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Matrix Metalloproteinases(MMPs) 및 Vascular Endothelial Growth Factor(VEGF)의 발현을 통한 구강 설암의 침윤 기전 연구
김세헌(Se Heon Kim),김지훈(Ji Hoon Kim),임재열(Jae Yul Lim),조남훈(Nam Hoon Cho),장정현(Jung Hyun Chang),최은창(Eun Chang Choi),김정홍(Jeong Hong Kim) 대한두경부종양학회 2005 대한두경부 종양학회지 Vol.21 No.1
Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p
향장기성 두경부 편평세포암종의 미세잔존암 모델에서 GM-CSF 유전자를 이입시킨 제한복제성 헤르페스바이러스 벡터를 이용한 종양백신의 유전자 치료
김세헌(Se Heon Kim),최은창(Eun Chang Choi),김한수(Han Su Kim),장정현(Jung Hyun Chang),김지훈(Ji Hoon Kim),김광문(Kwang Moon Kim) 대한두경부종양학회 2003 대한두경부 종양학회지 Vol.19 No.1
Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per 10 6 cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.
인체에서 분리된 Lactobacillus acidophilus가 생산하는 박테리오신의 선별과 정제
김세헌 ( Se Heon Kim ),김영교 ( Yeong Gyo Kim ),( Gilliland S E ) 한국유가공기술과학회 1997 Journal of Dairy Science and Biotechnology (JMSB) Vol.15 No.1
Lactobacillus acidophilus 223, 606, and NCFM-F among 21 isolated from fecal contents of humans demonstrated inhibitory activity attributed to bacteriocin(s). The bacteriocin(s) were heat stable and nondialyzable proteinous compounds and exhibited narrow inhibitory spectra of activity. Neither hydrogen peroxide nor pH were responsible for inhibitory action. All of the producer strains were resistant to their own bacteriocin(s). The bacteriocin(s) were purified by ammonium sulfate precipitation, gel chromatography and ion exchange chromatography for further characterization. The bacteriocin(s) of human origin exhibited similar characteristics.
방사선 치료에 내성이 유도된 두경부 편평세포암에 대한 종양살상 헤르페스 바이러스의 유전자 치료 효과
김세헌(Se-Heon Kim),최은창(Eun Chang Choi),이진석(Jin Seok Lee),천제영(Je Young Chun),변형권(Hyung Kwon Byun),송기재(Ki Jae Song),김광문(Kwang-Moon Kim) 대한두경부종양학회 2006 대한두경부 종양학회지 Vol.22 No.2
Introduction :The sensitivity of tumor cells to radiotherapy is a critical determinant of local control and po-tential cure in advanced head and neck squamous cell carcinoma(HNSCC). The emergence of radioresistant tumor cells is an obstacle to cancer therapy. Most radioresistant cells have a higher proportion of cells in the S-phase of the cell cycle and a lower apoptotic fraction than radiosensitive cells. HSV replication is increased in cells that have higher S-phase fractions. NV1066 is an oncolytic herpes simplex virus type-1 mutant. We hy-pothesized that NV1066 replication and cytotoxicity are increased in radioresistant cells. The purpose of this study is to evaluate the antitumor efficacy of NV1066 to treat radioresistant HNSCC. Methods :Radioresistant cells were selected by treating five HNSCC cell lines with repeated conventional fractionated doses of radiation(2Gy/day), using a Cs-137 irradiator, up to a cumulative dose of 70Gy. Clonogenic cell survival and S-phase fractions were compared between radioresistant and parental radiosensitive cells. The two cell populations were then treated with NV1066 to examine viral replication, by the viral plaque assay and viral cytotoxicity. Results :Fractionated irradiation resulted in the selection of radioresistant cells. Radioresistant cells had a higher S-phase fraction(42.9%) compared to parental cells(26.2%). NV1066 replication in radioresistant cells was 7.4times higher than in parental cells(p<0.01). Treatment with NV1066 resulted in increased cytotoxicity of 24.5% in radioresistant cells compared to parental cells(p<0.05). Conclusion :NV1066 showed increased viral replication and cytotoxicity in radioresistant HNSCC cell lines. These findings suggest a potential clinical application for this oncolytic viral therapy as treatment for radiore-sistant head and neck cancers.