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MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628
Diffuse midline glioma, H3 K27M-mutant (DMG) is a newly defined entity. The prognosis of DMG is poor. Because surgical resection is often incomplete for DMG, radiotherapy and chemotherapy are important. Temozolomide (TMZ) is an alkylating agent that adds a methyl group to DNA (O6-guanine, N7-guanine...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715830/ http://dx.doi.org/10.1093/neuonc/noaa222.589 |
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author | Ohba, Shigeo Hirose, Yuichi |
author_facet | Ohba, Shigeo Hirose, Yuichi |
author_sort | Ohba, Shigeo |
collection | PubMed |
description | Diffuse midline glioma, H3 K27M-mutant (DMG) is a newly defined entity. The prognosis of DMG is poor. Because surgical resection is often incomplete for DMG, radiotherapy and chemotherapy are important. Temozolomide (TMZ) is an alkylating agent that adds a methyl group to DNA (O6-guanine, N7-guanine, and N3-adenine). TMZ-induced cytotoxicity is mainly derived from O6-methylguanine, which is repaired by O6-methylguanine DNA methyltransferase (MGMT). It has been reported that most of DMG lacked MGMT promoter hypermethylation, which is thought to contribute to less effectiveness of TMZ to DMG. The purpose of the study is to explore the way to inhibit the proliferation of DMG. A DMG cell line, SF8628, was used for the experiments. SF8628 had the expression of MGMT and was revealed to be resistant to TMZ. Because N7-methylguanine and N3-methyladenine are repaired via base excision repair, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor combined with TMZ was considered to be effective to suppress the proliferation of SF8628. As expected, PARP inhibitor enhanced TMZ-induced cytotoxicity in SF8628. Dianhydrogalactiol (DAG) is a bifunctional DNA-targeting agent forming N7-alkylguanine and inter-strand DNA crosslinks. DAG reduced the clonogenicity of SF8628. Moreover, inhibition of homologous recombination enhanced the DAG-induced cytotoxicity in SF8629. The combination treatment of PARP inhibitor and TMZ, or DAG were revealed to be promising treatments in SF8628. |
format | Online Article Text |
id | pubmed-7715830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77158302020-12-09 MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 Ohba, Shigeo Hirose, Yuichi Neuro Oncol Preclinical Models/Experimental Therapy/Drug Discovery Diffuse midline glioma, H3 K27M-mutant (DMG) is a newly defined entity. The prognosis of DMG is poor. Because surgical resection is often incomplete for DMG, radiotherapy and chemotherapy are important. Temozolomide (TMZ) is an alkylating agent that adds a methyl group to DNA (O6-guanine, N7-guanine, and N3-adenine). TMZ-induced cytotoxicity is mainly derived from O6-methylguanine, which is repaired by O6-methylguanine DNA methyltransferase (MGMT). It has been reported that most of DMG lacked MGMT promoter hypermethylation, which is thought to contribute to less effectiveness of TMZ to DMG. The purpose of the study is to explore the way to inhibit the proliferation of DMG. A DMG cell line, SF8628, was used for the experiments. SF8628 had the expression of MGMT and was revealed to be resistant to TMZ. Because N7-methylguanine and N3-methyladenine are repaired via base excision repair, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor combined with TMZ was considered to be effective to suppress the proliferation of SF8628. As expected, PARP inhibitor enhanced TMZ-induced cytotoxicity in SF8628. Dianhydrogalactiol (DAG) is a bifunctional DNA-targeting agent forming N7-alkylguanine and inter-strand DNA crosslinks. DAG reduced the clonogenicity of SF8628. Moreover, inhibition of homologous recombination enhanced the DAG-induced cytotoxicity in SF8629. The combination treatment of PARP inhibitor and TMZ, or DAG were revealed to be promising treatments in SF8628. Oxford University Press 2020-12-04 /pmc/articles/PMC7715830/ http://dx.doi.org/10.1093/neuonc/noaa222.589 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Preclinical Models/Experimental Therapy/Drug Discovery Ohba, Shigeo Hirose, Yuichi MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 |
title | MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 |
title_full | MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 |
title_fullStr | MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 |
title_full_unstemmed | MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 |
title_short | MODL-15. THE COMBINATION TREATMENT OF PARP INHIBITOR AND TMZ, OR DAG WILL BE PROMISING TREATMENT IN SF8628 |
title_sort | modl-15. the combination treatment of parp inhibitor and tmz, or dag will be promising treatment in sf8628 |
topic | Preclinical Models/Experimental Therapy/Drug Discovery |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715830/ http://dx.doi.org/10.1093/neuonc/noaa222.589 |
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