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Retroviral Vector를 이용한 Herpes Simplex Virus-Thymidine Kinase 유전자의 도입과 발현이 인체 위암세포주의 Ganciclovir 감수성에 미치는 영향

Other Titles
 Gene Transfer Effects of Thymidine Kinase Gene of Herpes Simplex Type 1 on Ganciclovir Cytotoxicity in Gastric Cancer Cell Line 
 노재경  ;  공수정  ;  김주항  ;  엄효동  ;  유내춘  ;  송재진  ;  조재용  ;  라선영  ;  정현철  ;  민진식  ;  김병수 
 Journal of the Korean Cancer Association (대한암학회지), Vol.30(1) : 20-30, 1998 
Journal Title
Journal of the Korean Cancer Association(대한암학회지)
Issue Date
Gastric cancer ; Gene therapy ; Retroviral vector ; HSV-tk gene ; Ganciclovir
PURPOSE: Gastric cancer is the most common malignancy in Korea. Although treatment such as surgery, chemotherapy, and immunotherapy has greatly improved, the mortality rate of gastic cancer is still high, A new therapeutic trial is necessary to improve the cure rate of gastric cancer. Therefore we investigated the pre-clinical significance of HSV-tk gene therapy using retroviral vector for gastric cancer cell lines.
MATERIALS AND METHODS: LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk producer cell line were constructed. HSV-tk gene transduction and expression were detected by PCR. An in vitro ganciclovir(GCV) sensitivity test was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after tumor formation in the nude mice. Bystander effect was observed in vitro MTT assay using YCC- S-2 cell line and in vivo using N87 and YCC-S-2 cell lines.
RESULTS: The in vitro GCV sensitivity test showed that the growth inhibition was 30~32% with 0.5 uM GCV and 52~77% with 500 uM GCV in the HSV-tk transduced cell line in comparison with 0- 5% with 0.5 and 500 uM GCV in the parent cell line. The in vivo GCV administration showed that the tumors induced by HSV-tk transduced N87 cell line and YCC-S-2 cell line decreased completely, while the tumors with the parent cell lines continued to grow in nude mice. We observed no tumor cells in tissue specimen of the tumor induced by the N87/HSV-tk cell line after. GCV administration. In vitro and in vivo bystander effects were observed in HSV-tk/GCV system due to the resultant cell death exceeding the proportion of HSV-tk transduced cells in the mixtures of HSV-tk transduced and parent cells.
CONCLUSION: HSV-tk transduced gastric cancer cell lines showed sensitivity to GCV and a bystander effect was observed. These results suggested that HSV-tk/GCV system should be evaluated in the clinical settings.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Roh, Jae Kyung(노재경)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Yoo, Nae Choon(유내춘)
Chung, Byung Ha(정병하) ORCID logo https://orcid.org/0000-0001-9817-3660
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