- Hyperglycemia and Other Glycemic Measures Throughout Therapy for Pediatric Acute Lymphoblastic Leukemia and Lymphoma. [Journal Article]J Pediatr Hematol Oncol. 2023 Jan 12 [Online ahead of print]JP
- Transient hyperglycemia during induction chemotherapy is associated with increased morbidity and mortality in patients with acute lymphoblastic leukemia (ALL). Treatment with glucocorticoids, asparaginase, and stress are the proposed causal factors. Although these risks are not exclusive to induction, glycemic control throughout the remainder of ALL/lymphoma (ALL/ALLy) therapy has not been descri…
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- Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion: A case report. [Case Reports]
- CONCLUSIONS: Clinicians should enhance their understanding of NKTCL. Some key factors, including EUS characteristics, the right choice of FNB needle, and combination with MFCI, are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.
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- Expression of Long Non-Coding RNA H19 in Acute Lymphoblastic Leukemia. [Journal Article]
- CONCLUSIONS: Our findings suggest that H19 may have an important role in pathogenesis in ALL and may act as a promising and potential therapeutic target.
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- Hybrid Silica-Coated PLGA Nanoparticles for Enhanced Enzyme-Based Therapeutics. [Journal Article]
- Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and bi…
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- A rational approach for 3D recognition and removal of L-asparagine via molecularly imprinted membranes. [Journal Article]J Pharm Biomed Anal. 2023 Jan 14; 226:115250.JP
- In this study, a L-asparagine (L-Asn) imprinted membranes (L-Asn-MIPs) were synthesized via molecular imprinting for selective and efficient removal of L-Asn. The L-Asn-MIP membrane was prepared by using acrylamide (AAm) and hydroxyethyl methacrylate (HEMA) as a functional monomer and a comonomer, respectively. The membrane was characterized by scanning electron microscopy (SEM) and Fourier Trans…
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- Drugs and Lactation Database (LactMed): Pegaspargase [BOOK]Drugs and Lactation Database (LactMed). National Library of Medicine (US): Bethesda (MD)BOOK
- No information is available on the clinical use of pegaspargase during breastfeeding. . Because pegaspargase is a large protein molecule with a molecular weight of about 140,000 Da, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant's gastrointestinal tract. However, the manufacturer recommends that the drug not be used during bre…
- An acute lymphoblastic leukemia cell-based preclinical assay revealed functional differences between commercial brands of L-asparaginase administered in Colombia. [Journal Article]Pediatr Blood Cancer. 2023 Jan 12 [Online ahead of print]PB
- CONCLUSIONS: Differences found between the therapeutic formulations of L-ASNase distributed in Colombia raise concerns about the quality of the treatment administered to patients in low- and middle-income countries. Therefore, we recommend a preclinical evaluation of formulations of L-ASNase in order to prevent therapeutical impacts on the outcome of ALL patients.
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- Symptomatic hyperammonemia secondary to recombinant Erwinia asparaginase. [Editorial]Pediatr Blood Cancer. 2023 Jan 12 [Online ahead of print]PB
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- Effect of nutritional parameters on microbial production of L-Asparaginase by novel Brevibacillus borstelensis ML12. [Journal Article]Prep Biochem Biotechnol. 2023 Jan 10 [Online ahead of print]PB
- L-Asparaginase owes considerable significance in food and pharmaceutical applications. L-Asparaginase is an antineoplastic enzyme that finds application in the treatment of Acute Lymphoblastic Leukemia (ALL) and in mitigating acrylamide (a potent carcinogen) production during baking. In this study, we aimed to optimize nutritional parameters that are significant in initiating and regulating a bio…
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- Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics. [Review]
- Cancer is a heterogeneous disease characterized by various genetic and phenotypic aberrations. Cancer cells undergo genetic modifications that promote their proliferation, survival, and dissemination as the disease progresses. The unabated proliferation of cancer cells incurs an enormous energy demand that is supplied by metabolic reprogramming. Cancer cells undergo metabolic alterations to provi…
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- Asparaginyl endopeptidase contributes to cetuximab resistance via MEK/ERK signaling in RAS wide-type metastatic colorectal cancer. [Journal Article]Clin Transl Oncol. 2023 Jan 07 [Online ahead of print]CT
- CONCLUSIONS: The higher expression of AEP could contribute to the shorter PFS of cetuximab treatment in mCRC. The reason might be that AEP could promote the phosphorylation of MEK/ERK protein in the downstream signal pathway of EGFR.
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- Production, characterization and techno-economic evaluation of Aspergillus fusant L-asparaginase. [Journal Article]
- Protoplast fusion is one of the most reliable methods of introducing desirable traits into industrially-promising fungal strains. It harnesses the entire genomic repertoire of fusing microorganisms by routing the natural barrier and genetic incompatibility between them. In the present study, the axenic culture of a thermo-halotolerant strain of Aspergillus candidus (Asp-C) produced an anti-leukem…
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- Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response. [Journal Article]
- Contemporary chemotherapy for childhood acute lymphoblastic leukemia (ALL) is risk-adapted based on clinical features, leukemia genomics and minimal residual disease (MRD); however, the pharmacological basis of these prognostic variables remains unclear. Analyzing samples from 805 children with newly diagnosed ALL from three consecutive clinical trials, we determined the ex vivo sensitivity of pr…
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- Phenotypic Characterization and Identification of Potential L-Asparaginase-Producing Thermohalophilic Bacteria from Wawolesea Hot Spring, North Konawe, Southeast Sulawesi, Indonesia. [Journal Article]Pak J Biol Sci. 2022 Jan; 25(11):1021-1032.PJ
- <b>Background and Objective:</b> L-asparaginase-producing thermohalophilic bacteria have the potential of producing an enzyme tolerant to high heat and salt levels. This enzyme, L-asparaginase, can be used as a biological agent for the cancer therapy of acute lymphoblastic leukemia and melanosarcoma as it has a specific ability to inhibit the formation of nutrients for cancer cells. T…
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- Top advances of the year: Leukemia. [Journal Article]Cancer. 2022 Dec 30 [Online ahead of print]C
- In the year 2021, there were three new Food and Drug Administration approvals for all leukemia types: asciminib (Scemblix) for chronic myeloid leukemia, brexucabtagene autoleucel (Tecartus) for relapsed/refractory B-cell acute lymphocytic leukemia, and asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) for acute lymphocytic leukemia. This is down from 2017-2018 when eight new therapies…
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- A scoping review to compare and contrast quality assurance aspects of l-asparaginase biosimilars. [Review]Int J Pharm. 2022 Dec 26; 632:122523.IJ
- l-asparaginase is a first-line medicine used for the treatment of acute lymphoblastic leukemia. Differing quality of marketed l-asparaginase biosimilars has been reported to adversely influence treatment outcomes. Herein, the quality of l-asparaginase biosimilars intended for clinical use was reviewed in sight of quality assurance parameters using English and Chinese language database searching, …
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- Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia. [Journal Article]JAMA Netw Open. 2022 12 01; 5(12):e2248803.JN
- CONCLUSIONS: These results suggest a strong genetic basis for interpatient variability in hyperbilirubinemia and aminotransferase level elevations during leukemia chemotherapy.
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- Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine. [Journal Article]
- The impact of asparaginases on plasma asparagine and glutamine is well established. However, the effect of asparaginases, particularly those derived from Erwinia chrysanthemi (also called crisantaspase), on circulating levels of other amino acids is unknown. We examined comprehensive plasma amino acid panel measurements in healthy immunodeficient/immunocompetent mice as well as in preclinical mou…
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- ASRGL1 downregulation suppresses hepatocellular carcinoma tumorigenesis in a CDK1-dependent manner. [Journal Article]Dig Liver Dis. 2022 Dec 24 [Online ahead of print]DL
- The asparaginase-like protein 1 (ASRGL1) catalyzes the hydrolysis of L-asparagine to L-aspartic acid and ammonia. Emerging evidences have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear. Here, we explored anti-tumor activity and fundamental mechanisms of ASRGL1 blo…
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- Protein re-surfacing of E. coli L-Asparaginase to evade pre-existing anti-drug antibodies and hypersensitivity responses. [Journal Article]
- The optimal use of many biotherapeutics is restricted by Anti-drug antibodies (ADAs) and hypersensitivity responses which can affect potency and ability to administer a treatment. Here we demonstrate that Re-surfacing can be utilized as a generalizable approach to engineer proteins with extensive surface residue modifications in order to avoid binding by pre-existing ADAs. This technique was appl…
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- Apoptosis induction in leukemic cells by L-asparaginase preparation from Bacillus indicus: bench-scale production, purification and therapeutic application. [Journal Article]
- With the emergence of multiple side effects on the usage of commercial L-asparaginase formulations, keen interest is provoked to investigate new sources of L-asparaginases that possess antileukemic properties with minimal side effects. The present study reports the cost-effective bench-scale production, homogeneity purification and apoptosis induction potential of a new L-asparaginase preparation…
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- Characterization, Anti-proliferative Activity, and Bench-Scale Production of Novel pH-Stable and Thermotolerant L-Asparaginase from Bacillus licheniformis PPD37. [Journal Article]Appl Biochem Biotechnol. 2022 Dec 24 [Online ahead of print]AB
- Bacterial L-asparaginase (LA) is a chemotherapeutic drug that has remained mainstay of cancer treatment for several decades. LA has been extensively used worldwide for the treatment of acute lymphoblastic leukemia (ALL). A halotolerant bacterial strain Bacillus licheniformis sp. isolated from marine environment was used for LA production. The enzyme produced was subjected to purification and phys…
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- Enhancing CHO cell productivity through a dual selection system using Aspg and Gs in glutamine free medium. [Journal Article]Biotechnol Bioeng. 2022 Dec 23 [Online ahead of print]BB
- The dominant method for generating Chinese hamster ovary (CHO) cell lines that produce high titers of biotherapeutic proteins utilizes selectable markers such as dihydrofolate reductase (Dhfr) or glutamine synthetase (Gs), alongside inhibitory compounds like methotrexate or methionine sulfoximine, respectively. Recent work has shown the importance of asparaginase (Aspg) for growth in media lackin…
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- Post-refolding stability considerations for optimization of in-vitro refolding: L-asparaginase as a case study. [Journal Article]Biotechnol J. 2022 Dec 18 [Online ahead of print]BJ
- CONCLUSIONS: The current study elucidates how process intermediate stability needs to be given due consideration during process optimization, particularly for products such as L-asparaginase which are labile.
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- Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies. [Journal Article]
- Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained challenging. Here, we utilise clonal transcriptomics with WILD-seq; Wholistic Interrogation of Lineage Dynamics by sequencing, in mouse models of triple…
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- Escalated doses of methotrexate and L-asparaginase in critically ill children with a concurrent diagnosis of acute lymphoblastic leukemia and appendicitis. [Letter]Pediatr Blood Cancer. 2022 Dec 15 [Online ahead of print]PB
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- Efficacy and safety of PD-1 inhibitor alone or combined with chemotherapy in patients with relapsed or refractory extranodal natural Killer/T cell lymphoma: A retrospective study. [Journal Article]Hematol Oncol. 2022 Dec 14 [Online ahead of print]HO
- Extranodal natural killer/T cell lymphoma (ENKTL) patients typically face a grim prognosis after relapse or progression following asparaginase-based chemotherapy. Currently, programmed cell death protein-1 (PD-1) immune checkpoint blockade has shown promising efficacy as an optimal regimen for relapsed or refractory ENKTL (rrENKTL) patients. This study retrospectively investigated the efficacy, s…
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- Successful bridging to cell therapy for relapsed/refractory acute lymphoblastic leukaemia with a combination of venetoclax and PEG-asparaginase. [Letter]Br J Haematol. 2022 Dec 05 [Online ahead of print]BJ
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- Elucidation of the Reaction Mechanism of Cavia porcellus l-Asparaginase: A QM/MM Study. [Journal Article]J Chem Inf Model. 2023 Jan 09; 63(1):270-280.JC
- The l-asparaginase (l-ASNase) enzyme catalyzes the conversion of the non-essential amino acid l-asparagine into l-aspartic acid and ammonia. Importantly, the l-ASNases are used as a key part of the treatment of acute lymphoblastic leukemia (ALL); however, despite their benefits, they trigger severe side effects because they have their origin in bacterial species (Escherichia coli and Erwinia chry…
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- Feasibility of low-dose radiotherapy for patients with stage I/II extranodal NK-/T-cell lymphoma, nasal type achieving complete response after l-asparaginase-containing chemotherapy. [Journal Article]
- CONCLUSIONS: Achieving CR after chemotherapy was the most predictive factor of survival outcomes in early-stage ENKTCL-NT. Decreasing RT doses in patients with CR after l-ASP appeared to minimize the occurrence of AE without compromising LRR risk; however, longer follow-ups and cautious application are warranted.
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