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https://www.readbyqxmd.com/read/28331334/safety-efficacy-and-clinical-utility-of-asparaginase-in-the-treatment-of-adult-patients-with-acute-lymphoblastic-leukemia
#1
REVIEW
Jamie Koprivnikar, James McCloskey, Stefan Faderl
Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28330312/isolation-and-screening-of-l-asparaginase-free-of-glutaminase-and-urease-from-fungal-sp
#2
Kruthi Doriya, Devarai Santhosh Kumar
L-Asparaginase is a chemotherapeutic drug used in the treatment of acute lymphoblastic leukaemia (ALL), a malignant disorder in children. L-Asparaginase helps in removing acrylamide found in fried and baked foods that is carcinogenic in nature. L-Asparaginase is present in plants, animals and microbes. Various microorganisms such as bacteria, yeast and fungi are generally used for the production of L-asparaginase as it is difficult to obtain the same from plants and animals. L-Asparaginase from bacteria causes anaphylaxis and other abnormal sensitive reactions due to low specificity to asparagine...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330175/exploration-of-the-binding-modes-of-l-asparaginase-complexed-with-its-amino-acid-substrates-by-molecular-docking-dynamics-and-simulation
#3
Erva Rajeswara Reddy, Rajulapati Satish Babu, Potla Durthi Chandrasai, Pola Madhuri
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-glutamine (L-Gln) deamination plays crucial role in ALL treatment. Role of Erwinaze(®) (L-asparaginase from Erwinia chrysanthemi) in regulation of L-Asn and L-Gln has been confirmed by the experimental studies. Therapeutic research against ALL remained elusive with the lack of structural information on Erwinaze(®) enzyme. In this present study, homology model of the Erwinaze(®) was developed using MODELLER and the same was validated by various quality indexing tools...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330072/molecular-dynamic-simulations-of-escherichia-coli-l-asparaginase-to-illuminate-its-role-in-deamination-of-asparagine-and-glutamine-residues
#4
Rajeswara Reddy Erva, Satish Babu Rajulapati, Chandrasai Potla Durthi, Mayuri Bhatia, Madhuri Pola
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-Glutamine (L-Gln) deamination play a crucial role in ALL treatment. Role of Elspar(®) (L-asparaginase from Escherichia coli) in regulation of L-Asn and L-Gln has been confirmed by the other researchers through experimental studies. Therapeutic research against ALL remained elusive with the lack of information on molecular interactions of Elspar(®) with amino acid substrates. In the present study, using different docking tools binding cavities, key residues in binding and ligand binding mechanisms were identified...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28292680/robust-quantitation-of-basic-protein-higher-order-aggregates-using-size-exclusion-chromatography
#5
David Gervais, Andrew Downer, Darryl King, Patrick Kanda, Nicholas Foote, Stuart Smith
Detection of higher-order aggregates (HOA) using size-exclusion chromatography (SEC) was found to be variable for a basic protein, using exposed-silanol or diol-silica-based SEC columns. Preparations of the tetrameric biopharmaceutical enzyme Erwinia chrysanthemil-asparaginase (ErA), which has an isoelectric point of 8.6, were analysed using a diol-silica SEC column. Although the proportions of ErA main peak and octamer species were unaffected, HOA recovery and detection were extremely variable and had poor agreement with an orthogonal measurement technique, analytical ultracentrifugation (AUC)...
March 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28259867/review-of-pharmacogenetics-studies-of-l-asparaginase-hypersensitivity-in-acute-lymphoblastic-leukemia-points-to-variants-in-the-gria1-gene
#6
Maria Lopez-Santillan, Leire Iparraguirre, Idoia Martin-Guerrero, Angela Gutierrez-Camino, Africa Garcia-Orad
Acute lymphoblastic leukemia (ALL) is a major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients who experience severe adverse events. L-Asparaginase is an effective antineoplastic agent used in chemotherapy of ALL. Despite its indisputable indication, hypersensitivity reactions are common. In those cases, discontinuation of treatment is usually needed and anti-asparaginase antibody production may also attenuate asparaginase activity, compromising its antileukemic effect...
March 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28251953/-suppression-of-telomerase-activity-leukemic-cells-by-mutant-forms-of-rhodospirillum-rubrum-l-asparaginase
#7
M V Pokrovskaya, D D Zhdanov, M A Eldarov, S S Aleksandrova, A V Veselovskiy, V S Pokrovskiy, D V Grishin, Ju A Gladilina, N N Sokolov
The active and stable mutant forms of short chain cytoplasmic L-asparaginase type I of Rhodospirillum rubrum (RrA): RrA+N17, D60K, F61L, RrA+N17, A64V, E67K, RrA+N17, E149R, V150P, RrAE149R, V150P and RrAE149R, V150P, F151T were obtained by the method of site-directed mutagenesis. It is established that variants RrA-N17, E149R, V150P, F151T and RrАE149R, V150P are capable to reduce an expression hTERT subunit of telomerase and, hence, activity of telomeres in Jurkat cells, but not in cellular lysates. During too time, L-asparaginases of Escherichia coli, Erwinia carotovora and Wolinella succinogenes, mutant forms RrА+N17, D60K, F61L and RrА+N17, A64V, E67K do not suppress of telomerase activity...
January 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28250007/population-pharmacokinetics-of-intravenous-erwinia-asparaginase-in-pediatric-acute-lymphoblastic-leukemia-patients
#8
Sebastiaan D T Sassen, Ron A A Mathôt, Rob Pieters, Robin Q H Kloos, Valérie de Haas, Gertjan J L Kaspers, Cor van den Bos, Wim J E Tissing, Maroeska Te Loo, Marc B Bierings, Wouter J W Kollen, Christian M Zwaan, Inge M van der Sluis
Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough concentrations to ensure adequate asparaginase activity (≥100 IU/L). The aim of this study was to describe the population pharmacokinetics of intravenous Erwinia asparaginase to quantify and gather insight into inter-individual and inter-occasion variability...
March 2017: Haematologica
https://www.readbyqxmd.com/read/28245869/regulation-of-stem-like-cancer-cells-by-glutamine-through-%C3%AE-catenin-pathway-mediated-by-redox-signaling
#9
Jianwei Liao, Pan-Pan Liu, Guoxin Hou, Jiajia Shao, Jing Yang, Kaiyan Liu, Wenhua Lu, Shijun Wen, Yumin Hu, Peng Huang
BACKGROUND: Cancer stem cells (CSCs) are thought to play an important role in tumor recurrence and drug resistance, and present a major challenge in cancer therapy. The tumor microenvironment such as growth factors, nutrients and oxygen affect CSC generation and proliferation by providing the necessary energy sources and growth signals. The side population (SP) analysis has been used to detect the stem-like cancer cell populations based on their high expression of ABCG2 that exports Hoechst-33342 and certain cytotoxic drugs from the cells...
February 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28244643/plasma-asparaginase-activity-asparagine-concentration-and-toxicity-after-administration-of-erwinia-asparaginase-in-children-and-young-adults-with-acute-lymphoblastic-leukemia-phase-i-ii-clinical-trial-in-japan
#10
Chitose Ogawa, Fumi Taguchi, Hiroaki Goto, Katsuyoshi Koh, Daisuke Tomizawa, Akira Ohara, Atsushi Manabe
BACKGROUND: A phase I/II study of Erwinia asparaginase in Japanese children and young adults with acute lymphoblastic leukemia (ALL) was performed to investigate its activity and toxicity. PROCEDURE: Eligible patients were in remission and had developed allergy to Escherichia coli asparaginase. Erwina asparaginase was intramuscularly administrated on days 2, 5, 7, 9, 11, and 13. To measure the plasma l-asparagine concentration (PAC), amino acids were derivatized with N(α) -(5-fluoro-2,4-dinitrophenyl)-l-leucinamide...
February 28, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28244291/outcome-of-reinduction-chemotherapy-with-a-modified-dose-of-idarubicin-for-children-with-marrow-relapsed-acute-lymphoblastic-leukemia-results-of-the-childhood-acute-lymphoblastic-leukemia-call-0603-study
#11
Kyung Nam Koh, Ho Joon Im, Hyery Kim, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Young Tak Lim, Jun Eun Park, Byung Kiu Park, Hyeon Jin Park, Jong Jin Seo
This multicenter, prospective trial was conducted to develop an effective and safe reinduction regimen for marrow-relapsed pediatric acute lymphoblastic leukemia (ALL) by modifying the dose of idarubicin. Between 2006 and 2009, the trial accrued 44 patients, 1 to 21 years old with first marrow-relapsed ALL. The reinduction regimen comprised prednisolone, vincristine, L-asparaginase, and idarubicin (10 mg/m²/week). The idarubicin dose was adjusted according to the degree of myelosuppression. The second complete remission (CR2) rate was 72...
April 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28242759/obesity-challenges-the-hepatoprotective-function-of-the-integrated-stress-response-to-asparaginase-exposure-in-mice
#12
Inna A Nikonorova, Rana J T Al-Baghdadi, Emily T Mirek, Yongping Wang, Michael P Goudie, Berish B Wetstein, Joseph L Dixon, Christopher Hine, James R Mitchell, Christopher M Adams, Ronald C Wek, Tracy G Anthony
Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing of amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PERK, a major ISR transducer to ER stress...
February 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28235872/role-and-characterization-of-a-cyanide-induced-3-cyanoalanine-nitrilase-in-the-cyanide-assimilating-bacterium-pseudomonas-pseudoalcaligenes-cect-5344
#13
Felipe Acera, María Isabel Carmona, Francisco Castillo, Alberto Quesada, Rafael Blasco
Pseudomonas pseudoalcaligenes CECT 5344 is a bacterium able to assimilate cyanide as the sole nitrogen source. Under this growth conditions, a 3-cyanoalanine nitrilase enzymatic activity was induced. This activity was coded by nit4, one of the four nitrilases detected in the genome of this bacterium, and its expression in E. coli enabled the recombinant strain to fully assimilate 3-cyanoalanine. P. pseudoalcaligenes CECT 5344 showed a weak growth level with 3-cyanoalanine as N-source, unless KCN was also added...
February 24, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28224619/l-asparaginase-mediated-downregulation-of-c-myc-promotes-1-25-oh-2-d3-induced-myeloid-differentiation-in-acute-myeloid-leukemia-cells
#14
Ju Han Song, Eunchong Park, Myun Soo Kim, Kyung-Min Cho, Su-Ho Park, Arim Lee, Jiseon Song, Hyeoung-Joon Kim, Jeong-Tae Koh, Tae Sung Kim
Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28222789/is-ccnu-lomustine-valuable-for-treatment-of-cutaneous-epitheliotropic-lymphoma-in-dogs-a-critically-appraised-topic
#15
REVIEW
Aurore Laprais, Thierry Olivry
BACKGROUND: CCNU and other treatment protocols are commonly offered to owners for the treatment of dogs diagnosed with cutaneous (epitheliotropic) T-cell lymphoma (CTCL). Chemotherapy protocols provide variable benefits; they have different side-effects, and they typically require monitoring to detect drug toxicity at a non-negligible cost to the owner. At this time, even though CCNU is most often recommended to treat dogs with CTCL, there is no clear consensus on the benefit of this drug...
February 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28219133/-clinical-observation-on-lop-regimen-combined-with-imrt-treatment-for-early-nasal-nk-t-cell-lymphoma
#16
Y F Hu, Y H Huang, T Wu, Y Zhang, X M Liu, Y Song, J Y Gan
Objective: To observe the clinical efficacy and safety of the LOP regimen (L-asparaginase, vincristine, dexamethasone) combined with intensity modulated radiation therapy(IMRT)in the treatment of early nasal NK/T cell lymphoma. Method: Clinical data of 65 patients with nasal NK/T cell lymphoma treated with LOP chemotherapy combined with IMRT at the Guizhou Province Tumor Hospital between March 2010 and January 2015 were retrospectively analyzed. Results: Among the 65 patients, 39 cases obtained complete remission (CR), 18 cases obtained partial remission(PR), 1 case obtained stable disease (SD), 7 cases had progressive disease(PD)...
February 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28215935/comparative-study-of-l-asparaginase-based-lop-regimen-over-chop-regimen-before-radiotherapy-for-stage-iie-extranodal-nasal-type-nk-t-cell-lymphoma-a-study-of-2-centers
#17
Limin Huang, Bin Yuan, Haixia Wu, Hongliang Chu, Yayun Liu, Shuang Wu, Hong Li, He Lu, Hui Chen
BACKGROUND: In this study we evaluated the efficacy of an L-asparaginase-based LOP (L-asparaginase, vincristine, and dexamethasone) regimen in extranodal Natural Killer (NK)/T-cell lymphoma (ENKTL) patients in the Guizhou province of China. PATIENTS AND METHODS: Forty-eight patients were treated with the LOP (L-asparaginase, vincristine and dexamethasone) regimen chemotherapy (CT) and 32 patients with the CHOP (cyclophosphamide, tetrahydropyanyl adriamycin, vincristine, and prednisone) regimen...
March 2017: Clinical Lymphoma, Myeloma & Leukemia
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
#18
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
#19
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
#20
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
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