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6-mercaptopurine

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https://www.readbyqxmd.com/read/28301625/successful-treatment-of-generalized-essential-telangiectasia-with-6-mercaptopurine
#1
Alex M Glazer, Bryan D Sofen, Darrell S Rigel, Jerome L Shupack
<p>Generalized essential telangiectasia (GET) is a notoriously difficult to treat disorder with no current satisfactory treatments. This case and discussion report the use of 6-mercaptopurine (6-MP) as a successful treatment for GET. Moreover, we show that GET may represent a state of increased angiogenesis, a paradigm shift from the current understanding that these telangiectasias represent dilatations of only pre-existing vessels. This new view of GET may drive others to look at novel agents for treatment...
March 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28295989/pharmacokinetics-of-two-6-mercaptopurine-liquid-formulations-in-children-with-acute-lymphoblastic-leukemia
#2
Jaszianne A Tolbert, Shasha Bai, Susan M Abdel-Rahman, Keith J August, Scott J Weir, Gregory L Kearns, Kathleen A Neville
BACKGROUND: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. METHODS: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28278299/combination-treatment-with-6-mercaptopurine-and-allopurinol-in-hepg2-and-hek293-cells-effects-on-gene-expression-levels-and-thiopurine-metabolism
#3
Sofie Haglund, Svante Vikingsson, Sven Almer, Jan Söderman
Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28258828/dna-thioguanine-nucleotide-concentration-and-relapse-free-survival-during-maintenance-therapy-of-childhood-acute-lymphoblastic-leukaemia-nopho-all2008-a-prospective-substudy-of-a-phase-3-trial
#4
Stine Nygaard Nielsen, Kathrine Grell, Jacob Nersting, Jonas Abrahamsson, Bendik Lund, Jukka Kanerva, Ólafur Gísli Jónsson, Goda Vaitkeviciene, Kaie Pruunsild, Lisa Lyngsie Hjalgrim, Kjeld Schmiegelow
BACKGROUND: Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. METHODS: In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia...
February 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28257599/immunosuppressive-drugs-affect-ifn%C3%AE-and-pd1-kinetics-in-patients-with-newly-diagnosed-autoimmune-hepatitis
#5
Charlotte R Grant, Beth S Holder, Rodrigo Liberal, Michael A Heneghan, Yun Ma, Giorgina Mieli-Vergani, Diego Vergani, Maria Serena Longhi
Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs). Several lines of evidence indicate CD4 as the main effectors involved in the autoimmune liver damage. Herein we investigate the in vitro effects of prednisolone, 6-mercaptopurine, cyclosporine, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of pro-inflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4(+) CD25(-) cells, isolated from the peripheral blood of treatment-naïve patients with AIH...
March 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28228435/crohn-s-disease-complicated-by-epstein-barr-virus-driven-haemophagocytic-lymphohistiocytosis-successfully-treated-with-rituximab
#6
Grace Thompson, Dominic Pepperell, Ian Lawrence, Benjamin David McGettigan
We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication...
February 22, 2017: BMJ Case Reports
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
#7
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
#8
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...
March 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
#9
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/28153823/comparison-of-self-report-and-electronic-monitoring-of-6mp-intake-in-childhood-all-a-children-s-oncology-group-study
#10
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/28130685/metabolite-monitoring-to-guide-thiopurine-therapy-in-systemic-autoimmune-diseases
#11
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/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#12
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/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/28011186/nk-cells-are-biologic-and-biochemical-targets-of-6-mercaptopurine-in-crohn-s-disease-patients
#14
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
#15
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/27942204/loading-cisplatin-onto-6-mercaptopurine-covalently-modified-msns-a-nanomedicine-strategy-to-improve-the-outcome-of-cisplatin-therapy
#16
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
#17
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
#18
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
https://www.readbyqxmd.com/read/27916002/long-term-effect-of-stents-eluting-6-mercaptopurine-in-porcine-coronary-arteries
#19
Matthijs S Ruiter, Albert Doornbos, Vivian de Waard, Robbert J de Winter, Nico J M Attevelt, Rob Steendam, Carlie J M de Vries
BACKGROUND: Drug-eluting stents (DES) have dramatically reduced restenosis rates compared to bare metal stents and are widely used in coronary artery angioplasty. The anti-proliferative nature of the drugs reduces smooth muscle cell (SMC) proliferation effectively, but unfortunately also negatively affects endothelialization of stent struts, necessitating prolonged dual anti-platelet therapy. Cell-type specific therapy may prevent this complication, giving rise to safer stents that do not require additional medication...
December 5, 2016: Journal of Negative Results in Biomedicine
https://www.readbyqxmd.com/read/27895780/curcumin-potentiates-the-effect-of-chemotherapy-against-acute-lymphoblastic-leukemia-cells-via-downregulation-of-nf-%C3%AE%C2%BAb
#20
Helia Judith Pimentel-Gutiérrez, Lucina Bobadilla-Morales, César Cenobio Barba-Barba, Citlalli Ortega-De-La-Torre, Fernando Antonio Sánchez-Zubieta, Jorge Román Corona-Rivera, Betsy Annel González-Quezada, Juan S Armendáriz-Borunda, Rocío Silva-Cruz, Alfredo Corona-Rivera
Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers. Currently available treatments exhibit toxicity and certain patients may develop resistance. Thus, less toxic and chemoresistance-reversal agents are required. In the present study, the potential effect of curcumin, a component of Curcuma longa, as a pharmacological co-adjuvant of several chemotherapeutic agents against ALL, including prednisone, 6-mercaptopurine, dexamethasone, cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin, methotrexate and cytarabine, was investigated in the REH ALL cell line cultures treated in combination with chemotherapeutic agents and curcumin...
November 2016: Oncology Letters
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