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Asparaginase

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https://www.readbyqxmd.com/read/28424964/pharmacodynamic-effects-in-the-cerebrospinal-fluid-of-rats-after-intravenous-administration-of-different-asparaginase-formulations
#1
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...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28375864/risk-factors-for-asparaginase-associated-pancreatitis-a-systematic-review
#11
Judy-April Oparaji, Fateema Rose, Debra Okafor, Amari Howard, Rose L Turner, Abrahim I Orabi, Craig Byersdorfer, Qi Mi, Kim Ritchey, Mark E Lowe, Sohail Z Husain
GOALS: To evaluate potential risk factors for the development of asparaginase-associated pancreatitis (AAP), we performed a systematic review of the current literature from January 1946 through May 2015. BACKGROUND: Asparaginase, a primary treatment for the most common childhood cancer, acute lymphoblastic leukemia (ALL), is a well-described cause of pancreatitis. Further, pancreatitis is among the most burdensome and common complications of asparaginase treatment and represents a major reason for early-drug termination and inferior outcomes...
April 3, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28373755/peg-asparaginase-in-bfm-90-regimen-improves-outcomes-in-adults-with-newly-diagnosed-lymphoblastic-lymphoma
#12
Wen Zheng, Hanyun Ren, Xiaoyan Ke, Mei Xue, Yongqing Zhang, Yan Xie, Ningjing Lin, Meifeng Tu, Weiping Liu, Lingyan Ping, Zhitao Ying, Chen Zhang, Lijuan Deng, Xiaopei Wang, Yuqin Song, Jun Zhu
OBJECTIVE: Although L-asparaginase (L-ASP) is a standard treatment for lymphoblastic lymphoma (LBL), hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase (PEG-ASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia (ALL). In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90 regimen (PEG-ASP-BFM-90) for adult LBL. METHODS: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEG-ASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China...
February 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28358370/the-role-of-autophagy-in-asparaginase-induced-immune-suppression-of-macrophages
#13
Ping Song, Ziyu Wang, Xuyao Zhang, Jiajun Fan, Yubin Li, Qicheng Chen, Shaofei Wang, Peipei Liu, Jingyun Luan, Li Ye, Dianwen Ju
Erwinia asparaginase, a bacteria-derived enzyme drug, has been used in the treatment of various cancers, especially acute lymphoblastic leukemia (ALL). One of the most significant side effects associated with asparaginase administration is immune suppression, which limits its application in clinic. Macrophages are phagocytic immune cells and have a central role in inflammation and host defense. We reported here that asparaginase disturbed the function of macrophages including phagocytosis, proliferation, ROS and nitric oxide secretion, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) secretion, and major histocompatibility complex II (MHC-II) molecule expression, thus induced immune suppression in interferon-γ and lipopolysaccharide-stimulated macrophages...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28355969/incidence-of-asparaginase-related-hepatotoxicity-pancreatitis-and-thrombotic-events-in-adults-with-acute-lymphoblastic-leukemia-treated-with-a-pediatric-inspired-regimen
#14
Trevor N Christ, Wendy Stock, Randall W Knoebel
Asparaginase is a critical component of acute lymphoblastic leukemia (ALL) treatment in children; however, its use in adults is often avoided as a result of toxicities including hepatotoxicity, thrombosis, and pancreatitis which have been reported more commonly in adults than in children. In this retrospective analysis, short-acting L-asparaginase (L-ASP) and long-acting polyethylene glycol (PEG)-asparaginase (PEG-ASP) were compared for grade 3-4 toxicities and characterized by patient and drug-related factors to identify strategies for toxicity avoidance in adults with ALL...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28352997/deprivation-of-asparagine-triggers-cytoprotective-autophagy-in-laryngeal-squamous-cell-carcinoma
#15
Yunxiang Ji, Li Li, Qilei Tao, Xuyao Zhang, Jingyun Luan, Shuwei Zhao, Huanhai Liu, Dianwen Ju
Laryngeal squamous cell carcinoma (LSCC), one of the most common malignancies in the head and neck, has poor prognosis and high mortality. The need of novel and effective treatment for LSCC is urgent. Asparaginase, an enzyme-depriving asparagine, has been employed for the treatment of various cancers. In this study, we reported for the first time that asparaginase could induce remarkable cytotoxicity and caspase-dependent apoptosis in human LSCC Tu212 and Tu686 cells. Meanwhile, autophagy was triggered by asparaginase in LSCC cells, which was confirmed by accumulation of autophagosomes and the conversion of light chain 3-I (LC3-I) to LC3-II...
March 28, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28349445/prophylactic-use-of-octreotide-for-asparaginase-induced-acute-pancreatitis
#16
Sachi Sakaguchi, Takeshi Higa, Mitsuyoshi Suzuki, Junya Fujimura, Toshiaki Shimizu
In the present study, we sought to evaluate the prophylactic use of octreotide for asparaginase-induced acute pancreatitis. We reviewed the medical records of seven patients in two institutions who received prophylactic octreotide for re-administration of asparaginase after asparaginase-induced acute pancreatitis. Three patients completed asparaginase treatment without developing pancreatitis, and four experienced recurrence of pancreatitis. A literature search using PubMed identified four additional patients in whom asparaginase was successfully re-administered with octreotide...
March 27, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28349335/population-pharmacokinetics-to-model-the-time-varying-clearance-of-the-pegylated-asparaginase-oncaspar-%C3%A2-in-children-with-acute-lymphoblastic-leukemia
#17
Gudrun Würthwein, Claudia Lanvers-Kaminsky, Georg Hempel, Silke Gastine, Anja Möricke, Martin Schrappe, Mats O Karlsson, Joachim Boos
BACKGROUND AND OBJECTIVES: The pharmacokinetics of the polyethylene glycol (PEG)-conjugated asparaginase Oncaspar(®) are characterized by an increase in elimination over time. The focus of our analysis is the better understanding of this time-dependency. METHODS: In paediatric acute lymphoblastic leukemia therapy (AIEOP-BFM ALL 2009), two administrations of Oncaspar(®) (2500 U/m(2) intravenously) in induction phase (14-day interval) and one single administration in reinduction were followed by weekly monitoring of asparaginase activity...
March 27, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28346428/autophagy-is-required-for-cell-survival-under-l-asparaginase-induced-metabolic-stress-in-acute-lymphoblastic-leukemia-cells
#18
H Takahashi, J Inoue, K Sakaguchi, M Takagi, S Mizutani, J Inazawa
L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase-treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345313/acute-hyperglycemia-associated-with-anti-cancer-medication
#19
REVIEW
Yul Hwangbo, Eun Kyung Lee
Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28340876/clinical-features-and-current-optimal-management-of-natural-killer-t-cell-lymphoma
#20
REVIEW
Shinichi Makita, Kensei Tobinai
Extranodal natural killer/T-cell lymphoma, nasal type (ENKL), is a rare subtype of non-Hodgkin lymphoma, and its treatment outcome was previously poor. Novel treatment strategies have improved the outcomes of ENKL remarkably in the last decade. Nowadays, patients with localized nasal ENKL are recommended treatment with concurrent chemoradiotherapy, and their 5-year overall survival rate is approximately 70%. In patients with advanced or relapsed/refractory disease, the efficacy of l-asparaginase-containing therapy has been confirmed...
April 2017: Hematology/oncology Clinics of North America
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