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Asparaginase

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https://www.readbyqxmd.com/read/29784948/simultaneous-cell-disruption-and-semi-quantitative-activity-assays-for-high-throughput-screening-of-thermostable-l-asparaginases
#1
Xu Li, Xian Zhang, Shuqin Xu, Hengwei Zhang, Meijuan Xu, Taowei Yang, Li Wang, Haifeng Qian, Huiling Zhang, Haitian Fang, Tolbert Osire, Zhiming Rao, Shangtian Yang
L-asparaginase, which catalyses the hydrolysis of L-asparagine to L-aspartate, has attracted the attention of researchers due to its expanded applications in medicine and the food industry. In this study, a novel thermostable L-asparaginase from Pyrococcus yayanosii CH1 was cloned and over-expressed in Bacillus subtilis 168. To obtain thermostable L-asparaginase mutants with higher activity, a robust high-throughput screening process was developed specifically for thermophilic enzymes. In this process, cell disruption and enzyme activity assays are simultaneously performed in 96-deep well plates...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768231/enhanced-stability-of-l-asparaginase-by-its-bioconjugation-to-poly-styrene-co-maleic-acid-and-ecoflex-nanoparticles
#2
Jaleh Varshosaz, Negin Anvari
Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L-asparaginase (L-ASNase) is one of the first drugs used in ALL treatment. Anti-tumor activity of L-ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L-ASNase polymer bioconjugate to improve pharmacokinetic, increase half-life and stability of the enzyme. The conjugations were achieved by the cross-linking agent of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29767260/rnai%C3%A2-mediated-downregulation-of-asparaginase%C3%A2-like-protein-1-inhibits-growth-and-promotes-apoptosis-of-human-cervical-cancer-line-siha
#3
Xiao-Feng Lv, Han-Qing Hong, Ling Liu, Shi-Hong Cui, Chen-Chen Ren, Hong-Yu Li, Xiao-An Zhang, Lin-Dong Zhang, Tian-Xiang Wei, Jin-Jin Liu, Wen-Ying Xing, Han Fu, Shu-Jun Yan
Asparaginase like 1 (ASRGL1) protein belongs to the N‑terminal nucleophile group, cleaving the isoaspartyl‑dipeptides and L‑asparagine by adding water. It tends to be overexpressed in cancerous tumors including ovarian cancer and breast tumors. The present study assessed the potential ability of ASRGL1 as a molecular target in gene‑based cervical cancer treatment. The protein expression level of ASRGL1 was determined in paraffin‑embedded tumor specimen by immunohistochemistry. Additionally, in order to assess the activity of ASRGL1 during the process of cervical cancer cell multiplication, ASRGL1‑short hairpin (sh) RNA‑expressing lentivirus was established, which was used to infect SiHa cells...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29764116/circulating-low-absolute-cd4-t-cell-counts-may-predict-poor-prognosis-in-extranodal-nk-t-cell-lymphoma-patients-treating-with-pegaspargase-based-chemotherapy
#4
Ya-Ping Zhang, Run Zhang, Hua-Yuan Zhu, Li Wang, Yu-Jie Wu, Jin-Hua Liang, Wen-Yu Shi, Hong Liu, Wei Xu, Jian-Yong Li
Purpose: Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. Materials and Methods: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens...
May 14, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29761078/novel-immunotherapy-options-for-extranodal-nk-t-cell-lymphoma
#5
REVIEW
Boyu Hu, Yasuhiro Oki
Extranodal NK/T-cell lymphoma (ENKTCL) is a highly aggressive mature NK/T-cell neoplasm marked by NK-cell phenotypic expression of CD3ε and CD56. While the disease is reported worldwide, there is a significant geographic variation with its highest incidence in East Asian countries possibly related to the frequent early childhood exposure of Epstein-Barr virus (EBV) and specific ethnic-genetical background, which contributes to the tumorigenesis. Historically, anthracycline-based chemotherapy such as CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) was used, but resulted in poor outcomes...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29760798/a-multicenter-retrospective-comparison-of-sequential-versus-sandwich-chemoradiotherapy-for-stage-ie-iie-extranodal-natural-killer-t-cell-lymphoma-nasal-type
#6
Jin Li, Yajun Li, Meizuo Zhong, Wei Liu, Xianling Liu, Jiwei Li, Kunlun Li, Pingyong Yi
Background: Chemotherapy and radiotherapy are critical for treating early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL); however, the optimal therapy sequence remains unclear. Therefore, we performed this study to compare the efficacy of L-asparaginase/pegaspargase-based sequential versus sandwich chemoradiotherapy for patients newly diagnosed with stage IE-IIE ENKTL. Methods: Patients were categorized into sequential ( N = 111) and sandwich ( N = 104) groups. Chemotherapy regimens included GELOX, SMILE, and VLP...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29759551/genomics-and-pharmacogenomics-of-pediatric-acute-lymphoblastic-leukemia
#7
REVIEW
Chuan Wu, Wei Li
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29742281/analyzing-the-clinical-actionability-of-germline-pharmacogenomic-findings-in-oncology
#8
Rebecca Wellmann, Brittany A Borden, Keith Danahey, Rita Nanda, Blase N Polite, Walter M Stadler, Mark J Ratain, Peter H O'Donnell
BACKGROUND: Germline and tumor pharmacogenomics impact drug responses, but germline markers less commonly guide oncology prescribing. The authors hypothesized that a critical number of clinically actionable germline pharmacogenomic associations exist, representing clinical implementation opportunities. METHODS: In total, 125 oncology drugs were analyzed for positive germline pharmacogenomic associations in journals with impact factors ≥5. Studies were assessed for design and genotyping quality, clinically relevant outcomes, statistical rigor, and evidence of drug-gene effects...
May 9, 2018: Cancer
https://www.readbyqxmd.com/read/29739712/radiotherapy-is-essential-after-complete-response-to-asparaginase-containing-chemotherapy-in-early-stage-extranodal-nasal-type-nk-t-cell-lymphoma-a-multicenter-study-from-the-china-lymphoma-collaborative-group-clcg
#9
Xiu-Wen Deng, Jun-Xin Wu, Tao Wu, Su-Yu Zhu, Mei Shi, Hang Su, Ying Wang, Xia He, Li-Ming Xu, Zhi-Yong Yuan, Li-Ling Zhang, Gang Wu, Bao-Lin Qu, Li-Ting Qian, Xiao-Rong Hou, Fu-Quan Zhang, Yu-Jing Zhang, Yuan Zhu, Jian-Zhong Cao, Sheng-Min Lan, Mei Dong, Shu-Nan Qi, Yong Yang, Ye-Xiong Li
PURPOSE: This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT). PATIENTS AND METHODS: Of 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone). RESULTS: Compared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC)...
May 5, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29727043/efficacy-and-safety-of-recombinant-e-coli-asparaginase-in-children-with-previously-untreated-acute-lymphoblastic-leukemia-a-randomized-multicenter-study-of-the-dutch-childhood-oncology-group
#10
Inge M van der Sluis, Hester de Groot-Kruseman, Maroeska Te Loo, Wim J E Tissing, Cor van den Bos, Gertjan J L Kaspers, Marc Bierings, Wouter J W Kollen, Thorsten König, Uwe Pichlmeier, Hans-Jürgen Kühnel, Rob Pieters
BACKGROUND: The efficacy and safety of recombinant Escherichia coli-asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). METHODS: One hundred and ninety-nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high-risk patients; standard- and medium-risk patients received pegaspargase)...
May 4, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29715082/efficacy-of-asparaginase-erwinia-chrysanthemi-with-and-without-temozolomide-against-glioma-cells-and-intracranial-mouse-medulloblastoma
#11
Valentina Sanghez, Mengqing Chen, Shan Li, Tsui-Fen Chou, Michelina Iacovino, Henry J Lin, Joseph L Lasky, Eduard H Panosyan
BACKGROUND: Anti-metabolites are less-myelosuppressive than DNA-damaging anticancer drugs and may be useful against brain tumors. MATERIALS AND METHODS: We evaluated the asparagine/glutamine-deaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. RESULTS: Erwinaze treatment of cell lines and neurospheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC50 s) of 0...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29712887/short-course-versus-long-course-chemoradiotherapy-for-stage-ie-iie-extranodal-natural-killer-t-cell-lymphoma-nasal-type-a-multicenter-retrospective-study
#12
Jin Li, Yajun Li, Meizuo Zhong, Xianling Liu, Yinghui Song, Jiwei Li, Kunlun Li, Pingyong Yi
BACKGROUND This study compared clinical outcomes and adverse events between L-asparaginase/pegaspargase-based short-course and long-course chemoradiotherapy in newly diagnosed stage IE-IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL). MATERIAL AND METHODS Patients were categorized into a short-course (2-4 chemotherapy cycles, median: 4, n=153) and long-course group (5-6 cycles, median: 6, n=83). The chemotherapy regimens included GELOX, SMILE, and VLP. The radiotherapy dose was 40-63 Gy (median: 55 Gy)...
May 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29708643/efficient-and-easily-scalable-protein-folding-strong-anion-exchange-chromatography-pf-sax-for-renaturation-and-simultaneous-purification-of-recombinant-human-asparaginase-rhasp-from-e-coli
#13
Rajesh Kumar Kante, Sandeep Vemula, Maheswara Reddy Mallu, Srinivasa Reddy Ronda
Recombinant proteins are revolutionizing present day therapeutics. They are generally expressed as insoluble inclusion bodies in the E. coli and mis-folding, loss of protein, high cost of down streaming are the hurdles in their recovery. For the first time, we are reporting the refolding with simultaneous purification of rhASP in E. coli using a single step utilizing Protein Folding - strong anion exchange chromatography (PF-SAX). The purification method is also standardized for optimal concentration of solution additives, pH and mobile phase composition...
April 30, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/29705180/-activity-of-erwinia-asparaginase-after-anaphylactic-reaction-to-peg-asparaginase
#14
Maria Micaela Viña Romero, Sara García Gil, Gloria Julia Nazco Casariego, Javier Merino Alonso, Fernando Gutiérrez Nicolás
No abstract text is available yet for this article.
April 25, 2018: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/29703491/thrombosis-in-pediatric-patients-with-leukemia
#15
Sarina Levy-Mendelovich, Assaf Arie Barg, Gili Kenet
Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. It is reportedly the most common malignancy associated with thromboembolism in the pediatric age group. Over the last 2 decades, venous thromboembolism (VTE) has been increasingly diagnosed among pediatric ALL patients with an estimated incidence ranging from about 5% (for symptomatic cases) to about 30-70% (following sequential imaging studies in asymptomatic children). The etiology is multifactorial and may stem from alterations of the hemostatic system following various chemotherapy protocols (including use of l-Asparaginase), the presence of central venous lines (CVL), as well as comorbidities, e...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29697579/acid-suppressing-drugs-and-a-low-1-level-of-antithrombin-as-risk-factors-for-l-asparaginase-associated-pancreatitis-a-case-control-study-in-the-japan-association-of-childhood-leukemia-study-jacls
#16
Yoshiko Hashii, Makoto Yoshida, Junichi Hara, Shinichiro Nishimura, Keiko Yumura-Yagi, Keizo Horibe, Tatsutoshi Nakahata
L-Asparaginase has significantly improved outcome for children with acute lymphoblastic leukemia and has become an essential component of multiagent chemotherapy. However, there are many adverse events due to L-asparaginase, including acute pancreatitis. The pathology of L-asparaginase-associated pancreatitis (AAP) remains unclear. We compared patients who developed AAP (n=29) and random matched controls (n=36) who had been enrolled in the Japan Association of Childhood Leukemia Study of the ALL-02 protocol...
April 24, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29697113/engineering-l-asparaginase-for-spontaneous-formation-of-calcium-phosphate-bioinspired-microreactors
#17
Alexandra Louka, Irina Matlahov, Stefano Giuntini, Linda Cerofolini, Andrea Cavallo, Serena Pillozzi, Enrico Ravera, Marco Fragai, Annarosa Arcangeli, Ayyalusamy Ramamoorthy, Gil Goobes, Claudio Luchinat
Active bioinspired materials are appealing biotechnological targets, and their study is gaining momentum. These materials, which comprise of an inorganic matrix and one or more biomolecules, are extremely variable and therefore may result difficult to characterize in their intimate structure. In this work we have prepared a hydroxyapatite-l-asparaginase composite, with the perspective of using it in acute leukemia treatment. We demonstrate that the use of electron microscopy and powder X-ray diffraction, combined with the atomic-resolution information coming from solid-state NMR, allows us to understand the topology of the material and how the different components interplay to obtain an active composite...
April 26, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29683955/successful-management-of-a-child-with-drug-induced-necrotizing-pancreatitis-during-acute-lymphoblastic-leukemia-therapy-a-case-report
#18
Anna Płotka, Agnieszka Wziątek, Jacek Wachowiak, Katarzyna Derwich
Acute pancreatitis in children acute lymphoblastic leukemia is commonly caused by drugs, for example, L-Asparaginase, pegapargase, steroids. The incidence of this complication is estimated at 6.7% to 18%. Although the majority of drug-induced acute pancreatitis cases are mild, severe cases can rarely occur. This work presents a case of successful management of a child with drug-induced necrotizing pancreatitis during acute lymphoblastic leukemia therapy. This case illustrates that comprehensive care and immediate intensive treatment can rescue patient despite poor prognosis...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29661787/thromboembolism-in-acute-lymphoblastic-leukemia-results-of-nopho-all2008-protocol-treatment-in-patients-1-45-years
#19
Cecilie Utke Rank, Nina Toft, Ruta Tuckuviene, Kathrine Grell, Ove Juul Nielsen, Thomas Leth Frandsen, Hanne Vibeke Hansen Marquart, Birgitte Klug Albertsen, Ulf Tedgård, Helene Hallböök, Ellen Ruud, Kirsten Brunsvig Jarvis, Petter Quist-Paulsen, Pasi Huttunen, Ulla Wartiovaara-Kautto, Ólafur Gísli Jónsson, Sonata Saulyte Trakymiene, Laimonas Griškevičius, Kadri Saks, Mari Punab, Kjeld Schmiegelow
Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during treatment of 1772 consecutive Nordic/Baltic ALL patients 1-45years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (7/2008-4/2017). The 2.5-year cumulative incidence of thromboembolism (N=137) was 7.9% (95% confidence interval (CI) 6.6-9.1); higher in patients ≥10years ( P <.0001). Adjusted hazard ratios (HRa) were associated with greater age (10...
April 16, 2018: Blood
https://www.readbyqxmd.com/read/29619654/in-silico-characterization-of-a-cyanobacterial-plant-type-isoaspartyl-aminopeptidase-asparaginase
#20
Ronaldo Correia da Silva, Andrei Santos Siqueira, Alex Ranieri Jerônimo Lima, Adonis de Melo Lima, Alberdan Silva Santos, Délia Cristina Figueira Aguiar, Evonnildo Costa Gonçalves
Asparaginases are found in a range of organisms, although those found in cyanobacteria have been little studied, in spite of their great potential for biotechnological application. This study therefore sought to characterize the molecular structure of an L-asparaginase from the cyanobacterium Limnothrix sp. CACIAM 69d, which was isolated from a freshwater Amazonian environment. After homology modeling, model validation was performed using a Ramachandran plot, VERIFY3D, and the RMSD. We also performed molecular docking and dynamics simulations based on binding free-energy analysis...
April 4, 2018: Journal of Molecular Modeling
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