• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1357-1362
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• 2016

Metastatic gestational trophoblastic neoplasia (GTN) is an uncommon cancer. The principal treatment consists of chemotherapy with or without surgery or radiotherapy. We here retrospectively reviewed the outcomes of metastatic GTN treated at our institute between January, 1999 and December, 2013. Sixty-three patients met the criteria. The median age was 30.0 years and almost 90% were referral cases. Nearly 40% of the studied patients presented with vaginal bleeding while 22.2% were asymptomatic. The most common antecedent pregnancy was hydatidiform mole (57.1%) followed by term pregnancy (20.6%). The median interval time from antecedent pregnancy to the development of GTN was three months and the median pretreatment B-hCG was 58,274 mIU/ml. Stage III (74.6%) was the most common staging followed by stage IV (20.6%) and stage II (4.8%). The most frequent surgery was hysterectomy (31.7%). Thoracotomy and craniotomy were performed in three and two patients, respectively. The most common first line chemotherapy regimen was methotrexate and folinic acid (36.5%) followed by EMA (etoposide, methotrexate, actinomycin D) (34.9%), EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (17.5%) with the remission rate of 66.7%. Nearly one-third of the patients were given a subsequent chemotherapy regimen after failure with the first line therapy and showed a final response rate of 73.0%. However, in stage IV, the response to first line treatment was only 38.5%. In conclusion, the outcomes of metastatic GTN were poor especially with the higher stages.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.1-8
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• 2006

Methotrexate(MTX)는 소아 골육종 환자에서 $12g/m^2$의 고용량을 사용하고 있다. 현재, 소아 골육종 환자에서 신기 능에 따른 고용량 MTX의 임상 약동학은 연구되어 있지 않다. 따라서 본 연구에서는 신기능에 따른 MTX 약동학을 이용하여 구내염을 최소화하는 방법을 제시하고자 하였다. 방법: 환자들의 의무기록지를 후향적 방법으로 검토하였다. 한 병원에서 골육종으로 진단받고, 치료 받은 환자들을 대상으로 정상 신기능군과 비정상 신기능군으로 나누었다. 두 군에 MTX 투여 후 혈중 농도를 각각 비교하였고, 최고 혈중농도도 비교하였다. 혈중 농도와 구내염의 관련성, CL, AUC와 구내염의 상관관계를 분석하였다. 각 군의 terminal half-life, CL, Vss의 평균과 mea residence time(MRT)의 평균을 구하였고, 두 군간 각각을 비교하였다 $({\alpha}=0.05)$. 결과: 환자는 6명이었고, 평가 가능한 총 MTX 투여 회수는 34회였다. MTX 투여 후 최고혈중 농도, 24,48 시간의 혈중농도는 통계적으로 유의성 있는 차이가 있었고, 72,96 시간에서의 농도는 두 군간 유의성이 없었다. 각 군에서 혈중농도와 구내염의 상관관계, 그리고 CL, AUC와 구내염의 상관관계는 발견되지 않았다. Vss를 제외한 모든 파라미터들(terminal half-life, CL, MRT)은 통계적으로 유의성 있는 차이가 있었다. 결론: 비정상 신기능 군에서 MTX 투여 시작 후 24, 48 시간에서의 혈중농도가 더 높고, 변동이 심했다. 또한 MTX의 CL는 감소했고, 혈중농도는 증가하였다. 이러한 사실로 MTX 투여 전 후 혈중 크레아티닌이나 또는 크레아티닌 청소율 모니터링이 필요하다는 것을 알 수 있으며, MTX 투여가 끝난 직후 그리고 그 이후 24 시간 간격으로 혈중 농도를 측정해야함을 알 수 있다.

• 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.

• The Journal of Pediatrics of Korean Medicine
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• v.13 no.1
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• pp.253-275
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• 1999

The effects of Sagunjatang and Samultang on the immunosuppression induced by methotrexate(MTX) in rats were investigated in this study. The multiple parameters of immunity assessed in each rats included leukocyte count, lymphocyte rate, the number of lymphocyte in tibial bone marrow, contact hypersensitivity to DNFB, morphological change of thymocyte and IgG antibody on SDS-PAGE. Sprague-Dawley male rats were used and divided into five groups at random. Group A was normal control. Group B, the MTX treatment control, was injected i.v. with 2mg/kg of on days 9, 11 after sensitization with SRBC on 5th day. Group C, the experimental control, was treated Sagunjatang for 18days and MTX. Group D was treated Samultang for 18days and MTX. Group E was treated Sagunjatang-Samultang for 18days and MTX. The dosage of Sagunjatang and Samultang was $1m{\ell}/day$ respectively. In the case of Group E, rats Were fed Sagunjatang $1m{\ell}$ in the morning and Samultang $1m{\ell}$ in the afternoon. The results are summarized as follows: 1. Leukocyte count in rats induced by intravenous sensitization with SRBC was decreased significantly in Group E. 2. Leukocyte counts of 2weeks later after being treated MTX were increased significantly in Groups C and D. 3. Lymphocyte rate in rats induced by intravenous sensitization with SRBC wasn't changed significantly in all the experimental groups. 4. Lymphocyte rate of 2weeks. later after being treated MTX was increased significantly in Group D. 5. The number of lymphocyte in tibial bone marrow was incereased significantly in Group C. 6. Contact hypersensitivity wasn't changed significantly in all the experimental groups. 7. Morphological finding of thymocyte in group C was similar to normal group as compared with control group. 8. Purified IgG of all the experimental groups showed two bands of 50,000 and 25,000 on SDS-PAGE. But there was no difference among experimental groups.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.3
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• pp.211-220
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• 2021

Objective: The present study aimed to investigate the possibility that curcumin (CMN) protects against methotrexate (MTX)-induced testicular damage by affecting the phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Methods: Eighteen male Wistar albino rats were randomly divided into three groups. The control group was given an intragastric administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given intragastric CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single intraperitoneal dose of MTX (20 mg/kg) on the 11th day. At the end of the experiment, all animals were sacrificed and the testicular tissues were removed for morphometry, histology, and immunohistochemistry. Body and testicular weights were measured. Results: Body weights, seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. Whereas, the number of histologically damaged seminiferous tubules and interstitial space width significantly increased in the MTX group. In addition, the number of p-p38 MAPK immunopositive cells and the immunoreactivity of NF-κB also increased in the MTX group compared to the control group. CMN improved loss of body weight, morphometric values, and histological damage due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-κB immunoreactivity. Conclusion: CMN may reduce MTX-induced testicular damage by suppressing the p38 MAPK and NF-κB signaling pathways.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.105-112
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• 1996

The surface of albumin microspheres was modified with methotrexate(MTX) by using 1,3-dicyclohexylcarbodiimide (DCC). Surface-modified albumin microspheres entrapping no MTX (SAMS), free MTX (SAMSF) and MTX-bovine serum albumin(BSA) conjugates(SAMSC) were prepared. The organ-targeting ability of free $[^3H]MTX,\;[^3H]MTX-BSA$ conjugate and the above microspheres was evaluated after i.v. administration of the preparations, equivalent to 150 nCi via the tail vein of mice. The total radioactivity in the lung increased immediately in a few minutes after i.v. injection of the microspheres, and then declined for the period of 3-4 weeks. However, the radioactivity in the liver, spleen and kidney increased slowly during the rapid decrease in radioactivity in the lung. This suggested that the microspheres could be entrapped rapidly in the lung through mechanical filtration because of their large size and slowly redistributed to the liver, spleen and kidney due to either the microspheres being degraded enough for the size to allow passage through the capillary beds of the lung and/or the release of $[^3H]MTX\;or\;[^3H]MTX-BSA$ conjugates from the microspheres. The amount of $60{sim}70%$ of the dose was targeted to the liver after the i.v. injection of SAMS, SAMSF and SAMSC, and the values of $(R_e\;^*\;_{e)liver}$ from the microspheres were $5{\sim}7$ compared to free MTX. This suggested that the liver-targeting ability from surface-modified albumin microspheres could be $5{\sim}7$ times as that of free MTX. The liver-targeted drug was accumulated in the Kupffer cells at the initial stage, thereafter the drug in the Kupffer cell was slowly transferred into the hepatocytes. The value of AUQ for liver from SAMS was higher than that from SAMSF, but much lower than that from SAMSC. This suggest that MTX bound to their surface could be eliminated slower than the entrapped free MTX, and faster than the entrapped MTX-BSA conjugates. This is consistent with the in vitro release rates order in the presence of a proteolytic enzyme. Also, surface-modified MTX was scarcely released in the absence of a proteolytic enzyme. Therefore, the surface-modified MTX nay be released (or eliminated) rapidly from SAMSC at the target site, and thereafter MTX may be released (or eliminated) slowly from the entrapped MTX-BSA conjugates in SAMSC for a long period.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.203-209
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• 2004

Background : Methotrexate (MTX) has been used to treat a wide range of malignant and benign diseases including osteosarcoma, advanced stage non-Hodgkin's lymphoma, psoriasis, severe rheumatoid arthritis, sarcoidosis, and Wegener's granulomatosis. MTX-induced lung injury occurs in up to 10% of treated patients. Although both acute and chronic presentations have been described, typical manifestation of MTX-induced lung injury is subacute with symptoms usually developing within several months after starting therapy. Nonspecific interstitial pneumonia (NSIP) is the most common histopathologic manifestation of MTX-induced lung disease, while bronchiolitis obliterans organizing pneumonia (BOOP) and diffuse alveolar damage (DAD) are less common. Granuloma formation is reported in 34.7%. In Korea, Two reports of MTX pneumonitis have been published. The one presented with NSIP and the other with DAD. We recently experienced a case of MTX pneumonitis with presentation of hypersensitivity pneumonitis.

• BLOOD RESEARCH
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• v.53 no.4
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• pp.268-268
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• 2018

• Maxillofacial Plastic and Reconstructive Surgery
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• v.15 no.1
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• pp.35-48
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• 1993

The in vitro predictive tests in cancer chemotherapy of cancer cell lines to anticancer drugs were determined using novel dye exclusion assay [NDEA], [3H] thymidine incorporation, and clonogenic assay [CA>. Antitumor effect of Bleomycin, Cis-platin, Vinblastine, Methotrexate to HEp-2, B16 cell lines using rapid assays was compared with [CA> in this study. In dye exclusion assay of B l6 cell line, cancer cells were sensitive to Bleomycin at all concentrations, to Vinblastine at the level of peak plasma concentration [PPC], ${\times}1/10$ [PPC](P<0.05). And Bleomycin revealed relatively good cytotoxicity than that of CDDP and vinblastine at ${\times}10$[PPC], (P<0.05). HEp-2 cells were resistive to methotrexate at the level of ${\times}100$[PPC] (P<0.05) In [3H] thymidine incorporation assay, B 16 cells were sensitive to Bleomycin, CDDP, Vinblastine at the level of [PPC], ${\times}10$ [PPC](P<0.01). Dose-dependent drugs of bleomycin, CDDP were more sensitive than Vinblastine at high concentration (P<0.05). In clonogenic assay, HEp-2 cell line was sensitive to three drugs of all concentrations except ${\times}10$ [PPC] of CDDP. B 16 cell line was sensitive to all drugs(P<0,01). In comparison of chemosensitivity tests among three assays, the results were correlated(${\gamma}=0.99$, P<0.05).