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Asparaginase

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https://www.readbyqxmd.com/read/28523950/levocarnitine-and-vitamin-b-complex-for-the-treatment-of-pegaspargase-induced-hepatotoxicity-a-case-report-and-review-of-the-literature
#1
Alison Blackman, Alyssa Boutin, Alexei Shimanovsky, William J Baker, Nicholas Forcello
Asparaginase is a chemotherapeutic agent that is commonly used in combination with other medications for the treatment of acute lymphoblastic leukemia. An adverse effect of asparaginase includes hepatotoxicity, which can lead to severe liver failure and death. Several reports have documented successful treatment of asparaginase-induced hepatotoxicity using levocarnitine (l-carnitine) and vitamin B complex. Herein, we report a patient with acute lymphoblastic leukemia that experienced acute liver injury following pegaspargase administration...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28505420/immobilization-of-l-asparaginase-on-carrier-materials-a-comprehensive-review
#2
Ahmet Ulu, Burhan Ates
There are two major applications of L-asparaginase (L-ASNase): Cancer therapy and food industry. Especially, its chemotherapeutic effect has attracted interest of the scientific community and of 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 wasn't written until now. In this review, we lengthily discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications...
May 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28503810/a-minor-role-of-asparaginase-in-predisposing-to-cerebral-venous-thromboses-in-adult-acute-lymphoblastic-leukemia-patients
#3
Saara Roininen, Outi Laine, Marjut Kauppila, Marko Vesanen, Maria Rämet, Marjatta Sinisalo, Esa Jantunen, Marjaana Säily, Riikka Räty, Erkki Elonen, Ulla Wartiovaara-Kautto
Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000...
May 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28497204/the-biology-and-the-importance-of-photobacterium-species
#4
REVIEW
Ibrahim Musa Moi, Noordiyanah Nadhirah Roslan, Adam Thean Chor Leow, Mohd Shukuri Mohamad Ali, Raja Noor Zaliha Raja Abd Rahman, Azam Rahimpour, Suriana Sabri
Photobacterium species are Gram-negative coccobacilli which are distributed in marine habitats worldwide. Some species are unique because of their capability to produce luminescence. Taxonomically, about 23 species and 2 subspecies are validated to date. Genomes from a few Photobacterium spp. have been sequenced and studied. They are considered a special group of bacteria because some species are capable of producing essential polyunsaturated fatty acids, antibacterial compounds, lipases, esterases and asparaginases...
May 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28486976/tropicall-study-thromboprophylaxis-in-children-treated-for-acute-lymphoblastic-leukemia-with-low-molecular-weight-heparin-a-multicenter-randomized-controlled-trial
#5
Irene L M Klaassen, Mandy N Lauw, Marianne D van de Wetering, Bart J Biemond, Saskia Middeldorp, Floor C H Abbink, Marc Bierings, D Maroeska M W Te Loo, Rob Pieters, Inge M van der Sluis, Wim J E Tissing, C Michel Zwaan, C Heleen van Ommen
BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design...
May 10, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28482728/safety-and-feasibility-of-lower-antithrombin-replacement-targets-in-adult-patients-with-hematological-malignancies-receiving-asparaginase-therapy
#6
Jason N Barreto, Kristen B McCullough, Candy S Peskey, Ross A Dierkhising, Kristin C Mara, Michelle A Elliott, Dennis A Gastineau, Aref Al-Kali, Naseema Gangat, Louis Letendre, William J Hogan, Mark R Litzow, Mrinal M Patnaik
The optimal antithrombin(AT) activity parameters for replacement as thromboprophylaxis following asparaginase remains unclear. This single-center, retrospective study evaluated two sets of AT replacement thresholds and targets in adults receiving asparaginase-containing chemotherapy. AT supplementation adhered to institutional standards, which lowered the AT activity target from 100% to 80% in 6/2014. Ninety-two patients were evaluated. Cumulative thrombosis incidence was 16% at 6 months (95%CI:6.8-24.0, maximum follow-up 315 days) with similar incidence between the 80% and 100% target groups, 14% (2 of the 14) and 13% (10 of the 78), respectively, with a small non-Line-Related DVT incidence (3%)...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28472942/evaluation-for-inherited-and-acquired-prothrombotic-defects-predisposing-to-symptomatic-thromboembolism-in-children-with-acute-lymphoblastic-leukemia-a-protocol-for-a-prospective-observational-cohort-study
#7
Uma H Athale, Caroline Laverdiere, Trishana Nayiager, Yves-Line Delva, Gary Foster, Lehana Thabane, Anthony Kc Chan
BACKGROUND: Thromboembolism (TE) is a serious complication in children with acute lymphoblastic leukemia (ALL). The incidence of symptomatic thromboembolism is as high as 14% and case fatality rate of ~15%. Further, development of thromboembolism interferes with the scheduled chemotherapy with potential impact on cure rates. The exact pathogenesis of ALL-associated thromboembolism is unknown. Concomitant administration of asparaginase and steroids, two important anti-leukemic agents, is shown to increase the risk of ALL-associated TE...
May 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28461187/hyperthermophilic-l-asparaginase-bypasses-monomeric-intermediates-during-folding-to-retain-cooperativity-and-avoid-amyloid-assembly
#8
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/28455513/role-of-activating-transcription-factor-4-in-the-hepatic-response-to-amino-acid-depletion-by-asparaginase
#9
Rana J T Al-Baghdadi, Inna A Nikonorova, Emily T Mirek, Yongping Wang, Jinhee Park, William J Belden, Ronald C Wek, Tracy G Anthony
The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 (-/-), and Atf4 (-/-) mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 (+/-) mice...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28440015/hypertriglyceridemia-during-asparaginase-treatment-in-children-with-acute-lymphoblastic-leukemia-correlates-with-antithrombin-activity-in-adolescents
#10
Lisa Persson, Arja Harila-Saari, Ida Hed Myrberg, Mats Heyman, Anna Nilsson, Susanna Ranta
BACKGROUND: Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered to be transient and benign in children with ALL, whereas low AT activity predisposes to thrombosis. Studies on the incidence and significance of HTG in children with ALL are scarce, and their findings have not always been congruent...
April 25, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28424964/pharmacodynamic-effects-in-the-cerebrospinal-fluid-of-rats-after-intravenous-administration-of-different-asparaginase-formulations
#11
Andrea Ballerini, Federico Moro, Ilaria Fuso Nerini, Claudio Marcello Marzo, Angelo Di Clemente, Mariella Ferrari, Maurizio D'Incalci, Andrea Biondi, Antonella Colombini, Valentino Conter, Luca Porcu, Luigi Cervo, Carmelo Rizzari, Massimo Zucchetti
PURPOSE: Asparaginase (ASNase) is used to treat various hematological malignancies for its capacity to deplete asparagine (ASN) in serum and cerebrospinal fluid (CSF). Since the biological mechanisms underlying CSF asparagine depletion in humans are not yet fully elucidated, this study compared, for the first time, the pharmacological properties of three clinically used ASNase formulations in a rodent model. METHODS: Male Wistar rats were treated with E.coli-ASNase, PEG-ASNase, or ERW-ASNase at different doses...
June 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#12
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...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423502/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#13
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/28423235/hepatic-sinusoidal-obstruction-syndrome-during-maintenance-therapy-of-childhood-acute-lymphoblastic-leukemia-is-associated-with-continuous-asparaginase-therapy-and-mercaptopurine-metabolites
#14
Linea Natalie Toksvang, Silvia De Pietri, Stine N Nielsen, Jacob Nersting, Birgitte K Albertsen, Peder S Wehner, Steen Rosthøj, Päivi M Lähteenmäki, Daniel Nilsson, Tove A Nystad, Kathrine Grell, Thomas L Frandsen, Kjeld Schmiegelow
BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy...
April 19, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28416749/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#15
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
https://www.readbyqxmd.com/read/28413626/non-infectious-chemotherapy-associated-acute-toxicities-during-childhood-acute-lymphoblastic-leukemia-therapy
#16
REVIEW
Kjeld Schmiegelow, Klaus Müller, Signe Sloth Mogensen, Pernille Rudebeck Mogensen, Benjamin Ole Wolthers, Ulrik Kristoffer Stoltze, Ruta Tuckuviene, Thomas Frandsen
During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia...
2017: F1000Research
https://www.readbyqxmd.com/read/28410601/the-diagnosis-and-management-of-nk-t-cell-lymphomas
#17
REVIEW
Eric Tse, Yok-Lam Kwong
Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and rarely as disseminated disease with a leukemic phase...
April 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28404973/a-phase-ii-prospective-study-of-the-sandwich-protocol-l-asparaginase-cisplatin-dexamethasone-and-etoposide-chemotherapy-combined-with-concurrent-radiation-and-cisplatin-in-newly-diagnosed-i-ii-stage-nasal-type-extranodal-natural-killer-t-cell-lymphoma
#18
Ming Jiang, Li Zhang, Li Xie, Hong Zhang, Yu Jiang, Wei-Ping Liu, Wen-Yan Zhang, Rong Tian, Yao-Tiao Deng, Sha Zhao, Li-Qun Zou
Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is a special type of lymphomas with geographic and racial specificity. Up to now, the standard first-line treatment is still not unified. In our previous report, the "sandwich" protocol produced good results. Continuing to use the "sandwich" mode, a new chemotherapy composed of L-asparaginase, cisplatin, etoposide and dexamethasone (LVDP) plus concurrent chemoradiotherapy (CCRT) was conducted in more patients with newly diagnosed, I/II stage ENKTCL. The results showed that 66 patients were enrolled...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401107/is-n-acetylcysteine-infusion-an-effective-treatment-option-in-l-asparaginase-associated-hepatotoxicity
#19
Zeynep Canan Özdemir, Ayşe Bozkurt Turhan, Makbule Eren, Özcan Bor
No abstract text is available yet for this article.
March 2017: Blood Research
https://www.readbyqxmd.com/read/28398275/natural-killer-t-cell-lymphomas-in-pediatric-and-adolescent-patients
#20
REVIEW
Amanda M Termuhlen
Natural killer/T-cell (NK/T-cell) lymphomas are rare in children and adolescents and consist predominantly of nasal-type extranodal NK/T-cell lymphomas. More than half of pediatric/adolescent patients with NK/T-cell lymphomas present with localized nasal/sinus involvement, but the disease may involve many organs. NK/T-cell lymphoma cells are cytotoxic and associated with necrosis and angioinvasion; they express CD56, CD2, cytoplasmic CD3 epsilon, and to a variable degree CD30. The cells contain Epstein-Barr virus (EBV)-encoded RNA...
March 2017: Clinical Advances in Hematology & Oncology: H&O
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