Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation

Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteris...
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Autor*in:	Amira Zaher [verfasserIn] Kranti A. Mapuskar [verfasserIn] Jann N. Sarkaria [verfasserIn] Douglas R. Spitz [verfasserIn] Michael S. Petronek [verfasserIn] Bryan G. Allen [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 24(2023), 24, p 17158
Übergeordnetes Werk:	volume:24 ; year:2023 ; number:24, p 17158

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms242417158

Katalog-ID:	DOAJ098858696

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allfields	10.3390/ijms242417158 doi (DE-627)DOAJ098858696 (DE-599)DOAJc3c19b4b7f9c4bc287ad930bec92d9dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Amira Zaher verfasserin aut Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC. glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant Biology (General) Chemistry Kranti A. Mapuskar verfasserin aut Jann N. Sarkaria verfasserin aut Douglas R. Spitz verfasserin aut Michael S. Petronek verfasserin aut Bryan G. Allen verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 24, p 17158 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:24, p 17158 https://doi.org/10.3390/ijms242417158 kostenfrei https://doaj.org/article/c3c19b4b7f9c4bc287ad930bec92d9dd kostenfrei https://www.mdpi.com/1422-0067/24/24/17158 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 24, p 17158
spelling	10.3390/ijms242417158 doi (DE-627)DOAJ098858696 (DE-599)DOAJc3c19b4b7f9c4bc287ad930bec92d9dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Amira Zaher verfasserin aut Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC. glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant Biology (General) Chemistry Kranti A. Mapuskar verfasserin aut Jann N. Sarkaria verfasserin aut Douglas R. Spitz verfasserin aut Michael S. Petronek verfasserin aut Bryan G. Allen verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 24, p 17158 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:24, p 17158 https://doi.org/10.3390/ijms242417158 kostenfrei https://doaj.org/article/c3c19b4b7f9c4bc287ad930bec92d9dd kostenfrei https://www.mdpi.com/1422-0067/24/24/17158 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 24, p 17158
allfields_unstemmed	10.3390/ijms242417158 doi (DE-627)DOAJ098858696 (DE-599)DOAJc3c19b4b7f9c4bc287ad930bec92d9dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Amira Zaher verfasserin aut Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC. glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant Biology (General) Chemistry Kranti A. Mapuskar verfasserin aut Jann N. Sarkaria verfasserin aut Douglas R. Spitz verfasserin aut Michael S. Petronek verfasserin aut Bryan G. Allen verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 24, p 17158 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:24, p 17158 https://doi.org/10.3390/ijms242417158 kostenfrei https://doaj.org/article/c3c19b4b7f9c4bc287ad930bec92d9dd kostenfrei https://www.mdpi.com/1422-0067/24/24/17158 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 24, p 17158
allfieldsGer	10.3390/ijms242417158 doi (DE-627)DOAJ098858696 (DE-599)DOAJc3c19b4b7f9c4bc287ad930bec92d9dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Amira Zaher verfasserin aut Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC. glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant Biology (General) Chemistry Kranti A. Mapuskar verfasserin aut Jann N. Sarkaria verfasserin aut Douglas R. Spitz verfasserin aut Michael S. Petronek verfasserin aut Bryan G. Allen verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 24, p 17158 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:24, p 17158 https://doi.org/10.3390/ijms242417158 kostenfrei https://doaj.org/article/c3c19b4b7f9c4bc287ad930bec92d9dd kostenfrei https://www.mdpi.com/1422-0067/24/24/17158 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 24, p 17158
allfieldsSound	10.3390/ijms242417158 doi (DE-627)DOAJ098858696 (DE-599)DOAJc3c19b4b7f9c4bc287ad930bec92d9dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Amira Zaher verfasserin aut Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC. glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant Biology (General) Chemistry Kranti A. Mapuskar verfasserin aut Jann N. Sarkaria verfasserin aut Douglas R. Spitz verfasserin aut Michael S. Petronek verfasserin aut Bryan G. Allen verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 24, p 17158 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:24, p 17158 https://doi.org/10.3390/ijms242417158 kostenfrei https://doaj.org/article/c3c19b4b7f9c4bc287ad930bec92d9dd kostenfrei https://www.mdpi.com/1422-0067/24/24/17158 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 24, p 17158
language	English
source	In International Journal of Molecular Sciences 24(2023), 24, p 17158 volume:24 year:2023 number:24, p 17158
sourceStr	In International Journal of Molecular Sciences 24(2023), 24, p 17158 volume:24 year:2023 number:24, p 17158
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Amira Zaher @@aut@@ Kranti A. Mapuskar @@aut@@ Jann N. Sarkaria @@aut@@ Douglas R. Spitz @@aut@@ Michael S. Petronek @@aut@@ Bryan G. Allen @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	316340715
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language_de	englisch
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callnumber-first	Q - Science
author	Amira Zaher
spellingShingle	Amira Zaher misc QH301-705.5 misc QD1-999 misc glioblastoma misc chemoradiation misc glioblastoma subtypes misc pharmacological ascorbate misc antioxidant therapy misc prooxidant misc Biology (General) misc Chemistry Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation
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topic_title	QH301-705.5 QD1-999 Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation glioblastoma chemoradiation glioblastoma subtypes pharmacological ascorbate antioxidant therapy prooxidant
topic	misc QH301-705.5 misc QD1-999 misc glioblastoma misc chemoradiation misc glioblastoma subtypes misc pharmacological ascorbate misc antioxidant therapy misc prooxidant misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc glioblastoma misc chemoradiation misc glioblastoma subtypes misc pharmacological ascorbate misc antioxidant therapy misc prooxidant misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc glioblastoma misc chemoradiation misc glioblastoma subtypes misc pharmacological ascorbate misc antioxidant therapy misc prooxidant misc Biology (General) misc Chemistry
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title	Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation
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title_full	Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation
author_sort	Amira Zaher
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author_browse	Amira Zaher Kranti A. Mapuskar Jann N. Sarkaria Douglas R. Spitz Michael S. Petronek Bryan G. Allen
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title_sort	differential h<sub<2</sub<o<sub<2</sub< metabolism among glioblastoma subtypes confers variable responses to pharmacological ascorbate therapy combined with chemoradiation
callnumber	QH301-705.5
title_auth	Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation
abstract	Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC.
abstractGer	Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC.
abstract_unstemmed	Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH<sup<−</sup<) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH<sup<−</sup<. P-AscH<sup<−</sup< (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH<sup<−</sup< (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H<sub<2</sub<O<sub<2</sub< metabolism that potentially drives differential P-AscH<sup<−</sup< toxicity. Taken together, these data suggest that P-AscH<sup<−</sup< may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC.
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container_issue	24, p 17158
title_short	Differential H<sub<2</sub<O<sub<2</sub< Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation
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