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      • KCI등재
      • KCI등재후보

        진행 위암환자에서 Lymphokine-Activated Killer (LAK) 활성의 저하

        홍원선,김영환,송재관,강윤구,이진오,강태웅,김정룡 대한내과학회 1990 대한내과학회지 Vol.38 No.3

        Natural killer(NK) and lymphokine-activated killer(LAK) activities were determined in 31 patients with unresectable stomach cancer before and immediately after chemotherapy with 5-fluorouracil, adriamycin and mitomycin C(FAM) and 31 healthy volunteers. The major purposes of the study were focused on whether peripheral blood lymphocytes(PBL) in stomach cancer patients had a similar ability in the generation of LAK activity to those in healthy volunteers and what the effect was of chemotherapy with FAM on the generation of LAK activity. LAK cells were generated in vitro by culturing human PBL with 100 U/㎖ of recombinant human interleukin-2(rH-IL-2) for 72 hours. K562(human myelogenous leukemia cell line) and MKN-45(human stomach adenocarcinoma cell line) were used as target cells for NK and LAK activities. NK activity against K562, a sensitive line, was significantly depressed in patients with stomach cancer compared with that in healthy volunteers(p<0.01). However, LAK activity against K562 was similar to that of the controls. Age, sex and performance status(ECOG 0-2 and 3-4) did not have an influence on both NK and LAK activities. LAK activity was significantly higher than NK activity, either against K562 or MKN-45, in both healthy volunteers and patients with stomach cancer(p<0.001). NK and LAK activities against MKN-45, a NK-resistant line, in patients with stomach cancer showed significantly lower levels than those in healthy volunteers. We also analyzed the effect of chemotherapy with FAM on NK and LAK activities, with no suppression of NK and LAK activities being observed. In this study, we have demonstrated that PBL of stomach cancer have a reduced ability to generate LAK activity in response to rH-IL-2. However, LAK activity generated from PBL receiving chemotherapy with FAM was similar to that of PBL without chemotherapy.

      • KCI등재
      • 사람 위선암에서 cathepsin L의 발현증가

        홍원선,홍석일,박인철,손영숙,정훈용,양석균,김해련,민영일 울산대학교 의과대학 1996 울산의대학술지 Vol.5 No.1

        cathepsin L은 lysosomal cysteine 단백분해효소로서 기저막(basement membrane)과 세포외기질(extracellular matrix)을 파괴하여 암세포의 침윤과 전이에 중요한 역할을 하는 물질로 알려져 있다. 이러한 cathepsin L에 대한 mRNA 발현도를 5개의 사람 위선암(gastric adenocarcinoma) 세포주와 5명의 위선암 환자에서 채취한 조직에서 방사능으로 표지된 cathepsin L특이 cDNA를 사용한 Northern blot법으로 측정하였다. 위암의 전이병소에서 수립한 세포주인 SNU-5, SNU-16, MKN-45와 Kato Ⅲ에서는 cathepsin L mRNA가 발현되었으나 원발병소에서 수립한 AGS 세포주에서는 mRNA의 발현이 관찰되지 않았다. 5명의 위암 환자에서는 원발병소, 전이가 확인된 임파절 및 암 근처 정상 위점막에서 각각 조직을 채취하여 cathepsin L mRNA의 발현을 측정하였다. 원발병소와 전이병소에서는 모두 cathepsin L mRNA가 발현되었으나 정상 위점막조직에서는 전예에서 mRNA 발현이 관찰되지 않았다. 한편 mRNA의 발현도는 1예에서는 전이병소가 원발병소에 비해 높았으나, 2예에서는 전이병소에서 발현도가 낮았으며, 나머지 2예에서는 원발병소와 전이병소 사이에 차이가 없어, 원발병소와 전이병소 사이에 mRNA의 발현도의 일관성 있는 경향은 관찰되지 않았다. 이상의 결과는 cathepsin L은 위암의 발생과 진행에 있어 암세포의 침윤과 전이를 촉진하는 것 이외에 또 다른 역할을 할 가능성을 시사하고 있다고 사료된다. Cathepsin L, a lysosomal cysteine protease, is known to play an important role in cancer invasion and metastasis by degrading the components of basement membrane and extracellular matrix. The mRNA expression of cathepsin L was determined by Northern blot analysis using a radiolabeled cDNA specific for cathepsin L in five human gastric adenocarcinoma cell lines and five surgical specimens of primary gastric adenocarcinomas, their metastatic lymph nodes and matched adjacent normal mucosae. The mRNA of cathepsin L was expressed in all of the four cell lines established from the metastatic sites, SNU-5, SNU-16, MKN-45 and Kato Ⅲ, while not detected in one cell line established from the primary site, AGS. The mRNA was expressed in all of the five primary and five metastatic cancer specimens tested, while it was not detected in all matched normal mucosae. The intensities of the mRNA expressions, however, did not show the consistent pattern between primary sites and metastatic lymph nodes. These results suggest that cathepsin L may have the other function in addition to facilitation of the invasion and metastasis during the development and progression of stomach cancer.

      • 위암세포주에서 Recombinant Human Interferon-r와 Adriamycin의 투여순서가 항암효과에 미치는 영향

        홍원선,손영숙,김창민,강윤구,이춘택,김유철,임영혁,남현석,이진오,강태웅 大韓免疫學會 1993 大韓免疫學會誌 Vol.15 No.-

        Numerous previous studies, both in vitro and in vivo, have demonstrated that the cytotoxicity can be enhanced by the combination of chemotherapeutic agent and interferons(IFNs) in various types of cancer cells. We have previously reported that combined treatment of MKN-45, human gastric adenocarcinoma cells, with adriamycin(ADM) and recombinant human interferon-r(rh-IFN-r) increased in the cytotoxicity. In this study, the effects of combination timing of rh-IFN-r and ADM on the cytotoxicity against MKN-45 were investigated using MTT assay. MKN-45 was treated with rh-IFN-r and ADM in vitro on three schedules : Treat A ; rh-IFN-r and ADM were treated simultaneously, Treat B ; rh-IFN-r was treated 24 hours after the treatment with ADM, Treat C ; rh-IFN-r was treated for 72 hours and followed by the treatment with ADM. The survival of MKN -45 was inhibited by ADM dose-dependently. 102 and 103U/ml of rh-IFN-r significantly inhibited the survival of MKN-45(% survival : 35.1 ±-1.2% and 34.4 ±1.1% in Treat A and 42.5 ± 2.1% and 45.9-±2.5% in Treat C, respectively). However no difference in the survival was observed between 102 and 103U/ml of rh-IFN-r. Combined treatment with rh-IFN-r and ADM significantly augmented the cytotoxicity at low concentrations of ADM. Combined effects of rh-IFN-r and ADM were evaluated using IC30(,ag/ml) to ADM. IC30s of MKN-45 in Treat A, B and C at 102 U/ml of rh -IFN-r _ were 0.019 -?- 0.003, 0.045 :I:0.001 and 0.054 ± 0.012, respectively, while IC30 of MKN-45 treated with ADM alone was 0.052±0.004. IC30s of MKN-45 in ADM alone group, Treat A, Treat B and Treat C at 103U/ml of rh-IFN-r were 0.047 ±0.003, 0.004 -±0.001, 0.031 ±0.004 and 0.056 0.008, respectively. These results indicate IC30s of Treat A and B were significantly lower than those of ADM alone(p<0.05) and IC30s of Treat A was significantly lower than those of Treat B(p <0.01). IC30s of Treat C, however, were not different from those of ADM alone. From these results demonstrating that cytotoxic effects were increased by the combination of rh-IFN-r and ADM in the order, Treat A > Treat B> Treat C, it can be concluded that the simultaneous administration of rh-IFN-r and ADM may be the most effective method to combine these two therapeutic modalties.

      • KCI등재후보

        사람폐암세포주 (PC-14)에서 Cyclosporin A에 의한 Adriamycin 내성의 극복

        김영환,홍원선,송재관,강윤구,이진오,강태웅,김건열,한용철 대한내과학회 1990 대한내과학회지 Vol.38 No.3

        Cyclosporin A and verapamil were tested using MTT assay to evalute the modification effect on the resistance to adriamycin in a human lung cancer cell line(PC-14) and its resistant subline(PC-14/A). PC-14/A was derived by the continuous exposure of PC-14 to incremental concentrations of adriamycin. PC-14/A was 2.5 times more resistant to adriamycin in terms of ICso than PC-14. Cyclosporin A alone, at a concentration of 2.5㎍/㎖, inhibited the growth of PC-14 to 68.3%. 2.5㎍/ ㎖ and 5.0㎍/㎖ of cyclosporin A showed an increase in the cytotoxicity of adriamycin (p<0.01) with 5.0㎍/㎖ being greater than 2.5㎍/㎖(p<0.01). Excluding the direct cytotoxic effect, however, cyclosporin A did not increase in the sensitivity of PC-14 to adriamycin but only showed an additional cytotoxic effect with adriamycin. Verapamil (up to 6.0㎍/㎖) did not inhibit the growth of PC-14. 3.0㎍/㎖ of verapamil did not increase the cytotoxic effect of adriamycin. The combination of cyclosporin A and verapamil with adriamycin enhanced the cytotoxicity of adriamycin, but the result was similar to that of cyclosporin A with adriamycin. 5.0㎍/㎖ of cyclosporin A modified the adriamycin resistance of PC-14/A(SR, 3.2). However, 3.0㎍/㎖ of verapamil did not significantly reverse the adriamycin resistance of PC-14/A. The modified effect of the combination of 5.0㎍/㎖ of cyclosporin A and 3.0㎍/㎖ of verapamil was similar to that of 5.0㎍/㎖ of cyclosporin A alone in PC-14/A. These results demonstrate that cyclosporin A has an additional cytotoxic effect with adriamycin in PC-14 and PC-14/A and has overcome the acquired resistance to adriamycin in PC-14/A. They also suggest that cyclospoin A may have the therapeutic potential in the treatment of human lung cancer.

      • SCOPUSKCI등재

        출혈성 소화성 궤양의 장기 재발률

        심기남,정훈용,양석균,홍원선,박의련,박무인,김해련,민영일 대한소화기내시경학회 1999 Clinical Endoscopy Vol.19 No.2

        Background/Aims: Bleeding from a peptic ulcer is one of the common and serious complications associated with the rate of reported mortality, which ranges from 5% to 10%. Endoscopic therapy is effective in controlling active bleeding and reducing the emer-gency surgery, the immediate mortality rate and the incidence of early rebleeding. But few recent studies have documented the long-term recurrent bleeding rate after discharge in patients with bleeding peptic ulcers. The aim of this study was to determine the long-term recurrent bleeding rate and factors predisposing to recurrent bleeding. Methods: Eighty-eight patients with bleeding peptic ulcers discharged after medical treatment between Dec. 1990 and Jul. 1992 were included in this study and retrospectively followed up with medical records and telephone interviews. The end point of follow-up was recur-rent hemorrhage, surgery for treatment of ulcer complication, or death. Results: By July 1997, retrospective follow-up was available in 76 patients. Recurrent bleeding occurred in 23 patients (30.3%) with bleeding peptic ulcers and the median follow-up period was 69 months (range, 1 ∼79 months). The estimated cumulative recurrent bleeding rate after 1, 2, 3, 4, 5 and 6 years was 11.8%, 14.5%, 19.9%, 24.2%, 27.2% and 34.2%, respectively. There was no difference between the recurrent bleeding group and the non-recurrent bleed-ing group according to age, sex, prior NSAIDs use, previous history of bleeding or pepticulcer, site of ulcer, stigmata of recent hemorrhage at initial examination, method of treatment and amount of transfusion. Conclusion: Recurrent bleeding occurred in one-third of patients with bleeding peptic ulcers after 6 years of follow-up and one-third of recurrent bleeders rebled within 1 year. The factors predisposing to recurrent bleeding in the long-term follow-up could not be found. Therefore, further studies designed to identify factors predisposing to recurrent bleeding are needed and the evaluation of Helicobacter pylori status in bleeding pepic ulcer is needed because Helicobacter pylori is an important factor of peptic ulcer recurrence.

      • SCOPUSKCI등재

        세침 흡입 생검으로 진단된 간의 혈관근지방종 1 예

        이경아,유은실,민영일,김해련,심기남,정훈용,양석균,홍원선,박의련,이문규 대한소화기학회 1999 대한소화기학회지 Vol.33 No.6

        Hepatic angiomyolipoma is a rare benign tumor of the liver composed of blood vessel, smooth muscle cells, fat and myelocomponent. The preoperative diagnosed of the lesion is important because of its therapeutic implications. Radiologic findings are not specific because the composed elements are variable in proportion and distribution. Thus, the findings at computed tomography, ultrasono graphy and magnetic resonance imaging may be only suggestive and its definitive diagnosed requires histologic confirmation. We experienced a case of hepatic angiomyolipoma in patient with chronic hepatitis diagnosed preoperatively by fine-needle aspiraton biopsy under ultrasound guidance. To our knowledge, this is the first case of hepatic angiomyolipoma diagnosed preoperatively in Korea. We report it with review of literatures.

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