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l-asparaginase

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https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#1
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#2
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622171/reactions-to-cytostatic-agents-in-children
#3
Josefina R Cernadas
PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug...
June 14, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28621166/l-asparaginase-for-newly-diagnosed-extra-nodal-nk-t-cell-lymphoma-systematic-review-and-meta-analysis
#4
Vadim S Pokrovsky, Denis Vinnikov
OBJECTIVES: The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients. METHODS: The PRISMA protocol was used to search PubMed and Embase for both controlled and uncontrolled studies of ASP or alternative chemotherapy (CT) for newly diagnosed ENKTL, published in English by March 2017. The regimens were compared to calculate relative risk (RR) with 95% confidence interval (CI) of the overall response rate (ORR), complete response (CR) or partial response (PR)...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28596071/genetic-and-metabolic-engineering-approaches-for-the-production-and-delivery-of-l-asparaginases-an-overview
#5
REVIEW
Jalaja Vidya, Syed Sajitha, Mrudula Vasudevan Ushasree, Raveendran Sindhu, Parameswaran Binod, Aravind Madhavan, Ashok Pandey
L-asparaginase is one of the protein drugs for countering leukemia and lymphoma. A major challenge in the therapeutic potential of the enzyme is its immunogenicity, low-plasma half-life and glutaminase activity that are found to be the reasons for toxicities attributed to asparaginase therapy. For addressing these challenges, several research and developmental activities are going on throughout the world for an effective drug delivery for treatment of cancer. Hence there is an urgent need for the development of asparaginase with improved properties for efficient drug delivery...
May 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28588188/a-young-boy-with-l-asparaginase-induced-seizure
#6
M A Aziz, N K Singh, M H Rahman, M R Khan, A L Kabir, M Begum
L-Asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Seizures are uncommon symptoms. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events, completed in the department of Hematology of Bangabandhu Sheikh Mujib Medical University during March & April 2016...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28505420/immobilization-of-l-asparaginase-on-carrier-materials-a-comprehensive-review
#7
Ahmet Ulu, Burhan Ates
There are two major applications of l-asparaginase (L-ASNase): leukemia therapy and the food industry. Especially, its chemotherapeutic effect has attracted interest from the scientific community and 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 has not been written until now. In this review, we have thoroughly discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications...
June 21, 2017: Bioconjugate Chemistry
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/28424408/synthetic-lethality-of-glutaminolysis-inhibition-autophagy-inactivation-and-asparagine-depletion-in-colon-cancer
#9
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
#10
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/28416749/acute-lymphoblastic-leukemia-cells-are-sensitive-to-disturbances-in-protein-homeostasis-induced-by-proteasome-deubiquitinase-inhibition
#11
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/28410601/the-diagnosis-and-management-of-nk-t-cell-lymphomas
#12
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
#13
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
#14
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/28373755/peg-asparaginase-in-bfm-90-regimen-improves-outcomes-in-adults-with-newly-diagnosed-lymphoblastic-lymphoma
#15
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/28355969/incidence-of-asparaginase-related-hepatotoxicity-pancreatitis-and-thrombotic-events-in-adults-with-acute-lymphoblastic-leukemia-treated-with-a-pediatric-inspired-regimen
#16
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/28346428/autophagy-is-required-for-cell-survival-under-l-asparaginase-induced-metabolic-stress-in-acute-lymphoblastic-leukemia-cells
#17
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
#18
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
#19
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
https://www.readbyqxmd.com/read/28330312/isolation-and-screening-of-l-asparaginase-free-of-glutaminase-and-urease-from-fungal-sp
#20
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
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