신암 세포주와 동종이식 종양 모델에서 Arginine Deiminase의 종양억제 효과에 관한 연구
- 발행기관 고려대학교 대학원
- 발행년도 2004
- 학위명 박사
- 학과 대학원:의학과
- 식별자(기타) DL:000014913344
- 서지제어번호 000045199766
초록/요약
we studied the effect of arginine deiminase (ADI) as a new approach for the treatment of advanced renal cell carcinoma; first, anti-proliferative effect against human and murine renal cell carcinoma cell lines, second, anti-tumorigenic effect against RENCA allograft tumor model. i Materials and methods : Human and murine renal cell carcinoma cell lines (ACHN, RENCA) were incubated with increasing concentration of arginine deiminase (0.001-0.025 U/ml) for 24-72 hours. The growth-inhibitory activity and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and lactic dehydrogenase (LDH) assay, respectively. Cell count was performed with hemocytometer. All values were shown by the percentage of control. For in vivo testing, allograft tumors were produced by subcutaneous injection of RENCA tumor cells into female Balb/c mice and the tumorigenicity after treatment of ADI was evaluated. Expression of ASS in each cell lines was analyzed with western blotting. Human RCC specimens were immunohistochemically stained with ABC method for expression of ASS. Results : In both cell lines (ACHN and RENCA), the cell number and proliferation were significantly decreased after ADI treatment for 24-72 hours. ADI strongly inhibited, in a dose-dependent manner, the proliferation of renal cell carcinoma cell lines. After 24-72 hours treatment of ADI, LDH level was significantly increased and the degree of LDH level was in proportion to the concentration of ADI (0.001-0.025 U/ml). When the in vivo anti-tumorigenic activity of ADI was tested for allograft tumor models, average tumor volume was reduced to a greater degree in the ADI treated groups compared with control and the anti-tumor response was durable. Western blot analysis for ASS was expressed with low activity in the renal cell carcinoma cell lines compared with control. Immunohistochemical study proved that the expression of ASS was enhanced in the normal proximal convolut
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Abstract i
Ⅰ. 서 론 1
Ⅱ. 연구 방법 3
Ⅲ. 결 과 8
Ⅳ. 고 찰 11
Ⅴ. 결 론 17
Ⅵ. 참고 문헌 18
Ⅶ. Table & Figure 22
