l-asparaginase

BACKGROUND: L-Asparaginase is a crucial component of acute lymphoblastic leukemia (ALL) treatment. However, hypersensitivity is a common adverse event. This study aimed to identify risk factors for L-asparaginase hypersensitivity in childhood ALL. METHODS: Children treated for ALL at Chiang Mai University Hospital, Thailand, between 2005 and 2020 were included. Demographic data, clinical characteristics, and factors related to L-asparaginase were retrospectively reviewed...

INTRODUCTION: Escherichia coli l-asparaginase (EcA), an integral part of multi-agent chemotherapy protocols of acute lymphoblastic leukemia (ALL), is constrained by safety concerns and the development of anti-asparaginase antibodies. Novel variants with better pharmacological properties are desirable. METHODS: Thousands of novel EcA variants were constructed using protein engineering approach. After preliminary screening, two mutants, KHY-17 and KHYW-17 were selected for further development...

BACKGROUND: Asparaginases are a mainstay treatment for pediatric acute lymphoblastic leukemia (ALL). Recent reports identified hypoglycemia associated with asparaginases. Other reports describe hypoglycemia associated with 6-mercaptopurine (6-MP), another fundamental ALL therapy. Little is known about the risk of hypoglycemia associated with ALL therapy, an adverse event that puts children at risk of decreased level of consciousness, seizures, and possibly negative neurocognitive sequelae...

Genome sequence of Geobacillus thermopakistaniensis contains an open reading frame annotated as a type II L-asparaginase (ASNaseGt ). Critical structural analysis disclosed that ASNaseGt might be a type I L-asparaginase. In order to determine whether it is a type I or type II L-asparaginase, we have performed the structural-functional characterization of the recombinant protein as well as analyzed the localization of ASNaseGt in G. thermopakistaniensis. ASNaseGt exhibited optimal activity at 52 °C and pH 9...

L-Asparaginase is a key component in the treatment of leukemias and lymphomas. However, the glutamine affinity of this therapeutic enzyme is an off-target activity that causes several side effects. The modeling and molecular docking study of Yarrowia lipolytica L-asparaginase (YL-ASNase) to reduce its l-glutamine affinity and increase its stability was the aim of this study. Protein-ligand interactions of wild-type and different mutants of YL-ASNase against L-asparagine compared to l-glutamine were assessed using AutoDock Vina tools because the crystal structure of YL-ASNase does not exist in the protein data banks...

BACKGROUND: Feline large granular lymphocyte (LGL) lymphoma is an aggressive neoplasia characterised by short survival and poor response to chemotherapy. OBJECTIVES: In this study, the effect of different chemotherapeutic agents on the growth kinetics of the feline cell line S87, a non-MHC-restricted feline LGL cell line, was investigated. Where possible, IC50 (inhibitory concentration 50) values were determined. The IC50 values of the cell line as lymphoma models can provide clues to the situation in vivo and serve as a basis for studying resistance mechanisms...

Acute lymphoblastic leukemia (ALL), a hematologic cancer that involves the production of abnormal lymphoid precursor cells, primarily affects children aged 2 to 10 years. The bacterial enzyme L-asparaginase produced from Escherichia coli is utilised as first-line therapy, despite the fact that 30 % of patients have a treatment-limiting hypersensitivity reaction. The current study elucidates the biosynthesis of extremely stable, water-dispersible, anisotropic Ag nanoparticles at room temperature and investigation of its anti-tumor potency in comparison to L-asparaginase...

Silent inactivation of L-asparaginase (L-Asp) represents rapid clearance of L-Asp by anti-L-Asp IgG antibodies without clinical symptoms. Measurement of L-Asp activity is the gold standard for diagnosis of silent inactivation, but this test is not commercially available in Japan as of 2023. We evaluated ex vivo and in vivo ammonia production in relation to L-Asp activity. Blood samples from ten adult patients treated with L-Asp were collected to measure ammonia levels and L-Asp activity before the first dose and 24 h after the last dose of L-Asp, during each cycle of treatment...

INTRODUCTION: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare subtype of T-cell leukemia that phenotypically expresses mature T-cell markers and immature myeloid markers such as CD33. Gemtuzumab ozogamicin (GO) is a novel agent for the CD33 molecular targeting antibody conjugated to the cytotoxic agent calicheamicin. GO is anticipated to be effective against ETP-ALL. In vivo studies promise antileukemic effects in cell lines; however, clinical reports to support this research are lacking...

A thermostable L-asparaginase was produced from Bacillus licheniformis UDS-5 (GenBank accession number, OP117154). The production conditions were optimized by the Plackett Burman method, followed by the Box Behnken method, where the enzyme production was enhanced up to fourfold. It secreted L-asparaginase optimally in the medium, pH 7, containing 0.5% (w/v) peptone, 1% (w/v) sodium chloride, 0.15% (w/v) beef extract, 0.15% (w/v) yeast extract, 3% (w/v) L-asparagine at 50 °C for 96 h. The enzyme, with a molecular weight of 85 kDa, was purified by ion exchange chromatography and size exclusion chromatography with better purification fold and percent yield...

AIM: The evolving chemotherapy landscape continually introduces effective agents, but escalating costs call for an evaluation of drug wastage and financial consequences to enhance resource utilization. This study seeks to estimate chemotherapy drug wastage and its economic loss in paediatric cancer care. METHODS: In this cross-sectional study of paediatric cancer patients receiving parenteral chemotherapy, we evaluated both the drug used and wasted during each administration...

OBJECTIVE: To improve the understanding of aggressive NK-cell leukemia (ANKL) and summarize the progress of its diagnosis and treatment. METHODS: We retrospectively analyzed a case of a patient who was initially diagnosed with T-cell lymphoma (non-specific type) and later transformed into ANKL through examinations such as bone marrow smear, flow cytometry, Q-mNGS, and pathology. We described the patient's diagnostic and treatment journey and conducted a literature review...

With an increasing demand for L-asparaginase in pharmaceutical and food sectors for its cytostatic and acrylamide-reducing qualities, there's a need to discover novel, highly productive enzyme sources with improved pharmacokinetic profiles. Keeping this in mind, the present study aimed at maximizing the potential of Ganoderma australe GPC191 to produce L-asparaginase by fermentation medium optimization using statistical validation. Of the 11 physicochemical parameters evaluated under submerged fermentation conditions through one-factor-at-a-time approach and Plackett-Burman design, only four parameters (inoculum load, L-asparagine, soybean meal, and initial pH) influenced L-asparaginase production, significantly (p < 0...

l-Asparaginase (E.C. 3.5.1.1) is an indispensable analeptic anticancer enzyme used as an amalgam with additional cancer medicines for the cure of acute lymphoblastic leukemia (ALL). The presence of lAparaginase in tomato was confirmed byWestern blotting and DNA sequencing. The l-Asparaginase gene from tomato has been deposited in the NCBI database with accession number: OR736141. Crude enzyme was extracted from the fruit pulp of Solanum lycopersicum, and the activity was determined by the Nesslerization method...

In the present investigation, a soil isolate Pseudomonas aeruginosa CSPS4 was used for retrieving the l-asparaginase encoding gene ( Asn_PA ) of size 1089 bp. The gene was successfully cloned into the pET28a (+) vector and expressed into E. coli BL21( DE3 ) for characterization of the protein. The recombinant rAsn_PA enzyme was purified by affinity chromatography using Ni-NTA2+ resins. Molecular weight analysis using SDS-PAGE unveiled rAsn_PA as a monomeric protein of molecular weight ~ 35 kDa...

OBJECTIVES: Hyperglycemia is a known side effect of anticancer chemotherapeutic drugs. This entity known as drug-induced diabetes mellitus usually does not present with the development of diabetic ketoacidosis (DKA). We hereby report a case of drug induced diabetes mellitus in a child with acute leukemia presenting with DKA. CASE PRESENTATION: We report a case of a teenage boy diagnosed with B cell acute lymphoblastic leukemia and was started on induction phase chemotherapy as per the Indian Collaborative Childhood Leukemia group (ICICLe) acute lymphoblastic leukemia-14 protocol...

The influence of light regulation on fungal growth and enzyme production was tested on endophytic isolates of Fusarium proliferatum (CCH), Colletotrichum boninense (PL1, PL9, OL2), Colletotrichum gloeosporiodes (OL3) and Colletotrichum siamense (PL3). The isolates were treated with blue, red, green, and yellow light, while white fluorescent light (12 h light/12 h dark photoperiod) and 24 h dark conditions were applied as control. Results revealed that coloured light treatments induced formation of circadian rings, while exposure to white light and dark conditions showed less pronounced circadian rings...

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding...

Acrylamide is present in thermally processed foods, and it possesses toxic and carcinogenic properties. L-asparaginases could effectively regulate the formation of acrylamide at the source. However, current L-asparaginases have drawbacks such as poor thermal stability, low catalytic activity, and poor substrate specificity, thereby restricting their utility in the food industry. To address this issue, this study employed consensus design to predict the crucial residues influencing the thermal stability of Corynebacterium glutamicum L-asparaginase (CgASNase)...

Polyethylene glycol-asparaginase (PEGAsp) is an established component of acute leukemia therapy. Hypersensitivity reactions to PEGAsp occur in 10% to 15% of patients, with polyethylene glycol suggested as the antigenic culprit. As coronavirus disease 2019 (COVID-19) mRNA vaccines contain polyethylene glycol, the safety of administration of these vaccines to patients with prior PEGAsp hypersensitivity has been questioned. Between December 21, 2020 and March 3, 2022, 66 patients with acute leukemia and PEGAsp allergy received COVID-19 vaccination...