Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

The clinical observation of Compound Xuanju Capsules Combined with methotrexate treating rheumatoid arthritis / 中成药

AIM To evaluate the clinical effects of Compound Xuanju Capsules (CXC,Polyrhachis vicina Roger,Epimedii Folium,Lycii Fructus,Cnidii Fructus) combined with methotrexate (MTX) on patients with moderate or severe rheumatoid arthritis (RA).METHODS One hundred and eighty RA patients were randomized into 3 groups:CXC group,MTX group and combined group (dosed with both CXC and MTX) for a 48-week intervention.The clinical observation on the changes of the signs and symptoms,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),health assessment questionnaire (HAQ),visual analogue scale (VAS) and disease active score (DAS) 28 were performed before and after each treatment.ACR20,American College of Rheumatology 20％ improvement criteria was taken as the primary end point,and ACR50 and ACR70 as the secondary end points to standardize the patients' response measurement,and all adverse reactions were recorded as well.RESULTS At the time point right after the 12th week,the ACR20 response rate of the combined group (41.5％) was significantly higher than that of the CXC group (19.6％,P ＜ 0.05) and the MTX group (24.1％,P＜0.05).The respective ACR50 (2.1％) and ACR70 (20.8％) response rate of the combined group were significantly higher than those of CXC group and MTX group (P ＜ 0.05).At the time point right after the 24th week,the combined group still demonstrated its significantly higher ACR20 response rate (81.1％) to the CXC group (30.4％,P ＜ 0.05) and the MTX group (68.5％,P ＜ 0.05).The similar superiority in ACRS0 (60.4％) and ACR70 (54.7％) response rate of the combined group to the CXC group and the MTX group were found (P ＜0.05).After the 48th week,the combined group displayed its significantly higher ACR70 response rate (75.7％) to CXC group and MTX group (P ＜ 0.05).Given the reduction of DAS28,HAQ and VAS from the12thweek's5.26±0.83),(22.2±10.3),(6.0±0.4) to the 24thweek's (4.21 ±0.91),(17.1±10.3),(2.4±2.2),andthe48thweek's (2.19±0.56),(10.4±5.0),(0.8±0.9),the combined group's more outstanding performance compared to CXC group and MTX group started right after the 24th week (P ＜ 0.05).Generally,no difference in adverse events was detected between the combined group and MTX group (P ＞ 0.05).CONCLUSION The combined use of CXC and MTX can be an effective and safe treatment for moderate and severe rheumatoid arthritis.

Successful Treatment of Jesnner's Lymphocytic Infiltration of the Skin with Methotrexate / 대한피부과학회지

No abstract available.

Deoxyadenosine antagonizes MTX-induced suppression of inflammatory bone destruction / 实用口腔医学杂志

Objective:To study the effects of deoxyadenosine(dAdo) on methotrexate (MTX) induced suppression of inflammatory bone destruction.Methods:The culture system of whole bone marrow cells (WBMCs) was utilized to evaluate osteoclastogenesis.TRAP staining and μCT analysis were utilized to evaluate osteoclastogenesis and bone destruction in adjuvant arthritis rats.Results:In the bone marrow culture system,MTX-induced suppression of osteoclastogenesis was abrogated by the addition of dAdo.dAdo canceled MTX-induced suppression of osteoclastogenesis in the rats with arthritis,and significantly abolished the therapeutic effects of MTX on inflammatory bone destruction in the rats.Conclusion:The accumulation of dAdo may be one cause of the losing effectiveness of MTX in bone destruction.

Deoxyadenosine antagonized methotrexate-induced suppression of osteoclastogenesis / 实用口腔医学杂志

Objective:To study the mechanism of the effectiveness loss of methotrexate(MTX)in the treatment of rheumatoid arthri-tis.Methods:The culture system of rat whole bone marrow cells(WBMCs)and tartrateresistant acid phosphatase(TRAP)staining were utilized to evaluate osteoclastogenesis.The mRNA expression of osteoclastogenesis factors in the WBMCs culture system was examined by semi-quantitative RT-PCR.Results:Deoxyadenosine(dAdo)decreased MTX-induced suppression of osteoclastogenesis.The recov-ery effect of dAdo on MTX was partially prevented by caffeine.MTX significantly reduced mRNA expression of receptor activator of nu-clear factor kappa-B ligand(RANKL),dAdo partially recovered RANKL mRNA expression and inhibited osteoprotegerin(OPG)expres-sion.Conclusion:The accumulation of dAdo may induce the effectiveness loss of methotrexate in rheumatoid arthritis treatment.Com-bination of MTX and caffeine can be a potential therapeutic strategy.

Grade 4 oral mucositis and prolonged pancytopenia with high dose intravenous methotrexate in a patient of philadelphia positive acute lymphoblastic leukemia.

Antimetabolite drugs are rarely associated with grade 3 or 4 mucositis. However specific side effects such as bone marrow suppression, pancytopenia, hospitalization, high cost limit the use of intravenous methotrexate. Here we report a case of 25-year-old girl patient with Acute Lymphoblastic Leukemia (ALL) treated with 24 hour methotrexate in her continuous phase of chemotherapy. After 12 hours of completing the treatment she developed oral mucosal pain & she was not able to speak. After a week, her White Blood Cell (WBC) count was 600/cumm with fever and she could not speak and eat or drink. So she was hospitalized for few days till she can drink something. We report high grade mucositis with methotrexate. Hematologists should be aware of this possible side effect to undertake early intervention.

Profiling single nucleotide polymorphisms (SNPs) across intracellular folate metabolic pathway in healthy Indians.

Background & objectives: Many pharmacologically-relevant polymorphisms show variability among different populations. Though limited, data from Caucasian subjects have reported several single nucleotide polymorphism (SNPs) in folate biosynthetic pathway. These SNPs may be subjected to racial and ethnic differences. We carried out a study to determine the allelic frequencies of these SNPs in an Indian ethnic population. Methods: Whole blood samples were withdrawn from 144 unrelated healthy subjects from west India. DNA was extracted and genotyping was performed using PCR-RFLP and Real-time Taqman allelic discrimination for 12 polymorphisms in 9 genes of folate-methotrexate (MTX) metabolism. Results: Allele frequencies were obtained for MTHFR 677T (10%) and 1298 C (30%), TS 3UTR 0bp (46%), MDR1 3435T and 1236T (62%), RFC1 80A (57%), GGH 401T (61%), MS 2756G (34%), ATIC 347G (52%) and SHMT1 1420T (80%) in healthy subjects (frequency of underlined SNPs were different from published study data of European and African populations). Interpretation & conclusions: The current study describes the distribution of folate biosynthetic pathway SNPs in healthy Indians and validates the previous finding of differences due to race and ethnicity. Our results pave way to study the pharmacogenomics of MTX in the Indian population.

Serum methotrexate level is inversely related to the outcome of osteosarcoma patients / 소아과

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 (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). RESULTS: Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean+/-SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14+/-12.83 micrometer, 9.29+/-3.89 micrometer, 1.73+/-1.37 micrometer, and 0.58+/-0.44 micrometer, respectively. The peak MTX serum level was 1292.14+/-12.83 micrometer. 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 micrometer) 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 micrometer (P=0.002) and mean 24-h MTX level of less than 3.4 micrometer (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.

Serum methotrexate level is inversely related to the outcome of osteosarcoma patients / 소아과

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 (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). RESULTS: Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean+/-SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14+/-12.83 micrometer, 9.29+/-3.89 micrometer, 1.73+/-1.37 micrometer, and 0.58+/-0.44 micrometer, respectively. The peak MTX serum level was 1292.14+/-12.83 micrometer. 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 micrometer) 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 micrometer (P=0.002) and mean 24-h MTX level of less than 3.4 micrometer (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.

Detection of RFC,DHFR and GST-? expression in human osteosarcoma cell line with MTX-resistence by FQ-PCR / 中国矫形外科杂志

[Objective]To study the difference in expression of RFC, GST-?, DHFRmRNA between human osteosarcoma U2-OS cell line and the MTX-resisitant variants U2-OS/R1-R3, and to investigate the significance in MTX resistance for human osteosarcoma. [Methods]Three resistant MTX human osteosarcoma cell lines were established by pulse exposure parental cell line(U2-OS) in gradually increased dose of MTX . The expression of RFC,GST-?,DHFRmRNA were assayed by real-time fluorescence quantitative polymerase chain reaction(FQ-PCR).[Results]Three MTX-resistant variants(U2-OS/R1-R3) were successfully established , the results of the FQ-PCR revealed that the MTX resistance was associated with the decreased expression of the RFC mRNA and increased expression of DHFR mRNA and GST-? mRNA.[Conclusion]The author investigated the MTX resistant mechanism of human osteosarcoma cell line at a gene level. The decreased expression of RFC mRNA and the increased expression of DHFR mRNA and GST-? mRNA participate in the MTX resistance in human osteosarcoma cell lines U-2 OS. This provides the evidence for exploring the MTX resistance mechanism in clinical osteosarcoma patients ,and helps to screen the patients who are insensitive to MTX chemotherapy.

Cervical pregnancy and therapeutic options / 대한산부인과학회잡지

Of all forms of ectopic gestation, the possibility of fertility catastrophe is highest with a cervical pregnancy. Though rare, it is a potentially life-threatening condition. In the past it was diagnosed late, after there was profuse hemorrhage from the cervix and it usually required hysterectomy. With ultrasound, diagnosis can be made earlier and conservative management attempted in order to preserve the reproductive potential. Methotrexate has been used both systemically and intra-amniotically to treat cervical ectopic gestation conservatively.

A Case of Subungual Keratoacanthoma / 대한피부과학회지

Subungual keratoacanthoma is a rare, benign tumor occurring mainly on the thumb of middle-aged Caucasians. It presents as a painful keratotic papule or nodule accompanied by consequential partial onycholysis and bacterial infections. Unlike keratoacanthoma of other sites, subungual keratoacanthoma is not spontaneously resolved and surgical interventions have been recommended for treatment. It also needs to be differentiated from other subungual lesions, especially squamous cell carcinoma. We describe a case of subungual keratoacanthoma, which was completely resolved with extraction of the nail followed by oral methotrexate(MTX) medication.

A high performance capillary electrophoresis method for determination of methotrexate in serum / 中华检验医学杂志

Objective To establish a rapid assay for the determination of methotrexate (MTX) in serum.Method The assay was based on the ultraviolet absorbance of methotrexate at 306 nm. The separation of the drug was done by high performance capillary electrophoresis (HPCE). The bare fused-silica capillary was 60 cm in total length, 50.5 cm in efficient length and 75?m in diameter. The voltage of 25 kV was applied. The running buffer was 75 mmol/L phosphate, pH7.4. The performance of methodology was evaluated.Result The complete separation of MTX was achieved within 10 min. The linearity of the assay was from 1.1 ?mol/L to 1100.0 ?mol/L. The minimal detection limit was 0.55 ?mol/L.The recovery of MTX was from 88.2% to 98.2%. Within-run precision was 4.2% and between-run precision was ~5.4%. Conclusion The result indicated that the method was an effective method for clinical and scientific research with advantages of rapidity, simplicity and accuracy.

A Case of Primary idiopathic Polymyositis with Hypoalbuminemia and Thrombocytopenia / 대한내과학회지

Primary idiopathic polymyositis is a condition of presumed autoimmune etiology in which the skeletal muscle is damaged by a nonsuppurative inflammatory process dominated by lymphocytic infiltration. We recently experienced a patient with primary idiopathic Polymyositis associated with hypoalbuminemia and thrombocytopenia. About 4 months prior to admission, he was diagnosed as primary idiopathic polymyositis, and improved by treatment with prednisolone 60 mg/day. During steroid tapering, muscle weakness was recurred and accompanied by hypoalbuminemia and thrombocytopenia. Despite retreatment with prednisolone 60 mg/day, muscle weakness, hypoalbuminemia and thrombocytopenia persisted. He was then started to administer methotrexate(MTX) 15 mg/week which resulted in prompt improvement of muscle weakness, hypoalbuminemia and thrombocytopenia. These findnigs suggest that primary idiopathic polymyositis is one of the cause of hypoalbuminemia and thrombocytopenia, and that the hypoalbuminemia and thrombocytopenia can be improved promptly by methotrexate treatment.

Analysis of Correlation Factors on Methotrexate(MTX)Concentration in Children with Acute Lymphoblastic Leukemia / 中国药房

OBJECTIVE:To study the correlation between MTX concentration and hydration volume,alkalization volume,urine volume,body weight and biochemical indexes in Children with acute lymphoblastic leukemia(ALL).METHODS:The case histories of pediatric ALL patients hospitalized between 2003 and 2006 who were treated with MTX antitumor thrapy were reviewed retrospectively for a recording of MTX concentration,hydration volume,alkalization volume,urine volume,body weight and biochemical indexes etc.The data were analyzed with multiple linear regression method by SPSS(10.0)software.RESULTS:No significant correlation was noted between log MTX concentration and most of the biochemical indexes,hydration volume,alkalization volume and urine volume;however,log MTX concentration at 24 h was negatively correlated with body weight but positively correlated with TBIL(total bilirubin)(P