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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
Y Ilan
BACKGROUND: The systemic immune system plays a role in inflammation and fibrogenesis associated with non-alcoholic steatohepatitis (NASH) and has become a potential target for drug development. In particular, the gut immune system has been suggested as a means for generating signals that can target the systemic immune system. AIM: To describe seven novel methods being developed for the treatment of NASH that target the gut immune system for alleviation of the systemic inflammatory response, including oral administration of fatty-liver-derived proteins, anti-CD3 antibodies, tumour necrosis factor fusion protein, anti-lipopolysaccharide antibodies, glucosylceramide, delayed-release mercaptopurine, and soy-derived extracts...
October 24, 2016: Alimentary Pharmacology & Therapeutics
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
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
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
Kayo Tokeji, Sachi Sakaguchi, Tomoko Kurimoto, Junya Fujimura, Toshiaki Shimizu
We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP) after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children...
2016: Case Reports in Hematology
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%)...
June 14, 2016: Journal of Clinical Gastroenterology
Daphne Bertholee, Jan Gerard Maring, André B P van Kuilenburg
Cancer treatment is becoming more and more individually based as a result of the large inter-individual differences that exist in treatment outcome and toxicity when patients are treated using population-based drug doses. Polymorphisms in genes encoding drug-metabolizing enzymes and transporters can significantly influence uptake, metabolism, and elimination of anticancer drugs. As a result, the altered pharmacokinetics can greatly influence drug efficacy and toxicity. Pharmacogenetic screening and/or drug-specific phenotyping of cancer patients eligible for treatment with chemotherapeutic drugs, prior to the start of anticancer treatment, can identify patients with tumors that are likely to be responsive or resistant to the proposed drugs...
September 19, 2016: Clinical Pharmacokinetics
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
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
Zhihong Li, Shuyun Bi, Tianjiao Wang, Yu Wang, Huifeng Zhou, Jun Wu
A highly sensitive method for the detection of 6-mercaptopurine (MP) by resonance Rayleigh light scattering (RLS) method was developed. Gold nanoparticles (AuNPs) were synthesized by a modified seed method and characterized using transmission electron microscopy (TEM). AuNPs were bound to MP via covalent bonding to form the MP-AuNPs complex, which increased the RLS intensity of MP at 347 nm (increased by 65.7%). Under optimum conditions, the magnitude of the enhanced RLS intensity for MP-AuNPs was proportional to MP concentration in the range 0...
September 4, 2016: Luminescence: the Journal of Biological and Chemical Luminescence
Nathalie K Zgheib, Reem Akika, Rami Mahfouz, Carol Al Aridi, Khaled M Ghanem, Raya Saab, Miguel R Abboud, Nidale Tarek, Hassan El Solh, Samar A Muwakkit
BACKGROUND: Interindividual variability in thiopurine-related toxicity could not be completely explained by thiopurine S-methyltransferase (TPMT) polymorphisms, as a number of patients who are homozygous wild type or normal for TPMT still develop toxicity that necessitates 6-mercaptopurine (MP) dose reduction or protocol interruption. Recently, few studies reported on an inherited nucleoside diphosphate-linked moiety X motif 15 (NUDT15) c.415C>T low-function variant that is associated with decreased thiopurine metabolism and leukopenia in childhood acute lymphoblastic leukemia (ALL) and other diseases...
August 31, 2016: Pediatric Blood & Cancer
Chengcheng Liu, Wenjian Yang, Deqing Pei, Cheng Cheng, Colton Smith, Wendy Landier, Lindsey Hageman, Yanjun Chen, Jun J Yang, Kristine R Crews, Nancy Kornegay, Seth E Karol, F Lennie Wong, Sima Jeha, John T Sandlund, Raul R Ribeiro, Jeffrey E Rubnitz, Monika L Metzger, Ching-Hon Pui, William E Evans, Smita Bhatia, Mary V Relling
We performed a genome-wide association study of primary erythrocyte TPMT activity in children with leukemia (n = 1026). Adjusting for age and ancestry, TPMT was the only gene that reached genome-wide significance (top hit rs1142345 or 719A>G, P = 8.6 × 10(-61) ). Additional genetic variants (besides the 3 SNPs rs1800462, rs1800460 and rs1142345 defining TPMT clinical genotype) did not significantly improve classification accuracy for TPMT phenotype. Clinical mercaptopurine tolerability in 839 patients was related to TPMT clinical genotype (P = 2...
August 26, 2016: Clinical Pharmacology and Therapeutics
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
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
Hassan Karimi-Maleh, Abdollah Fallah Shojaei, Khalil Tabatabaeian, Fatemeh Karimi, Shahryar Shakeri, Reza Moradi
6-Mercaptopurine, 6-thioguanine and dasatinib are three important anticancer drugs with high adverse effects in human body. In this study, a Pt/MWCNTs-1-butyl-3-methylimidazolium hexafluoro phosphate-modified carbon paste electrode was developed for the simultaneously determination of 6-mercaptopurine, 6-thioguanine and dasatinib for the first time. The Pt/MWCNTs synthesized by polyol method and have been characterized by transmission electron microscopy and X-ray diffraction methods. The obtained data revealed that the electro-oxidation of 6-mercaptopurine, 6-thioguanine and dasatinib is facilitated as a novel voltammetric sensor...
December 15, 2016: Biosensors & Bioelectronics
Katarzyna Klimczak, Liliana Łykowska-Szuber, Iwona Krela-Kaźmierczak, Piotr Eder, Aleksandra Szymczak, Kamila Stawczyk-Eder, Krzysztof Linke
M ethotrexate (MTX) as an immunomodulatory drug has numerous applications in autoimmune diseases. Autoimmune patomechanism is one of the factors responsible for development of inflammatory bowel diseases (IBD). MTX is an alternative therapy in the treatment of IBD. Over the past several years clinical trials has confirmed the efficacy of MTX in the treatment of Crohn's disease (CD). Data concerning use of MTX in ulcerative colitis (UC) are not as numerous as in the CD. Currently, MTX is recommended for the induction treatment and maintenance therapy in CD patients, especially in steroid-dependent patients, disease refractory to corticosteroids, no improvement after treatment with azathioprine and 6-mercaptopurine, or in case of intolerance to these drugs...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Kathleen Walsh, Jamie Ryan, Nancy Daraiseh, Ahna Pai
BACKGROUND: Nonadherence and medication error both limit the effectiveness of oral chemotherapy. The overlap between nonadherence and medication error is not well studied in children, and interventions strategies differ for each. Our objective was to describe nonadherence and errors in children with cancer to inform future interventions. METHODS: Nonadherence was measured using two self-report tools. Medication error was measured using medication review and observation of administration at home...
2016: Oncology
Margien L Seinen, Geerten P van Nieuw Amerongen, Nanne K H de Boer, Chris J J Mulder, Jan van Bezu, Adriaan A van Bodegraven
BACKGROUND: Azathioprine and mercaptopurine (MP) are effective in treating patients with inflammatory bowel disease (IBD). Immunosuppressive effects of thiopurines involve T-cell apoptosis after inhibition of GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1). This study aimed to assess whether expression and activity of Rac1 or phosphorylated ezrin-radixin-moesin (pERM) in patients with IBD could provide a useful biomarker for the pharmacodynamic thiopurine effect and might be related to clinical effectiveness...
October 2016: Therapeutic Drug Monitoring
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
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