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Conference Paper: Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide
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TitleHyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide
 
AuthorsLeung, GKK
Sun, S
Lee, DYC
Lee, NP
Pu, JKS
 
Issue Date2012
 
PublisherAsian Society for Neuro-oncology.
 
CitationThe 9th Meeting of Asian Society for Neuro-Oncology (ASNO 2012), Taipei, Taiwan, 20-22 April 2012. [How to Cite?]
 
AbstractOBJECTIVE: Temozolomide (TMZ) is the standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and is associated with TMZ-resistance. We investigated whether and how induced hyperoxia may resensitize chemoresistant GBM cells to TMZ. STUDY DESIGN: In vitro study on the effects of atmospheric oxygen at different concentrations on TMZ-sentivity in GBM cells. MATERIALS AND METHODS: TMZ-sensitive human GBM cells (D54-S and U87-S) were chronically treated with TMZ to develop isogenic subclones of TMZ-resistant cells (D54-R and U87-R). Cells were then exposed to different concentrations of oxygen – hypoxia (1%), normoxia (20%) and hyperoxia (80%) - under ambient atmospheric pressure with or without concomitant TMZ treatment. Chemosensitivity was measured using sulforhodamine B assay. Apoptotic and mitogen-activated protein kinase (MAPK)-related pathways were also studied. RESULTS: TMZ-sensitivity was enhanced by hyperoxia especially in chemoresistant cells. Under hyperoxia, D54-R/U87-R cells regained the same responses towards TMZ as D54-S/U87-S cells under normoxia through caspase-dependent pathway. Both TMZ and hyperoxia were associated with increased phosphorylation of MAPK, but to lesser extents in D54-R cells. The findings suggested that MAPK activities may have a protective role against hyperoxia. This effect appeared to be downregulated in chemoresistant cells, rendering them more susceptible to hyperoxic stress. CONCLUSION: Induced hyperoxia may resensitize chemoresistant GBM to TMZ. The role of MAPK-related pathway in response to oxidative stress in GBM remains to be explored. Further in vivo study is required to investigate the potential application and mechanism of hyperoxia as a chemotherapy adjunct for GBM.
 
DC FieldValue
dc.contributor.authorLeung, GKK
 
dc.contributor.authorSun, S
 
dc.contributor.authorLee, DYC
 
dc.contributor.authorLee, NP
 
dc.contributor.authorPu, JKS
 
dc.date.accessioned2012-08-16T06:11:09Z
 
dc.date.available2012-08-16T06:11:09Z
 
dc.date.issued2012
 
dc.description.abstractOBJECTIVE: Temozolomide (TMZ) is the standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and is associated with TMZ-resistance. We investigated whether and how induced hyperoxia may resensitize chemoresistant GBM cells to TMZ. STUDY DESIGN: In vitro study on the effects of atmospheric oxygen at different concentrations on TMZ-sentivity in GBM cells. MATERIALS AND METHODS: TMZ-sensitive human GBM cells (D54-S and U87-S) were chronically treated with TMZ to develop isogenic subclones of TMZ-resistant cells (D54-R and U87-R). Cells were then exposed to different concentrations of oxygen – hypoxia (1%), normoxia (20%) and hyperoxia (80%) - under ambient atmospheric pressure with or without concomitant TMZ treatment. Chemosensitivity was measured using sulforhodamine B assay. Apoptotic and mitogen-activated protein kinase (MAPK)-related pathways were also studied. RESULTS: TMZ-sensitivity was enhanced by hyperoxia especially in chemoresistant cells. Under hyperoxia, D54-R/U87-R cells regained the same responses towards TMZ as D54-S/U87-S cells under normoxia through caspase-dependent pathway. Both TMZ and hyperoxia were associated with increased phosphorylation of MAPK, but to lesser extents in D54-R cells. The findings suggested that MAPK activities may have a protective role against hyperoxia. This effect appeared to be downregulated in chemoresistant cells, rendering them more susceptible to hyperoxic stress. CONCLUSION: Induced hyperoxia may resensitize chemoresistant GBM to TMZ. The role of MAPK-related pathway in response to oxidative stress in GBM remains to be explored. Further in vivo study is required to investigate the potential application and mechanism of hyperoxia as a chemotherapy adjunct for GBM.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationThe 9th Meeting of Asian Society for Neuro-Oncology (ASNO 2012), Taipei, Taiwan, 20-22 April 2012. [How to Cite?]
 
dc.identifier.hkuros204805
 
dc.identifier.urihttp://hdl.handle.net/10722/160438
 
dc.languageeng
 
dc.publisherAsian Society for Neuro-oncology.
 
dc.publisher.placeTaipei
 
dc.relation.ispartof9th Meeting of Asian Society for Neuro-oncology, ASNO 2012
 
dc.titleHyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide
 
dc.typeConference_Paper
 
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<item><contributor.author>Leung, GKK</contributor.author>
<contributor.author>Sun, S</contributor.author>
<contributor.author>Lee, DYC</contributor.author>
<contributor.author>Lee, NP</contributor.author>
<contributor.author>Pu, JKS</contributor.author>
<date.accessioned>2012-08-16T06:11:09Z</date.accessioned>
<date.available>2012-08-16T06:11:09Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>The 9th Meeting of Asian Society for Neuro-Oncology (ASNO 2012), Taipei, Taiwan, 20-22 April 2012.</identifier.citation>
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<description.abstract>OBJECTIVE: Temozolomide (TMZ) is the standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and is associated with TMZ-resistance. We investigated whether and how induced hyperoxia may resensitize chemoresistant GBM cells to TMZ. STUDY DESIGN: In vitro study on the effects of atmospheric oxygen at different concentrations on TMZ-sentivity in GBM cells. MATERIALS AND METHODS: TMZ-sensitive human GBM cells (D54-S and U87-S) were chronically treated with TMZ to develop isogenic subclones of TMZ-resistant cells (D54-R and U87-R). Cells were then exposed to different concentrations of oxygen &#8211; hypoxia (1%), normoxia (20%) and hyperoxia (80%) - under ambient atmospheric pressure with or without concomitant TMZ treatment. Chemosensitivity was measured using sulforhodamine B assay. Apoptotic and mitogen-activated protein kinase (MAPK)-related pathways were also studied. RESULTS: TMZ-sensitivity was enhanced by hyperoxia especially in chemoresistant cells. Under hyperoxia, D54-R/U87-R cells regained the same responses towards TMZ as D54-S/U87-S cells under normoxia through caspase-dependent pathway. Both TMZ and hyperoxia were associated with increased phosphorylation of MAPK, but to lesser extents in D54-R cells. The findings suggested that MAPK activities may have a protective role against hyperoxia. This effect appeared to be downregulated in chemoresistant cells, rendering them more susceptible to hyperoxic stress. CONCLUSION: Induced hyperoxia may resensitize chemoresistant GBM to TMZ. The role of MAPK-related pathway in response to oxidative stress in GBM remains to be explored. Further in vivo study is required to investigate the potential application and mechanism of hyperoxia as a chemotherapy adjunct for GBM.</description.abstract>
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