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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/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#3
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/28011186/nk-cells-are-biologic-and-biochemical-targets-of-6-mercaptopurine-in-crohn-s-disease-patients
#4
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
#5
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/27920553/meta-analysis-of-the-impact-of-thioprine-s-methyltransferase-polymorphisms-on-the-tolerable-6-mercaptopurine-dose-considering-initial-dose-and-ethnic-difference
#6
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/27916002/long-term-effect-of-stents-eluting-6-mercaptopurine-in-porcine-coronary-arteries
#7
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/27803465/improvement-in-the-anticancer-activity-of-6-mercaptopurine-via-combination-with-bismuth-iii
#8
Yang Yang, Shuang Zhou, Ruizhuo Ouyang, Yaoqin Yang, Huihong Tao, Kai Feng, Xiaoshen Zhang, Fei Xiong, Ning Guo, Tianyu Zong, Penghui Cao, Yuhao Li, Yuqing Miao
6-Mercaptopurine (6-MP) is a clinically important antitumor drug and its commercially available form is provided as monohydrate, belonging to biopharmaceuticals classification system (BCS) class II category. The combination of bismuth(III) (Bi(III)) with 6-MP was proved to significantly improve the anticancer activity of 6-MP, leading to the discovery of a new amorphous complex ([Bi(MP)3(NO3)2]NO3). The prepared [Bi(MP)3(NO3)2]NO3 was characterized by the matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF)-MS, etc...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27759787/management-of-acute-severe-ulcerative-colitis-a-clinical-update
#9
Carlos Walter Sobrado, Lucas Faraco Sobrado
Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches...
July 2016: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
https://www.readbyqxmd.com/read/27648552/azathioprine-and-6-mercaptopurine-induced-liver-injury-clinical-features-and-outcomes
#10
Einar S Björnsson, Jiezhun Gu, David E Kleiner, Naga Chalasani, Paul H Hayashi, Jay H Hoofnagle
OBJECTIVE: The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. BACKGROUND: Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. METHODS: Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. RESULTS: Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%)...
January 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27498738/pharmacogenomics-for-leukemia-treatment
#11
Yoichi Tanaka
The pharmacokinetics and pharmacodynamics of therapeutic drugs can greatly vary among individuals. For example, it is sometimes necessary to alter the treatment of childhood acute lymphoblastic leukemia from the standard protocol. Genetic variation is one important factor, which can exert a wide range of effects on sensitivities and responses to therapeutic agents. Thiopurine S-methyl transferase (TPMT) is a useful test for predicting 6-mercaptopurine (6-MP) sensitivity in Caucasians. However, it is not effective for predicting the 6-MP therapeutic responses of Japanese patients because the frequency of TPMT deficiency is lower in the Japanese population (approximately 1% versus approximately 10% in Caucasians)...
July 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27496503/determination-of-concentrations-of-azathioprine-metabolites-6-thioguanine-and-6-methylmercaptopurine-in-whole-blood-with-the-use-of-liquid-chromatography-combined-with-mass-spectrometry
#12
D Zochowska, J Zegarska, E Hryniewiecka, E Samborowska, R Jazwiec, W Tszyrsznic, A Borowiec, M Dadlez, L Paczek
BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are used in many autoimmune diseases and after solid-organ transplantation. Their properties are mediated by active metabolites, 6-thioguanine nucleotides (6-TGN), and 6-methylmercaptopurine (6-MMP). The most common adverse effects are myelo- and hepato-toxicity. The aim of the study was quantification of 6-TG and 6-MMP, with the use of liquid chromatography combined with tandem mass spectrometry (LC/MS/MS) in solid-organ transplant recipients...
June 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27463043/treatment-of-acute-promyelocytic-leukemia-a-report-of-70-cases
#13
P Fenaux, J P Pollet, L Vandenbossche-Simon, P Morel, M Zandecki, J P Jouet, F Bauters
Over a period of 14 years, we treated 70 cases of acute promyelocytic leukemia (APL) with 3 different chemotherapy protocols. In protocol 1, patients received high dose daunorubicin (DNR) alone for induction, followed by regular reinduction courses and continuous maintenance therapy with 6 mercaptopurine (6 MP) and methotrexate (MTX) during 3 years. In protocol 2, induction with high dose DNR and Ara C was also followed by regular reinduction courses, but without continuous maintenance therapy. Protocol 3 randomized high dose Amsacrine (AMSA) or Rubidazone in association with Ara C, for induction and consolidation, this was followed by reinduction courses and continuous maintenance therapy with 6 MP and MTX...
1991: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27456154/reassuring-results-on-birth-outcomes-in-children-fathered-by-men-treated-with-azathioprine-6-mercaptopurine-within-3%C3%A2-months-before-conception-a-nationwide-cohort-study
#14
B M Nørgård, B Magnussen, M D Larsen, S Friedman
OBJECTIVE: Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception and adverse birth outcomes. DESIGN: This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624)...
July 25, 2016: Gut
https://www.readbyqxmd.com/read/27452984/pacsin2-polymorphism-is-associated-with-thiopurine-induced-hematological-toxicity-in-children-with-acute-lymphoblastic-leukaemia-undergoing-maintenance-therapy
#15
Alenka Smid, Natasa Karas-Kuzelicki, Janez Jazbec, Irena Mlinaric-Rascan
Adequate maintenance therapy for childhood acute lymphoblastic leukemia (ALL), with 6-mercaptopurine as an essential component, is necessary for retaining durable remission. Interruptions or discontinuations of the therapy due to drug-related toxicities, which can be life threatening, may result in an increased risk of relapse. In this retrospective study including 305 paediatric ALL patients undergoing maintenance therapy, we systematically investigated the individual and combined effects of genetic variants of folate pathway enzymes, as well as of polymorphisms in PACSIN2 and ITPA, on drug-induced toxicities by applying a multi-analytical approach including logistic regression (LR), classification and regression tree (CART) and generalized multifactor dimensionality reduction (GMDR)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27414842/6-mercaptopurine-still-valuable-for-the-palliative-treatment-of-acute-myeloid-leukaemia
#16
S M Daenen, J T De Wolf, E Vellenga, G W Van Imhoff, J W Smit, E V Berg-De Rutter
Although 6-mercaptopurine (6-MP) is frequently used in the treatment of acute myeloid leukaemia (AML), its effect on disease progression has not been studied systematically. In a small retrospective analysis, we found that 6-MP could induce marked haematological improvement in a considerable number of AML patients who were not treated with intensive remission induction courses. Due to the inherent limitations of retrospective analyses, we then investigated prospectively in 51 consecutive patients over a 3-year period in a single centre, to what extent, oral 6-MP 250 mg twice a week could be beneficial to AML patients who were not-or no longer-eligible for intensive chemotherapy...
2001: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27392985/-not-available
#17
May Fakhoury, Evelyne Jacqz-Aigrain, Tiphaine de Beaumais, Yves Médard
6-mercaptopurine, a key drug for the treatment of acute lymphoblastic leukaemia in children, is a prodrug metabolized into 6-thioguanine (6-TGN) which are the active compounds and into methylated metabolites, primary by thiopurine S-methyltransferase enzyme (TPMT). This enzyme displays important inter subject variability linked to a genetic polymorphism: when treated with standard doses of thiopurine, TPMT-deficient and heterozygous patients are at great risk for developing severe and potentially life-threatening toxicity (hematopoietic, hepatic, mucositis...
May 2010: Thérapie
https://www.readbyqxmd.com/read/27310705/plasmonic-targeted-and-dual-drugs-loaded-polypeptide-composite-nanoparticles-for-synergistic-cocktail-chemotherapy-with-photothermal-therapy
#18
Xingjie Wu, Linzhu Zhou, Yue Su, Chang-Ming Dong
To integrate cocktail chemotherapy with photothermal therapy into one biocompatible and biodegradable nanocarrier, the plasmonic, lactose-targeted, and dual anticancer drugs-loaded polypeptide composite nanoparticles were for the first time fabricated under mild conditions. The glyco-PEGylated polypeptide micelles that self-assembled from the lactose (LAC) and PEG grafted polycysteine terpolymer were used as templates to generate the plasmonic composite nanoparticles, as mainly characterized by DLS, TEM, SEM, and XPS...
July 11, 2016: Biomacromolecules
https://www.readbyqxmd.com/read/27193222/genotyping-nudt15-can-predict-the-dose-reduction-of-6-mp-for-children-with-acute-lymphoblastic-leukemia-especially-at-a-preschool-age
#19
Hisato Suzuki, Hiroko Fukushima, Ryoko Suzuki, Sho Hosaka, Yuni Yamaki, Chie Kobayashi, Aiko Sakai, Kazuo Imagawa, Atsushi Iwabuchi, Ai Yoshimi, Tomohei Nakao, Keisuke Kato, Masahiro Tsuchida, Nobutaka Kiyokawa, Kazutoshi Koike, Emiko Noguchi, Takashi Fukushima, Ryo Sumazaki
The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP)...
September 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27163515/association-between-combined-presence-of-hepatitis-c-virus-and-polymorphisms-in-different-genes-with-toxicities-of-methotrexate-and-6-mercaptopurine-in-children-with-acute-lymphoblastic-leukemia
#20
Doaa H Abdelaziz, Noha M Elhosseiny, Sahar A Khaleel, Nirmeen A Sabry, Ahmed S Attia, Manal H El-Sayed
BACKGROUND: The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). PROCEDURE: One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase...
September 2016: Pediatric Blood & Cancer
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