeutic approaches that can improve efficacy and reduce complications. The purpose of this research is to identify the role of adenoviral vector to transfer HCCS-1 tumor suppressor gene in oral cancer cells and to find out whether there is a possibility for it to serve in the field of gene therapy. The human SCC-25 cell line was used for transfection. To determine the efficiency of the adenovirus as a gene delivery vector cell line was transduced with LacZ gene and analysed with X-gal staining. Northern blot was performed to confirm the tranfection with HSCC-1 gene and cell viability was assessed by cell cytotoxicity assay. We had successfully construct the recombinant HSCC-1 adenovirus(Ad5CMV-HCCS-1). DNA extracted from Ad5CMV-HCCS-1 revealed HCCS-1 gene is incorporated. The transduction efficiencies were over than 50% of SCC-25 cells with a MOI of 2 and over 95% with a MOI of 50. Northern blot analysis showed that a single 0.6kb mRNA transcript was expressed in Ad5CMV-HCCS-1 transduced SCC-25 cells. There was no or very low transcription HCCS-1 mRNA in wild and Ad5CMV-LacZ transduced SCC-25 cells. Cells transduced with Ad5CMV-HCCS-1 showed significant growth inhibition. By day 6, Ad5CMV-HCCS-1 treated cell count was decreased to 30% of mock-infected cells, while that of Ad5CMV-LacZ treated cells was 90% of mock-infected cells (p<0.05). Finally, these result suggest that the Ad5CMV-HCCS-1 has potential as a gene therapy tool for oral cancer.

Prisoners' Perception of Tobacco Use and Cessation in Chhatisgarh, India - The Truth from Behind the Bars

  • Tiwari, Ram Vinod;Megalamanegowdru, Jayachandra;Parakh, Abhinav;Gupta, Anjali;Gowdruviswanathan, Shailarani;Nagarajshetty, Praveen Malavalli
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권1호
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    • pp.413-417
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    • 2014
  • Background: Prisoners represent a population group that is disadvantaged, socially deprived and underprivileged, needing particular attention with regard to provision of necessary oral health care, health promotion and motivation and tobacco cessation. Considering the situation in prisons, smoking and tobacco chewing are burning issues related to health deterioration and economic loss that seem to be overlooked by the public health sectors. Aim: To assess prisoners' perception of tobacco use and cessation in Chhatisgarh, India. Materials and Methods: A pre-tested, close ended questionnaire was administered in the form of extensive face to face interviews, to assess perceptions regarding tobacco use and cessation in the central jail of Durg District of Chhattisgarh state, India. Results: Prevalence of tobacco usage amongst the prisoners was found to be 61%. Some 27% reported smoking, 44% used tobacco in the chewable form and 29% indulged in consuming tobacco in both forms i.e. smoked as well as chewed. Results suggest several recommendations for policy relevance such as provision of a prison dentist, a tobacco cessation counseling program and targeted eradication of oral cancer by educating the prisoners. Conclusions: Health is a fundamental human "right of everyone to the enjoyment of the highest attainable standard of physical and mental well-being". This applies to prisoners just as it does to every other human being. The alarming findings in the study suggest the need for dental treatment facilities and tobacco cessation counseling in prisons.

A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

  • Melath, Anil;Santhakumar, Gopi Krishnan;Madhavannair, Shyam Sunder;Nedumgottil, Binoy Mathews;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권11호
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    • pp.6803-6806
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    • 2013
  • Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC). Materials and Methods: Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y). Conclusions: The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC.

Interferon Induced Transmembrane Protein-1 Gene Expression is a Biomarker for Early Detection of Invasive Potential of Oral Squamous Cell Carcinomas

  • Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.2297-2299
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    • 2016
  • Background: Early detection of malignant transformation with expression biomarkers has significant potential to improve the survival rate of patients as such biomarkers enable prediction of progression and assess sensitivity to chemotherapy. The expression of interferon inducible transmembrane protein 1 (IFITM1) has been associated with early invasion events in several carcinomas, including head and neck cancers, and hence has been proposed as a novel candidate biomarker. As the incidence of oral squamous cell carcinoma (OSCC) is highest in the Indian population, we sought to investigate: 1) the expression pattern of IFITM1 in OSCC tissue samples obtained from Indian patients of Dravidian origin; and 2) the possibility of using IFITM1 expression as a potential biomarker. Materials and Methods: Total RNA extracted from thirty eight OSCC biopsy samples was subjected to semi-quantitative RT-PCR with IFITM1 and GAPDH specific primers. Results: Of the thirty eight OSCC samples that were analyzed, IFITM1 overexpression was identified in fifteen (39%). Seven expressed a low level, while the remainder expressed high level of IFITM1. Conclusions: The overexpression of IFITM1 in OSCC samples indicates that IFITM1 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers. To the best of our knowledge, this is the first time that IFITM1 overexpression is being reported in Indian OSCC samples.

A Cytotoxic Activity of Panax Ginseng Extract Against Bome Cancer Cells In Vivo and In Vitro.

  • Hwang, Woo-Ik;Park, Gil-Hong;Paik, Jeong-Mi
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1987년도 Proceedings of Korea-Japan Panax Ginseng Symposium 1987 Seoul Korea
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    • pp.29-37
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    • 1987
  • This study was devised to observe the cytotoxlc activities of petroleum-ether extract of Panax ginseng root(crude Gx) and its partially purified fraction from silicon acid column chromatography(7:3 CX) against sarcoma-180(5-180) and Walker carcinosarcoma 256(Walker 256) in vivo, and murine leukemic lymphocytes(L1210) and human rectal cancer cell(HRT-18) and human colon cancer cells(HT-29 and HCT-48) in vitro . Each cell-line was cultured in medium containing serial concentrations of the crude Gx or 7:3 Gx in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro In the meantime, ginseng saponin derivatives did not cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7:3 Gx was about 3 times more potent than that of crude Gx, one unit of cytotoxic activity against L121f cells being equivalent to 2.54$\mu\textrm{g}$ and 0.88 $\mu\textrm{g}$ for the crude Gx and 7:3 Gx, respectively. The Rf value of the active compound on silica -gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90:10:1, v/v/v) as a developing solvent was 0.23. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7:3 Gx treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gx. The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude Gx, which can explain a part of the origin of its anticancer activity.

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구강 편평세포암종 KB세포에서 아미노산 수송억제제 BCH에 의한 세포성장 억제 (Induction of Growth Inhibition by BCH in KB Human Oral Epidermoid Carcinoma Cells)

  • 윤정훈;김윤배;김도경
    • 한국식품영양과학회지
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    • 제32권5호
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    • pp.758-763
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    • 2003
  • 구강 편평 세포암종 KB 세포를 이용하여 아미노산 수송계 L억제제인 BCH의 세포 성장억제에 미치는 효과를 밝히기 위해, KB세포에서 uptake실험, MTT분석 및 DNA frag-mentation분석 등을 시행하여 다음과 같은 결과를 얻었다. KB 세포에서는 아미노산 수송계 L 중에서 LAT1과 그 보조인자 4F2hc를 통해 BCH및 중성 아미노산들이 수송되었다. BCH는 시간과 농도에 의존적으로 KB세포의 성장을 억제시켰다. BCH를 처리한 실험군에서 DNA fragmentation 현상은 볼 수 없었다. 본 연구의 결과로서 구강암 세포주인 구강 편평세포암종 KB 세포에서 LAT1과 그 보조인자 4F2hc를 통해 BCH및 중성 아미노산의 수송이 이루어지고 있다는 것을 확인할 수 있었으며 BCH는 이 LAT1을 차단하여 중성 아미노산들의 세포 내 고갈을 유도함으로서 KB 세포 성장의 억제를 유도하는 것으로 사료된다.

Correlation between glucose transporter type-1 expression and $^{18}F$-FDG uptake on PET in oral cancer

  • Kim, Chul-Hwan;Kim, Moon-Young
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제38권4호
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    • pp.212-220
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    • 2012
  • Objectives: Fluorine-18 fluorodeoxyglucose positron emission tomography ($^{18}F$-FDG PET) is a non-invasive diagnostic tool for many human cancers wherein glucose uptake transporter-1 (GLUT-1) acts as a main transporter in the uptake of $^{18}F$-FDG in cancer cells. Increased expression of glucose transporter-1 has been reported in many human cancers. In this study, we investigated the correlation between $^{18}F$-FDG accumulation and expression of GLUT-1 in oral cancer. Materials and Methods: We evaluated 42 patients diagnosed with oral squamous cell carcinoma (OSCC) and malignant salivary gland tumor as confirmed by histology. 42 patients underwent pre-operative $^{18}F$-FDG PET, with the maximum standardized uptake value ($SUV_{max}$) measured in each case. Immunohistochemical staining was done for each histological specimen, and results were evaluated post-operatively according to the percentage (%) of positive area, intensity, and staining score. Results: For OSCC, $SUV_{max}$ significantly increased as T stage of tumor classification increased. For malignant salivary gland tumor, $SUV_{max}$ significantly increased as T stage of tumor classification increased. For OSCC, GLUT-1 was expressed in all 36 cases. GLUT-1 staining score (GSS) increased as T stage of tumor classification increased, with the difference statistically significant. For malignant salivary gland tumor, GLUT-1 expression was observed in all 6 cases; average GSS was significantly higher in patients with cervical lymph node metastasis than that in patients without cervical lymph node metastasis. Average GSS was higher in OSCC ($11.11{\pm}1.75$) than in malignant salivary gland tumor ($5.33{\pm}3.50$). No statistically significant correlation between GSS and $SUV_{max}$ was observed in OSCC or in malignant salivary gland tumor. Conclusion: We found no statistically significant correlation between GSS and $SUV_{max}$ in OSCC or in malignant salivary gland tumor. Studies on the various uses of GLUT during $^{18}F$-FDG uptake and SUV and GLUT as tumor prognosis factor need to be conducted through further investigation with large samples.

Expression of Matrix Metalloproteinase-10 at Invasive Front of Squamous Cell Carcinoma and Verrucous Carcinoma in the Oral Cavity

  • Kadeh, Hamideh;Saravani, Shirin;Heydari, Fatemeh;Keikha, Mohammad;Rigi, Vahab
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6609-6613
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    • 2015
  • Background: Matrix metalloproteinases (MMPs) are a family of zinc metalloproteinases capable of degrading components of connective tissues. MMP-10 is frequently expressed in human cancers. The aim of this study was to immunohistochemically evaluate its expression in oral squamous cell carcinoma (OSCC) and verrucous carcinoma (OVC). Materials and Methods: A retrospective analysis of 73 samples (31 OSCC, 22 OVC and 20 non-neoplastic epithelium) was performed. All samples were immunohistochemically stained with monoclonal MMP-10 antibody and expression levels and staining intensity were evaluated with respect to microscopic features. Data were analyzed by SPSS (V.21), Mann-Whitney and Kruskal Wallis tests. Results: MMP-10 was detected in all OSCC and OVC cases. The expression of MMP-10 in OSCC was intensive (score 3) and in OVC was low and moderate (score 1 and score 2) more frequently. Non- neoplastic epithelium did not show MMP-10 expression. Differences between groups was statistically significant (p<0.05). However, the expression of MMP-10 was not obviously different between various grades of OSCC. Conclusions: According to our study, MMP-10 protein can be important possible factor in the transformation of normal oral epithelium to OVC and OSCC, also the level of MMP-10 expression at invasion front of the lesions can be helpful in the differentiation of OVC and OSCC.

Common Docking Domain Mutation E322K of the ERK2 Gene is Infrequent in Oral Squamous Cell Carcinomas

  • Valiathan, Gopalakrishnan Mohan;Thenumgal, Siji Jacob;Jayaraman, Bhaskar;Palaniyandi, Arunmozhi;Ramkumar, Hemalatha;Jayakumar, Keerthivasan;Bhaskaran, Sajeev;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권12호
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    • pp.6155-6157
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    • 2012
  • Background: Mutations in the MAPK (Mitogen Activated Protein Kinase) signaling pathway - EGFR/Ras/RAF/MEK have been associated with the development of several carcinomas. ERK2, a downstream target of the MAPK pathway and a founding member of the MAPK family is activated by cellular signals emanating at the cell membrane. Activated ERK2 translocates into the nucleus to transactivate genes that promote cell proliferation. MKP - a dual specific phosphatase - interacts with activated ERK2 via the common docking (CD) domain of the later to inactivate (dephosphorylate) and effectively terminate further cell proliferation. A constitutively active form of ERK2 carrying a single point mutation - E322K in its CD domain, was earlier reported by our laboratory. In the present study, we investigated the prevalence of this CD domain E322K mutation in 88 well differentiated OSCC tissue samples. Materials and Method: Genomic DNA specimens isolated from 88 oral squamous cell carcinoma tissue samples were amplified with primers flanking the CD domain of the ERK2 gene. Subsequently, PCR amplicons were gel purified and subjected to direct sequencing to screen for mutations. Results: Direct sequencing of eighty eight OSCC samples identified an E322K CD domain mutation in only one (1.1%) OSCC sample. Conclusions: Our result indicates that mutation in the CD domain of ERK2 is rare in OSCC patients, which suggests the role of genetic alterations in other mitogenic genes in the development of carcinoma in the rest of the patients. Nevertheless, the finding is clinically significant, as the relatively rare prevalence of the E322K mutation in OSCC suggests that ERK2, being a common end point signal in the multi-hierarchical mitogen activated signaling pathway may be explored as a viable drug target in the treatment of OSCC.

Hesa-A Improves Clinical Outcome of Oral Carcinoma by Affecting p53 Gene Expression in vivo

  • Abbasi, Mehran Mesgari;Helli, Sanaz;Monfaredan, Amir;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권10호
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    • pp.4169-4172
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    • 2015
  • Background: Oral carcinoma (OC) remains as one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties on various human cancer cells, although the mechanisms of action remain to be addressed. This study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of p53 as a main prognosticator of OC. Materials and Methods: 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500 mg/kg body weight of Hesa-A three times a day. The two other groups considered as treated and untreated healthy groups. At the end of experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results indicated that compared to healthy group, p53 over expressed ~ 40% in untreated carcinoma group. After treatment with 250mg/kg and 500mg/kg body weights of Hesa-A, p53 level dropped by 53.4% and 13.6 %, respectively, compared to untreated carcinoma group (p<0.05, p<0.0001). Moreover, there was a significant relation between p53 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insights into the mechanism(s) by which Hesa-A improves clinical outcome of oral carcinoma by modulation of p53 expression.