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

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

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

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

This study was purposed to explore the relationship between asparagine synthetase (AsnS) mRNA expression level and the sensitivity of leukemic cell lines to L-asparaginase. The AsnS mRNA expression level in 8 cell lines (Jurkat, HL-60, U937, NB4, THP-1, Namalwa, Karpas299 and K562) was determined by real-time quantitative PCR (RQ-PCR) based on fluorescence dye Eva Green before and after treatment with L-Asp, and the cell proliferation rates were analyzed by CCK-8 assay. The results showed that there was a significant disparity of AsnS expression level in 8 cell lines, and there were significant increases of AsnS expression level in cells co-cultured with L-Asp (p < 0.05). Of all these eight cell lines, cells sensitive to L-asparaginase had lower AsnS expression level and cells resistant to L-asparaginase had higher AsnS expression. U937 which was the most sensitive to L-asparaginase had the lowest AsnS expression level, while K562 was natural resistant to L-asparaginase and possessed of the highest AsnS level. It is concluded that the AsnS plays a critical role in regulating cellular biological behavior after depletion of asparagine, the AsnS mRNA expression level in cells reflects the sensitivity of cells to L-Asp. The results may imply the possibility for the use of L-asparaginase in leukemia with lower AsnS expression level.
Asparaginase ; metabolism ; pharmacology ; Aspartate-Ammonia Ligase ; metabolism ; Cell Line, Tumor ; Humans ; Leukemia ; enzymology

Apoptosis ; drug effects ; Asparaginase ; pharmacology ; HL-60 Cells ; Humans ; K562 Cells ; U937 Cells

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 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

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