• 대한한방종양학회지
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• 제4권1호
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• pp.159-175
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• 1998

1. 연구배경 최근 놀라운 과학기술의 발전에 힘입어 난치병이라고 생각되어 오던 질환들이 하나씩 정복되어 가고 있으나 평균수명의 연장, 생활수준 향상으로 인한 고지방식, 스트레스 및 과학기술발전의 부작용 등을 이유로 새로운 질환들이 나타나고 있는 실정이다. 종양도 이런 대표적인 질환중 하나로 최근 경제적, 시간적으로 많은 투자를 해왔으나 아직까지 그 발생원인이나 성장기전 등이 자세히 밝혀지지 않았다. 이에 본 연구는 효후(哮吼)를 치료하는 청상보하환(淸上補下丸)을 이용하여 흑색종의 폐전이 억제능과 이에 의한 면역증강에 관하여 연구하고자 하였다. 2. 연구결과 B-16 세포를 이용한 C57BL/6계 마우스에 있어서의 폐전이 억제능을 측정한 결과 청상보하환(淸上補下丸) 투여군이 대조군에 비해 검액처리 7일후에는 52.70%, 14일후에는 19.43%의 유의성있는 억제율을 보였으며, 청상보하환(淸上補下丸)의 B-16 세포에 대한 직접적인 항암작용을 알아 보기 위한 시험관내 세포독성 실험에서는 청상보하환(淸上補下丸)의 용량이 $5{\mu}g/well$, $2.5{\mu}g/well$, $1.25{\mu}g/well$, and $0.625{\mu}g/well$인 경우 유의성있는 효과를 얻을수 있었으며 생존율에 의한 $IC_{50}$은 $2.17{\mu}g/well$이었다. NK-activity를 측정한 결과 청상보하환(淸上補下丸) 투여군이 작동세포와 표적세포의 비율이 100:1, 50:1의 경우에 있어서 $72.63{\pm}5.17%$, $26.94{\pm}2.43%$를 보여 대조군에 비하여 각각 31.12%, 43.68% 유의성있는 증가를 보였다. IL-2의 생산능을 측정한 결과 청상보하환(淸上補下丸) 투여군은 $1392.00{\pm}22.31pg/ml$을 보여 대조군에 비해 4.04%의 유의성 있는 증가를 보였다.

• 대한한의학회지
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• 제38권1호
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• pp.34-45
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• 2017

Objectives: This study aimed to investigate the effect of banhasasim-tang intravenous herbal acupuncture (BST-IVHA) on emesis induced by chemotherapy in rats. Methods: This study used methotrexate(MTX)-induced Rat-Pica model. The rats were randomly allocated into seven groups; normal group, two saline groups, four Banhasasim-tang(BST) groups (groups treated with BST-IVHA). All the experimental animals except those in the normal group were injected with MTX. Those in the pre-treatment groups were treated with saline injection (saline group) or BST-IVHA (BST group) before MTX injection. Those in the post-treatment groups were treated with saline injection or BST-IVHA after MTX injection. Two different dosages of BST-IVHA solution (low dose; BST-1 group, high dose; BST-2 group) were used. The changes in body weight, food intake, and kaolin consumption at 24h, 48h, and 60h were monitored and analyzed. Results: 1. No significant change was found in body weight. 2. The food intake at 48h was increased significantly in the BST-1 pre-treatment group($19.89{\pm}0.01g$) compared to the pre-saline group($18.68{\pm}0.26g$). 3. The kaolin consumption was significantly decreased in the BST-1 pre-treatment group at 24h($0.24{\pm}0.02g$) and 60h($0.36{\pm}0.14g$), in the BST-2 pre-treatment group at 48h($0.02{\pm}0.01g$) and 60h($0.80{\pm}0.31g$) compared to the pre-saline group($24h:0.81{\pm}0.37g$, $48h:0.76{\pm}0.43g$, $60h:1.56{\pm}0.03g$). The kaolin consumption was also significantly decreased in the in the BST-1 post-treatment group at 24h($0.05{\pm}0.02g$), 48h($0.64{\pm}0.06g$) and 60h($0.14{\pm}0.05g$), in the BST-2 post-treatment group at 48h($0.01{\pm}0.01g$) and 60h($0.01{\pm}0.01g$) compared to the post-saline group($24h:0.51{\pm}0.4g$, $48h:3.58{\pm}0.33g$, $60h:2.5{\pm}0.2g$). Conclusions: BST-IVHA showed an anti-emetic effect in MTX-induced rat-pica model. This result suggests that BST-IVHA could be an effective treatment for chemotherapy-induced emesis.

• Clinical and Experimental Pediatrics
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• 제46권11호
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• pp.1112-1117
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• 2003

목 적 : 소아의 악성 종양에 대한 새로운 치료법의 개발로 환아의 생존 기간이 증가하는 추세에 있으나 이로 인한 신경계 합병증의 발생도 증가하고 있다. 저자들은 항암 치료를 시행한 소아 종양 환아에서 나타난 중추 신경계 합병증에 대한 임상 양상을 알아보고자 하였다. 방 법 : 1995년 1월부터 2002년 11월까지 동산병원 소아과에서 항암치료를 시행한 환아 중 신경계 합병증이 동반되었던 15례의 환아를 대상으로 그 임상상을 후향적으로 검토하였다. 결 과 : 전체 15례 중에서 방사선학적 검사로 원인 질환을 밝힌 경우는 모두 13례로 백질뇌병증이 7례, 무기질화 미세혈관병증이 4례, 뇌경색이 3례, 뇌출혈이 1례, 저산소성 허혈성 뇌증이 1례, 2가지 이상의 합병증을 함께 나타낸 경우는 2례였으며, 혈액학적 방사선학적 검사상에서 이상 소견이 없이 MTX의 부작용으로 생각되는 경련성 질환이 2례였다. 뇌출혈과 뇌경색이 나타낸 경우는 예후가 나빴으며 전해질 불균형으로 인한 저산소성 허혈성 뇌증에서는 원인 교정 후 후유증 없이 회복되었다. 결 론 : 소아 종양 환아에서 치료 중 발생한 신경계 합병증은 질환의 예후에 큰 영향을 미치고 신경인지 발달에 장애를 남기므로 이들 합병증에 대한 예방, 진단 및 즉각적인 치료와 추적관찰이 필요할 것이다.

• 동의생리병리학회지
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• 제23권5호
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• pp.1106-1115
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• 2009

Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th1 7 cells. DBA/1OlaHsd mice were immunized with bovine type II collagen (CII). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-$\alpha$, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-$\alpha$, IL-6, IL-17 and collagen II-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 mg/kg or 200 mg/kg) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 mg/kg) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

• 대한한방내과학회지
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• 제19권1호
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• pp.221-246
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• 1998

The aim of this experimental study was to evaluate the anti-tumor effects of Chungsimbohyeltang through investigation about viability of tumor cell by MTT assay, survival period of mice transplanted with L-1210 cells, growth inhibition on the tumor cell, body weight variation in mice transplanted with sarcoma-180 cells and its immunomodulatory effects through the investigation on delayed type hyper-sensitivity, the hemagglutinin and hemolysin titers for humoral immune response, the appearance of rosette forming cells for cell-mediated immune response, the natural killer cell activity, the transformation of lymphocyte, the productivity of Interleukin-2 and phagocytic index K was performed in immune-depressed ICR mice induced by methotrexate treatments. The results were as follows ; 1. $IC_{50}$ of Chungsimbohyeltang treated group was 5.85mg/ml in SNU-C4 cell, 1.38mg/ml in SNU-396 cell, 0.21mg/ml in SNU-1 cell, so it had low anti-tumor activity. 2. The both groups of Chungsimbohyeltang extract 10mg/kg and Chungsimbohyeltang extract 20mg/kg had no toxicity and the group of Chungsimbohyeltang 20mg/kg which was shown 120% in ILS had the effect of life prolongation in mice transplanted with L-1210 cells. 3. In the growth inhibition on the tumor cells, only the group of Chungsimbohyeltang extract 20mg/kg was noted and in the weight variation in mice transplanted with sarcoma-180 cells, both groups of Chungsimbohyeltang extract had a significant effect. 4. In the delayed type hypersensitivity and appearance of rosette forming cells, both groups of Chungsimbohyeltang extract didn't have any significant effect. 5. The hemagglutinin titers was slightly increased with no significance, and the hemolysin titers was significantly increased in the only group of Chungsimbohyeltang extract 20mg/kg. 6. The natural killer cell activity of the Chungsimbohyeltang extract groups was significantly increased in the ratio of 100:1 of effector and target cells, but it was not significantly increased in the ratio of 50:1, 10:1. 7. The transformation of lymphocyte and the productivity of Interleukin-2 were increased significantly and in dose-dependent manner in both group of Chungsimbohyeltang extract. 8. The phagocytic effect of macropage was significantly increased in both groups of Chungsimbohyeltang extract. Considering the results above, we could conclude that Chungsimbohyeltang have an indirect anti-tumor effect through the modulation of immunme response, although it had not toxicity on the tumor cell it self.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3403-3410
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• 2014

Context: Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA). Objectives: To analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs). Methods: A systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-${\alpha}$ antagonists with placebo or methotrexate (MTX) (or TNF-${\alpha}$ antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNote${\times}6$. Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies. Results: 28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-${\alpha}$ therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis. Conclusions: This study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-${\alpha}$ antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-${\alpha}$ antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses.

• Clinical and Experimental Pediatrics
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• 제53권2호
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• pp.262-266
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• 2010

$TNF-{\alpha}$ 는 소아기 류마티스모양 관절염의 병태생리학에 관여하는 주요 cytokine 이다. Etanercept 는 $TNF-{\alpha}$ 억제제 중 하나로 소아기 류마티스모양 관절염에 효과적인 약물로 각광받고 있다. Etanercept의 주요 부작용은 면역력 저하에 의한 감염으로, 대게 중등도의 상기도 감염이 대부분으로 알려져 있으나, 최근 중증의 감염도 보고되고 있다. 저자들은 소아기 류마티스모양 관절염 환자가 etanercept를 14개월간 투약 후 발생한 뇌염 1예를 경험하였기에 보고하는 바이다.

• 대한한방종양학회지
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• 제1권1호
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• pp.141-165
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• 1995

In order to investigate the effects of Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang on antitumor effects after Sarcoma-180 cells transplantation into the peritoneal cavity or left groin in mice, and immune responses in mice induced by methotrexate, the extracts of its herbal medicines were orally administered for 14 or 21 days. Experimental studies were performed for measurance of mean survival days, tumor and body weight for antitumor effects, and delayed type hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and phagocytic activity for immune responses in ICR mice. Following results were obtained : 1. Mean survival time in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly prolonged, as compared with the control group(P<0.010, P<0.005). 2. Tumor weight in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly depressed, as compared with the control group(P<0.050, P<0.050). 3. Body weight in Banhabaekchulcheonmatang-treated group was significantly increased (P<0.050), but in Banhabackchulcheonmatanggamibang-treated group was slightly increased with no effectivenes, as compared with the control group. 4. Delayed type hypersensitivity in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly increased, as compared with the control group(P<0.010, P<0.050). 5. Hemagglutinin titer in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was significantly increased, as compared with the control group(P<0.050, P<0.050). 6. Hemolysin titer in Banhabaekchulcheonmatanggamibang-treated group was significantly increased (P<0.050), but in Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 7. Rosette forming cells in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 8. Natural Killer cell activity in Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang-treated group was slightly increased with no effectiveness, as compared with the control group. 9. Phagocytic activity in Banhabaekchulcheonmatanggamibang-treated group group was significantly increased (P<0.050), but in Banhabaekchulcheonmatanggamibang-treated group was increased with no effectiveness, as compared with the control group. According to the above results, it could be suggested that Banhabaekchulcheonmatang and Banhabaekchulcheonmatanggamibang have prominent antitumor effects, and enhance both cellular and humoral immunity.

• Radiation Oncology Journal
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• 제11권2호
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• pp.403-409
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• 1993

가톨릭대학교 의과대학 성모병원 치료방사선과에서 1988년부터 1992년도까지 적절한 중추신경계 예방요법후 뇌척수액내 재발을 경험한 급성 임파구성 백혈병 환자 7명을 대상으로 간헐적인 전중추신경계 방사선조사 및 척수강내 화학요법(IIIC)을 실시하였다. 추적관찰기간은 8개월에서 41개월이었고 그 중앙값은 20개월이었다. 7명의 대상환자중 3명이 다시 뇌척수액내 재발을 경험하였고, 중추신경계 관해유지기간은 각각 8, 9, 13, 20, 34, 36개월이었다. 무병 생존기 간은 2개월에서 36개월로 그 중앙값은 11개월이었다. 생존율은 8개월에서 41개월로 그 중앙값은 28개월이었다. 5명이 치료기간중 골수재발에 따른 패혈증 및 출혈로 사망하였고, 2명의 생존자는 치료종료 10개월 및 11개월째 다시 뇌척수액내 재발을 경험하였다. 치료결과를 향상시키기 위해서는 치료중 휴식기간을 단축시키고, 치료후에도 일정기간동안 척수강내 유지화학요법을 연장하여 실시하는등 치료계획의 변형이 필요할 것으로 사료되었다.

• 대한한의학방제학회지
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• 제5권1호
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• pp.127-145
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• 1997

This study was aimed to investigate the anti-tumor and immune response effect of Samyongtang(S1; this medicine represents for 'ENERGIZER'), Yangjeongjejeoktang(S2; this is the 'INTERMEDIATE METHOD' of S1 and S3) and Onbeakwon(S3; this is 'ATTACK' the disease of mass) on the experimental rats induced by Sarcoma-180 and Methotrexate. And to observed the differences S1, S2, and S3 treatment groups. Tumor weight(TW) in vivo, interleukin-2(IL-2), hemagglutinin titer(H.A), hemolysin titer(HL), rossete forming cell(RFC), delayed type hypersensitivity(DTH), and natural killer cell activity(NKCA) in vivo were measured in rats. The obtained results were summarized as follows. 1. Tumor weight was decreased in all treatment groups (S2>S3>S1) as compared with control group, but the difference was not statistically significant each treatment groups. 2. Interleukin-2 was increased in all treatment groups (S1>S2>Ss) as compared with control group, but the difference was not statistically significant each treatment groups. 3. Hemagglutinin titer was increased in all treatment groups (S1>S2>S3) as compared with control group, but the difference was not statistically significant each treatment groups. 4. Hemolysin titer was increased in all treatment groups (S1>S2>S3) as compared with control group, but the difference was not statistically significant each treatment groups. 5. Rossete forming cell(RFC) was increased in all treatment groups (S1>S2>S3) as compared with control group, but the difference was not statistically significant each treatment groups. 6. Delayed type hyperseneitivity(DTH) was increased in S1, S2 treatment groups (S1>S2) as compared with control group, but it was decreased in S3 treatment group. Therefore, S1 group was statistically significant compared with S3 groups. 7. Natural killer cell activity(NKCA) was increased in all treatment groups (S2>S3>S1) as compared with control group, but the difference was not statistically significant each treatment groups. Based on the above mentioned results, it is suggested that S1, S2 and S3 will have anti-tumor substances and enhance effect of immune response. But the differences were not statistically significant in each treatment groups, except for delayed type hypersensitivity.