• Korean Journal of Clinical Pharmacy
• /
• v.27 no.3
• /
• pp.143-149
• /
• 2017

Background: L-asparaginase (L-ASP) is a critical agent for the treatment of acute lymphoblastic leukemia and lymphoma, which is associated with serious toxicities including hypersensitivity, pancreatitis and thrombosis. Methods: To evaluate the toxicity of L-ASP in real clinical settings, we included the patients with L-ASP adverse drug reactions (ADRs) reported in a regional pharmacovigilance center of Seoul St. Mary's hospital from January 2014 to December 2015. Results: A total of 83 cases of L-ASP related ADRs were reported in 54 patients. Of these 83 cases, 65 cases (78.3%, 65/83) were spontaneously reported and 18 cases (21.7%, 18/83) were detected by further medical records review. Of the patients with ADRs, pediatric patients accounted for 83.3% of the cases (45/54) and median age was 9 years. The most common clinical manifestations of ADRs were hematology manifestations (31.3%, 26/83), followed by hepatobiliary manifestations (18.1%, 15/83). Thirty-four serious ADRs were reported in 19 patients. The sserious ADR group showed significantly longer hospitalization and higher rate of discontinuation of L-ASP than the non-serious ADR group (p = 0.005, 0.03). The most common clinical manifestations of serious ADRs were hepatobiliary manifestations (41.2%, 14/34). In total, 8 cases (9.6%, 8/83) of unlabeled ADRs were identified. They were serious ADRs. Conclusion: We identified unlabeled serious ADRs of L-ASP. Also, correlations were observed between serious ADRs and length of hospitalization, discontinuation rate respectively. Further investigations and developed spontaneous ADR reporting systems are needed to evaluate these correlations.

• Journal of Marine Life Science
• /
• v.7 no.2
• /
• pp.121-128
• /
• 2022

L-asparaginase (ASNase) is a therapeutic enzyme used to treat acute lymphoblastic leukemia. Currently, the most widely used ASNases are originated from bacteria. However, owing to the adverse effects of bacterial ASNases, new resources for ASNase production should be explored. Fungal enzymes are considered efficient and compatible resources of natural products for diverse applications. In particular, fungal species belonging to the genus Trichoderma are well-known producers of several commercial enzymes including cellulase, chitinase, and xylanase. However, enzyme production by marine-derived Trichoderma spp. remains to be elucidated. While screening for extracellular ASNase-producing fungi from marine environments, we found four strains showing extracellular ASNase activity. Based on the morphological and phylogenetic analyses using sequences of translation elongation factor 1-alpha (tef1α), the Trichoderma isolates were identified as T. afroharzianum, T. asperellem, T. citrinoviride, and Trichoderma sp. 1. All four strains showed different ASNase activities depending on the carbon sources. T. asperellem MABIK FU00000795 showed the highest ASNase value with lactose as a carbon source. Based on our findings, we propose that marine-derived Trichoderma spp. are potential candidates for novel ASNase production.

• YAKHAK HOEJI
• /
• v.39 no.2
• /
• pp.113-117
• /
• 1995

Garlic tissue cells are employed for the conversion of L-asparagine into ammonia. An ammonia gas electrode is used as a detector. The effect of pH, buffer solution, temperature and life time of electrode to have used were investigated in order to optimize the electrode response. The combination of L-asparaginase in garlic tissue cells and the gas electrode response linearly to Lasparagine over the concentration range 1.0$\times$10$^{-4}$~1.0$\times$10$^{-1}$ M with a slope of 72.0 mV/decade and is selective with respect to other L-amino acids.

• Journal of Plant Biology
• /
• v.32 no.4
• /
• pp.235-245
• /
• 1989

The contents and the compositions of total free amino acids were investigated in the rice(Oryza sativa L. cv. Chuncheong) seedlings under low temperatures. Activities of some enzymes associated with the markedly changed amino acid content were also investigaetd. Under low temperature, the contents of soluble protein and the total free amino acids increased, while the content of total nitrogen decreased. Although asparagine＋glycine were the most abundant amino acid speceis in the rice seedlings at the control temeprature, low temperature treatment for 3days brought about the decrease in their amount to about 60% level of the control plants. On the other hand, alanine showed the highest increase in the content among all the free amino acids, though glutamine, proline, asprtic acid, valine and tyrosine also increased after low temperature treatment. To eludicate the decrease of asparagine＋glycine level under low temperature, the activities of asparagine aminotransferase and asparaginase which metabolize asparagine were investigated in the rice seedlings under low temperature. The activity of asparaginase increased markedly, while that of asparagine aminotransferase decreased under low temperatures. Therefore, it was suggested that asparaginase metabolizes asparagine predominatly in the rice seedlings under low temperatures.

• Journal of Plant Biotechnology
• /
• v.29 no.2
• /
• pp.99-104
• /
• 2002

Suppression subtractive hybridization (SSH) was used to isolate wound-induced cDNAs from wounded soybean. One of low-temperature-inducible cDNA, slti182 showed high homology with genes encoding 1-asparaginase. The full length cDNA of slti182, deginated GmASP1, is 1258 bp long and contains an open reading frame consisted of 326 amino acids. CmASP1 protein showed the highest identity (84%) with putative asparaginase from A. thaliana (AB012247), but it showed only 55% identity with another isoform of A. tathaliana (Z34884). The expression of GmASP1 during low temperature stress started to increase 3 hours after treatment, reached the maximum at 6 hour, and then decreased to the initial level at 48 hours. The amount of GmASP1 transcripts increased again when low-temperature-treated plants were transferred to room temperature, The present study suggests that GmASP1 may function to accelerate the protein synthesis which is important in the early response to low temperature.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.11
• /
• pp.4515-4520
• /
• 2015

GELOX (gemcitabine, oxaliplatin and L-asparaginase) regimen showed an impressive result in our previous study, but the effect of this new regimen is still dissatisfying for some patients, so it is necessary to identify which patients will benefit from this regimen. A total of fifty-one cases with nasal natural killer/T-cell lymphoma receiving initial GELOX chemotherapy were enrolled in this study. The ki-67 expression detected by immunohistochemistry (IHC) in the specimens ranged from 10% to 90%, with a median value of 70%, so cases higher than the median value (${\geq}70%$) were defined as high ki-67 expression, and the others were designated as low ki-67 expression. The response rate had no statistical difference between low ki-67 expression group and high ki-67 expression group (P=0.291) though the value in the former group was relatively high. After a median follow-up of 18.03 months, the 3-year progression-free survival (PFS) for patients with low ki-67 expression was significantly higher than those with high ki-67 expression (83.8% vs. 47.9%, P=0.038). In the stage I/II subgroup, 3-year PFS and overall survival (OS) were statistically higher in the patients with low ki-67 expression than those with high ki-67 expression. Multivariate analysis revealed high ki-67 expression was an independent prognostic factor for PFS. These results suggest that low ki-67 expression can predict a good response of GELOX in these patients, and the combination of ki-67 expression and early stage is helpful to identify an excellent prognosis subgroup from patients receiving GELOX in this disease.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.7
• /
• pp.3155-3160
• /
• 2016

Background: L-asparaginase (ASNase) is commonly used in the treatment of acute lymphoblastic leukemia (ALL) and natural killer (NK)/T-cell lymphoma. This study was designed to describe the incidence of toxicity associated with ASNase in Asian adults. Secondary objectives were to investigate the management and impact of toxicity on subsequent ASNase use, and to compare the actual management against current recommendations. Materials and Methods: In this retrospective, multi-center, observational study, Asian patients ${\geq}18$ years old who received ${\geq}1$ dose of the native E. coli ASNase from 2008 to 2013 were included. Patients were excluded if they did not receive ASNase. Endpoints of this study were development of specific toxicities, whether ASNase was discontinued or re-challenged, and developmentg of recurrent toxicity. All data analyses were performed using SPSS version 20.0. Results: A total of 56 patients were analyzed. Mean (${\pm}SD$) age was 36.2 (${\pm}15.2$) years old, with 62.5% being males, 55.4% with ALL and 28.6% with NK/T-cell lymphoma. Hypersensitivity (12.5%) was associated with the highest incidence of toxicity (6 out of 7 patients had Grade 3 and 4 toxicity), followed by 10.7% for hepatic transaminitis, 3.6% for non-CNS thrombosis and 1.8% each for hyperbilirubinemia and pancreatitis. Hypersensitivity recurred in the 3 patients who were re-challenged with E. coli ASNase. Conclusions: ASNase is associated with a wide range of toxicities, with hypersensitivity being the most commonly observed among Asian adult patients.

• Proceedings of the Korean Society of Life Science Conference
• /
• 2007.10a
• /
• pp.110.2-110.2
• /
• 2007

See Full Text

• Journal of the korean veterinary medical association
• /
• v.24 no.1
• /
• pp.25-29
• /
• 1988

An attempt to treat canine lymphosarcoma with the combination chemotherapy protocol consisting of cyclophosphamide, vincristine, L-asparaginase and methotrexate was made for 3 weeks. The chemotherapy to the patient showed good responses such as better cha

• Proceedings of the Korean Society of Crop Science Conference
• /
• 2002.10a
• /
• pp.46-46
• /
• 2002