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사람 암세포주 K562 , U937 및 쥐 암세포주 P388 , FM3A 에서의 항암제 다제내성 기전 및 내성극복
도현국(Hyun Kuk Doh),김재석(Jae Seok Kim),손지원(Ji Weon Son),성명식(Myung Sik Sung),김종성(Jong Seong Kim),김선희(Sun Hee Kim),정병선(Byung Sun Jung) 대한내과학회 1992 대한내과학회지 Vol.43 No.3
N/A Background: To study the mechanism of multidrug resistnce (MDR) and overcome MDR in cancer cells, we investigated the combination effects of anticancer agents with calmodulin inhibitors (e,g trifluoroperazine (TFP) and W-7), calcium function modifiers (e.g., quinidine and verapamil) and a protein kinase-C activator (e.g., phorbol ester) in chronic myelogenous leukemic cells, histiocytic lymphoma cells and breast cancer cells. Methods: Some MDR mutant sublines which had cross-resistance to colchicine, actinomycm D, adriamycin and vinblastine were isolated from K562, U937 and FM3A cell lines. MTT analysis was used to measure the level of the cytotoxicity, The cytotoxicity and the combination effects were compared by IC50 (1nhibition concentration50) to control group. Results: In case of U937/MDR, TFP increased the combination effect to tenfold in colchicine (COL), eightfold in vinblastine (VLB) and thirteenfold in actinomycin D (ACT-D). Quinidine increased the effect to threefold in COL, fourfold in VLB and sevenfold in ACT-D. Verapamil also increased the effect to sevenfold in COL, sixfold in VLB fivefold in ACT-D. In case of K562/MDR, TFP, quinidine and verapamil each increased the combination effect to sixfold, twelvefold and thirteenfold in COL and sixfold, fivefold and fivefold in adriamycin (ADM). W-7 in concentration of 20uM increased the combination effect to six point sevenfold in ACT-D, twofold in COL and two point threefold in ADM. In the combination of COL with 0.48uM TPA, the cytotoxicity was reduced to two point eightfold in case of FM3A/MDR. TPA (12-0-tetradecanoyl phorbol 13-acetate), in concentration of 0.48uM, a phorbol ester, reduced the cytotoxicity to two point eightfold in case of FM3A/ MDR. Conclusion: When the combination effects of anticancer agents with calmodulin inhibitors (e.g TFP and W -7) and calcium function modifiers (e.g., quinidine and verapamil) were examined, the cytotoxicity changes of anticancer agents were small in drug sensitive cells. But in MDR cells, the combination effects were prominent. The reduced cytotoxicity of anticancer agents by TPA suggested that protein kinase-C might be related with the mechanism of acquiring drug resistance on cancer cells.
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특발성신중후군 환자의 혈청 및 요단백 전기영동분획상에 관한 연구
김재석(Jae Seok Kim),이주일(Ju Il Lee),도현국(Hyun Kuk Doh),김성은(Seong Eun Kim),김기현(Ki Hyun Kim),김종성(Jong Seong Kim) 대한내과학회 1993 대한내과학회지 Vol.45 No.5
N/A Background: The idiopathic nephrotic syndrome is classified into minimal change nephrotic syndrome, focal glomerulosclerosis, membranous glomerulonephritis and membranoproliferative glomerulonephritis. They have different histological features and different capillary wall permeability to serum protein. The difference of capillary wall permeability to serum protein may leads to changes of serum and urinary protein composition. But there has been no report about that. Thereby we had carried out the electrophoresis of the serum and urinary protein obtained from the patient with idiopathic nephrotic syndrome. Methods: To investigate the change in serum proteins and patterns of proteinuria in 42 patients with idiopathic nephrotic syndrome(13 minimal change nephrotic syndrome-MCNS group, 7 focal glomerulosclerosis-FGS group, 12 membranous glomerulonphritis-MGN group and 10 patients with membranoproliferative glomerulonephritis Type I -MPGN group) cellulose acetate protein electrophoresis was done. Results: 1) In the percent composition of serum protein. the albumin and γ-globulin fraction of all the patient groups investigated decreased more significantly than those of the normal control group, but the α1-, α2-, γ-grobulin fraction increased(p<0.001, but that of α1-globulin of MGN group was p>0.05). 2) In the amount composition of serum proteins, the albumin and γ-globulin fraction of all the patient groups decreased more than those of the normal control group(p<0.001). The a-globulin fraction of MCNS group increased(p<0.001). but the β-globulin decreased(p<0.05). The α1-globulin fraction of FGS group decreased(p<0.01), but the α2-globulin increased(p<0.001). The α2-globulin fraction of MGN group increased(p<0.001). The α2-globulin fraction of MPGN group decreased(p<0.01). 3) In the percent composition of urine protein, the albumin fraction of FGS group showed the lowest value in comparison of the other groups, but the α1-, β-globulin fraction showed higher value. And the value of the α2-globulin fraction of MGN group was higher. A similar pattern appeared in the MCNS and the MPGN group. 4) 1n the amount composition of urine protein, the α1-, α2-, β-globulin fraction of FGS group, compared with the others, showed the highest value. Conclusion: The albumin fraction and the γ-globulin fraction in the percent composition of serum protein in patients with idiopathic nephrotic syndrome decreased and the fractions of α1-, α2-, β-globulin increased more than those of the normal control group. The α1-globulin fraction showed increased value regardless the level of serum albumin or proteinuria, but the α2, β-globulin showed and increased value according to decreases of serum albumin and increases of proteinuria. There were some differences in each disease group in serum protein composition, but that was insufficient when used as one of the criteria for differential diagnosis. A more sensitive method is needed in the evaluation of urine protein in idiopathic nephrotic syndeome.
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