دورية أكاديمية
Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion
| العنوان: | Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion |
|---|---|
| المؤلفون: | Bishop, Eleanor, Dimitrova, Monika, Froggatt, Alexander, Estevez-Cebrero, Maria, Storer, Lisa C. D., Mussai, Francis, Paine, Simon, Grundy, Richard G., Dandapani, Madhumita |
| المساهمون: | Prodam, Flavia |
| بيانات النشر: | Hindawi Limited |
| سنة النشر: | 2022 |
| المجموعة: | University of Nottingham: Repository@Nottingham |
| مصطلحات موضوعية: | General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine |
| الوصف: | Despite significant improvements in treatment and survival in paediatric cancers, outcomes for children with brain tumours remain poor. Novel therapeutic approaches are needed to improve survival and quality of survival. Extracellular arginine dependency (auxotrophy) has been recognised in several tumours as a potential therapeutic target. This dependency is due to the inability of cancer cells to recycle or synthesise intracellular arginine through the urea cycle pathway compared to normal cells. Whilst adult glioblastoma exhibits this dependency, the expression of the arginine pathway enzymes has not been delineated in paediatric brain tumours. We used immunohistochemical (IHC) methods to stain for arginine pathway enzymes in paediatric high-grade glioma (pHGG), low-grade glioma (pLGG), ependymoma (EPN), and medulloblastoma (MB) tumour tissue microarrays (TMAs). The antibodies detected protein expression of the metaboliser arginase (Arg1 and Arg2); recycling enzymes ornithine transcarbamoylase (OTC), argininosuccinate synthetase (ASS1), and argininosuccinate lyase (ASL); and the transporter SLC7A1. Deficiency of OTC, ASS1, and ASL was seen in 87.5%, 94%, and 79% of pHGG samples, respectively, consistent with an auxotrophic signature. Similar result was obtained in pLGG with 96%, 93%, and 91% of tumours being deficient in ASL, ASS1, and OTC, respectively. 79%, 88%, and 85% of MB cases were ASL, ASS1, and OTC deficient whilst ASL and OTC were deficient in 57% and 91% of EPN samples. All tumour types highly expressed SLC7A1 and Arginase, with Arg2 being the main isoform, demonstrating that they could transport and utilise arginine. Our results show that pHGG, pLGG, EPN, and MB demonstrate arginine auxotrophy based on protein expression and are likely to be susceptible to arginine depletion. Pegylated arginase (BCT-100) is currently in phase I/II trials in relapsed pHGG. Our results suggest that therapeutic arginine depletion may also be useful in other tumour types and IHC analysis of patient tumour samples could ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2314-6133 |
| العلاقة: | https://nottingham-repository.worktribe.com/output/8636707Test; BioMed Research International; Volume 2022; https://nottingham-repository.worktribe.com/file/8636707/1/Arginine%20Pathway%20Enzymes%20in%20Childhood%20Brain%20TumoursTest |
| DOI: | 10.1155/2022/9008685 |
| الإتاحة: | https://doi.org/10.1155/2022/9008685Test https://nottingham-repository.worktribe.com/file/8636707/1/Arginine%20Pathway%20Enzymes%20in%20Childhood%20Brain%20TumoursTest https://nottingham-repository.worktribe.com/output/8636707Test |
| حقوق: | openAccess ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.BF8A2B42 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 23146133 |
|---|---|
| DOI: | 10.1155/2022/9008685 |