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편도암의 발암 원인으로 Human Papilloma Virus를 통한 발암 기전과의 상관 관계
이소윤(So Yoon Lee),정진세(Jin Sei Jung),박영민(Young Min Park),천제영(Jei Young Cheon),변형권(Hyung Kwon Byun),김세헌(Se Heon Kim) 대한두경부종양학회 2007 대한두경부 종양학회지 Vol.23 No.1
Background :Squamous cell carcinoma(SCC)of the palatine tonsils represents approximately 15-23% of all intraoral SCC. The most frequently reported risk factors for oropharyngeal cancer are smoking and alcohol. In a recent overview of HPV and tonsillar squamous cell carcinoma(TC), 51% contained HPV DNA, and HPV-16 being the most frequent type. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of TC by comparison with infection prevalence, and physical status of virus. Material and Method :We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5’-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results :We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%)and non-episomal(94.1%)state. Conclusions :This study regarding HPV infection prevalence and mechanism in the largest population of palatine tonsillar squamous cell carcinoma with chronic follicular tonsillitis revealed significant difference pf HPV prevalence between TC and CFT. Most of HPV were 16 type and integrated or mixed, HPV-16 inte-gration could be directly related to tonsillar carcinogenesis.
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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.
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