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A Review on L-Asparaginase
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Asparaginase is recently engaged in the treatment of acute lymphoblastic leukemia. Due to a lack of capability of synthesizing L-asparagine, an essential amino acid, the tumor cells starve for exogenous asparagine and ultimately will be forced to die (Gurung et al., 2013).
Marine Algal Secondary Metabolites Are a Potential Pharmaceutical Resource for Human Society Developments
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Somasundaram Ambiga, Raja Suja Pandian, Lazarus Vijune Lawrence, Arjun Pandian, Ramu Arun Kumar, Bakrudeen Ali Ahmed Abdul
Almelysin, a new metalloproteinase with significant efficiency in low temperatures, is also other proteinase isolated from the culture filtrate of Alteromonas sp. The metalloprotease secreted by Alteromonas sp. is essential in the strain’s chitin degradation pathway. Aeromonas salmonicida subsp. has been found as a protamine-reducing marine bacterium obtained from marine soil. Extremophile hydrolases have benefits over chemical biocatalysts. These catalysts are non- polluting, environmentally acceptable, extremely specific, and occur in mild reaction circumstances. Such hydrolases may activate in the form of organic liquids, which is crucial for the production of single-isomer chiral medicines. These hydrolases have been used in a variety of ways. L-asparaginase is a hydrolase which produces L-aspartic and ammonia from L-asparagine. L-glutaminase activities is also present in this enzyme. Antileukemia/antilymphoma drugs made from microbial L-asparaginase preparations for biomedical applications presently account for one-third of global demand. L-asparaginases have been widely utilized in children particularly its act as chemotherapy for acute lymphoblastic leukemia, which is considerably greater than various therapeutic enzymes. L-asparaginase has been treated as an anti-tumor therapy in non-lymphoma, bovine lymphoma sarcoma, chronic lymphocytic leukemia Hodgkin’s pancreatic carcinoma, lymphosarcoma, lymphosarcoma, reticulum sarcoma, acute myelomonocytic leukemia, melanoma sarcoma and acute myelocytic leukemia.
Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No studies are published about use of asparaginase drug during the first trimester of pregnancy. Pancytopenia was associated with asparaginase treatment during the second and third trimesters. It is classified as FDA fetal risk category C under the old system, and is not yet classified in the new FDA system. No reports of asparaginase monotherapy are published. No birth defects were reported among seven infants whose mothers took L-asparaginase as part of polydrug therapy regimen for leukemia (Caliguri and Mayer, 1989). It is important to note that none was exposed to the drug during the first trimester.
Broad Anti-Cancer Activity Produced by Targeted Nutrients Deprivation (TND) of Multiple Non-Essential Amino Acids
Published in Nutrition and Cancer, 2022
Zehui Li, Shuang Zhou, Xiaodong Yang, Xiyan Li, Grace Xiaolu Yang, John Chant, Michael Snyder, Xin Wang
As mentioned previously, multiple studies lend support to the notion that amino acid deprivation might be a promising therapeutic approach in certain tumor types. In humans, injected asparaginase to reduce asparagine levels in the bloodstream is used for the treatment of ALL (Egler, Ahuja et al. 2016). Small molecule inhibitor-based approaches are also being taken to interrupt amino acid metabolism. CB-839, a small molecule glutaminase inhibitor, prolonged progression free survival when combined with everolimus in a Phase II clinical trial for the treatment of renal cell carcinoma (27, 28). The glutaminase inhibitor blocks the conversion of glutamine to glutamic acid, thereby preventing cells from utilizing glutamine as an alternate energy source to glucose under metabolic stress conditions.
Novel systemic treatment approaches for metastatic pancreatic cancer
Published in Expert Opinion on Investigational Drugs, 2022
Klara Dorman, Volker Heinemann, Sebastian Kobold, Michael von Bergwelt-Baildon, Stefan Boeck
The chemotherapeutic drug asparaginase hydrolyzes asparagine to aspartic acid and ammonia, this way depriving cells of circulating asparagine, an amino acid important for cell growth and proliferation. Most cells are able to produce asparagine themselves through the asparagine synthetase (ASNS), however tumors with low ASNS expression, such as PDAC, might benefit from asparaginase therapy [34]. Despite the effectiveness of asparaginase as a chemotherapeutic treatment in acute lymphoblastic leukemia, associated toxicities such as hepatotoxicity, pancreatitis, thrombosis and hypersensitivity limit the broader use [34,35]. Encapsulating asparaginase within erythrocytes (eryaspase) leads to prolonged half-life and good tolerability of the drug. A randomized phase IIb trial showed that eryaspase combined with gemcitabine or mFOLFOX-6 was associated with improved overall survival and progression-free survival, warranting further investigation in the currently ongoing phase III trial Trybeca-1 as a second-line therapy (NCT03665441, Table 1) [36] as well as a phase I trial combining eryaspase with FOLFIRINOX in a first-line setting (NCT04292743)
Lipid Apheresis to Manage Severe Hypertriglyceridemia during Induction Therapy in a Child with Acute Lymphoblastic Leukemia
Published in Pediatric Hematology and Oncology, 2020
Christina Mayerhofer, Carsten Speckmann, Friedrich Kapp, Ulrike Teufel-Schäfer, Wolfram Kluwe, Johanna Schneider, Christian Flotho
Asparaginase is widely used in induction and intensification protocols for the treatment of acute lymphoblastic leukemia (ALL) in children. While asparaginase clearly improves the leukemia-free survival of children with ALL, known adverse effects are hypersensitivity reaction, pancreatitis, liver damage, coagulation anomalies, thromboembolism and hyperglycemia. Hypertriglyceridemia is a rare side effect of asparaginase in combination with glucocorticoids in ALL therapy.1,2 No specific guidelines are available for the management of this complication. Here, we report a case of acute severe hypertriglyceridemia in a child during ALL induction therapy which was successfully treated by lipid apheresis. We review the literature on the management of hypertriglyceridemia occurring in children during polychemotherapy for ALL.