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l-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/28766374/biotechnological-production-and-practical-application-of-l-asparaginase-enzyme
#2
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/28754100/identifying-genomic-targets-for-protein-over-expression-by-omics-analysis-of-quiescent-escherichia-coli-cultures
#3
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/28735432/eucalyptol-sabinene-and-cinnamaldehyde-potent-inhibitors-of-salmonella-target-protein-l-asparaginase
#4
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
#5
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/28690619/characterization-of-three-l-asparaginases-from-maritime-pine-pinus-pinaster-ait
#6
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
#7
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/28671681/extracellular-vesicles-are-independent-metabolic-units-with-asparaginase-activity
#8
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
#9
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
https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#10
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#11
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...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622171/reactions-to-cytostatic-agents-in-children
#12
Josefina R Cernadas
PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug...
August 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28621166/l-asparaginase-for-newly-diagnosed-extra-nodal-nk-t-cell-lymphoma-systematic-review-and-meta-analysis
#13
REVIEW
Vadim S Pokrovsky, Denis Vinnikov
OBJECTIVES: The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients. METHODS: The PRISMA protocol was used to search PubMed and Embase for both controlled and uncontrolled studies of ASP or alternative chemotherapy (CT) for newly diagnosed ENKTL, published in English by March 2017. The regimens were compared to calculate relative risk (RR) with 95% confidence interval (CI) of the overall response rate (ORR), complete response (CR) or partial response (PR)...
August 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28596071/genetic-and-metabolic-engineering-approaches-for-the-production-and-delivery-of-l-asparaginases-an-overview
#14
REVIEW
Jalaja Vidya, Syed Sajitha, Mrudula Vasudevan Ushasree, Raveendran Sindhu, Parameswaran Binod, Aravind Madhavan, Ashok Pandey
L-asparaginase is one of the protein drugs for countering leukemia and lymphoma. A major challenge in the therapeutic potential of the enzyme is its immunogenicity, low-plasma half-life and glutaminase activity that are found to be the reasons for toxicities attributed to asparaginase therapy. For addressing these challenges, several research and developmental activities are going on throughout the world for an effective drug delivery for treatment of cancer. Hence there is an urgent need for the development of asparaginase with improved properties for efficient drug delivery...
May 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28588188/a-young-boy-with-l-asparaginase-induced-seizure
#15
M A Aziz, N K Singh, M H Rahman, M R Khan, A L Kabir, M Begum
L-Asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Seizures are uncommon symptoms. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events, completed in the department of Hematology of Bangabandhu Sheikh Mujib Medical University during March & April 2016...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28505420/immobilization-of-l-asparaginase-on-carrier-materials-a-comprehensive-review
#16
REVIEW
Ahmet Ulu, Burhan Ates
There are two major applications of l-asparaginase (L-ASNase): leukemia therapy and the food industry. Especially, its chemotherapeutic effect has attracted interest from the scientific community and individual scientists. Therefore, to protect the intrinsic activity and half-time of L-ASNase, several carriers and immobilization techniques for immobilization of L-ASNase have been described in articles. Unfortunately, a comprehensive review about immobilization of L-ASNase has not been written until now. In this review, we have thoroughly discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28461187/hyperthermophilic-l-asparaginase-bypasses-monomeric-intermediates-during-folding-to-retain-cooperativity-and-avoid-amyloid-assembly
#17
Dushyant K Garg, Bishwajit Kundu
In obligate dimeric proteins of hyperthermophilic origin the question whether the native dimer is obtained by association of folded monomers or through concomitant folding and assembly of subunits has intrigued researchers. To find an answer we studied the folding of a dimeric enzyme l-asparaginase from Pyrococcus furiosus (PfA) for which we reported earlier that it unfolds cooperatively without populating folded monomeric intermediates. However, in the present study we report the finding of a folded monomeric intermediate of PfA under acidic condition...
May 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#18
Jiaqiu Li, Ping Song, Liyuan Zhu, Neelum Aziz, Qiyin Zhou, Yulong Zhang, Wenxia Xu, Lifeng Feng, Dingwei Chen, Xian Wang, Hongchuan Jin
Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule biosynthesis. In this study, we report that glutamine deprivation retarded cell growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine significantly enhanced glutamine starvation induced growth inhibition and apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth inhibition induced by glutamine starvation and autophagy blockage...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423502/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#19
Magdalena Mazurkiewicz, Ellin-Kristina Hillert, Xin Wang, Paola Pellegrini, Maria Hägg Olofsson, Karthik Selvaraju, Padraig D'Arcy, Stig Linder
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive to treatment with VLX1570, resulting in the accumulation of polyubiquitinated proteasome substrates and loss of cell viability...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416749/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#20
Magdalena Mazurkiewicz, Ellin-Kristina Hillert, Xin Wang, Paola Pellegrini, Maria Hägg Olofsson, Karthik Selvaraju, Padraig D'Arcy, Stig Linder
The non-genotoxic nature of proteasome inhibition makes it an attractive therapeutic option for the treatment of pediatric malignancies. We recently described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase (DUB) activity that induces proteotoxic stress and apoptosis in cancer cells. Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive to treatment with VLX1570, resulting in the accumulation of polyubiquitinated proteasome substrates and loss of cell viability...
February 18, 2017: Oncotarget
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