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https://www.readbyqxmd.com/read/29052026/high-dose-chemotherapy-and-autologous-peripheral-blood-stem-cell-transplantation-with-bcvac-regimen-followed-by-maintenance-chemotherapy-for-children-with-very-high-risk-acute-lymphoblastic-leukemia
#1
Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended treatment for children with very high risk acute lymphoblastic leukemia (ALL), but it requires adequate institutional infrastructure, experience, and expertise, especially for alternative donor HSCT. We review our experience with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (APBSCT), followed by post-APBSCT maintenance chemotherapy for children with very high risk ALL. Between August 1997 and November 2012, our institute was not successful with HLA-haploidentical HSCT...
October 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29050696/pharmacogenomics-in-acute-lymphoblastic-leukemia
#2
REVIEW
Shawn H R Lee, Jun J Yang
Pharmacogenomics is a fast-growing field of personalized medicine using a patient's genomic profile to determine drug disposition or response to drug therapy, in order to develop safer and more effective pharmacotherapy. Childhood acute lymphoblastic leukemia (ALL), being the most common malignancy in childhood, which is treated with uniform and standardized clinical trials, is remarkably poised for pharmacogenomic studies. In the last decade, unbiased genome-wide association studies have identified multiple germline risk factors that strongly modify host response to drug therapy...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28983968/individualized-6-mercaptopurine-increments-in-consolidation-treatment-of-childhood-acute-lymphoblastic-leukemia-a-nopho-randomized-controlled-trial
#3
Morten Tulstrup, Thomas L Frandsen, Jonas Abrahamsson, Bendik Lund, Kim Vettenranta, Olafur Gisli Jonsson, Hanne Vibeke Hansen Marquart, Birgitte Klug Albertsen, Mats Heyman, Kjeld Schmiegelow
OBJECTIVES: This randomized controlled trial tested the hypothesis that children with non-high risk acute lymphoblastic leukemia could benefit from individualized 6-mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event-free survival. METHODS: 392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6-mercaptopurine (25 mg/m(2) /day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m(2) /day beginning on days 50 and/or 71 unless dose-limiting myelosuppression had occurred...
October 6, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28966507/thiopurine-s-methyltransferase-polymorphisms-in-korean-dermatologic-patients
#4
Minseok Lee, Jimyung Seo, Dongsik Bang, Do Young Kim
BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurines including azathioprine (AZA), 6-mercaptopurine, and 6-thioguanine. TPMT genotyping is widely used for screening of AZA-related toxicity during routine clinical practice in Korea. However, the data of TPMT genotypes and its AZA-related toxicity have not been studied in the field of dermatology. OBJECTIVE: The aim of this study was to evaluate the genetic basis of TPMT polymorphism in Korean dermatologic patients and subsequently to investigate the relationship between mutant TPMT and adverse responses to AZA treatment...
October 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28963908/emerging-role-of-nudt15-polymorphisms-in-6-mercaptopurine-metabolism-and-dose-related-toxicity-in-acute-lymphoblastic-leukaemia
#5
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...
September 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28962762/construction-of-6-thioguanine-and-6-mercaptopurine-carriers-based-on-%C3%AE-cyclodextrins-and-gold-nanoparticles
#6
R Sierpe, Michael Noyong, Ulrich Simon, D Aguayo, J Huerta, Marcelo J Kogan, N Yutronic
As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in βcyclodextrin (βCD) to form the complexes βCD-TG and βCD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: βCD-TG-AuNPs and βCD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages...
December 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28961308/nelarabine-induced-peripheral-and-central-neurotoxicity-can-sequential-mri-brain-imaging-help-to-define-its-natural-history
#7
Karl Ewins, Andrea Malone, Ethna Phelan, David Webb, J C McHugh, Owen Smith
A 14-year-old boy with relapsed T cell acute lymphoblastic leukaemia received reinduction chemotherapy that included nelarabine, a purine nucleoside analogue known to cause dose-dependent neurotoxicity. Although he achieved aminimal residual disease negative remission after two cycles of chemotherapy he also developed severe, progressive peripheral and central neurotoxicities. Loss of grey-white differentiation was seen on a T2-weighted magnetic resonance imaging brain scan. This unusual clinical picture and previously unreported radiological findings are thought to be due to nelarabine toxicity...
October 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28924550/establishment-and-characterization-of-arsenic-trioxide-resistant-kb-ato-cells
#8
Yun-Kai Zhang, Chunling Dai, Chun-Gang Yuan, Hsiang-Chun Wu, Zhijie Xiao, Zi-Ning Lei, Dong-Hua Yang, X Chris Le, Liwu Fu, Zhe-Sheng Chen
Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28921647/pharmacogenomics-implementation-at-the-national-institutes-of-health-clinical-center
#9
Tristan M Sissung, Jon W McKeeby, Jharana Patel, Juan J Lertora, Parag Kumar, Willy A Flegel, Sharon D Adams, Ellen J Eckes, Frank Mickey, Teri M Plona, Stephanie D Mellot, Ryan N Baugher, Xiaolin Wu, Daniel R Soppet, Mary E Barcus, Vivekananda Datta, Kristen M Pike, Gary DiPatrizio, William D Figg, Barry R Goldspiel
The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28917805/hemoglobin-becomes-electroactive-upon-interaction-with-surface-protected-au-nanoparticles
#10
Rafael Del Caño, Lucia Mateus, Guadalupe Sánchez-Obrero, José Manuel Sevilla, Rafael Madueño, Manuel Blázquez, Teresa Pineda
In this work, we report on the electrochemical behavior of bioconjugates prepared with gold nanoparticles (AuNP) capped with three different molecular layers (citrate anions, 6-mercaptopurine and ω-mercaptoundecanoic acid) and the protein hemoglobin (Hb). Freshly formed bioconjugates are deposited on a glassy carbon electrode and assayed for electroactivity. A pair of redox peaks with formal potential at -0.37V is obtained, in contrast with the free Hb protein that is inactive on the glassy carbon substrate...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28914446/risk-factors-for-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype
#11
M M T J Broekman, M J H Coenen, G J Wanten, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, D R Wong, D J de Jong
BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial...
September 15, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28903549/nudt15-variants-cause-hematopoietic-toxicity-with-low-6-tgn-levels-in-children-with-acute-lymphoblastic-leukemia
#12
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/28899477/-research-advances-in-pharmacogenomics-of-mercaptopurine
#13
Xiao-Xiao Chen, Shu-Hong Shen
Mercaptopurine is a common chemotherapeutic drug and immunosuppressive agent and plays an important role in the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. It may cause severe adverse effects such as myelosuppression, which may result in the interruption of treatment or complications including infection or even threaten patients' lives. However, the adverse effects of mercaptopurine show significant racial and individual differences, which reveal the important role of genetic diversity...
September 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28883280/susceptibility-to-6-mercaptopurine-toxicity-related-with-nudt15-and-abcc4-variants-in-japanese-childhood-acute-lymphoblastic-leukemia
#14
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/28882023/apex1-polymorphism-and-mercaptopurine-related-early-onset-neutropenia-in-pediatric-acute-lymphoblastic-leukemia
#15
Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang
Purpose: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. Materials and Methods: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients...
September 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28878993/differential-metal-binding-properties-of-dynamic-acylhydrazone-polymers-and-their-sensing-applications
#16
Siheng Gao, Lijie Li, Ismail Vohra, Daijun Zha, Lei You
As one of common dynamic covalent bonds, acylhydrazone bond plays an important role in developing intelligent responsive materials. In this report, we present acylhydrazone-based dynamic polymers with multi-stimuli responsiveness, particularly metal recognition behaviours and their modulation. A series of polyacylhydrazones with different metal-binding sites were designed and prepared in a modular fashion. Titration of these receptors with a diverse set of metal ions, including Cu(2+), Zn(2+) and La(3+), resulted in unique optical changes, and both the sensitivity and selectivity profiles can be regulated...
August 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28877686/disease-stabilizing-treatment-based-on-all-trans-retinoic-acid-and-valproic-acid-in-acute-myeloid-leukemia-identification-of-responders-by-gene-expression-profiling-of-pretreatment-leukemic-cells
#17
Håkon Reikvam, Randi Hovland, Rakel Brendsdal Forthun, Sigrid Erdal, Bjørn Tore Gjertsen, Hanne Fredly, Øystein Bruserud
BACKGROUND: Acute myeloid leukemia (AML) is an aggressive malignancy only cured by intensive therapy. However, many elderly and unfit patients cannot receive such treatment due to an unacceptable risk of treatment-related morbidity and mortality. Disease-stabilizing therapy is then the only possible strategy, one alternative being treatment based on all-trans retinoic acid (ATRA) combined with the histone deacetylase inhibitor valproic acid and possibly low-toxicity conventional chemotherapy...
September 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28877179/adherence-to-6-mercaptopurine-in-children-and-adolescents-with-acute-lymphoblastic-leukemia
#18
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/28874608/correction-to-6-mercaptopurine-decreases-the-bcl-2-bax-ratio-and-induces-apoptosis-in-activated-splenic-b-lymphocytes
#19
(no author information available yet)
No abstract text is available yet for this article.
October 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28857898/prevalence-of-thiopurine-s-methyltransferase-gene-polymorphisms-in-patients-with-inflammatory-bowel-disease-from-the-island-of-crete-greece
#20
Constantina Coucoutsi, George Emmanouil, George Goulielmos, Ourania Sfakianaki, Ioannis E Koutroubakis, Elias A Kouroumalis
BACKGROUND: There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of TPMT gene polymorphisms in a genetic homogenous population of IBD patients in Crete and to correlate the results with adverse reactions to thiopurine drugs. PATIENTS AND METHODS: Genotyping for the most common TPMT variants TPMT*2, TPMT*3A, TPMT3*C, and TPMT*3B was performed using the PCR-restriction fragment length polymorphism method in 223 consecutive IBD patients and 119 age-matched and sex-matched healthy controls...
November 2017: European Journal of Gastroenterology & Hepatology
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