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Asparaginase

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https://www.readbyqxmd.com/read/28801829/cloning-and-characterization-of-halomonas-elongata-l-asparaginase-a-promising-chemotherapeutic-agent
#1
Ali Ghasemi, Sedigheh Asad, Mahboubeh Kabiri, Bahareh Dabirmanesh
L-asparaginase has been used in the treatment of patients with acute lymphoblastic leukemia (ALL) for more than 30 years. Rapid clearance of the enzyme from blood stream and its L-glutaminase-dependent neurotoxicity has led to searching for new L-asparaginases with more desirable properties. In the present study, L-asparaginase coding gene of Halomonas elongata was isolated, expressed in Escherichia coli, purified, and characterized. The purified protein was found to have a molecular mass of 39.5 kDa and 1000-folds more activity towards L-asparagine than L-glutamine...
August 11, 2017: Applied Microbiology and Biotechnology
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
#2
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/28766887/a-cost-analysis-of-individualized-asparaginase-treatment-in-pediatric-acute-lymphoblastic-leukemia
#3
Robin Q H Kloos, Carin A Uyl-de Groot, Raphaële R L van Litsenburg, Gertjan J L Kaspers, Rob Pieters, Inge M van der Sluis
BACKGROUND: Therapeutic drug monitoring (TDM) of asparaginase is necessary to respond to variability in asparaginase activity levels, detect silent inactivation, and distinguish between real allergies and allergic-like reactions with and without asparaginase neutralization, respectively. In this study, the costs of an individualized and fixed asparaginase dosing schedule were compared. PROCEDURE: Patients, treated according to the Dutch Childhood Oncology Group ALL-11 protocol (individualized PEGasparaginase treatment, starting dose: 1,500 IU/m(2) ) or ALL-10 protocol (native Escherichia coli asparaginase followed by 2,500 IU/m(2) PEGasparaginase), were included...
August 2, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28766374/biotechnological-production-and-practical-application-of-l-asparaginase-enzyme
#4
Archana Vimal, Awanish Kumar
L-asparaginase is a vital enzyme of medical importance, and renowned as a chemotherapeutic agent. The relevance of this enzyme is not only limited as an anti-cancer agent, it also possesses a wide range of medical application. The application includes the antimicrobial property, treatment of infectious diseases, autoimmune diseases, canine and feline cancer. Apart from the health care industry, its significance is also established in the food sector as a food processing agent to reduce the acrylamide concentration...
August 2, 2017: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/28766184/frequency-and-nature-of-adverse-drug-reactions-due-to-non-prescription-drugs-in-children-a-retrospective-analysis-from-the-french-pharmacovigilance-database
#5
Geneviève Durrieu, Mathieu Maupiler, Vanessa Rousseau, Leila Chebane, François Montastruc, Emmanuelle Bondon-Guitton, Jean-Louis Montastruc
INTRODUCTION: Studies that evaluate the safety of non-prescription drugs in children remain scarce. OBJECTIVES: The aim of the present study was to compare adverse drug reactions (ADRs) due to prescription versus non-prescription drugs in children. METHODS: We conducted a retrospective analysis of ADR notifications for a pediatric population (aged <18 years) registered in the French PharmacoVigilance Database (FPVD) between January 1985 and December 2016 by the Midi-Pyrénées PharmacoVigilance Center (in the south of France)...
August 1, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28754100/identifying-genomic-targets-for-protein-over-expression-by-omics-analysis-of-quiescent-escherichia-coli-cultures
#6
Shubhashree Mahalik, Ashish Kumar Sharma, Priyanka Jain, Krishna Jyoti Mukherjee
BACKGROUND: A cellular stress response is triggered upon induction of recombinant protein expression which feedback inhibits both growth as well as protein synthesis. In order to separate these two effects, it was decided to study "quiescent cultures" which continue to be metabolically active and express recombinant proteins even after growth cessation. The idea was to identify and up-regulate genes which are responsible for protein synthesis in the absence of growth. This would ensure that, even if growth were adversely affected post induction, there would be no attendant reduction in the protein expression capability of the cells...
July 28, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28753578/autophagy-suppression-potentiates-the-anti-glioblastoma-effect-of-asparaginase-in-vitro-and-in-vivo
#7
Qicheng Chen, Li Ye, Jiajun Fan, Xuyao Zhang, Huan Wang, Siyang Liao, Ping Song, Ziyu Wang, Shaofei Wang, Yubin Li, Jingyun Luan, Yichen Wang, Wei Chen, Wenjing Zai, Ping Yang, Zhonglian Cao, Dianwen Ju
Asparaginase has been reported to be effective in the treatment of various leukemia and several malignant solid cancers. However, the anti-tumor effect of asparaginase is always restricted due to complicated mechanisms. Herein, we investigated the mechanisms of how glioblastoma resisted asparaginase treatment and reported a novel approach to enhance the anti-glioblastoma effect of asparaginase. We found that asparaginase could induce growth inhibition and caspase-dependent apoptosis in U87MG/U251MG glioblastoma cells...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751566/prolonged-versus-standard-native-e-coli-asparaginase-therapy-in-childhood-acute-lymphoblastic-leukemia-and-non-hodgkin-lymphoma-final-results-of-the-eortc-clg-randomized-phase-iii-trial-58951
#8
Veerle Mondelaers, Stefan Suciu, Barbara De Moerloose, Alina Ferster, Françoise Mazingue, Geneviève Plat, Karima Yakouben, Anne Uyttebroeck, Patrick Lutz, Vitor Costa, Nicolas Sirvent, Emmanuel Plouvier, Martine Munzer, Maryline Poirée, Odile Minckes, Frédéric Millot, Dominique Plantaz, Philip Maes, Claire Hoyoux, Hélène Cave', Pierre Rohrlich, Yves Bertrand, Yves Benoit
Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma. The value of asparaginase was further addressed in a group of non-very high risk patients by comparing a prolonged (long-asparaginase) versus standard (short-asparaginase) native E.coli asparaginase treatment through a randomized question as part of the phase III 58951 trial of the European Organisation for Research and Treatment of Cancer Children's Leukemia Group. The main endpoint was disease-free survival...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28742131/biochemical-characterization-and-comparison-of-aspartylglucosaminidases-secreted-in-venom-of-the-parasitoid-wasps-asobara-tabida-and-leptopilina-heterotoma
#9
Quentin Coulette, Séverine Lemauf, Dominique Colinet, Geneviève Prévost, Caroline Anselme, Marylène Poirié, Jean-Luc Gatti
Aspartylglucosaminidase (AGA) is a low-abundance intracellular enzyme that plays a key role in the last stage of glycoproteins degradation, and whose deficiency leads to human aspartylglucosaminuria, a lysosomal storage disease. Surprisingly, high amounts of AGA-like proteins are secreted in the venom of two phylogenetically distant hymenopteran parasitoid wasp species, Asobara tabida (Braconidae) and Leptopilina heterotoma (Cynipidae). These venom AGAs have a similar domain organization as mammalian AGAs. They share with them key residues for autocatalysis and activity, and the mature α- and β-subunits also form an (αβ)2 structure in solution...
2017: PloS One
https://www.readbyqxmd.com/read/28736188/asparaginase-associated-pancreatitis-in-childhood-acute-lymphoblastic-leukaemia-an-observational-ponte-di-legno-toxicity-working-group-study
#10
Benjamin O Wolthers, Thomas L Frandsen, André Baruchel, Andishe Attarbaschi, Shlomit Barzilai, Antonella Colombini, Gabriele Escherich, Kathrine Grell, Hiroto Inaba, Gábor Kovacs, Der-Cherng Liang, Marion Mateos, Veerle Mondelaers, Anja Möricke, Tomasz Ociepa, Sujith Samarasinghe, Lewis B Silverman, Inge M van der Sluis, Martin Stanulla, Lynda M Vrooman, Michihiro Yano, Ester Zapotocka, Kjeld Schmiegelow
BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. METHODS: Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis...
July 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28735432/eucalyptol-sabinene-and-cinnamaldehyde-potent-inhibitors-of-salmonella-target-protein-l-asparaginase
#11
Archana Vimal, Dharm Pal, Timir Tripathi, Awanish Kumar
Salmonella typhimurium is a severe threat to human life. The treatment became more difficult with the emergence of multidrug resistance. In the present in silico study, a novel drug target L-asparaginase was tested against three ligands eucalyptol, sabinene, and cinnamaldehyde, major components of cardamom, nutmeg, and cinnamon, respectively. The lowest docking score was obtained for sabinene followed by eucalyptol and cinnamaldehyde i.e. -5.648, -3.939 and -3.469. The docking score of sabinene is also better than the standard drug, Ciprofloxacin (-4...
August 2017: 3 Biotech
https://www.readbyqxmd.com/read/28728499/acute-central-nervous-system-complications-and-ammonium-levels-in-adult-patients-with-acute-lymphoblastic-leukemia-receiving-l-asparaginase
#12
Nicole Strickler, Stefan Balabanov, Katharina Casauro, Urs Schanz, Markus G Manz, Bernhard Gerber
We analyzed ammonium levels and acute central nervous complications in adult patients receiving chemotherapy for acute lymphoblastic leukemia with or without asparaginase (l-asp). Twenty patients with a median age of 40.3 years were included. Ammonium-levels were measured during 88 chemotherapy cycles, 60 cycles (68%) with l-asp, and 28 cycles (32%) without l-asp. Ammonium was elevated in 87% of all l-asp containing cycles, with median ammonium levels of 169 μmol/l (interquartile range (IQR) 91-269 μmol/l)...
July 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28718698/pegging-down-risk-factors-for-peg-asparaginase-hepatotoxicity-in-patients-with-acute-lymphoblastic-leukemia-%C3%A2
#13
Caitlin R Rausch, Bernard L Marini, Lydia L Benitez, Allison Elias, Patrick W Burke, Dale Bixby, Anthony J Perissinotti
Asparaginase is commonly de-emphasized/omitted in adult acute lymphoblastic leukemia regimens due to poor tolerability, including hepatotoxicity (HTX). Adult patients (n = 100) given induction therapy containing pegylated asparaginase (PEG) from January 2008 to February 2016 were evaluated for HTX. Sixteen patients met criteria for HTX (direct bilirubin >3 g/dL). A multivariable model identified body surface area >2m(2) (OR 7.40; 95% CI: 1.73-31.61, p = .007), albumin <3 mg/dL (OR 4.62; 95% CI: 1...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28698205/an-fc-engineered-cd19-antibody-eradicates-mrd-in-patient-derived-mll-rearranged-acute-lymphoblastic-leukemia-xenografts
#14
Denis M Schewe, Ameera Alsadeq, Cornelia Sattler, Lennart Lenk, Fotini Vogiatzi, Gunnar Cario, Simon Vieth, Thomas Valerius, Sophia Rosskopf, Fabian Meyersieck, Julia Alten, Martin Schrappe, Martin Gramatzki, Matthias Peipp, Christian Kellner
Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, an Fc engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE) was tested. Patient derived xenografts (PDX) of pediatric MLL-rearranged ALL were established in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28697948/catalyzing-improvements-in-all-therapy-with-asparaginase
#15
REVIEW
Bernard L Marini, Anthony J Perissinotti, Dale L Bixby, Julia Brown, Patrick W Burke
Asparaginase remains a cornerstone of ALL therapy and is one of the key contributing factors to improved outcomes in adolescent and young adult (AYA) patients treated on pediatric protocols. Asparagine depletion has been associated with improved outcomes in ALL patients; this has led to an increased emphasis on optimizing asparagine depletion in ALL patients of all ages. To ensure adequate asparagine depletion, the use of therapeutic drug monitoring of asparaginase therapy holds much promise, yet remains underutilized in practice...
July 5, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28690619/characterization-of-three-l-asparaginases-from-maritime-pine-pinus-pinaster-ait
#16
Sonia H Van Kerckhoven, Fernando N de la Torre, Rafael A Cañas, Concepción Avila, Francisco R Cantón, Francisco M Cánovas
Asparaginases (ASPG, EC 3.5.1.1) catalyze the hydrolysis of the amide group of L-asparagine producing L-aspartate and ammonium. Three ASPG, PpASPG1, PpASPG2, and PpASPG3, have been identified in the transcriptome of maritime pine (Pinus pinaster Ait.) that were transiently expressed in Nicotiana benthamiana by agroinfection. The three recombinant proteins were processed in planta to active enzymes and it was found that all mature forms exhibited double activity asparaginase/isoaspartyl dipeptidase but only PpASPG1 was able to catalyze efficiently L-asparagine hydrolysis...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28675023/comparison-of-native-escherichia-coli-l-asparaginase-versus-pegylated-asparaginase-in-combination-with-ifosfamide-methotrexate-etoposide-and-prednisolone-imep-in-extranodal-nk-t-cell-lymphoma-nasal-type-ntcl
#17
Hyun Jee Kim, Chan-Young Ock, Tae Min Kim, Sung Hee Lee, Ju-Yeun Lee, Sun Hoi Jung, Yoon Sook Cho, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Il Han Kim, Dae Seog Heo
Purpose: The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli (E. coli) L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in NK/T-cell lymphoma (NTCL). Materials and Methods: A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016...
July 3, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28671857/neurocognitive-functioning-of-children-treated-for-high-risk-b-acute-lymphoblastic-leukemia-randomly-assigned-to-different-methotrexate-and-corticosteroid-treatment-strategies-a-report-from-the-children-s-oncology-group
#18
Kristina K Hardy, Leanne Embry, John A Kairalla, Shanjun Helian, Meenakshi Devidas, Daniel Armstrong, Stephen Hunger, William L Carroll, Eric Larsen, Elizabeth A Raetz, Mignon L Loh, Wenjian Yang, Mary V Relling, Robert B Noll, Naomi Winick
Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue...
August 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28671681/extracellular-vesicles-are-independent-metabolic-units-with-asparaginase-activity
#19
Nunzio Iraci, Edoardo Gaude, Tommaso Leonardi, Ana S H Costa, Chiara Cossetti, Luca Peruzzotti-Jametti, Joshua D Bernstock, Harpreet K Saini, Maurizio Gelati, Angelo Luigi Vescovi, Carlos Bastos, Nuno Faria, Luigi G Occhipinti, Anton J Enright, Christian Frezza, Stefano Pluchino
Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1)...
September 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28660740/prolonged-first-line-peg-asparaginase-treatment-in-pediatric-acute-lymphoblastic-leukemia-in-the-nopho-all2008-protocol-pharmacokinetics-and-antibody-formation
#20
Louise Tram Henriksen, Sofie Gottschalk Højfeldt, Kjeld Schmiegelow, Thomas Leth Frandsen, Peder Skov Wehner, Henrik Schrøder, Birgitte Klug Albertsen
BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies...
June 29, 2017: Pediatric Blood & Cancer
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