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https://www.readbyqxmd.com/read/28628691/eruptive-melanocytic-acral-nevi-in-the-setting-of-6-mercaptopurine-therapy
#1
Arpan V Prabhu, Kristin Bibee, Joseph C English
<p>Eruptive melanocytic nevi (EMN) are a rare clinical finding characterized by sudden-onset nevi that often present in a grouped distribution. They have been associated with chemotherapy, immunosuppression, bullous diseases, and medications including multikinase and BRAF inhibitors. It is important for dermatologists to be able to identify patients with sudden development of new melanocytic nevi secondary to particular medications. Herein, we describe a case of eruptive melanocytic acral nevi secondary to 6-mercaptopurine therapy...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28602355/retraction-notice-to-clinical-significance-of-itpa-rs67002563-polymorphism-in-patients-with-acute-lymphoblastic-leukemia-treated-with-6-mercaptopurine-pharmacol-res-2015-61-62
#2
Fatemeh Azimi, Abdolreza Esmaeilzadeh, Ali Ramazani
No abstract text is available yet for this article.
July 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28574837/6-mercaptopurine-promotes-energetic-failure-in-proliferating-t-cells
#3
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...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566883/thiopurine-use-associated-with-reduced-b-and-natural-killer-cells-in-inflammatory-bowel-disease
#4
James D Lord, Donna M Shows
AIM: To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo. METHODS: The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28566433/mtorc1-inhibition-induces-resistance-to-methotrexate-and-6-mercaptopurine-in-ph-and-ph-like-b-all
#5
Thanh-Trang T Vo, Jong-Hoon S Lee, Duc Nguyen, Brandon Lui, William Pandori, Andrew Khaw, Sharmila Mallya, Mengrou Lu, Markus Müschen, Marina Konopleva, David A Fruman
Elevated activity of the mechanistic target of rapamycin (mTOR) is associated with poor prognosis and higher incidence of relapse in B-cell acute lymphoblastic leukemia (B-ALL). Thus, ongoing clinical trials are testing mTOR inhibitors in combination with chemotherapy in B-ALL. However, the combination of mTOR inhibitors with standard of care chemotherapy drugs has not been studied extensively in high risk B-ALL subtypes. Therefore, we tested whether mTOR inhibition can augment the efficacy of current chemotherapy agents in Ph(+) and Ph-like B-ALL models...
May 31, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28554266/tolerability-profile-of-thiopurines-in-inflammatory-bowel-disease-a-prospective-experience
#6
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...
May 29, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28542496/zinc-blocks-sos-induced-antibiotic-resistance-via-inhibition-of-reca-in-escherichia-coli
#7
Bryan E Bunnell, Jillian F Escobar, Kirsten L Bair, Mark D Sutton, John K Crane
Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases...
2017: PloS One
https://www.readbyqxmd.com/read/28532139/systemic-amyloidosis-in-a-teenage-boy-with-inflammatory-bowel-disease
#8
Farzaneh Motamed, Rita Bagherian, Gholamhossin Adalat, Mohammad Hassan Moradinejad, Nilofar Hajizadeh, Mohammad Vasei, Mehrzad Mehdizadeh, Nima Rezaei
Systemic amyloidosis is a very rare complication of inflammatory bowel disease (IBD). The reported cases of secondary amyloidosis in children with IBD are much fewer than those reported in adults. Herein, a teenage boy with Crohn's disease is presented who developed nephrotic syndrome due to renal involvement secondary to amyloidosis, whereas the patient was under treatment with corticosteroid and 6-mercaptopurine. To our best knowledge, this is the first reported case of secondary amyloidosis in a teenage Iranian boy with Crohn's disease...
April 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28525791/determination-of-thiopurine-s-methyltransferase-activity-by-hydrophilic-interaction-liquid-chromatography-hyphenated-with-mass-spectrometry
#9
Daniel Pecher, Svetlana Dokupilová, Zuzana Zelinková, Maikel Peppelenbosch, Veronika Mikušová, Peter Mikuš
Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines used in the therapy of inflammatory bowel diseases (IBD). In this work a new progressive method for the determination of TPMT activity in red blood cells lysates was developed. Analysis was carried out by means of hydrophilic interaction liquid chromatography (HILIC) hyphenated with mass spectrometry (MS). In comparison with reversed-phase high-performance liquid chromatography (RP-HPLC), that has been typically applied in determination of TPMT activity, the HILIC significantly improved the analytical signal provided by MS, shortened analysis time, and improved chromatographic resolution...
May 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28484608/ordinary-differential-equations-and-boolean-networks-in-application-to-modelling-of-6-mercaptopurine-metabolism
#10
Anastasia I Lavrova, Eugene B Postnikov, Andrey Yu Zyubin, Svetlana V Babak
We consider two approaches to modelling the cell metabolism of 6-mercaptopurine, one of the important chemotherapy drugs used for treating acute lymphocytic leukaemia: kinetic ordinary differential equations, and Boolean networks supplied with one controlling node, which takes continual values. We analyse their interplay with respect to taking into account ATP concentration as a key parameter of switching between different pathways. It is shown that the Boolean networks, which allow avoiding the complexity of general kinetic modelling, preserve the possibility of reproducing the principal switching mechanism...
April 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28476189/analysis-of-thiopurine-s-methyltransferase-deficient-alleles-in-acute-lymphoblastic-leukemia-patients-in-mexican-patients
#11
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
#12
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
https://www.readbyqxmd.com/read/28423235/hepatic-sinusoidal-obstruction-syndrome-during-maintenance-therapy-of-childhood-acute-lymphoblastic-leukemia-is-associated-with-continuous-asparaginase-therapy-and-mercaptopurine-metabolites
#13
Linea Natalie Toksvang, Silvia De Pietri, Stine N Nielsen, Jacob Nersting, Birgitte K Albertsen, Peder S Wehner, Steen Rosthøj, Päivi M Lähteenmäki, Daniel Nilsson, Tove A Nystad, Kathrine Grell, Thomas L Frandsen, Kjeld Schmiegelow
BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy...
April 19, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28418010/interaction-between-nudt15-and-abcc4-variants-enhances-intolerability-of-6-mercaptopurine-in-japanese-patients-with-childhood-acute-lymphoblastic-leukemia
#14
Y Tanaka, H Nakadate, K Kondoh, K Nakamura, K Koh, A Manabe
6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic leukemia (ALL) treatment. Some candidate gene variants are associated with its toxicities, but the major variants and effects of combined variants remain unclear. We used Cox regression analysis to evaluate the time-dependent association between candidate variants and the cumulative incidence of 6-MP intolerability in 95 Japanese patients. The major risk factors for severe leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi-covariate analysis (P<0...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28406092/safety-of-azathioprine-and-6-mercaptopurine-in-patients-with-inflammatory-bowel-disease-na%C3%A3-ve-to-thiopurine-treatment%C3%A2
#15
Ram Alaish, David Lundgren, Ole B Suhr, Mårten Werner, Pontus Karling
OBJECTIVES: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naïve to thiopurine treatment. STUDY: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naïve to thiopurines (82 patients treated with AZA and 31 patients with MP)...
April 13, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28391009/the-promise-of-pharmacogenomics-in-reducing-toxicity-during-acute-lymphoblastic-leukemia-maintenance-treatment
#16
REVIEW
Shoshana Rudin, Marcus Marable, R Stephanie Huang
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity...
April 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28348471/role-of-allopurinol-in-optimizing-thiopurine-therapy-in-patients-with-autoimmune-hepatitis-a-review
#17
REVIEW
Shivani Deswal, Anshu Srivastava
Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. The metabolism of AZA is complex and mediated by multiple enzymes...
March 2017: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/28301625/successful-treatment-of-generalized-essential-telangiectasia-with-6-mercaptopurine
#18
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
#19
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
#20
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
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