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226 PIK3CB/p1102 is a Selective Survival Factor for Glioblastoma

Abstract INTRODUCTION PIK3CB is an isoform of phosphoinositide3-kinase (PI3K) shown to be a biomarker for glioblastoma recurrence. We sought to assess the relationship between PIK3CB expression and recurrence and whether it could provide a novel therapeutic target in the treatment of glioblastoma. M... Full description

Journal Title: Neurosurgery 2017, Vol.64 (CN_suppl_1), p.262-262
Main Author: Simonds, Gary R
Other Authors: Rogers, Cara , Pridham, Kevin , Sheng, Zhi , Guo, Sujuan
Format: Electronic Article Electronic Article
Language: English
Subjects:
Medical prognosis
Publisher: Oxford: Oxford University Press
ID: ISSN: 0148-396X
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recordid: cdi_proquest_journals_2096697196
title: 226 PIK3CB/p1102 is a Selective Survival Factor for Glioblastoma
format: Article
creator:
  • Simonds, Gary R
  • Rogers, Cara
  • Pridham, Kevin
  • Sheng, Zhi
  • Guo, Sujuan
subjects:
  • Medical prognosis
ispartof: Neurosurgery, 2017, Vol.64 (CN_suppl_1), p.262-262
description: Abstract INTRODUCTION PIK3CB is an isoform of phosphoinositide3-kinase (PI3K) shown to be a biomarker for glioblastoma recurrence. We sought to assess the relationship between PIK3CB expression and recurrence and whether it could provide a novel therapeutic target in the treatment of glioblastoma. METHODS We assessed for trends in PI3K expression in glioblastoma patients from the TCGA database. We cultured glioblastoma cell lines and analyzed the expression of PIK3CB/p110ß and its role in AKT activation. Genetic knockdown was utilized to silence PIK3CB/p110ß to evaluate the effect on AKT activation. We inoculated tumor cells into immune deficient mice to form subcutaneous xenograft tumors and then treated mice with TGX-221 which is a p110ß inhibitor. RESULTS >Expression of high levels of PIK3CB showed a statistically significant increase in the incidence of glioblastoma recurrence (P = 0.01), shorted time to tumor recurrence (P = 0.03), and shorter survival after recurrence (P
language: eng
source:
identifier: ISSN: 0148-396X
fulltext: no_fulltext
issn:
  • 0148-396X
  • 1524-4040
url: Link


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title226 PIK3CB/p1102 is a Selective Survival Factor for Glioblastoma
creatorSimonds, Gary R ; Rogers, Cara ; Pridham, Kevin ; Sheng, Zhi ; Guo, Sujuan
creatorcontribSimonds, Gary R ; Rogers, Cara ; Pridham, Kevin ; Sheng, Zhi ; Guo, Sujuan
descriptionAbstract INTRODUCTION PIK3CB is an isoform of phosphoinositide3-kinase (PI3K) shown to be a biomarker for glioblastoma recurrence. We sought to assess the relationship between PIK3CB expression and recurrence and whether it could provide a novel therapeutic target in the treatment of glioblastoma. METHODS We assessed for trends in PI3K expression in glioblastoma patients from the TCGA database. We cultured glioblastoma cell lines and analyzed the expression of PIK3CB/p110ß and its role in AKT activation. Genetic knockdown was utilized to silence PIK3CB/p110ß to evaluate the effect on AKT activation. We inoculated tumor cells into immune deficient mice to form subcutaneous xenograft tumors and then treated mice with TGX-221 which is a p110ß inhibitor. RESULTS >Expression of high levels of PIK3CB showed a statistically significant increase in the incidence of glioblastoma recurrence (P = 0.01), shorted time to tumor recurrence (P = 0.03), and shorter survival after recurrence (P < 0.05). The p110ß isoform of PIK3CB was consistently expressed at high levels which coincided with robust activation of pAKT which is involved in cell survival. We silenced was with shRNA-mediated knockdown and found a 70–80% reduction in p110ß. Silencing PIK3CB/p110ß induced an 80% decrease in pAKT levels and lead to apoptosis. In inoculated mouse studies, TGX-221 significantly decreased the tumor volumes compared to the control (P = 0.029). Tumor growth inhibition (TGI) of TGX-221 was approximately 57. CONCLUSION Higher levels of PIK3CB in glioblastoma are correlated with higher incidence of recurrence, shorter time to recurrence, and worse prognosis of tumor recurrence. Higher levels of PIK3CB/p110ß correlate with phosphorylated AKT levels which is associated with cell survival. TGX-221, a selective inhibitor of PIK3CB/p110ß, suppresses AKT activation and inhibits cell survival and glioblastoma growth. Our results demonstrate that PIK3CB/p110ß is an essential survival factor for glioblastoma, and inhibitors like TGX-221 may serve as adjuncts to treatment.
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0226 PIK3CB/p1102 is a Selective Survival Factor for Glioblastoma
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descriptionAbstract INTRODUCTION PIK3CB is an isoform of phosphoinositide3-kinase (PI3K) shown to be a biomarker for glioblastoma recurrence. We sought to assess the relationship between PIK3CB expression and recurrence and whether it could provide a novel therapeutic target in the treatment of glioblastoma. METHODS We assessed for trends in PI3K expression in glioblastoma patients from the TCGA database. We cultured glioblastoma cell lines and analyzed the expression of PIK3CB/p110ß and its role in AKT activation. Genetic knockdown was utilized to silence PIK3CB/p110ß to evaluate the effect on AKT activation. We inoculated tumor cells into immune deficient mice to form subcutaneous xenograft tumors and then treated mice with TGX-221 which is a p110ß inhibitor. RESULTS >Expression of high levels of PIK3CB showed a statistically significant increase in the incidence of glioblastoma recurrence (P = 0.01), shorted time to tumor recurrence (P = 0.03), and shorter survival after recurrence (P < 0.05). The p110ß isoform of PIK3CB was consistently expressed at high levels which coincided with robust activation of pAKT which is involved in cell survival. We silenced was with shRNA-mediated knockdown and found a 70–80% reduction in p110ß. Silencing PIK3CB/p110ß induced an 80% decrease in pAKT levels and lead to apoptosis. In inoculated mouse studies, TGX-221 significantly decreased the tumor volumes compared to the control (P = 0.029). Tumor growth inhibition (TGI) of TGX-221 was approximately 57. CONCLUSION Higher levels of PIK3CB in glioblastoma are correlated with higher incidence of recurrence, shorter time to recurrence, and worse prognosis of tumor recurrence. Higher levels of PIK3CB/p110ß correlate with phosphorylated AKT levels which is associated with cell survival. TGX-221, a selective inhibitor of PIK3CB/p110ß, suppresses AKT activation and inhibits cell survival and glioblastoma growth. Our results demonstrate that PIK3CB/p110ß is an essential survival factor for glioblastoma, and inhibitors like TGX-221 may serve as adjuncts to treatment.
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authorSimonds, Gary R ; Rogers, Cara ; Pridham, Kevin ; Sheng, Zhi ; Guo, Sujuan
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abstractAbstract INTRODUCTION PIK3CB is an isoform of phosphoinositide3-kinase (PI3K) shown to be a biomarker for glioblastoma recurrence. We sought to assess the relationship between PIK3CB expression and recurrence and whether it could provide a novel therapeutic target in the treatment of glioblastoma. METHODS We assessed for trends in PI3K expression in glioblastoma patients from the TCGA database. We cultured glioblastoma cell lines and analyzed the expression of PIK3CB/p110ß and its role in AKT activation. Genetic knockdown was utilized to silence PIK3CB/p110ß to evaluate the effect on AKT activation. We inoculated tumor cells into immune deficient mice to form subcutaneous xenograft tumors and then treated mice with TGX-221 which is a p110ß inhibitor. RESULTS >Expression of high levels of PIK3CB showed a statistically significant increase in the incidence of glioblastoma recurrence (P = 0.01), shorted time to tumor recurrence (P = 0.03), and shorter survival after recurrence (P < 0.05). The p110ß isoform of PIK3CB was consistently expressed at high levels which coincided with robust activation of pAKT which is involved in cell survival. We silenced was with shRNA-mediated knockdown and found a 70–80% reduction in p110ß. Silencing PIK3CB/p110ß induced an 80% decrease in pAKT levels and lead to apoptosis. In inoculated mouse studies, TGX-221 significantly decreased the tumor volumes compared to the control (P = 0.029). Tumor growth inhibition (TGI) of TGX-221 was approximately 57. CONCLUSION Higher levels of PIK3CB in glioblastoma are correlated with higher incidence of recurrence, shorter time to recurrence, and worse prognosis of tumor recurrence. Higher levels of PIK3CB/p110ß correlate with phosphorylated AKT levels which is associated with cell survival. TGX-221, a selective inhibitor of PIK3CB/p110ß, suppresses AKT activation and inhibits cell survival and glioblastoma growth. Our results demonstrate that PIK3CB/p110ß is an essential survival factor for glioblastoma, and inhibitors like TGX-221 may serve as adjuncts to treatment.
copOxford
pubOxford University Press
doi10.1093/neuros/nyx417.226