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https://www.readbyqxmd.com/read/29321348/influence-of-thiopurine-methyltransferase-gene-polymorphism-on-egyptian-children-with-acute-lymphoblastic-leukaemia
#1
Azza A G Tantawy, Fatma S E Ebeid, Amira A M Adly, Eman El-Ghoroury, Mai Mostafa
Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29197275/a-sensitive-turn-on-fluorescent-probe-for-detection-of-biothiols-using-mno2-carbon-dots-nanocomposites
#2
Dimple Garg, Akansha Mehta, Amit Mishra, Soumen Basu
Presently, the combination of carbon quantum dots (CQDs) and metal oxide nanostructures in one frame are being considered for the sensing of purine compounds. In this work, a combined system of CQDs and MnO2 nanostructures was used for the detection of anticancer drugs, 6-Thioguanine (6-TG) and 6-Mercaptopurine (6-MP). The CQDs were synthesized through microwave synthesizer and the MnO2 nanostructures (nanoflowers and nanosheets) were synthesized using facile hydrothermal technique. The CQDs exhibited excellent fluorescence emission at 420nm when excited at 320nm wavelength...
November 21, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29194039/validation-of-a-high-performance-liquid-chromatography-method-for-thiopurine-s-methyltransferase-activity-in-whole-blood-using-6-mercaptopurine-as-substrate
#3
Hannah Rieger, Patrik Schmidt, Elke Schaeffeler, Manabu Abe, Mira Schiffhauer, Matthias Schwab, Nicolas von Ahsen, Gabriela Zurek, Hartmut Kirchherr, Maria Shipkova, Eberhard Wieland
BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely performed in patients to adjust drug therapy. METHODS: We further optimized a previously established high-performance liquid chromatography (HPLC) method by measuring TPMT activity in whole blood instead of isolated erythrocytes, which is based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S-adenosyl-methionine as methyl donor...
December 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29192347/pharmacogenetics-of-thiopurines-for-inflammatory-bowel-disease-in-east-asia-prospects-for-clinical-application-of-nudt15-genotyping
#4
REVIEW
Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa
The thiopurine drugs 6-mercaptopurine (6-MP) and azathiopurine (AZA) are widely used to treat inflammatory bowel disease. However, the incidence of adverse reactions is high, particularly in Asia, and the mechanisms of toxicity in Asian populations remain unclear. Thiopurine S-methyltransferase (TPMT) is a well-known enzyme that inactivates AZA or 6-MP through methylation and is one of the few pharmacogenetic predictors used in clinical settings in Western countries. Individuals carrying TPMT-deficient genetic variants require reduced drug doses, but this treatment modification is are not applicable to East Asian populations...
November 30, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29175587/design-synthesis-and-molecular-modeling-studies-of-new-series-of-antitumor-1-2-4-triazines-with-potential-c-met-kinase-inhibitory-activity
#5
Marwa H El-Wakil, Hayam M Ashour, Manal N Saudi, Ahmed M Hassan, Ibrahim M Labouta
The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives based on our lead NCI 748494/1, possessing different N-linkers to aromatic and heterocyclic rings. In addition, a molecular hybrid series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-mercaptopurine (6-MP) was synthesized in order to explore its "double-drug" antitumor effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45)...
November 16, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29147133/allopurinol-in-combination-with-thiopurine-induces-mucosal-healing-and-improves-clinical-and-metabolic-outcomes-in-ibd
#6
Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G Seidman
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28967008/the-n-allyl-substituted-effect-on-wormlike-micelles-and-salt-tolerance-of-a-c22-tailed-cationic-surfactant
#7
Pengxiang Wang, Wanli Kang, Hongbin Yang, Yilu Zhao, Xia Yin, Zhou Zhu, Xiangfeng Zhang
Wormlike micelles (WLMs) have been observed in a wide variety of cationic surfactants. Here we developed WLMs based on an N-allyl substituted cationic surfactant with an unsaturated C22-tail, N-erucamidopropyl-N,N-dimethyl-N-allyl-ammonium bromide (EDAA), and compared them with UC22AMPM at the same concentration. The viscoelasticity, aggregate microstructure and salt tolerance of EDAA solutions were investigated by rheology, surface tension and Cryo-TEM measurements. It was found that EDAA exhibited a higher viscosity and a high salt tolerance...
October 18, 2017: Soft Matter
https://www.readbyqxmd.com/read/28963908/emerging-role-of-nudt15-polymorphisms-in-6-mercaptopurine-metabolism-and-dose-related-toxicity-in-acute-lymphoblastic-leukaemia
#8
REVIEW
Minu Singh, Prateek Bhatia, Sanjeev Khera, Amita Trehan
Despite more than 80% long term survival in ALL, morbidity due to drug related myelotoxicity remains high. Germline variants of thiopurine metabolizing enzymes (TPMT and ITPA) have been described which are associated with increased drug toxicity during maintenance phase, but their prevalence in different ethnic groups is variable to account for relatively high myelotoxicity incidence. NUDT15 variant (rs116855232) has been recently identified as a novel polymorphism related with thiopurine-induced leucopenia in inflammatory bowel disease and ALL...
November 2017: Leukemia Research
https://www.readbyqxmd.com/read/28903549/nudt15-variants-cause-hematopoietic-toxicity-with-low-6-tgn-levels-in-children-with-acute-lymphoblastic-leukemia
#9
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Purpose: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). Materials and Methods: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant)...
September 13, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28883280/susceptibility-to-6-mercaptopurine-toxicity-related-with-nudt15-and-abcc4-variants-in-japanese-childhood-acute-lymphoblastic-leukemia
#10
Yoichi Tanaka
6-Mercaptopurine (6-MP) is one of the main components for the treatment of childhood acute lymphoblastic leukemia (ALL). However, many patients require a dose reduction of 6-MP due to its severe toxicities. NUDT15 variants are one of the factors that cause 6-MP intolerability in Asians. In each patient with heterozygous variants of NUDT15, 6-MP intolerability differs. Therefore, we hypothesized that the combination of NUDT15 genotype with ABCC4 genotype, which is associated with 6-MP efflux, might enable to accurately predict 6-MP intolerability...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28877179/adherence-to-6-mercaptopurine-in-children-and-adolescents-with-acute-lymphoblastic-leukemia
#11
Mervat Alsous, Rana Abu Farha, Eman Alefishat, Suha Al Omar, Deema Momani, Alia Gharabli, James McElnay, Robert Horne, Rawad Rihani
OBJECTIVE: Studies on children with Acute Lymphoblastic Leukemia (ALL) reported non-adherence in 2-54% of cases. The primary objective of this study was to assess rates of adherence to 6-MP using two different methods in children and adolescents with ALL. Secondary aim was to identify factors that influence adherence to 6-MP in children with ALL. METHODS: All eligible children with ALL who are (≤ 19) years old and receive 6-MP therapy for at least 1 month were approached to participate in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28844800/paternal-use-of-azathioprine-6-mercaptopurine-or-methotrexate-within-3-months-before-conception-and-long-term-health-outcomes-in-the-offspring-a-nationwide-cohort-study
#12
S Friedman, M D Larsen, B Magnussen, L R Jølving, P de Silva, B M Nørgård
PURPOSE: We examined the effect of preconception paternal use of azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate (MTX) and the risk of adverse long-term outcomes in the offspring. METHODS: This study included all children born in Denmark from 1 January 1997 through 2013. Exposed cohort: children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524)...
August 24, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28835099/glutathione-sensitive-hyaluronic-acid-mercaptopurine-prodrug-linked-via-carbonyl-vinyl-sulfide-a-robust-and-cd44-targeted-nanomedicine-for-leukemia
#13
Jie Qiu, Ru Cheng, Jian Zhang, Huanli Sun, Chao Deng, Fenghua Meng, Zhiyuan Zhong
6-Mercaptopurine (6-MP) is an essential medicine used for treating leukemia in the clinics. 6-MP suffers, however, from poor water solubility, low bioavailability, and significant side effects. Here, we designed CD44-targeted glutathione-sensitive hyaluronic acid-mercaptopurine prodrug (HA-GS-MP) linked via carbonyl vinyl sulfide for safer and enhanced treatment of acute myeloid leukemia (AML). HA-GS-MP obtained with 50 kDa HA and 6-MP conjugation content of 6.9 wt % showed excellent water solubility with a hydrodynamic size of ca...
September 1, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28818801/development-and-validation-of-a-reliable-method-for-thiopurine-methyltransferase-tpmt-enzyme-activity-in-human-whole-blood-by-lc-ms-ms-an-application-for-phenotypic-and-genotypic-correlations
#14
Supaporn Wiwattanakul, Santirhat Prommas, Nuttawut Jenjirattithigarn, Siwalee Santon, Apichaya Puangpetch, Samart Pakakasama, Usanarat Anurathapan, Chonlaphat Sukasem
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of thiopurine methyltransferase (TPMT) activity in human whole blood lysate, based on conversion of 6-mercaptopurine (6-MP) by TPMT to 6-methylmercaptopurine (6-MMP) using S-adenosyl-l-methionine (SAM) as the methyl donor. This method was improved from the previous laborious method for washing of red cell lysate preparation to develop whole blood EDTA lysate. In addition, the TPMT incubation was optimized and the chromatography was performed in a short runtime of 7min on a C18-column by detection via triple quadrupole mass spectrometry...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28710878/6-mercaptopurine-modifies-cerebrospinal-fluid-t-cell-abnormalities-in-paediatric-opsoclonus-myoclonus-as-steroid-sparer
#15
M R Pranzatelli, E D Tate, T J Allison
The purpose of this study was to evaluate the capacity of 6-mercaptopurine (6-MP), a known immunosuppressant, to normalize cerebrospinal fluid (CSF) lymphocyte frequencies in opsoclonus-myoclonus syndrome (OMS) and function as a steroid sparer. CSF and blood lymphocytes were immunophenotyped in 11 children with OMS (without CSF B cell expansion) using a comprehensive panel of cell surface adhesion, activation and maturation markers by flow cytometry, and referenced to 18 paediatric controls. Drug metabolites, lymphocyte counts and liver function tests were used clinically to monitoring therapeutic range and toxicity...
November 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28681659/the-relationship-of-genetics-nursing-practice-and-informatics-tools-in-6-mercaptopurine-dosing-in-pediatric-oncology-formula-see-text
#16
REVIEW
Wendy J Haylett
An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for myelosuppression or other toxicities. Informatics tools such as clinical decision support systems are useful for the application of this and similar pharmacogenetics information to the realm of nursing and clinical practice for safe and effective patient care...
September 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28574837/6-mercaptopurine-promotes-energetic-failure-in-proliferating-t-cells
#17
Ana A Fernández-Ramos, Catherine Marchetti-Laurent, Virginie Poindessous, Samantha Antonio, Pierre Laurent-Puig, Sylvie Bortoli, Marie-Anne Loriot, Nicolas Pallet
The anticancer drug 6-mercaptopurine (6-MP) inhibits de novo purine synthesis and acts as an antiproliferative agent by interfering with protein, DNA and RNA synthesis and promoting apoptosis. Metabolic reprogramming is crucial for tumor progression to foster cancer cells growth and proliferation, and is regulated by mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) as well as the oncogenes Myc and hypoxia inducible factor 1α (HIF-1α). We hypothesized that 6-MP impacts metabolic remodeling through its action on nucleotide synthesis...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554266/tolerability-profile-of-thiopurines-in-inflammatory-bowel-disease-a-prospective-experience
#18
Fabio Salvatore Macaluso, Sara Renna, Marcello Maida, Mariangela Dimarco, Chiara Sapienza, Marco Affronti, Emanuele Orlando, Giulia Rizzuto, Rosalba Orlando, Marco Ventimiglia, Mario Cottone, Ambrogio Orlando
OBJECTIVES: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting. MATERIALS AND METHODS: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported...
September 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28476189/analysis-of-thiopurine-s-methyltransferase-deficient-alleles-in-acute-lymphoblastic-leukemia-patients-in-mexican-patients
#19
Silvia Jiménez-Morales, Mireya Ramírez-Florencio, Juan Manuel Mejía-Aranguré, Juan Carlos Núñez-Enríquez, Carolina Bekker-Mendez, José Luis Torres-Escalante, Janet Flores-Lujano, Elva Jiménez-Hernández, María Del Carmen Rodríguez-Zepeda, Yelda A Leal, Pablo Miguel González-Montalvo, Francisco Pantoja-Guillen, José Gabriel Peñaloza-Gonzalez, Erick Israel Gutiérrez-Juárez, Nora Nancy Núñez-Villegas, Maria Luisa Pérez-Saldivar, Francisco Xavier Guerra-Castillo, Luz Victoria Flores-Villegas, María Teresa Ramos-Cervantes, José Manuel Fragoso, María Guadalupe García-Escalante, Doris Del Carmen Pinto-Escalante, Julián Ramírez-Bello, Alfredo Hidalgo-Miranda
BACKGROUND AND AIMS: It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28436311/role-of-6-mercaptopurine-in-the-potential-therapeutic-targets-dna-base-pairs-and-g-quadruplex-dna-insights-from-quantum-chemical-and-molecular-dynamics-simulations
#20
R Radhika, R Shankar, S Vijayakumar, P Kolandaivel
The theoretical studies on DNA with the anticancer drug 6-Mercaptopurine (6-MP) are investigated using theoretical methods to shed light on drug designing. Among the DNA base pairs considered, 6-MP is stacked with GC with the highest interaction energy of -46.19 kcal/mol. Structural parameters revealed that structure of the DNA base pairs is deviated from the planarity of the equilibrium position due to the formation of hydrogen bonds and stacking interactions with 6-MP. These deviations are verified through the systematic comparison between X-H bond contraction and elongation and the associated blue shift and red shift values by both NBO analysis and vibrational analysis...
May 24, 2017: Journal of Biomolecular Structure & Dynamics
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