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6-mercaptopurine

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https://www.readbyqxmd.com/read/28771784/a-qualitative-study-of-decision-making-on-phase-iii-randomized-clinical-trial-participation-in-pediatric-oncology-adolescents-and-parents-perspectives-and-preferences
#1
Marianne Vie Ingersgaard, Morten Tulstrup, Kjeld Schmiegelow, Hanne Baekgaard Larsen
AIM: To explore parents' and adolescents' motives for accepting/declining participation in the ALL2008 trials and adolescents' involvement in the decision-making process. BACKGROUND: Children and adolescents with acute lymphoblastic leukemia treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol were eligible for two randomizations testing 6-mercaptopurine treatment intensifications to improve efficacy and Asparaginase de-escalation to reduce toxicity...
August 3, 2017: Journal of Advanced Nursing
https://www.readbyqxmd.com/read/28748542/pediatric-intracerebral-histiocytic-sarcoma-with-rhabdoid-features-case-report-and-literature-review
#2
Young Hye Kim, Gie-Taek Yie, Na Rae Kim, In-Sang Jeon, Hyun Yee Cho, Jae Yeon Seok, Eung Yeop Kim, Kyu Chan Lee
A 16-year-old boy presented with marked weight loss, weakness of the left extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI showed an approximately 6.5 × 5.3 cm-sized huge heterogeneous enhancing mass located in the corpus callosum, extending into the lateral ventricle. Open biopsy showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with rhabdoid morphology, which were stained with S-100 protein, CD68 (KP1) and negative for CD1a. Histiocytic tumor was initially diagnosed...
July 27, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28731668/-azathioprine-induced-pancytopenia-case-series
#3
Cristina Martínez Faci, Ignacio Ros Arnal, José M Martínez de Zabarte Fernández, Jordi Sorribes Estorch, Mónica López Campos, Carmen Rodríguez-Vigil Iturrate
Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts...
August 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28723125/pharmacokinetics-on-a-chip-using-label-free-sers-technique-for-programmable-dual-drug-analysis
#4
Jiayuan Fei, Lei Wu, Yizhi Zhang, Shenfei Zong, Zhuyuan Wang, Yiping Cui
Synergistic effects of dual or multiple drugs have attracted great attention in medical fields, especially in cancer therapies. We provide a programmable microfluidic platform for pharmacokinetic detection of multiple drugs in multiple cells. The well-designed microfluidic platform includes two 2 × 3 microarrays of cell chambers, two gradient generators, and several pneumatic valves. Through the combined use of valves and gradient generators, each chamber can be controlled to infuse different kinds of living cells and drugs with specific concentrations as needed...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28715860/hemoglobin-bioconjugates-with-surface-protected-gold-nanoparticles-in-aqueous-media-the-stability-depends-on-solution-ph-and-protein-properties
#5
Rafael Del Caño, Lucia Mateus, Guadalupe Sánchez-Obrero, José Manuel Sevilla, Rafael Madueño, Manuel Blázquez, Teresa Pineda
The identification of the factors that dictate the formation and physicochemical properties of protein-nanomaterial bioconjugates are important to understand their behavior in biological systems. The present work deals with the formation and characterization of bioconjugates made of the protein hemoglobin (Hb) and gold nanoparticles (AuNP) capped with three different molecular layers (citrate anions (c), 6-mercaptopurine (MP) and ω-mercaptoundecanoic acid (MUA)). The main focus is on the behavior of the bioconjugates in aqueous buffered solutions in a wide pH range...
July 5, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28710878/6-mercaptopurine-modifies-cerebrospinal-fluid-t-cell-abnormalities-in-paediatric-opsoclonus-myoclonus-as-steroid-sparer
#6
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...
July 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28710036/effect-of-polymorphisms-in-transporter-genes-on-dosing-efficacy-and-toxicity-of-maintenance-therapy-in-children-with-acute-lymphoblastic-leukemia
#7
Guillermo Gervasini, Silvia G de Murillo, Mercedes Jiménez, María D de la Maya, Jose M Vagace
The aim of the present work was to assess whether polymorphisms in genes coding for drug transport proteins may influence dosing, efficacy and toxicity of maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6MP) in childhood acute lymphoblastic leukemia (ALL). A total of 41 children with ALL were screened for 10 SNPs in the SLC19A1, ABCB1, ABCC2, ABCC4 and ABCG2 transporter genes by means of direct sequencing. Carriers of the ABCC4 934CC and ABCB1 1236TT genotypes received a lower percentage of the protocol-recommended starting dose of MTX (62...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28682767/in-vitro-effects-of-purine-and-pyrimidine-analogues-on-leishmania-donovani-and-leishmania-infantum-promastigotes-and-intracellular-amastigotes
#8
Samira Azzouz, Philippe Lawton
Inhibition of parasite metabolic pathways is a rationale for new chemotherapeutic strategies. The pyrimidine and purine salvage pathways are thus targets against Leishmania donovani and L. infantum, causative agents of visceral human leishmaniasis and canine leishmaniosis. The antiproliferative effect of the pyrimidine analogues Cytarabine and 5-fluorouracil and of the purine analogues Azathioprine and 6-mercaptopurine was evaluated in vitro on the promastigote and the intracellular amastigote stages of the parasite...
September 26, 2017: Acta Parasitologica
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
#9
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/28677646/quantitative-evaluation-of-drug-resistance-profile-of-cells-expressing-wild-type-or-genetic-polymorphic-variants-of-the-human-abc-transporter-abcc4
#10
Megumi Tsukamoto, Shiori Sato, Kazuhiro Satake, Mizuki Miyake, Hiroshi Nakagawa
Broad-spectrum resistance in cancer cells is often caused by the overexpression of ABC transporters; which varies across individuals because of genetic single-nucleotide polymorphisms (SNPs). In the present study; we focused on human ABCC4 and established cells expressing the wild-type (WT) or SNP variants of human ABCC4 using the Flp-In™ system (Invitrogen, Life Technologies Corp, Carlsbad, CA, USA) based on Flp recombinase-mediated transfection to quantitatively evaluate the effects of nonsynonymous SNPs on the drug resistance profiles of cells...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28670229/nudt15-fto-and-runx1-genetic-variants-and-thiopurine-intolerance-among-japanese-patients-with-inflammatory-bowel-diseases
#11
Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect...
July 2017: Intestinal Research
https://www.readbyqxmd.com/read/28628691/eruptive-melanocytic-acral-nevi-in-the-setting-of-6-mercaptopurine-therapy
#12
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
#13
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
#14
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/28566883/thiopurine-use-associated-with-reduced-b-and-natural-killer-cells-in-inflammatory-bowel-disease
#15
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
#16
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
#17
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/28542496/zinc-blocks-sos-induced-antibiotic-resistance-via-inhibition-of-reca-in-escherichia-coli
#18
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
#19
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
#20
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
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