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6-mercaptopurine

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https://www.readbyqxmd.com/read/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#1
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
#2
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
#3
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
#4
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)...
December 9, 2016: 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
#5
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
#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/27920397/optimizing-combination-therapy-for-acute-lymphoblastic-leukemia-using-a-phenotypic-personalized-medicine-digital-health-platform-retrospective-optimization-individualizes-patient-regimens-to-maximize-efficacy-and-safety
#7
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 5, 2016: Journal of Laboratory Automation
https://www.readbyqxmd.com/read/27916002/long-term-effect-of-stents-eluting-6-mercaptopurine-in-porcine-coronary-arteries
#8
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
#9
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
https://www.readbyqxmd.com/read/27882164/inflammatory-bowel-disease-in-chinese-children-a-retrospective-analysis-of-49-cases
#10
Ying Zhou, Ying Huang
To present study reports the clinical characteristics, diagnosis and management of pediatric patients with inflammatory bowel disease (IBD) in China. Clinical records of 49 pediatric patients with IBD at Fudan University Children's Hospital (Shanghai, China) between July 2001 and May 2012 were reviewed. Of 49 patients (30 males and 19 females), 8 patients had ulcerative colitis (UC) and 41 patients had Crohn's disease (CD). The mean age was 10.4 years in patients with UC and 10.1 years in patients with CD. The percentages of patients with UC with abdominal pain, diarrhea or rectal bleeding were 62...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27803465/improvement-in-the-anticancer-activity-of-6-mercaptopurine-via-combination-with-bismuth-iii
#11
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/27802917/development-and-validation-of-lc-ms-ms-assay-for-the-simultaneous-determination-of-methotrexate-6-mercaptopurine-and-its-active-metabolite-6-thioguanine-in-plasma-of-children-with-acute-lymphoblastic-leukemia-correlation-with-genetic-polymorphism
#12
Medhat A Al-Ghobashy, Said A Hassan, Doaa H Abdelaziz, Noha M Elhosseiny, Nirmeen A Sabry, Ahmed S Attia, Manal H El-Sayed
Individualized therapy is a recent approach aiming to specify dosage regimen for each patient according to its genetic state. Cancer chemotherapy requires continuous monitoring of the plasma concentration levels of active forms of cytotoxic drugs and subsequent dose adjustment. In order to attain optimum therapeutic efficacy, correlation to pharmacogenetics data is crucial. In this study, a specific, accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed for determination of methotrexate (MTX), 6-mercaptopurine (MP) and its metabolite 6-thioguanine nucleotide (TG) in human plasma...
December 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27800472/shorter-maintenance-therapy-in-childhood-acute-lymphoblastic-leukemia-the-experience-of-the-prospective-randomized-brazilian-gbtli-all-93-protocol
#13
Silvia R Brandalise, Marcos B Viana, Vitória R P Pinheiro, Núbia Mendonça, Luiz F Lopes, Waldir V Pereira, Maria L M Lee, Elitânia M Pontes, Gláucia P Zouain-Figueiredo, Alita C A C Azevedo, Nilma Pimentel, Maria Z Fernandes, Hilda M Oliveira, Sônia R Vianna, Carlos A Scrideli, Fernando A Werneck, Maria N Álvares, Érica Boldrini, Sandra R Loggetto, Paula Bruniera, Maria J Mastellaro, Eni M Souza, Rogério A Araújo, Flávia Bandeira, Doralice M Tan, Nelson A Carvalho, Maria A S Salgado
AIM: Maintenance therapy is an important phase of the childhood ALL treatment, requiring 2-year long therapy adherence of the patients and families. Weekly methotrexate with daily 6-mercaptopurine (6MP) constitutes the backbone of maintenance therapy. Reduction in the maintenance therapy could overweight problems related with poverty of children with ALL living in limited-income countries (LIC). OBJECTIVE: To compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs...
2016: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/27783843/azathioprine-or-6-mercaptopurine-for-induction-of-remission-in-crohn-s-disease
#14
REVIEW
Nilesh Chande, Cassandra M Townsend, Claire E Parker, John K MacDonald
BACKGROUND: The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease have been conflicting and controversial. An updated meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. OBJECTIVES: The primary objective was to determine the efficacy and safety of azathioprine and 6-mercaptopurine for induction of remission in active Crohn's disease...
October 26, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27760078/experts-opinion-on-the-practical-use-of-azathioprine-and-6-mercaptopurine-in-inflammatory-bowel-disease
#15
Christian Mottet, Alain M Schoepfer, Pascal Juillerat, Jacques Cosnes, Florian Froehlich, Vera Kessler-Brondolo, Frank Seibold, Gerhard Rogler, Stephan R Vavricka, Pierre Michetti
The relevance of azathioprine and 6-mercaptopurine therapy in inflammatory bowel disease, Crohn's disease, and ulcerative colitis, has been challenged in recent publications. In this article, a panel of experts gives advice, based on the relevant literature, on indications and practical use of azathioprine/6-mercaptopurine, prevention, and management of drug adverse reactions and special situations such as vaccination, pregnancy, and lactation.
November 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27714158/the-role-of-the-crystalline-face-in-the-ordering-of-6-mercaptopurine-self-assembled-monolayers-on-gold
#16
Flavia Lobo Maza, Doris Grumelli, Pilar Carro, Carolina Vericat, Klaus Kern, Roberto C Salvarezza
Well-ordered molecular films play an important role in nanotechnology, from device fabrication to surface patterning. Self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) on the Au(100)-(1 × 1) and Au(111)-(1 × 1) have been used to understand the interplay of molecule-substrate interactions for heterocyclic thiols capable of binding to the surface by two anchors, which spontaneously form a highly disordered film on Au(111). Our results reveal that for the same surface coverage the simple change of the substrate from Au(111)-(1 × 1) to Au(100)-(1 × 1) eliminates molecular disorder and yields well-ordered SAMs...
October 6, 2016: Nanoscale
https://www.readbyqxmd.com/read/27689330/interconnections-between-apoptotic-and-autophagic-pathways-during-thiopurine-induced-toxicity-in-cancer-cells-the-role-of-reactive-oxygen-species
#17
Wiem Chaabane, Malin Lindqvist Appell
Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of genotoxic drugs extensively used in the treatment of various illnesses including leukemia. Their underlying molecular mechanism of action involves the activation of apoptosis and autophagy but remains widely unclear. Here we present evidence that autophagy induction by thiopurines is a survival mechanism that antagonizes apoptosis and is involved in degrading damaged mitochondria through mitophagy. On the other hand, apoptosis is the main cell death mechanism by thiopurines as its inhibition prohibited cell death...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27648552/azathioprine-and-6-mercaptopurine-induced-liver-injury-clinical-features-and-outcomes
#18
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/27636927/-long-term-infliximab-therapy-for-ulcerative-colitis-in-real-clinical-practice
#19
O V Knyazev, A I Parfenov, A V Kagramanova, I N Ruchkina, P L Shcherbakov, N K Shakhpazyan, K K Noskova, T I Ivkina, S G Khomeriki
AIM: to retrospectively evaluate the efficiency of long-term infliximab (INF) therapy in patients with refractory ulcerative colitis (UC). SUBJECTS AND METHODS: The investigation enrolled 48 patients with refractory UC who had taken IFL in 2008 to 2014. Steroid-dependent or steroid-refractory UC was established in 40 (83.3%) patients; 8 (16.7%) were noted to be refractory to therapy with azathioprine or 6-mercaptopurine. Cytomegalovirus DNA was identified in the biopsy specimens of the large intestinal mucosa (LIM) from 7 patients...
2016: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/27600880/measures-of-6-mercaptopurine-and-methotrexate-maintenance-therapy-intensity-in-childhood-acute-lymphoblastic-leukemia
#20
Stine Nygaard Nielsen, Kathrine Grell, Jacob Nersting, Thomas Leth Frandsen, Lisa Lyngsie Hjalgrim, Kjeld Schmiegelow
PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree of myelosuppression is unknown for the individual child and we wanted to evaluate this. METHODS: A median of 22 (range 8-27) 6MP/MTX metabolite samples and 100 (range 25-130) blood counts during therapy and 10 (range 2-15) off therapy were collected in 50 children with ALL...
September 6, 2016: Cancer Chemotherapy and Pharmacology
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