신세포암 동물모델에서 면역치료와 동반한 냉동요법의 항암 효과
Antitumor effect of in situ cryoablation with systemic immunotherapy on murine renal cell tumor
- 주제(키워드) Cryoablation , Immunotherapy , Renal cell carcinoma
- 발행기관 고려대학교 대학원
- 지도교수 윤덕기
- 발행년도 2008
- 제출일 2008-6-30
- 학위수여년월 2008. 8
- 학위명 박사
- 학과 일반대학원 의학과
- 세부전공 비뇨기과학
- 원문페이지 31 p
- 본문언어 한국어
- 제출원본 000045501045
초록/요약
Objective : To investigate synergic effect of local cryoablation with systemic immunotherapy, the tumor control efficacy and immunologic responses of combination therapy was compared with that of cryoablation, surgical excision, and immunotherapy in a tumor re-challenge model. Material and Methods : Preliminary experiments were performed in two stages. The first stage consisted of thirty six BALB/c mice with RENCA bearing tumors imbedded in the right thigh, and was treated with immunotherapy using IL-2 and IFN-a to estimate the adequate dosage of treatment and to evaluate the efficacy of immunotherapy. The second stage was performed on 10 mice, sacrificed at 2 days and 7 days with 5 mice each, after treatment with cryoablation to evaluate and document histological changes and efficacy. The main experiment was performed on 48 mice, divided into 6 groups of control with tumor implantation (group 1), excision of tumor (group 2), excision combined with immunotherapy (group 3), cryoablation of tumor (group 4), cryoablation with immunotherapy (group 5) and control without tumor (group 6). After treatment, tumor re-challenge was performed with RENCA cell, the pattern of growth was evaluated with physical measurements and immune response was investigated with fluorescent activated cell sorter (FACS) and cytotoxicity assay (Thymidine incorporation assay). Results : Preliminary studies on immunologic efficacy revealed IL-2 and IFN-a to have a dose dependent inhibition of tumor growth. Each agent showed maximum efficacy at 1X105 without induction of significant change in body weight. All five mice showed viable tumors at 2 days after cryoablation, but was decreased to a single mouse on the 7th day after operation. The main experiment evaluating the efficacy of combination treatment revealed that cryoablation with immunotherapy (group 5) proved to be most effective in terms of tumor recurrence, tumor growth inhibition and FACS, yet the difference was not statistically significant from monotherapy with cryoablation (group 4). However cytotoxicity was significantly increased with combination treatment (group 5) compared with other groups. Conclusions: Combination treatment on tumor re-challenge mice model showed advantages with immunologic agents such as IFN-a and IL-2, most prominently in cytotoxicity. With current limitations of modalities employed in the treatment of RCC, we may expect promising results with synergistic effects in humans as well.
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Abstract i
Ⅰ. 서 론 1
Ⅱ. 연구 방법 3
Ⅲ. 연구 결과 7
Ⅳ. 고 찰 9
Ⅴ. 결 론 12
Ⅵ. 참고 문헌 13
Ⅶ. Figures and Figure legend 16
