• Title/Summary/Keyword: Methotrexate(MTX)

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Preliminary Results of Management for Primary CNS Lymphoma (원발성 중추신경계 림프종의 치료에 관한 예비적 결과)

  • Ahn, Seung-Do;Chang, Hye-Sook;Choi, Eun-Kyong
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.79-82
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    • 1993
  • From October 1989 to March 1992, ten patients diagnosed as primary central nervous system (CNS) lymphoma were treated with radiation therapy at Asan Medical Center. To obtain pathologic diagnosis, five patients had stereotactic biopsy and the others underwent craniotomy & tumor removal. According to the classification by International Working Formulation, seven of 10 patients showed diffuse large cell types and the remaining 3 had diffuse mixed cell types. Computed tomographic scans of the brain disclosed solitary (6 cases) or multiple (4 cases) intracranial lesions. All patients received 4000 cGy/20 fx to the whole brain followed by an additional 2000 cGy/10 fx boost to the primary lesion. Six patients with initial cerebrospinal fluid (CSF involvement were treated with whole brain irradiation and intrathecal Methotrexate (IT-MTX) chemotherapy. One of them received an additional spinal irradiation after 3 cycles of IT-MTX chemotherapy because of MTX induced arachnoiditis. One patient received 3 cycles of systemic chemotherapy prior to rodiation therapy and one received 5 cycles of salvage chemotherapy for recurrence. With a median follow up time of 8 months, all patients were followed from 7 to 26 months. Radiologically seven patients showed complete remission and the remaining three showed partial remission at one month after radiotherapy. The 1 and 2 year survival rate was $86{\%}\;and\;69{\%}$ respectively. Until now, two patients expired at 7 and 14 months. These patients developed extensive CSF seeding followed by local failure. Considering initial good response to radiation therapy and low incidence of extraneural dissemination in primary CNS lymphoma, we propose to increase total tumor dose to the primary lesion by hyperfractionated radiotherapy or stereotactic radiosurgery. For the patients with CSF involvement at diagnosis, we propose craniospinal irradiation with IT MTX chemotherapy.

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Suppressive Effects of JTT on Collagen-Induced Arthritis in Mice (정통탕(定痛湯)이 콜라젠으로 유도한 관절염 동물 병태 모델에 미치는 효과)

  • Cho, Jong-Cheol;Koo, Young-Sun;Kim, Dong-Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.39-49
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    • 2007
  • Rheumatoid arthritis is an autoimmune disease involving multiple joint. In order to access the suppressive effects of JTT on rheumatoid arthritis and it's effects on immune system we investigated whether JTT could suppress the disease progression of collagen-induced arthritis. DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with DW, JTT (200 or 400 mg/kg) or methotrexate (MTX, 30 mg/kg) as a positive control. Oral administration of JTT significantly suppressed the progression of CIA, which extend is comparable to that of MTX. Histological examination reveled that JTT inhibited infiltration of inflammatory cells into affected paw joint and bone erosion and cartilage destruction were greatly reduced compared with control. Total cell number of spleen, lymph node and peripheral blood were significantly reduced. The absolute number of CD19$^+$, CD3$^+$/CD69$^+$, CD4$^+$/CD25$^+$ cell in spleen from JTT treated mice were significantly decreased. The absolute number of CD19$^+$, CD3$^+$, CD3$^+$/CD69$^+$, CD4$^+$, CD4$^+$/CD25$^+$ CD8$^+$, CD49b, CD3/CD49b cells in draining lymph node were significantly increased compared with control. In peripheral blood mononuclear cells of JTT treated mice, the absolute number of CD4$^+$, CD4$^+$/CD25$^+$, CD3$^+$/CD69$^+$ cells were significantly decreased compared with control, while that of CD49b$^+$ was slightly increased. Infiltration of CD3$^+$ cells and CD11b$^+$/Gr-1$^+$ cells into paw joint was significantly reduced in JTT treated mice. The levels of pathologic cytokines including TNF-a and IL-6 in serum were significantly decreased by oral treatment with JTT The levels of IFN-g in the culture supernatant of splenocyte stimulated with CD3$^+$/CD28$^+$ or collagen were dramatically decreased, while the levels of IL-4 was increased under CD3$^+$/CD28$^+$ or collagen stimulation. Rheumatoid factors including IgG, IgM and collagen specific antibody were present much lower in the serum of JTT treated mice than control. Taken together, JTT has suppressive effects on rheumatoid arthritis by modulating immune system, and has potential to use anti-rheumatic arthritic agent in human.

The Preventive Effects of Nanopowdered Peanut Sprout-added Caciocavallo Cheese on Collagen-induced Arthritic Mice

  • Kim, Dong-Hwi;Chang, Yoon Hyuk;Kwak, Hae-Soo
    • Food Science of Animal Resources
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    • v.34 no.1
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    • pp.49-56
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    • 2014
  • The present study was carried out to investigate the effects of nanopowdered peanut sprout-added Caciocavallo cheese (NPCC) on the prevention and treatment of rheumatoid arthritis in DBA/IJ mice immunized with type II collagen. After the induction of arthritis, the mice were being divided into five groups: (1) normal, no immunization; (2) CIA, collagen-induced arthritis; (3) MTX, collagen-induced arthritis treated with methotrexate (0.3 mg/kg body weight); (4) CC, collagen-induced arthritis treated with Caciocavallo cheese (0.6 g/d); (5) NPCC, collagen-induced arthritis treated with nanopowdered peanut sprout-added Caciocavallo cheese (0.6 g/d). Nanopowdered peanut sprout was ranged from 300 to 350 nm, while regular powdered peanut sprouts were ranged from 50 to $150{\mu}m$. The NPCC group had considerable reductions of clinical scores and paw thicknesses at the end of experiment as compared to the CIA group. In the serum analysis, the TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and $IgG_1$ levels in the NPCC group have decreased by 69.4, 75.9, 66.6, and 61.9%, respectively, when compared to the CIA group. The histological score and spleen index of the NPCC group were significantly lower than the CIA group. In conclusion, the feeding NPCC method could delay and/or prevent the rheumatoid arthritis in the collagen-induced arthritis mouse model. Based on this study, nanopowdered peanut sprouts could be applied to various functional cheeses.

Suppressive Effects of GHS in Knee Joint, Regional Lymph Nodes, and Spleen on Collagen-induced Arthritis in Mice (Collagen II로 유도된 CIA 관절염 생쥐의 대한 가미해동피산(加味海桐皮散)의 억제 효과)

  • Kim, Nam-Uk;Kim, Dong-Hui
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1233-1242
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    • 2007
  • Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which might be mediated by the altered activation of Immune system, ultimately leading to the destruction of cartilage and bone. To examine effects of GHS on rheumatoid arthritis DBA/1J mice were immunized with bovine type II collagen to induced arthritis and then treated with GHS once a day for 7 weeks. Oral administration of GHS (200 mg/Kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/Kg), a positive control. The severity of arthritis within the knee joints, which was evaluated by histological assessment of cartilage destruction and pannus formation, was also lowered by GHS. The production of TNF-and IL-6 in serum was significantly suppressed. The levels of IFN-g in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. The levels of IgG and IgM RA factor were also decreased in the serum. FACS analysis indicated that B cells (in DLN), CD3+ T cells (in spleen, and paw joint), CD11b+Gr-1+ cells (in paw joint), CD3+CD49b(DX5) (in PBMC) were decreased and there was increased proportion of CD3+, CD4+, CD8+, CD4+CD25+ T cells in DLN. In conclusion, our results demonstrates that GHS significantly suppressed the progression of CIA and this action was characterized by the decreased production of TNF-a, IL-6, and rheumatoid factors, and modulations of immune cell populations.

Inhibitory Effect of a Decoction Combined with Ostericum koreanum Maxim. and Aralia continentalis Kitagawa on Collagen II-induced Arthritis Mice (Type II Collagen으로 유도된 관절염에 대한 강활(羌活), 독활(獨活) 배합약물의 억제 효과)

  • Yoon, Ho-Suk;Lee, Young Cheol;Lee, Jang-Cheon
    • Herbal Formula Science
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    • v.21 no.1
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    • pp.161-176
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    • 2013
  • Objectives : To clarify the anti-arthritic activity of Ostericum koreanum Maxim. (OS) plus Aralia continentalis Kitagawa (AC) in vivo. Methods : All mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with OS plus AC once a day for 7 weeks. Oral administration of OS plus AC (200 or 50 mg/kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/kg), a positive control. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Results : Administration of OS plus AC significantly suppressed the progression of CIA and inhibited the production of TNF-${\alpha}$ and IL-6 in serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with OS plus AC. In conclusion, our results demonstrates that OS plus AC significantly suppressed the progression of CIA and that this action was characterized by the decreased production of IL-6, IFN-${\gamma}$ and collagen II specific antibody in serum, CD3+CD69+ T cells, MHC class II+/CD11c+ (in DLN), CD11b+Gr-1+ cells (in PBMC), CD11b +Gr-1+ cells, B220+/CD23+ (in paw joint). Conclusions : The the levels of IFN-${\gamma}$ in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. In the serum of OS and AC-treated mice, the levels of IgM RA factor were decreased.

Effect of Original Kyungokgo & Iksuyongjingo plus Sparassis crispa on Antioxidant, Immunity Improvement and Sensory Evaluation (경옥고의 원방과 가미방 익수영진고가(加)꽃송이버섯이 항산화, 면역력 활성 및 기호도에 미치는 영향)

  • Na, Chang-Su;Shin, Wook;Lee, Yu-Mi;Moon, Yang-Seon;Noh, Hee-kyung;Seo, Seong-Ho;Son, Hong-Seok
    • The Korea Journal of Herbology
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    • v.31 no.4
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    • pp.43-51
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    • 2016
  • Objectives : This study was conducted with objectives of comparatively investigating effects of original Kyungokgo and Iksuyongjingo plus Sparassis crispa which is gamibang of Kyungokgo on antioxidant improvement, immunity improvement, and sensory evaluation.Methods : Total phenol and DPPH scavenging activity were measured to determine antioxidant improvement of original Kyungokgo and Iksuyongjingo plus Sparassis crispa. While, blood and serum study were conducted and effect on the cytokines were observed from the immunosuppressed rat induced by methotrexate (MTX). Control group was administered with a drinking water, Kyungokgo group was administered with a original Kyungokgo 200 mg/kg, and Iksuyongjingo plus Sparassis crispa group was administered with a Iksuyongjingo plus Sparassis crispa 200 mg/kg for 20 days. Further, intensity and preference evaluation were performed as sensory evaluation.Results : It was observed that Iksuyongjingo plus Sparassis crispa significantly increased total phenol and DPPH scavenging activity, proving that these can improve antioxidant activities. In the immunosuppressed rat, Iksuyongjingo plus Sparassis crispa significantly decreased IL-2 level, significantly increased Il-10 level, and significantly increased neutrophils, RBC, HGB, and HCT levels, indicating that it is effective in increasing immunity. Further, Iksuyongjingo plus Sparassis crispa significantly improved intensity and preference in the sensory evaluation.Conclusions : From the above results, it is concluded that Iksuyongjingo plus Sparassis crispa which is gamibang of Kyungokgo can act effectively on improving antioxidant activity and immunity, and can attribute convenient intake by improving diet preference.

Inhibitory Effect of a Decoction of Eucommiae ulmides OLIVER and Dipsacus asperoides C. Y. Cheng et T.M.Ai on Collagen II-induced Arthritis Mice (Collagen II-induced Arthritis 생쥐에 대한 두충(杜仲).속단(續斷) 배합약물의 관절염 억제 효과)

  • Lee, Boo-Kyun;Lee, Young-Cheol;Lee, Jang-Cheon
    • The Korea Journal of Herbology
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    • v.25 no.1
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    • pp.55-63
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    • 2010
  • Objectives : The object of this study was to verify the inhibitory effect of a decoction of Eucommiae ulmides OLIVER (EU) and Dipsacus asperoides C. Y. Cheng et T.M.Ai (DA) on Collagen II-induced Arthritis Mice (CIA mice). Methods : DBA/1OlaHsd mice were immunized with bovine type II collagen. Boostnig same collagen 21 days later, arthritis was induced and then administrated orally the extract of EU+DA (200 or 50 mg/kg) once a day for 4 weeks and compared with that of methotrexate (MTX, 0.3 mg/kg) as a positive control. Results : Administration of EU+DA suppressed the inflammatory progression of CIA mice and the results were 1. Arthritis index of CIA mice was decreased. 2. EU+DA decreased the production of TNF-$\alpha$, IL-6, IL-$1{\beta}$ in the serum of CIA mice. 3. EU+DA decreased the level of IgM. 4. EU+DAincreasaed $CD3^+$, $CD4^+$, $CD4^+$/CD25 but decreased $CD19^+$, $CD3^+/CD49b^+$(NKT), $CD3^-/CD49b^+$(NK), $B220^+/CD23^+$ in PBMC of CIA mice. 5. EU+DA decreased $CD3^+$, $CD4^+$, $CD3^+/CD69^+$ of paw joint in CIA mice. 6. EU+DA decreased subsynovial inflammation. Conclusions : This results demonstrated that extract of EU+DA suppressed the inflammatory progression of CIA mice and supported further studies are required to clarify a mechanism of therapeutic role.

The effect of prescriptions prepared by adding medicinal herbs(Rehmannia glutinosa Residue, Poria cocos Bark) and fermenting herbal materials based on formulas Iksuyoungjingo on immunological activity (익수영진고가미방의 지황박, 복령피 배합과 발효에 따른 제제가 면역활성에 미치는 영향)

  • Lee, Yu-Mi;Kim, Wang-In;Choi, Dong-Hee;Kim, Mi-Rae;Moon, Yang-Seon;Kim, Ji-Eun;Youn, Dae-Hwan;Son, Hong-Seok;Na, Chang-Su
    • Herbal Formula Science
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    • v.26 no.1
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    • pp.13-26
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    • 2018
  • Objectives : This study was carried out to enhance the activity of Iksuyoungjingo, which has the tonify Qi, nourish Yin effect of oriental medicine, and to study the effect of the prescriptions on the immunological activities. Methods : Immunosuppression was induced by methotrexate (MTX) 2 mg / kg, the experimental group was divided into IYGgami-I, IYGgami-I-F, IYGgami-II and IYGgami-II-F groups. Each prescription was administered with drinking water for 20 days, and body weight was measured every 5 days during this period. Leukocyte, $TNF-{\alpha}$, IL-2, IL-6, IgE, spleen weight and body weight were measured Results : In the changes of $TNF-{\alpha}$, IL-2 and IL-6 as pro-inflammatory elements, all of the experimental groups showed a significant increase compared to the control group. In the IgE changes, the IYGgami-I-F, IYGgami-II and IYGgami-II-F groups showed a significant decrease compared to the control group. In the changes of spleen weight, the IYGgami-II-F group showed a significant increase compared to the control group. In the changes of WBC and lymphocytes, the IYGgami-I-F group showed a significant increase compared to the control group. Conclusions : From the above results, it can be observed that the efficacy against immunity is exerted in all of the preparations, and it was confirmed that the efficacy was maintained constant even when utilizing the Rehmannia glutinosa Residue and Poria cocos Bark, and that a more beneficial effect can be exerted in the effectiveness when the fermentation is carried out.

CNS Complications in Childhood Cancer (소아 종양 환아의 중추 신경계 합병증)

  • Jeong, Yoo Jin;Seo, Yeon Kyong;Hong, Seung-A;Kim, Heung Sik;Kim, Jun Sik;Lee, Hee Jung
    • Clinical and Experimental Pediatrics
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    • v.46 no.11
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    • pp.1112-1117
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    • 2003
  • Purpose : Recent advances in the methods of treating cancer in young patients have led to both an increased frequency of CNS complications as well as prolonged life expectancy. We intend to analyze the clinical aspects and laboratory findings of patients with CNS complications during and after treatment. Methods : We reviewed the medical records of 174 childhood cancer patients treated with chemotherapy admitted to the Dept. of Pediatrics, Keimyung University Dongsan Hospital, from January 1995 to November 2002. Among them, 15 cases with CNS complications were investigated in this study. Results : CNS abnormalities were found in 13 patients by CT or MRI during treatment such as leukoencephalopathy(n=7), mineralizing microangiopathy(n=4), brain infarction(n=3), intracranial hemorrhage(n=1), and hypoxic ischemic encephalopathy(n=1). It was found that two patients had two or more CNS abnormalities. Two patients who had no imaging abnormalities had convulsions, possibly after the addition of intrathecal methotrexate. The patients with intracranial hemorrhage and brain infarction had rapid and fatal clinical courses. The hypoxic ischemic encephalopathy following electrolyte imbalance completely recovered after correction of electrolyte. Conclusion : The CNS complications that occur during and after chemotherapy influence prognoses significantly, and remain neurologic sequelae. Therefore early diagnosis and prophylaxis for CNS complications and regular physical examination of patients who have recieved cancer therapy are strongly recommended.

Effects of Mori Ramulus on Collagen-induced Arthritis Rat - Expression of Immunocells in Draining Lymph Node - (상지가 콜라겐 유발 관절염 랫트에 미치는 영향 - 배액림프절의 면역세포 발현 -)

  • Roh, Seong-Soo;Ku, Sae-Kwang;Seo, Young-Bae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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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.