• The Journal of Korean Medicine
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• v.29 no.3
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• pp.21-37
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• 2008

Objectives: The purpose of this study was to verify the effect of Palmiboshinwhan (PMBSW) in methotrexate (MTX)-induced immunosuppressed SD rats. Methods: The test articles were once a day dosed for 14 days by gastric gavage from 2 days after last MTX-dosing, and changes in body weight, spleen weight and total blood leukocyte numbers were observed with total lymphocyte numbers, B and T lymphocyte percentages, CD3+CD4+, CD3+/CD8+, CD4+/CD8+ T lymphocyte percentages in the blood and spleen, the serum interleukin (IL)-2 levels and the productivity of IL-2 of splenic cells. Result & Conclusion: It is concluded that PMBSW has relatively good immunostimulating effect in the MTX-induced immunosuppressed SD rats. Theefficient dosage was considered above 500mg/kg. In addition, it is considered that the immunostimulating effect of PMBSW was mediated to both the B and T lymphocytes. The more favorable effects were detected in T lymphocytes rather than B lymphocytes, and PMBSW showedrelatively good stimulating potential against CD4+ T lymphocytes but not any stimulating effect against CD8+ T lymphocytes in the present study.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.4
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• pp.167-172
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• 2009

Methotrexate (MTX) in one of the antineoplastic drug and it is known to effective to management of acute lymphoblastic leukemia in children, management of choriocarcinoma and related trophoblastic tumors in women, management of carcinomas of the breast, tongue, pharynx, and tests, maintenance of remission in leukemia and treatment of serve, debilitating psoriasis. Intermediate to high-dose methotrexate administration followed by leucovorin rescue is effective in treatment of carcinoma of the lung and osteogenic sarcoma. Intrathecal administration is effective in treating meningeal leukemia or lymphoma. There are FPIA (Fluorescence polarization immunoassay) and EMIT (Enzyme multiplied immunotechique) methods that measure for MTX. We evaluated the FPIA and EMIT methods. MTX were measured by Hitachi-7600 P-module using EMIT and FPIA using TDX in the sera 60 patients. The performance characteristics evaluated were, light influence, linearity, comparison with FPIA. Also, precision evaluated were three level controls through put following CLSI evaluation protocols (EP10-A). When the MTX value of $4.16{\pm}5.78{\mu}{\mu}mol/L$ (mean, SD) by the Hitachi-7600 P-module was compared with that of $4.05{\pm}5.47{\mu}{\mu}mol/L$ by FPIA, coefficients of correlation of 0.988 was obtained. The regression equation was Y (Hitachi-7600 P-module) = 0.9408 x (FPIA) + 0.1316 (r=0.9885, n=60). CVs of MTX measured by Hitachi 7600 P-module was 6.78% at $0.33{\mu}{\mu}mol/L$, 0.96% at $1.16{\mu}{\mu}mol/L$, and 0.96% at $8.04{\mu}{\mu}mol/L$. The precision was excellent in each group. The linearity was acceptable. We evaluated that MTX is light-sensitive on prolonged exposure to direct sunlight. Comparing with the FPIA using TDX, the Hitachi-7600 P-module using EMIT showed good coefficient of correlation and precision. Therefore the Hitachi-7600 P-module can replace the FPIA for quantitative analysis of MTX.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9823-9829
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• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

• Clinical and Experimental Pediatrics
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• v.56 no.11
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• pp.490-495
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• 2013

Purpose: The use of cyclosporine and mini-dose methotrexate (MTX) is a common strategy for graftversus- host disease (GVHD) prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. Methods: The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 $mg/m^2$ each. Within the cohort, 76 patients (74%) received all 4 doses of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3) group]. Results: Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4) group (median, 15 days), compared to the MTX(0- 3) group (median, 25 days; P =0.034). The incidence of grades II-IV acute GVHD was not different between the MTX(4) and MTX(0-3) groups (P =0.417). In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II-IV acute GVHD (P =0.002), followed by female donor to male recipient transplant (P =0.034). No difference was found between the MTX(4) and MTX (0-3) groups regarding grades III-IV acute GVHD, chronic GVHD, and disease-free survival. Conclusion: Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.581-587
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• 2009

Purpose : To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). Methods : To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX ($12g/m^2$), cisplatin ($100mg/m^2$), and doxorubicin ($60mg/m^2$). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels ($mean{\pm}SE$) at 4 h (peak), 24 h, 48 h, and 72 h were $1292.14{\pm}12.83{\mu}m$, $9.29{\pm}3.89{\mu}m$, $1.73{\pm}1.37{\mu}m$, and $0.58{\pm}0.44{\mu}m$, respectively. The peak MTX serum level was $1292.14{\pm}12.83{\mu}m$. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level ($3.4{\mu}m$) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than $1,400{\mu}m$ (P=0.002) and mean 24-h MTX level of less than $3.4{\mu}m$ (P=0.011). Conclusion : The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3461-3464
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• 2012

Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.509-523
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• 1997

This study was carried out for investigating antitumor effects of 5-fluorouracil(5-FU), methotrexate(MTX) and retinoic acid(RA) on hepatocellular carcinoma induced in Sprague-Dawley rat. Antitumor effects were examined a flow cytometric DNA distributions by flow cytometry and stuied ATP/Pi using nuclear magnetic resorance, and the enzymatic activity of thymidylate synthetase and dihydrofolate reductase as well as contents of total collagen and sialic acid were measured with spectrophotometer. In this study, S phase fraction, contents of sialic acid and total collagen were decreased in the induced hepatocellular carcinoma treated with 5-FU and MTX, and synergistic effects of anticancer drugs were exhibited in the hepatocellular carcinoma treated with 5-FU and MTX simultaneously, and the inhibition of thymidylate synthetic and dihydrofolate reductase activity were shown in the hepatocellular carcinoma treated with 5-FU, MTX, and 5-FU and MTX simultaneously. On the other hand, the ratio of ATP/Pi were increased in all groups except group treated with RA. The experimental results suggest that above method may be valuable for evaluating antitumor effect of anticancer drugs.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.28-31
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• 2013

Methotrexate (MTX) has been established as a standard disease-modifying anti-rheumatic drug. If adequate disease control is achieved for a reasonable period of time, tapering the MTX dosage is recommended because the chronic use of MTX can result in opportunistic infection. We present here a case of a woman with rheumatoid arthritis taking MTX, and the woman developed actively caseating endobronchial Mycobacterium intracellulare disease with pulmonary infiltrations. After discontinuing the MTX, the patient was able to tolerate 18 months of antimycobacterial treatment without flare ups of rheumatoid arthritis, and she completely recovered from nontuberculous mycobacterial respiratory disease.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.287-287
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• 1996

Long-circulating liposomes have prompted interests in using them as a drug delivery system. This improvements in delivery has been thought to be the results from sustained action of liposomes in plasma without RES uptake. Although methotrexate(MTX) has been one of the most widely used antineoplastc drug, its use was limited by prompt RES uptake. The purpose of this study was to prepare long-circulating liposomes for MTX using highly water-soluble polymer (PEG-PE). In vitro, release of MTX from liposomes in phosphate buffer (pH 7.4), rat liver homogenate, and rat plasma was investigated. The pharmacokinetics and organ distribution of fee drug, conventional and long-circulating liposomes were also compared with one another after intravenous administration to rats.

• Annals of Clinical Neurophysiology
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• v.22 no.1
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• pp.41-45
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• 2020

Acute sarcoid myositis is rarely complicated by sarcoidosis, and steroid therapy is considered the standard treatment. We experienced a patient with acute sarcoid myositis who did not respond to aggressive high-dose corticosteroid therapy, but showed a dramatic improvement after the addition of weekly low-dose oral methotrexate (MTX). This intervention allowed the resumption of normal daily activities after 6 months. Our case strongly suggests that MTX should be considered in patients with acute sarcoid myositis that is resistant to corticosteroid therapy.