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6-mercaptopurine

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https://www.readbyqxmd.com/read/29760546/thiopurines-are-negatively-associated-with-anthropometric-parameters-in-pediatric-crohn-s-disease
#1
Neera Gupta, Robert H Lustig, Cewin Chao, Eric Vittinghoff, Howard Andrews, Cheng-Shiun Leu
AIM: To determine the distribution of anthropometric parameter (AP)- z -scores and characterize associations between medications/serum biomarkers and AP- z -scores in pediatric Crohn's disease (CD). METHODS: CD patients [< chronological age (CA) 21 years] were enrolled in a cross-sectional study. Descriptive statistics were generated for participants' demographic characteristics and key variables of interest. Paired t -tests were used to compare AP- z -scores calculated based on CA (CA z -scores) and bone age (BA) (BA z -scores) for interpretation of AP's...
May 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29759551/genomics-and-pharmacogenomics-of-pediatric-acute-lymphoblastic-leukemia
#2
REVIEW
Chuan Wu, Wei Li
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29754190/allergic-and-immunologic-perspectives-of-inflammatory-bowel-disease
#3
REVIEW
Kofi Clarke, Jayakrishna Chintanaboina
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition primarily involving the gastrointestinal tract. It includes Crohn's disease (CD), ulcerative colitis (UC), and a less common phenotype-indeterminate colitis. It is thought to result from a complex interplay of environmental, microbial, and host factors including genetic factors, although the exact mechanism is not known. Dietary factors have been shown to play a role in the pathogenesis of IBD and can potentially alter the intestinal microbiota as well as disrupt the immune function in the gut...
May 12, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29720126/optimal-predictor-for-6-mercaptopurine-intolerance-in-chinese-children-with-acute-lymphoblastic-leukemia-nudt15-tpmt-or-itpa-genetic-variants
#4
Hong Zhou, Lei Li, Peng Yang, Lin Yang, Jin E Zheng, Ying Zhou, Yong Han
BACKGROUND: 6-mercaptopurine (6-MP) contributes substantially to remarkable improvement in the survival of childhood acute lymphoblastic leukemia (ALL) patients. However, 6-MP also has dose-limiting toxicities, particularly life-threatening myelosuppression, due to genetic polymorphisms in enzymes that metabolize 6-MP. Promising biomarkers for predicting 6-MP-induced leukopenia is still unclear in Chinese population. Here, we evaluated the associations of NUDT15, TPMT and ITPA genotypes with 6-MP intolerance in our cohort of childhood ALL patients...
May 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29718278/the-impact-of-combination-therapy-on-infliximab-levels-and-antibodies-in-children-and-young-adults-with-inflammatory-bowel-disease
#5
Lisa Yue Chi, Naamah Levy Zitomersky, Enju Liu, Sophia Tollefson, Julia Bender-Stern, Snehal Naik, Scott Snapper, Athos Bousvaros
Goal: The aim of this study was to evaluate the effect of combination therapy with methotrexate or 6-mercaptopurine on infliximab levels (IFXL) and antibodies to infliximab (ATI). Background: Infliximab (IFX) is a highly effective therapy for inflammatory bowel disease (IBD). Unfortunately, 25%-50% of patients will lose response to IFX. Loss of response is correlated with low IFXL and ATI formation which accelerates drug clearance. Combination therapy is thought to decrease ATI formation...
April 26, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29715033/electronic-structure-of-a-self-assembled-monolayer-with-two-surface-anchors-6-mercaptopurine-on-au-111
#6
Cynthia Carolina Fernandez, Evangelina Pensa, Pilar Carro, Roberto Carlos Salvarezza, Federico José Williams
The electronic structure of aromatic and aliphatic thiols on Au(111) has been extensively studied in relation to possible applications in molecular electronics. In this work, the effect on the electronic structure of an additional anchor to the S-Au bond using 6-mercaptopurine as a model system has been investigated. Results from XPS, NEXAFS and DFT confirm that this molecule adsorbs on Au(111) with S-Au and iminic N-Au bonds. Combined UPS and DFT data reveal that formation of the 6MP self-assembled monolayer generates a molecular dipole perpendicular to the surface with negative charges residing at the metal/monolayer interface and positive charges at the monolayer/vacuum interface which lowers the substrate work function...
May 1, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29693618/quantification-of-6-mercaptopurine-and-its-metabolites-in-patients-with-acute-lympoblastic-leukemia-using-dried-blood-spots-and-uplc-ms-ms
#7
Supandi Supandi, Yahdiana Harahap, Harmita Harmita, Rizka Andalusia
This research aimed to quantitatively bioanalyze 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanosine-5&prime;-monophosphate (6-TGMP) in dried blood spots (DBS) prepared from a small volume of acute lymphoblastic leukemia (ALL) patients. Analytes on the DBS card were extracted using 90% methanol with 5-fluorouracil (5-FU) as an internal standard. Analytical separation was performed on a Waters Acquity&reg; UPLC BEH AMIDA column of 1.7 &mu;m (2.1 &times; 100 mm) with a mobile phase mixture of 0...
April 25, 2018: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/29683944/slco1b1-polymorphisms-are-associated-with-drug-intolerance-in-childhood-leukemia-maintenance-therapy
#8
İrem Eldem, Duygu Yavuz, Özge Cumaoğullari, Talia İleri, Elif Ünal İnce, Mehmet Ertem, Beyza Doğanay Erdoğan, Recep Bindak, Hilal Özdağ, N Lale Şatiroğlu-Tufan, L Zümrüt Uysal
BACKGROUND: Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29615003/role-of-cytarabine-in-paediatric-acute-promyelocytic-leukemia-treated-with-the-combination-of-all-trans-retinoic-acid-and-arsenic-trioxide-a-randomized-controlled-trial
#9
Li Zhang, Yao Zou, Yumei Chen, Ye Guo, Wenyu Yang, Xiaojuan Chen, Shuchun Wang, Xiaoming Liu, Min Ruan, Jiayuan Zhang, Tianfeng Liu, Fang Liu, Benquan Qi, Wenbin An, Yuanyuan Ren, Lixian Chang, Xiaofan Zhu
BACKGROUND: The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. METHODS: We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016...
April 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29588843/protracted-severe-systemic-cytomegalovirus-disease-in-an-immunosuppressed-patient-with-ulcerative-colitis
#10
Matthew James Armstrong, Tom Thomas, Tariq Iqbal, Ralph Boulton, Jason Goh
A 33-year-old man with ulcerative colitis presented with 5-day history of fever, night sweats, abdominal pain and increased stool frequency. He was on mesalazine M/R 1 g once daily, 6-mercaptopurine (6-MP) 75 mg once daily and prednisolone 40 mg once daily. Examination revealed fever and tachycardia. Blood examinations identified a persistent leucopenia, C reactive protein of 23 mg/L and an initial alanine transaminase of 855 IU/L. Flexible sigmoidoscopy revealed well-demarcated, punched-out ulcers in the proximal rectum and distal sigmoid, with histology pathognomonic of cytomegalovirus (CMV)...
April 2018: Frontline Gastroenterology
https://www.readbyqxmd.com/read/29576767/comparison-of-concomitant-mesalamine-and-immunomodulator-therapy-and-immunomodulator-monotherapy-for-crohn-s-disease
#11
Min Seob Kwak, Kyung-Jo Kim, Jae Hee Cheon, Wan Soo Kim, Jeong-Mi Lee, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang
Background: Although immunomodulators are increasingly used in Crohn's disease (CD), a significant number of gastroenterologists still use 5-aminosalicylate (5-ASA) in combination with azathioprine (AZA) or 6-mercaptopurine (6-MP); there is limited evidence regarding the benefit of concomitant 5-ASA with AZA/6-MP compared with AZA/6-MP monotherapy for the treatment of CD. Study Design: A total of 106 patients who received AZA/6-MP for more than 3 months between January 1991 and May 2014 were identified retrospectively...
2018: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29512864/treatment-of-langerhans-cell-histiocytosis-with-a-modified-risk-adapted-protocol-experience-from-a-tertiary-cancer-institute-in-india
#12
Gaurav Narula, Nirmalaya D Pradhan, Brijesh Arora, Sripad D Banavali
BACKGROUND: Involvement of risk-organs (RO+) in Langerhans cell histiocytosis (LCH) and inadequate early response identifies patients at high risk for relapse and mortality requiring intensive salvage therapy including stem cell transplant, adding cost and toxicity. To mitigate this, we used a standard induction, augmented with metronomic etoposide, and prolonged maintenance-similarly augmented for RO+, and retrospectively analyzed its impact. PROCEDURE: LCH patients from 2009 through 2014 were included...
March 7, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29449434/msh6-haploinsufficiency-at-relapse-contributes-to-the-development-of-thiopurine-resistance-in-pediatric-b-lymphoblastic-leukemia
#13
Nikki A Evensen, P Pallavi Madhusoodhan, Julia Meyer, Jason Saliba, Ashfiyah Chowdhury, David J Araten, Jacob Nersting, Teena Bhatla, Tiffaney L Vincent, David Teachey, Stephen P Hunger, Jun Yang, Kjeld Schmiegelow, William L Carroll
Survival of children with relapsed acute lymphoblastic leukemia is poor, and understanding mechanisms underlying resistance is essential to developing new therapy. Relapse-specific heterozygous deletions in MSH6 , a crucial part of DNA mismatch repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance, or if it leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents...
May 2018: Haematologica
https://www.readbyqxmd.com/read/29430323/declining-use-of-combination-infliximab-and-immunomodulator-for-inflammatory-bowel-disease-in-the-community-setting
#14
Joshua C Berkowitz, Joanna Stein-Fishbein, Sundas Khan, Richard Furie, Keith S Sultan
AIM: To describe trends of combination therapy (CT) of infliximab (IFX) and immunomodulator (IMM) for inflammatory bowel disease (IBD) in the community setting. METHODS: A retrospective study was conducted of all IBD patients referred for IFX infusion to our community infusion center between 04/01/01 and 12/31/14. CT was defined as use of IFX with either azathioprine, 6-mercaptopurine, or methotrexate. We analyzed trends of CT usage overall, for Crohn's disease (CD) and ulcerative colitis (UC), and for the subgroups of induction patients...
February 6, 2018: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29387964/role-of-tpmt-and-itpa-variants-in-mercaptopurine-disposition
#15
Tina Gerbek, Maria Ebbesen, Jacob Nersting, Thomas L Frandsen, Malin Lindqvist Appell, Kjeld Schmiegelow
PURPOSE: To explore the levels of thioguanine incorporated into DNA (DNA-TG), and erythrocyte levels of 6-thioguanine nucleotides (Ery-TGN) and methylated metabolites (Ery-MeMP) during 6-mercaptopurine (6MP)/Methotrexate (MTX) therapy of childhood acute lymphoblastic leukemia (ALL) and the relation to inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT) gene variants. METHODS: Blood samples were drawn during 6MP/MTX maintenance therapy from 132 children treated for ALL at Rigshospitalet, Copenhagen...
March 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29373914/genetic-polymorphism-of-thiopurine-s-methyltransferase-in-children-with-acute-lymphoblastic-leukemia-in-jordan
#16
Mervat Alsous, Al-Motassem Yousef, Mariam Abdel Jalil, Mohammed Zawiah, Shorouq Yacoub, Deema Momani, Alia Gharabli, Suha Omar, Rawad Rihani
Background and Aims: It has been demonstrated that homozygote and heterozygote mutant allele carriers for thiopurine S-methyltransferase (TPMT) are at high risk of developing myelosuppression after receiving standard doses of 6-mercaptopurine (6-MP). The aim of this study was to determine the frequency of TPMT deficient alleles in children with acute lymphoblastic leukemia (ALL) in Jordan and to compare it with other ethnic groups. Methods: We included 52 ALL childhood cases from King Hussein Cancer Research Center in Jordan...
January 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29361083/antibody-response-to-hepatitis-b-virus-vaccine-is-impaired-in-patients-with-inflammatory-bowel-disease-on-infliximab-therapy
#17
Perry K Pratt, Nunes David, Horst C Weber, Frédéric F Little, Themistoklis Kourkoumpetis, Gregory J Patts, Janice Weinberg, Francis A Farraye
Background: Studies have demonstrated an association between anti-TNF/immunomodulator agents used in inflammatory bowel disease (IBD) and impaired hepatitis B virus (HBV) vaccine immunogenicity, but little data exist on whether specific medication types affect protective HBsAb titers. Our aim was to analyze this association. Methods: This is a retrospective cohort study. Inclusion criteria: age ≥18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), previous HBV vaccination series and/or ≥1 positive HBsAb, and record of IBD therapy in 6 months before titer level...
January 18, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#18
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
February 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29342136/clonal-evolution-mechanisms-in-nt5c2-mutant-relapsed-acute-lymphoblastic-leukaemia
#19
Gannie Tzoneva, Chelsea L Dieck, Koichi Oshima, Alberto Ambesi-Impiombato, Marta Sánchez-Martín, Chioma J Madubata, Hossein Khiabanian, Jiangyan Yu, Esme Waanders, Ilaria Iacobucci, Maria Luisa Sulis, Motohiro Kato, Katsuyoshi Koh, Maddalena Paganin, Giuseppe Basso, Julie M Gastier-Foster, Mignon L Loh, Renate Kirschner-Schwabe, Charles G Mullighan, Raul Rabadan, Adolfo A Ferrando
Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29338679/therapeutic-role-of-methotrexate-in-pediatric-crohn-s-disease
#20
REVIEW
Zlatko Djurić, Ljiljana Šaranac, Ivana Budić, Voja Pavlović, Jelena Djordjević
The main role of therapy in Crohn's disease is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in Crohn's disease include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate. Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines independently or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of methotrexate in children suffering from Crohn's disease...
January 16, 2018: Bosnian Journal of Basic Medical Sciences
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