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https://www.readbyqxmd.com/read/28212467/comparison-of-6-mercaptopurine-with-6-thioguanine-for-the-analysis-of-thiopurine-s-methyltransferase-activity-in-human-erythrocyte-by-lc-ms-ms
#1
Shenghui Mei, Xindi Li, Xiaoqing Gong, Xiaoyi Zhang, Xingang Li, Li Yang, Leting Zhu, Heng Zhou, Yonghong Liu, Anna Zhou, Xinghu Zhang, Zhigang Zhao
Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Thiopurine S-methyltransferase activity (TPMT), a major determinant of TPDs toxicity, was suggested to be evaluated before TPDs treatment by using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG...
February 17, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28205273/in-vitro-responses-to-known-in-vivo-genotoxic-agents-in-mouse-germ-cells
#2
Khaled Habas, Martin H Brinkworth, Diana Anderson
Genotoxic compounds have induced DNA damage in male germ cells and have been associated with adverse clinical outcomes including enhanced risks for maternal, paternal and offspring health. DNA strand breaks represent a great threat to the genomic integrity of germ cells. Such integrity is essential to maintain spermatogenesis and prevent reproduction failure. The Comet assay results revealed that the incubation of isolated germ cells with n-ethyl-n-nitrosourea (ENU), 6-mercaptopurine (6-MP) and methyl methanesulphonate (MMS) led to increase in length of Olive tail moment and % tail DNA when compared with the untreated control cells and these effects were concentration-dependent...
February 16, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28167261/redox-and-ph-responsive-gold-nanoparticles-as-a-new-platform-for-simultaneous-triple-anti-cancer-drugs-targeting
#3
Marjan Ghorbani, Hamed Hamishehkar
Cancer is considered to be one of the leading causes of morbidity and mortality worldwide and nanotechnology was shown to have a unique potential to enhance the therapeutic performance of anti-cancer agents. A novel dual stimuli-responsive polyethylene glycol (PEG) block copolymer was synthesized for the decoration and stabilization of gold nanoparticles (NPs) to carry multiple anti-cancer drugs, doxorubicin (DOX), methotrexate (MTX) and 6-mercaptopurine (MP). DOX, MTX and MP were successfully loaded (the loading capacity of 37%, 12%, and 49%, respectively) into the NPs by ionic interaction (DOX and MTX) and disulphide-covalent bond formation (MP) in the polymeric shell of NPs...
February 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28160250/thiopurines-and-methotrexate-use-in-ibd-patients-in-a-biologic-era
#4
REVIEW
Gerassimos J Mantzaris
Although we have been living in the era of biologic therapy for several decades, the use of immunomodulators (primarily thiopurines [azathioprine and mercaptopurine] and less so methotrexate) still remains an important component of the inflammatory bowel disease (IBD) pharmaceutical arsenal. Thiopurines as monotherapy exert corticosteroid-sparing effects and can maintain long-term remission in a considerable proportion of patients who have frequent relapses and are or have become mesalazine and/or corticosteroid intolerant or refractory...
February 3, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28153823/comparison-of-self-report-and-electronic-monitoring-of-6mp-intake-in-childhood-all-a-children-s-oncology-group-study
#5
Wendy Landier, Yanjun Chen, Lindsey Hageman, Heeyoung Kim, Bruce C Bostrom, Jacqueline N Casillas, David S Dickens, William E Evans, Kelly W Maloney, Leo Mascarenhas, A Kim Ritchey, Amanda M Termuhlen, William L Carroll, Mary V Relling, F Lennie Wong, Smita Bhatia
Adequate exposure to oral 6-mercaptopurine (6MP) during maintenance therapy for childhood acute lymphoblastic leukemia (ALL) is critical for sustaining durable remissions; the accuracy of self-reported 6MP intake is unknown. We aimed to directly compare self-report to electronic monitoring (Medication Event Monitoring System [MEMS]), and identify predictors of over-reporting in a cohort of 416 children with ALL in first remission over 4 study months per patient (1,344 patient-months for the cohort) during maintenance therapy...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28152123/association-of-therapy-for-autoimmune-disease-with-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#6
Natalie Ertz-Archambault, Heidi Kosiorek, Gretchen E Taylor, Katalin Kelemen, Amylou Dueck, Janna Castro, Robert Marino, Susanne Gauthier, Laura Finn, Lisa Z Sproat, Jeanne Palmer, Ruben A Mesa, Aref Al-Kali, James Foran, Raoul Tibes
Importance: Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon. Objective: To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm. Design, Setting, and Participants: This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)...
February 2, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28151717/synergistic-drug-combinations-with-a-cdk4-6-inhibitor-in-t-cell-acute-lymphoblastic-leukemia
#7
Yana Pikman, Gabriela Alexe, Giovanni Roti, Amy Saur Conway, Andrew Furman, Emily S Lee, Andrew E Place, Sunkyu Kim, Chitra Saran, Rebecca Modiste, David M Weinstock, Marian Harris, Andrew L Kung, Lewis B Silverman, Kimberly Stegmaier
PURPOSE: While significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease. EXPERIMENTAL DESIGN: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28130685/metabolite-monitoring-to-guide-thiopurine-therapy-in-systemic-autoimmune-diseases
#8
Aurélie Chapdelaine, Anne-Marie Mansour, Yves Troyanov, David R Williamson, Maxime Doré
6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity. Outside inflammatory bowel disease literature, few data exist regarding individualized thiopurine therapy based on metabolite monitoring. This study sought to describe metabolite monitoring in patients receiving weight-based thiopurine for systemic autoimmune diseases...
January 27, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28129526/addition-of-androgens-improves-survival-in-elderly-patients-with-acute-myeloid-leukemia-a-goelams-study
#9
Arnaud Pigneux, Marie C Béné, Philippe Guardiola, Christian Recher, Jean-Francois Hamel, Mathieu Sauvezie, Jean-Luc Harousseau, Olivier Tournilhac, Francis Witz, Christian Berthou, Martine Escoffre-Barbe, Denis Guyotat, Nathalie Fegueux, Chantal Himberlin, Mathilde Hunault, Martine Delain, Bruno Lioure, Eric Jourdan, Frederic Bauduer, Francois Dreyfus, Jean-Yves Cahn, Jean-Jacques Sotto, Norbert Ifrah
Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study...
February 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28129286/methotrexate-for-refractory-crohn-s-disease-compared-with-thiopurines-a-retrospective-non-head-to-head-controlled-study
#10
Zicheng Huang, Kang Chao, Miao Li, Min Zhi, Jian Tang, Pinjin Hu, Xiang Gao
BACKGROUND: This study assessed the efficacy and safety of methotrexate (MTX) compared with thiopurines (TPs) for refractory Crohn's disease. METHODS: Fifty-one consecutive patients who were refractory or intolerant to TPs and steroid-dependent were retrospectively analyzed. MTX (20 mg/wk, subcutaneous) was adopted for inducing and maintaining clinical remission (CR). Fifty-seven patients who were naive to immunosuppressant and prescribed azathioprine (2 mg·kg·d) or mercaptopurine (1 mg·kg·d) were simultaneously recruited...
January 26, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#11
Maria S Ebbesen, Ulrikka Nygaard, Susanne Rosthøj, Ditte Sørensen, Jacob Nersting, Kim Vettenranta, Finn Wesenberg, Jon Kristinsson, Arja Harila-Saari, Kjeld Schmiegelow
Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransferases (ALAT) levels and relapse rate. We included 385 patients enrolled in the NOPHO ALL-92 protocol. Data on ALAT levels, 6 MP and MTX doses, cytotoxic MTX/6 MP metabolites, and thiopurine methyltransferase (TPMT) activity were prospectively registered...
January 5, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28045129/the-glutathione-transferase-mu-null-genotype-leads-to-lower-6-mmpr-levels-in-patients-treated-with-azathioprine-but-not-with-mercaptopurine
#12
M M T J Broekman, D R Wong, G J A Wanten, H M Roelofs, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, M J H Coenen, D J de Jong
The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 10(8) RBCs; P<0...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28038706/hepatosplenic-t-cell-lymphoma-arising-in-patients-with-immunodysregulatory-disorders-a-study-of-7-patients-who-did-not-receive-tumor-necrosis-factor-%C3%AE-inhibitor-therapy-and-literature-review
#13
Mariko Yabe, L Jeffrey Medeiros, Yahya Daneshbod, Masoud Davanlou, Carlos E Bueso-Ramos, Elisa J Moran, Ken H Young, Roberto N Miranda
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28028303/dismal-outcome-of-therapy-related-myeloid-neoplasm-associated-with-complex-aberrant-karyotypes-and-monosomal-karyotype-a-case-report
#14
Y L Tang, W K Chia, E C S W Yap, M I Julia, C F Leong, S Salwati, C L Wong
INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission...
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28011186/nk-cells-are-biologic-and-biochemical-targets-of-6-mercaptopurine-in-crohn-s-disease-patients
#15
Susy Yusung, Dermot McGovern, Lin Lin, Daniel Hommes, Venu Lagishetty, Jonathan Braun
NK cells, which contribute to immune defense against certain viral infections and neoplasia, are emerging as modifiers of chronic immunologic diseases including transplant rejection and autoimmune diseases. Immunobiology and genetic studies have implicated NK cells as a modifier of Crohn's disease, a condition often treated with thiopurine agents such as 6-mercaptopurine (6-MP). Here, we demonstrate that thiopurines mediate NK cell apoptosis via a caspase 3 and 9 inclusive pathway, and that this process is triggered by thiopurine-mediated inhibition of Rac1...
December 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28006684/an-efficient-ratiometric-fluorescence-sensor-based-on-metal-organic-frameworks-and-quantum-dots-for-highly-selective-detection-of-6-mercaptopurine
#16
Meng Jin, Zhao-Li Mou, Rui-Ling Zhang, Si-Si Liang, Zhi-Qi Zhang
The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed based on a dual-emission nanosensor. The nanosensor was fabricated by combining a blue-emission metal-organic framework (MOF) NH2-MIL-53(Al) (λem=425nm) with green-emission 3-mercaptopropionic acid-capped CdTe quantum dots (MPA-CdTe QDs) (λem=528nm) under a single excitation wavelength (335nm)...
May 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27943397/early-prediction-of-thiopurine-induced-hepatotoxicity-in-inflammatory-bowel-disease
#17
D R Wong, M J H Coenen, L J J Derijks, S H Vermeulen, C J van Marrewijk, O H Klungel, H Scheffer, B Franke, H-J Guchelaar, D J de Jong, L G J B Engels, A L M Verbeek, P M Hooymans
BACKGROUND: Hepatotoxicity, gastrointestinal complaints and general malaise are common limiting adverse reactions of azathioprine and mercaptopurine in IBD patients, often related to high steady-state 6-methylmercaptopurine ribonucleotide (6-MMPR) metabolite concentrations. AIM: To determine the predictive value of 6-MMPR concentrations 1 week after treatment initiation (T1) for the development of these adverse reactions, especially hepatotoxicity, during the first 20 weeks of treatment...
February 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27942204/loading-cisplatin-onto-6-mercaptopurine-covalently-modified-msns-a-nanomedicine-strategy-to-improve-the-outcome-of-cisplatin-therapy
#18
Xiaojie Lv, Ming Zhao, Yuiji Wang, Xi Hu, Jianhui Wu, Xueyun Jiang, Shan Li, Chunying Cui, Shiqi Peng
In the treatment of cancer patients, cisplatin (CDDP) exhibits serious cardiac and renal toxicities, while classical combinations related to CDDP are unable to solve these problems and may result in worse prognosis. Alternately, this study covalently conjugated 6-mercaptopurine (6MP) onto the surface of mercapto-modified mesoporous silica nanoparticles (MSNS) to form MSNS-6MP and loaded CDDP into the holes on the surface of MSNS-6MP to form MSNS-6MP/CDDP, a tumor-targeting nano-releasing regime for CDDP and 6MP specifically...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27920553/meta-analysis-of-the-impact-of-thioprine-s-methyltransferase-polymorphisms-on-the-tolerable-6-mercaptopurine-dose-considering-initial-dose-and-ethnic-difference
#19
Myeong Gyu Kim, Minoh Ko, In-Wha Kim, Jung Mi Oh
A meta-analysis was conducted to decide whether to reduce an initial 6-mercaptopurine (6-MP) dose in TPMT heterozygote in the case of an initial 6-MP dose of <75 mg/m(2)/d and to compare the tolerable 6-MP dose among different ethnic groups. The study was undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The differences in mean values of the tolerable 6-MP dose were calculated by using Comprehensive Meta-Analysis version 3. The results of the meta-analysis indicated that the tolerable 6-MP dose was significantly lower in the TPMT heterozygote group (difference in mean values =11...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27920397/optimizing-combination-therapy-for-acute-lymphoblastic-leukemia-using-a-phenotypic-personalized-medicine-digital-health-platform
#20
Dong-Keun Lee, Vivian Y Chang, Theodore Kee, Chih-Ming Ho, Dean Ho
Acute lymphoblastic leukemia (ALL) is a blood cancer that is characterized by the overproduction of lymphoblasts in the bone marrow. Treatment for pediatric ALL typically uses combination chemotherapy in phases, including a prolonged maintenance phase with oral methotrexate and 6-mercaptopurine, which often requires dose adjustment to balance side effects and efficacy. However, a major challenge confronting combination therapy for virtually every disease indication is the inability to pinpoint drug doses that are optimized for each patient, and the ability to adaptively and continuously optimize these doses to address comorbidities and other patient-specific physiological changes...
December 1, 2016: Journal of Laboratory Automation
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