Adult ; Asparaginase ; Humans ; Hypertriglyceridemia

The aim of this work was to study radiation and the effects of temperature on conductivity properties of polyvinyl alcohol (PVA)-based potassium hydroxide (KOH) and propylene carbonate (PC), where the ionic conduction preferentially occurs in the amorphous phase by free radicals ions through gamma-irradiation. Alkaline composite polymer electrolyte (ACPE) consisting of PVA, KOH and PC of different concentration ratios were prepared by solvent-casting technique. The ACPE were irradiated with different doses from 5 kGy up to 200 kGy. The conductivity properties of the electrolyte films were measured at different frequencies in the range 20 Hz to 1 MHz using LCR meter. The results showed that the conductivity properties were dependent on the radiation dose, temperature and the concentration of the polymer blends.
Radiation ; asparaginase/prednisone/vincristine ; Personal Computers ; Temperature ; Concentration

PURPOSE: L-asparaginase is a crucial chemotherapeutic agent for the treatment of acute lymphoblastic leukemia. However, hypersensitivity to L-asparaginase is common which limits its clinical use. METHODS: We performed 44 cases of premedication and 3 cases of desensitization in 16 patients with hypersensitivity to L-asparaginase. RESULTS: With premedication, 33 cases completed L-asparaginase injection with no hypersensitivity reactions. Eleven cases showed mild hypersensitivity reactions, such as urticaria. Desensitization was performed in 3 cases: in 2 cases, desensitization was successful, and in 1 case the medication was switched to Erwinia asparaginase. CONCLUSION: Premedication and desensitization appear to be useful in helping patients receive desired doses of L-asparaginase in pediatric patients with acute lymphoblastic leukemia.
Asparaginase ; Desensitization, Immunologic ; Drug Hypersensitivity ; Erwinia ; Humans ; Hypersensitivity* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Premedication* ; Urticaria

Objective: To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience. Methods: Clinical data of patients who received chemotherapy including pegaspargase in the Department of Hematology of Beijing Tongren hospital during August 2011 to December 2015 were retrospective analyzed, and the adverse effects of pegaspargase and the management experience was summarized. Results: A total of 129 patients with 443 times of pegaspargase used during this period. The common adverse reactions included allergic reactions in 2 cases (1.6%), acute pancreatitis in 19 (14.7%) including 6 acute symptomatic pancreatitis and 13 chemical pancreatitis with elevated pancreatin, hypertriglyceridemia in 15 cases(11.6%), hyperglycemia in 85 (65.9%), hypoglycemia in 7 (5.4%), elevated aminotransferase in 25 (19.4%), hyperbilirubinemia in 21 (15.5%), hypoalbuminemia in 62 (48.1%), prolonged APTT in 61 (47.3%), prolonged PT in 22 (17.1%), prolonged TT in 15 (11.6%), hypofibrinogen in 75 (58.1%), thrombus in 11 (8.5%) and bleeding in 3 (2.3%). The above adverse reactions were improved by symptomatic treatment of anti allergy, inhibition of secretion of pancreatic juice, lipid lowering, hypoglycemic, liver preservation, supplementation of plasma and hemostasis, respectively. Some serious adverse reactions affected the application of pegaspargase, even lead to discontinuation of the aspartate. Conclusion: Though adverse effects associated with pegaspargase are extensive, most patients can successfully complete the chemotherapy containing the pegaspargase with close monitoring and timely treatment.
Asparaginase/metabolism* ; Humans ; Polyethylene Glycols/metabolism* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies

OBJECTIVE: To investigate the effects and its potential mechanism of asparaginase on proliferation, cell cycle and apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines. METHODS: CCK-8 assay was used to detect the effect of asparaginase on proliferation of DLBCL cell lines. Flow cytometry was used to analyze cell cycle and apoptosis. Western blot was used to analyze apoptosis and its potential mechanism. RESULTS: Asparaginase obviously inhibited the proliferation of multiple DLBCL cell lines and caused G/G cell arrest. Furtherly, asparaginase inhibited the expression of HIF-1α which related to poor prognosis of patients with DLBCL, up-regulated the expression of DR4 and caspase 8, reduce the expression of c-FLIP. Meanwhile, asparaginase induced the expression of pro-apoptotic protein BAX and inhibited the expression of anti-apoptotic protein MCL-1. CONCLUSION Asparaginase can inhibit the proliferation of DLBCL cell lines, cause the arrest of cells in G/G and induce apoptosis via the endogenous and exogenous apoptotic pathways.
Apoptosis ; Asparaginase ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lymphoma, Large B-Cell, Diffuse

PURPOSE: The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL). MATERIALS AND METHODS: A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups. RESULTS: The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067). CONCLUSION: IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.
Ambulatory Care Facilities ; Asparaginase* ; Escherichia coli* ; Escherichia* ; Etoposide* ; Humans ; Ifosfamide* ; Length of Stay ; Lymphoma* ; Methotrexate* ; Prednisolone* ; Seoul

Objective: To investigate the clinical characteristics and treatment of pancreatic pseudocyst after pegaspargase treatment in children. Methods: The clinical data of 6 children with pancreatic pseudocyst after pegaspargase treatment in the Department of Pediatrics in Peking University Third Hospital from July 2018 to February 2021 were analyzed retrospectively. Results: There were 4 males and 2 females, and their age of onset was 9.5 (5.8, 13.0) years. The total number of pegaspargase applications was 2.5 (2.0, 3.5) times. The course from the last dose of pegaspargase to the onset of pancreatitis was 11.0 (9.0, 17.2) days, and 42.5 (35.0, 129.5) days from the onset of pancreatitis to the diagnosis of pancreatic pseudocyst. Abdominal pain was the most prominent manifestation of pancreatitis (6/6). All of the 6 children were asymptomatic when pancreatic pseudocyst was noted, and were treated conservatively at first, but one case later developed intermittent abdominal distension or nausea after eating. All the cases had pancreatic pseudocyst enlargement during the conservative treatment. Three children were treated with endoscopic ultrasound-guided transgastric drainage, and the cyst disappeared from 10 days to 4 months after the operation. The other 3 children received endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage, but one of them turned to surgery due to pancreatic duct stricture, and in the rest 2 children the cyst disappeared at 1 and 3 months after operation respectively. Regarding safety issues, 1 child who received ERCP-guided transpapillary drainage had acute postoperative pancreatitis, which were improved after treatment, and the other 5 had no complications. Conclusions: Pancreatic pseudocyst after pegaspargase chemotherapy can be asymptomatic in the early stage, and should be diagnosed with a history of pegaspargase treatment and timely imaging examination. Conservative treatment is the first choice for asymptomatic pseudocyst. When the pseudocyst enlarges, different endoscopic drainage treatments are required according to whether the pseudocyst is connected with the main pancreatic duct.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Asparaginase ; Polyethylene Glycols/adverse effects* ; Pancreatitis

L-asparaginase hydrolyzes L-asparagine to produce L-aspartic acid and ammonia. It is widely distributed in microorganisms, plants and serum of some rodents, and has important applications in the pharmaceutical and food industries. However, the poor thermal stability, low catalytic efficiency and low yield hampered the further application of L-asparaginase. In this paper, rational design and 5' untranslated region (5'UTR) design strategies were used to increase the specific enzyme activity and protein expression of L-asparaginase derived from Rhizomucor miehei (RmAsnase). The results showed that among the six mutants constructed through homology modeling combined with sequence alignment, the specific enzyme activity of the mutant A344E was 1.5 times higher than the wild type. Subsequently, a food-safe strain Bacillus subtilis 168/pMA5-A344E was constructed, and the UTR strategy was used for the construction of recombinant strain B. subtilis 168/pMA5 UTR-A344E. The enzyme activity of B. subtilis 168/pMA5 UTR-A344E was 7.2 times higher than that of B. subtilis 168/pMA5-A344E. The recombinant strain B. subtilis 168/pMA5 UTR-A344E was scaled up in 5 L fermenter, and the final yield of L-asparaginase was 489.1 U/mL, showing great potential for industrial application.
Asparaginase/genetics* ; Bacillus subtilis/genetics* ; Industrial Microbiology ; Protein Engineering ; Rhizomucor/enzymology* ; Sequence Alignment

NK/T cell lymphoma (NKTCL) is a rare type of non-Hodgkin's lymphoma, occurs more frequently in Asia and Latin America. In China, NKTCL accounts for 30.1% in T-NHL and is highly related with EBV (Epstein-Barr virus) infection. This disease is highly aggressive, not sensitive to chemotherapy, with poor prognosis. The mean survival time is about 12-38 months. It is important to accurately assess the patient's stage of progression for an optimal treatment. For stageI-II, the combined chemotherapy and radiotherapy have better therapeutic effects. As for stage III-IV NKTCL, especially for non-nasal and aggressive subtypes, the chemotherapy is the main treatment method. For advanced disease, combining therapy is the most commonly selected approach, such as high-intensity chemotherapy combined with radiation and a regimen containing L-asparaginase (L-Asp) will benefit to patients. Recently, some studies have demonstrated that promising outcomes have been found in selected cases by high-dose chemotherapy supplemented with auto-or allo-HSCT. Targeting therapy is also an optimal choice. This review mainly focuses on the advance of treatment for NKTCL.
Asparaginase ; China ; Herpesvirus 4, Human ; Humans ; Killer Cells, Natural ; Lymphoma, T-Cell ; diagnosis ; therapy ; Prognosis

This study was purposed to compare the anti-leukemic effects of E.coli-L-Asp and Erwinia-L-Asp in vitro, and to investigate their mechanism. The cell apoptosis and proliferation inhibition rate were measured by CCK-8 kit, and IC50 of two drugs was calculated by using SPSS software. Pro-apoptosis effect of E.coli-L-Asp and Erwinia-L-Asp on REH and Jurkat cell lines was also determined by flow cytometry with Annexin V/PI double staining. Concentration changes of 4 amino acids (Asn, Aspa, Gln, and Glu) before and after medication were detected by using high pressure liquid chromatography (HPLC) assay. The results showed that both REH and Jurkat cell lines were sensitive to L-Asp drugs from two different strains, and E.coli-L-Asp and Erwinia-L-Asp displayed the inhibition effect on the proliferation of Jurkat and REH cell lines in dose-dependent and time-dependent manners. The inhibition cell of proliferation and cell apoptosis in Erwinia-L-Asp group were higher than those in E.coli-L-Asp group after 24 hours (P < 0.05) . However, after treatment of REN and Jurkat cells with 2 kind of L-Asp for 48 hours, the inhibition of cell proliferation and apoptosis rates were not significantly different between the 2 L-Asp drugs (P > 0.05). The Asn in medium could be depleted by two different L-Asp drugs with low concentration. Both the two L-Asp drugs had the same capability to deplete the Asn surrounding leukemia cells (P > 0.05). The Gln in medium could be depleted by two L-Asp drugs with high concentration. The hydrolysis effect of Erwinia-L-Asp on Gln was stronger than that of E.coli-L-Asp (P < 0.05). It is concluded that in a certain range of concentrations, E.coli-L-Asp and Erwinia-L-Asp exert anti-leukemia effect in dose-dependent manner. Depletion of Gln and Asn in surrounding environment and induction of cell apoptosis are two potential mechanisms, by which leukemia cells can be killed. Erwinia-L-Asp may be chosen as the first-line drug to treat childhood ALL for its fast action and stronger hydrolysis effect on Gln.
Apoptosis ; drug effects ; Asparaginase ; pharmacology ; Cell Proliferation ; drug effects ; Flow Cytometry ; Humans ; Jurkat Cells