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Asparaginase

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https://www.readbyqxmd.com/read/29350496/venoocclusive-disease-due-to-chemotherapy-for-pediatric-acute-lymphoblastic-leukemia-is-associated-with-increased-levels-of-plasminogen-activator-inhibitor-1
#1
Margherita Mauro, Graziella Saggiorato, Maria Teresa Sartori, Giuseppe Gallo, Massimiliano De Bortoli, Elisa Bonetti, Ada Zaccaron, Virginia Vitale, Rita Balter, Matteo Chinello, Simone Cesaro
We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29343523/a-novel-l-asparaginase-with-low-l-glutaminase-coactivity-is-highly-efficacious-against-both-t-and-b-cell-acute-lymphoblastic-leukemias-in-vivo
#2
Hien Anh Nguyen, Ying Su, Jenny Yu Zhang, Aleksandar Antanasijevic, Michael Caffrey, Amanda M Schalk, Li Liu, Damiano Rondelli, Annie Oh, Dolores L Mahmud, Maarten C Bosland, Andre Kajdacsy-Balla, Sofie Peirs, Tim Lammens, Veerle Mondelaers, Barbara De Moerloose, Steven Goossens, Michael J Schlicht, Kasim K Kabirov, Alexander V Lyubimov, Bradley J Merrill, Yogen Saunthararajah, Pieter Van Vlierberghe, Arnon Lavie
Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 of every 10 cases occur in adults. The enzyme drug L-asparaginase serves as a cornerstone of ALL therapy and exploits the asparagine-dependency of ALL cells. In addition to hydrolyzing the amino acid L-asparagine, all FDA-approved L-asparaginases also have significant L-glutaminase coactivity. Since several reports suggest that L-glutamine depletion correlates with many of the side effects of these drugs, enzyme variants with reduced L-glutaminase coactivity might be clinically beneficial if their anti-leukemic activity would be preserved...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29337136/as-extracellular-glutamine-levels-decline-asparagine-becomes-an-essential-amino-acid
#3
Natalya N Pavlova, Sheng Hui, Jonathan M Ghergurovich, Jing Fan, Andrew M Intlekofer, Richard M White, Joshua D Rabinowitz, Craig B Thompson, Ji Zhang
When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell survival and growth. Here we report that this rescue results from use of asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic asparaginase activity and could not utilize asparagine to produce other amino acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines are capable of sufficient glutamine synthesis to maintain essential amino acid uptake and production of glutamine-dependent biosynthetic precursors, with the exception of asparagine...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29334534/symptomatic-hyperammonemia-with-erwinia-chrysanthemi-derived-asparaginase-in-pediatric-leukemia-patients
#4
Nathan Gossai, Michael Richards, Lara Boman, Yoav Messinger, Sara Gernbacher, Joanna Perkins, Bruce Bostrom
Erwinia chrysanthemi-derived asparaginase is increasingly integral to acute lymphoblastic leukemia therapy. In our series, 16% of patients developed symptomatic hyperammonemia following Erwinia administration with symptoms including refractory nausea, vomiting, profound fatigue, malaise, and coma. This series of patients receiving Erwinia indicates higher than expected incidence of hyperammonemia, correlation between ammonia and asparaginase levels and therapeutic asparaginase activity levels despite dose reduction...
January 12, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29328996/acute-and-sub-acute-neurological-toxicity-in-children-treated-for-acute-lymphoblastic-leukemia
#5
REVIEW
Natalia C Millan, Analía Pastrana, Myriam R Guitter, Pedro A Zubizarreta, María S Monges, María S Felice
Eighty percent of children with acute lymphoblastic leukemia (ALL) survive with current treatments. Neurotoxicity is an infrequent adverse event. We describe clinical presentations of neurological toxicity, phases of treatment when these adverse events were more frequent and patients ́ outcome. From January-1995 to December-2015, 1379 ALL cases were admitted. Neurotoxicity was diagnosed in 49 patients (3.6%) and classified according to neurological syndromes. Medical records, laboratory-tests and images were reviewed...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29319209/effectiveness-of-antibacterial-prophylaxis-during-induction-chemotherapy-in-children-with-acute-lymphoblastic-leukemia
#6
M L Sulis, T M Blonquist, K E Stevenson, S K Hunt, S Kay-Green, U H Athale, L A Clavell, P D Cole, K M Kelly, C Laverdiere, J M Leclerc, B Michon, M A Schorin, J G Welch, D S Neuberg, S E Sallan, L B Silverman
BACKGROUND: Pediatric patients receiving induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk of developing life-threatening infections. We investigated whether uniform antibacterial guidelines, including mandatory antibacterial prophylaxis in afebrile patients during induction, decreases the incidence of microbiologically documented bacteremia. METHODS: Between 2012 and 2015, 230 patients with newly diagnosed ALL (aged 1-21) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 11-001 (DFCI 11-001)...
January 10, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29316436/oncogenic-kras-regulates-amino-acid-homeostasis-and-asparagine-biosynthesis-via-atf4-and-alters-sensitivity-to-l-asparaginase
#7
Dana M Gwinn, Alex G Lee, Marcela Briones-Martin-Del-Campo, Crystal S Conn, David R Simpson, Anna I Scott, Anthony Le, Tina M Cowan, Davide Ruggero, E Alejandro Sweet-Cordero
KRAS is a regulator of the nutrient stress response in non-small-cell lung cancer (NSCLC). Induction of the ATF4 pathway during nutrient depletion requires AKT and NRF2 downstream of KRAS. The tumor suppressor KEAP1 strongly influences the outcome of activation of this pathway during nutrient stress; loss of KEAP1 in KRAS mutant cells leads to apoptosis. Through ATF4 regulation, KRAS alters amino acid uptake and asparagine biosynthesis. The ATF4 target asparagine synthetase (ASNS) contributes to apoptotic suppression, protein biosynthesis, and mTORC1 activation...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29307802/glutaminase-free-l-asparaginase-from-vibrio-cholerae-heterologous-expression-purification-and-biochemical-characterization
#8
Remya Radha, Nagarajan Arumugam, Sathyanarayana N Gummadi
l-asparaginase is used as a pivotal agent in treatment of lympho proliferative disorders and holds an excessive demand for food processing aids. Most of the l-asparaginases possess glutaminase activity which might lead to side effects during the treatment. There is a need for new therapeutic enzymes is of great interest in both medical and food applications. In this study, Vibrio cholerael-asparaginase was recombinantly overexpressed in E. coli, purified to homogeneity and molecular size was estimated to be 36...
January 4, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29299118/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#9
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29279817/multi-level-statistical-optimization-of-l-asparaginase-from-bacillus-subtilis-vuvd001
#10
Rajeswara Reddy Erva, T C Venkateswarulu, Bangaraiah Pagala
Physical and chemical factors influencing the anti-leukemic l-asparaginase enzyme production by Bacillus subtilis VUVD001 were optimized using multi-stage optimization on the basis of preliminary experimental outcomes obtained by conventional one-factor-at-a-time approach using shake flasks. Process variables namely carbon, nitrogen sources, pH and temperature were taken into consideration during response surface methodology (RSM) optimization. The finest enzyme activity of 0.51 IUml-1 obtained by OFAT method was enhanced by 3...
January 2018: 3 Biotech
https://www.readbyqxmd.com/read/29260426/the-use-of-prophylactic-anticoagulation-during-induction-and-consolidation-chemotherapy-in-adults-with-acute-lymphoblastic-leukemia
#11
Rachael F Grace, Daniel J DeAngelo, Kristen E Stevenson, Donna Neuberg, Stephen E Sallan, Yasser R Abou Mourad, Julie Bergeron, Matthew D Seftel, Caroline Kokulis, Jean M Connors
Treatment for acute lymphoblastic leukemia (ALL) in adults confers a high risk of venous thromboembolic (VTE) complications. We describe the implementation and results of prophylactic anticoagulation guidelines in adults (18-50 years) treated on a Dana-Farber Cancer Institute ALL pediatric inspired consortium protocol from 2007 to 2013. A high rate of asparaginase related toxicity events, including thrombosis, resulted in a protocol amendment adding guidelines for prophylactic anticoagulation and a modified asparaginase dose and schedule...
December 19, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#12
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29229487/proteomics-reveals-key-proteins-participating-in-growth-difference-between-fall-dormant-and-non-dormant-alfalfa-in-terminal-buds
#13
Hongqi Du, Yinghua Shi, Defeng Li, Wenna Fan, Yanhua Wang, Guoqiang Wang, Chengzhang Wang
To explore the molecular mechanism of growth differences between fall dormant (FD) and non-FD alfalfa, we conducted iTRAQ-based quantitative proteomics on terminal buds of Maverick (FD) and Cuf101 (non-FD) cultivars, identified differential abundance protein species (DAPS) and verified expression profiling of the corresponding mRNA by qRT-PCR. A total of 3872 protein species were annotated. Of the 90 DAPS, 56 and 34 were respectively up- and down-accumulated in Maverick, compared to Cuf101. They were grouped into 35 functional categories and enriched in seven pathways...
December 8, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29217160/interaction-between-gallic-acid-and-asparaginase-to-potentiate-anti-proliferative-effect-on-lymphoblastic-leukemia-cell-line
#14
Zahra Sourani, Hedayatollah Shirzad, Moein Shirzad, Batoul Pourgheysari
BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) fails in some cases and the side effects cause mortality in certain patients. Gallic acid (GA), a polyhydroxyphenolic compound has biological functions including anti-proliferative properties. The aim of the present study was to investigate the growth inhibition effects of GA in combination with asparaginase (ASP), as a component of combination chemotherapy, in a lymphoblastic leukemia cell line. METHODS: Jurkat cells were incubated with different concentrations of GA with or without ASP...
December 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29210976/therapeutic-drug-monitoring-of-asparaginase-activity-method-comparison-of-maattm-and-aha-test-used-in-the-international-aieop-bfm-all-2009-trial
#15
Claudia Lanvers-Kaminsky, Andrea Rüffer, Gudrun Würthwein, Joachim Gerss, Massimo Zucchetti, Andrea Ballerini, Andishe Attarbaschi, Petr Smisek, Christa Nath, Samiuela Lee, Sara Elitzur, Martin Zimmermann, Anja Möricke, Martin Schrappe, Carmelo Rizzari, Joachim Boos
BACKGROUND: In the international AIEOP-BFM ALL 2009 trial, asparaginase (ASE) activity was monitored after each dose of pegylated E. coli ASE (PEG-ASE). Two methods were used: the AHA test and MAAT. As the latter method overestimates PEG-ASE activity because it calibrates using E. coli ASE, method comparison was performed using samples from the AIEOP-BFM ALL 2009 trial. METHODS: PEG-ASE activities were determined by MAAT and AHA test in two sets of samples (1st set: 630 samples; 2nd set: 91 samples)...
November 23, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29207624/autophagy-suppression-potentiates-the-anti-glioblastoma-effect-of-asparaginase-in-vitro-and-in-vivo
#16
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...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204688/pharmacokinetics-of-recombinant-asparaginase-in-children-with-acute-lymphoblastic-leukemia
#17
Swantje Völler, Uwe Pichlmeier, Anke Zens, Georg Hempel
PURPOSE: The objective of this study was to assess the pharmacokinetics of recombinant asparaginase (rASNase, Spectrila®) in children with acute lymphoblastic leukemia using a population pharmacokinetic approach in order to explore potential dosing recommendations. METHODS: Data on serum asparaginase activities of 124 children from three clinical studies were included in the analysis, covering an age range from 3 days to 17 years. Most patients received 5000 U/m2 rASNase intravenously every 3 days...
December 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29200702/affordable-and-safe-health-care-for-all-children-lessons-learned-from-the-use-of-peg-asparaginase-in-a-developing-country
#18
Dhaarani Jayaraman, Ramya Uppuluri, Venkateswaran Vellaichamy Swaminathan, Meena Sivasankaran, Shivani Patel, Revathi Raj
Peg-asparaginase has widely replaced the use of conventional asparaginase in treatment of children with acute lymphoblastic leukaemia in developed countries. In developing countries like India, with financial constraints being a part of clinical challenge to the treatment of cancers, uniform use of Peg-asparaginase in all children is not practically possible. However, we found by a retrospective analysis of 211 children treated for acute lymphoblastic leukaemia, uniform use of this drug was feasible with indigenous techniques like storing the drug with strict cold chain maintenance and sharing the drug amongst 2 or 3 patients to reduce the burden on each family...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29198332/optimization-and-purification-of-l-asparaginase-from-fungi-a-systematic-review
#19
REVIEW
Paula Monteiro Souza, Marcela Medeiros de Freitas, Samuel Leite Cardoso, Adalberto Pessoa, Eliete Neves Silva Guerra, Pérola Oliveira Magalhães
The purpose of this systematic review was to identify the available literature of the l-asparaginase producing fungi. This study followed the Preferred Reporting Items for Systematic Reviews. The search was conducted on five databases: LILACS, PubMed, Science Direct, Scopus and Web of Science up until July 20th, 2016, with no time or language restrictions. The reference list of the included studies was crosschecked and a partial gray literature search was undertaken. The methodology of the selected studies was evaluated using GRADE...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29197742/asparaginase-inhibits-the-lectin-pathway-of-complement-activation
#20
M P Keizer, C Aarts, A M Kamp, H N Caron, M D van de Wetering, D Wouters, T W Kuijpers
Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated...
November 30, 2017: Molecular Immunology
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