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Asparaginase

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https://www.readbyqxmd.com/read/28205049/construction-of-potent-recombinant-strain-through-intergeneric-protoplast-fusion-in-endophytic-fungi-for-anticancerous-enzymes-production-using-rice-straw
#1
Mervat Morsy Abbas Ahmed El-Gendy, Salha Hassan Mastour Al-Zahrani, Ahmed Mohamed Ahmed El-Bondkly
Among all fungal endophytes isolates derived from different ethno-medical plants, the hyper-yield L-asparaginase and L-glutaminase wild strains Trichoderma sp. Gen 9 and Cladosporium sp. Gen 20 using rice straw under solid-state fermentation (SSF) were selected. The selected strains were used as parents for the intergeneric protoplast fusion program to construct recombinant strain for prompt improvement production of these enzymes in one recombinant strain. Among 21 fusants obtained, the recombinant strain AYA 20-1, with 2...
February 15, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28197753/asparaginase-pharmacology-challenges-still-to-be-faced
#2
REVIEW
Claudia Lanvers-Kaminsky
PURPOSE: The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated. METHODS: We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo...
February 14, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28195091/coagulation-profile-during-induction-chemotherapy-in-childhood-acute-lymphoblastic-leukemia
#3
Shivali Sehgal, Sunita Sharma, Jagdish Chandra, Anita Nangia
CONTEXT: Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy. AIMS: To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients. SETTINGS AND DESIGN: Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28188133/pd1-blockade-with-pembrolizumab-is-highly-effective-in-relapsed-or-refractory-nk-t-cell-lymphoma-failing-l-asparaginase
#4
Yok-Lam Kwong, Thomas S Y Chan, Daryl Tan, Seok Jin Kim, Li-Mei Poon, Benjamin Mow, Pek-Lan Khong, Florence Loong, Rex Au-Yeung, Jabed Iqbal, Colin Phipps, Eric Tse
Natural killer (NK)/T-cell lymphomas failing L-asparaginse-regimens have no known salvage and are almost invariably fatal. Seven male NK/T-cell lymphoma patients (age: 49, 31-68, years) failing 2 (1-5) regimens (including L-asparaginase-regimens, and allogeneic hematopoietic stem cell transplantation, HSCT, in 2 cases), were treated with the anti-programmed-death-1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic and molecular (circulating Epstein-Barr virus, EBV, DNA) criteria...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28183647/adsorption-and-enzyme-activity-of-asparaginase-at-lipid-langmuir-and-langmuir-blodgett-films
#5
Carlos da Rocha Junior, Luciano Caseli
In this present work, the surface activity of the enzyme asparaginase was investigated at the air-water interface, presenting surface activity in high ionic strengths. Asparaginase was incorporated in Langmuir monolayers of the phospholipid dipalmitoylphosphatidylcholine (DPPC), forming a mixed film, which was characterized with surface pressure-area isotherms, surface potential-area isotherms, polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM)...
April 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28177776/characterization-of-a-salmonella-sugar-kinase-essential-for-utilization-of-fructose-asparagine
#6
Pradip K Biswas, Edward J Behrman, Venkat Gopalan
Salmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation due to the toxic build-up of the deglycase substrate. The limited distribution of this metabolic pathway in the animal gut microbiome raises the prospects for antibacterial discovery...
August 10, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28152898/safety-of-using-escalated-doses-of-enoxaparin-prophylaxis-in-adults-with-acute-lymphoblastic-leukemia-receiving-asparaginase-based-intensification-therapy
#7
Jack Toshimine Seki, Tian Wang, Lalit Saini, Andrew Stessman, Joseph Samuel, Naoko Sakurai, Andre C Schuh, Karen W L Yee, Mark D Minden, Aaron David Schimmer, Vikas Gupta, Mohamed Shanavas, Joseph M Brandwein
: 141 Background: Venous thromboembolism (VTE) is a known complication in adults receiving asparaginase (ASNase) for acute lymphoblastic leukemia (ALL). We previously reported a 27.3% VTE rate in patients (pts) receiving a modified Dana Farber Cancer Institute (DFCI).We report updated results using two different dosing of enoxaparin as primary VTE prophylaxis. METHODS: 62 pts ALL in complete remission, who were treated with a weekly ASNase-based DFCI intensification phase for at least 7 cycles (21 weeks) and received prophylaxis with enoxaparin targeted to 1 mg/kg subcutaneously (SC) daily (escalated dose group), were evaluated ...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28151717/synergistic-drug-combinations-with-a-cdk4-6-inhibitor-in-t-cell-acute-lymphoblastic-leukemia
#8
Yana Pikman, Gabriela Alexe, Giovanni Roti, Amy Saur Conway, Andrew Furman, Emily S Lee, Andrew E Place, Sunkyu Kim, Chitra Saran, Rebecca Modiste, David M Weinstock, Marian Harris, Andrew L Kung, Lewis B Silverman, Kimberly Stegmaier
PURPOSE: While significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease. EXPERIMENTAL DESIGN: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28150907/venous-thromboembolism-following-l-asparaginase-treatment-for-lymphoid-malignancies-in-korea
#9
J H Lee, J Lee, H-Y Yhim, D Oh, S-M Bang
BACKGROUND: L-asparaginase (L-asp) associated venous thromboembolism (VTE) is a serious adverse complication associated with acute lymphoblastic leukemia (ALL) and lymphoma treatment. The incidence rate of L-asp related VTE in Asian cancer patients is not well known. METHODS: We performed a population-based study between 2009 and 2013 using claim databases including both diagnostic and medication codes, such as anti-cancer treatment with L-asp, and VTE diagnoses from the starting date until 3 months after cessation of L-asp...
February 2, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28139703/the-differential-ability-of-asparagine-and-glutamine-in-promoting-the-closed-active-enzyme-conformation-rationalizes-the-wolinella-succinogenes-l-asparaginase-substrate-specificity
#10
Hien Anh Nguyen, Donald L Durden, Arnon Lavie
Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P121) was found to have L-glutaminase activity in contrast to Uniprot entry P50286 (WoA-S121) that has a serine residue at this position. Towards understanding how this residue impacts the L-glutaminase property, kinetic analysis was coupled with crystal structure determination of these WoA variants...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28124210/a-temporal-and-spatial-contribution-of-asparaginase-to-asparagine-catabolism-during-development-of-rice-grains
#11
Yui Yabuki, Miwa Ohashi, Fumi Imagawa, Keiki Ishiyama, Marcel Pascal Beier, Noriyuki Konishi, Toshiko Umetsu-Ohashi, Toshihiko Hayakawa, Tomoyuki Yamaya, Soichi Kojima
BACKGROUND: Asparagine is one of the most dominant organic nitrogen compounds in phloem and xylem sap in a wide range of plant species. Asparaginase (ASNase; EC, 3.5.1.1) catabolizes asparagine into aspartate and ammonium; therefore, it is suggested to play a key role in asparagine metabolism within legume sink organs. However, the metabolic fate of asparagine in source and sink organs during rice seed production remains to be elucidated. Therefore, the main objective of this study is to investigate the asparagine metabolism in a temporal and spatial manner during rice seed production...
December 2017: Rice
https://www.readbyqxmd.com/read/28119366/bioluminescence-imaging-enhances-analysis-of-drug-responses-in-a-patient-derived-xenograft-model-of-pediatric-all
#12
Luke Jones, Jennifer Richmond, Kathryn Evans, Hernan Carol, Duohui Jing, Raushan T Kurmasheva, Catherine A Billups, Peter J Houghton, Malcolm A Smith, Richard B Lock
PURPOSE: Robust preclinical models of pediatric acute lymphoblastic leukemia (ALL) are essential in prioritizing promising therapies for clinical assessment in high-risk patients. Patient-derived xenograft (PDX) models of ALL provide a clinically relevant platform for assessing novel drugs, with efficacy generally assessed by enumerating circulating human lymphoblasts in mouse peripheral blood (PB) as an indicator of disease burden. While allowing indirect measurement of disease burden in real-time, this technique cannot assess treatment effects on internal reservoirs of disease...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28118965/asparaginase-use-for-the-treatment-of-acute-lymphoblastic-leukemia
#13
Pere Barba, José Luis Dapena, Pau Montesinos, Susana Rives
No abstract text is available yet for this article.
January 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28117395/utility-of-baseline-interim-and-end-of-treatment-18-f-fdg-pet-ct-in-extranodal-natural-killer-t-cell-lymphoma-patients-treated-with-l-asparaginase-pegaspargase
#14
Yu Chang, Xiaorui Fu, Zhenchang Sun, Xinli Xie, Ruihua Wang, Zhaoming Li, Xudong Zhang, Guangyao Sheng, Mingzhi Zhang
Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28116786/the-combination-of-bortezomib-with-chemotherapy-to-treat%C3%A2-relapsed-refractory-acute-lymphoblastic-leukaemia-of-childhood
#15
Alice Bertaina, Luciana Vinti, Luisa Strocchio, Stefania Gaspari, Roberta Caruso, Mattia Algeri, Valentina Coletti, Carmelo Gurnari, Mariateresa Romano, Maria Giuseppina Cefalo, Katia Girardi, Valentina Trevisan, Valentina Bertaina, Pietro Merli, Franco Locatelli
Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively...
January 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28110669/in-vitro-screening-and-in-silico-validation-revealed-key-microbes-for-higher-production-of-significant-therapeutic-enzyme-l-asparaginase
#16
Archana Vimal, Awanish Kumar
l-asparaginase is an enzyme of medical prominence and reputable as a chemotherapeutic agent. It also has immense potential to cure autoimmune and infectious diseases. The vast application of this enzyme in healthcare sector increases its market demand. However, presently the huge market demand is not achieved completely. This serves the basis to explore better producer microbial strains to bridge the gap between huge demand and supply of this therapeutic enzyme. The present study deals with the successful screening of potent microorganisms producing l-asparaginase...
March 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28110661/understanding-the-process-induced-formation-of-minor-conformational-variants-of-erwinia-chrysanthemil-asparaginase
#17
David Gervais, Justin Hayzen, Charlotte Orphanou, Alexandra McEntee, Christine Hallam, Rossalyn Brehm
During Erwinia chrysanthemil-asparaginase (ErA) manufacture, minor conformational variants are formed that elute in the acidic region of the analytical ion-exchange HPLC chromatogram. These variants retain enzymatic activity and form part of the biopharmaceutical product, but must be kept within acceptable limits through controlled operation of the manufacturing process. The high isoelectric point of the ErA native tetramer (8.6) leads to certain process steps being operated in the alkaline pH region. Previously, the formation of these species during processing was not fully understood...
March 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28105864/expression-and-purification-of-l-asparaginase-from-escherichia-coli-and-the-inhibitory-effects-of-cyclic-dipeptides
#18
Yanan Zhang, Dan Li, Yan Li
L-asparaginase, a key enzyme involved in nitrogen metabolism, is an effective anti-tumour agent. Cyclic dipeptides, a group of compounds, contain several important biological functions. In this paper, we proposed a novel method for L-asparaginase expression and purification from Echerichia coli and determined the effect of cyclic dipeptides on the enzymatic activity of recombinant L-asparaginase. The gene ansB encoding L-asparaginase was amplified from the genome of E. coli BL21 (DE3) by polymerase chain reaction and sub-cloned into pET-15b vector to construct expressing plasmid pET-15b-ansB...
January 20, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28101462/identification-and-molecular-characterization-of-genes-coding-pharmaceutically-important-enzymes-from-halo-thermo-tolerant-bacillus
#19
Azam Safary, Rezvan Moniri, Maryam Hamzeh-Mivehroud, Siavoush Dastmalchi
Purpose: Robust pharmaceutical and industrial enzymes from extremophile microorganisms are main source of enzymes with tremendous stability under harsh conditions which make them potential tools for commercial and biotechnological applications. Methods: The genome of a Gram-positive halo-thermotolerant Bacillus sp. SL1, new isolate from Saline Lake, was investigated for the presence of genes coding for potentially pharmaceutical enzymes. We determined gene sequences for the enzymes laccase (CotA), l-asparaginase (ansA3, ansA1), glutamate-specific endopeptidase (blaSE), l-arabinose isomerase (araA2), endo-1,4-β mannosidase (gmuG), glutaminase (glsA), pectate lyase (pelA), cellulase (bglC1), aldehyde dehydrogenase (ycbD) and allantoinases (pucH) in the genome of Bacillus sp...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28100766/comparison-of-a-chop-lasp-based-protocol-with-and-without-maintenance-for-canine-multicentric-lymphoma
#20
E M Lautscham, M Kessler, T Ernst, L Willimzig, R Neiger
The recommendation to treat canine lymphoma with a discontinuous protocol is based on small case numbers and mostly historic controls. This study compares duration of first remission (DFR) and overall survival time (ST) with a discontinuous protocol to the same protocol with maintenance phase. 408 dogs were treated with a CHOP-LAsp (C=cyclophosphamide; H=hydroxydaunorubicin; O=Oncovin; P=prednisolone; LAsp=l-asparaginase)-based 28-week induction protocol. In 75 dogs (cohort 1), this was followed by a maintenance phase consisting of vincristine, chlorambucil and actinomycin-D with a total treatment duration of two years...
January 18, 2017: Veterinary Record
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