Cargando…

HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO

BACKGROUND: Glioblastoma (GBM) is a highly aggressive CNS tumor that is associated with poor outcome. This dire prognosis is due in part to its poor response to the limited treatment options available. Iron and iron proteins play a key role in the growth of brain tumors, with our published studies s...

Descripción completa

Detalles Bibliográficos
Autores principales: Al-Gizawiy, Mona M, Wujek, Robert T, Zoss, Casey J, Tanaka, Ryuma, Mirza, Shama P, Chitambar, Christopher R, Schmainda, Kathleen M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260053/
http://dx.doi.org/10.1093/neuonc/noad073.155
_version_ 1785057777589157888
author Al-Gizawiy, Mona M
Wujek, Robert T
Zoss, Casey J
Tanaka, Ryuma
Mirza, Shama P
Chitambar, Christopher R
Schmainda, Kathleen M
author_facet Al-Gizawiy, Mona M
Wujek, Robert T
Zoss, Casey J
Tanaka, Ryuma
Mirza, Shama P
Chitambar, Christopher R
Schmainda, Kathleen M
author_sort Al-Gizawiy, Mona M
collection PubMed
description BACKGROUND: Glioblastoma (GBM) is a highly aggressive CNS tumor that is associated with poor outcome. This dire prognosis is due in part to its poor response to the limited treatment options available. Iron and iron proteins play a key role in the growth of brain tumors, with our published studies showing that the ferrobiology of adult GBM can be exploited for therapeutic purposes. Here, we further elucidate the inhibitory effects of oral gallium maltolate (GaM) in pediatric GBM in vivo. METHODS: Pediatric SJ-GBM2 cells were stereotactically implanted into the right striatum of male athymic rats. Advanced MR imaging at 9.4T was carried out weekly starting two weeks after implantation. Daily oral GaM (50mg/kg) or vehicle were provided on tumor confirmation. Longitudinal advanced MRI parameters were processed for enhancing tumor ROIs in OsiriX 8.5.1 (lite) with Imaging Biometrics Software (Imaging Biometrics LLC). Statistical analyses included Kaplan-Meier survival plots, linear mixed model comparisons, and t-statistic for slopes comparison. RESULTS: The sensitivity of the in vivo pediatric GBM xenografts to GaM was consistent with our previous in vitro work. Median overall survival was 21 days in the controls and 49 days in the treatment group (p=0.014). GaM-treated xenograft tumors grew significantly slower than control tumors (p=0.031). Histologically, xenograft tumors recapitulated the aggressive growth features of clinical specimens, such as invasive margins. Unlike adult GBM xenografts in our previous studies, pediatric GBM xenografts did not exhibit vessel normalization or a reduction in pro-angiogenic markers in response to GaM. Additionally, MIB-1% (p=0.6583) and mitotic index (p=0.7097) were not affected by treatment. Yet, transferrin receptor and H-ferritin expression patterns in GaM-treated tumors suggested cellular iron deprivation. CONCLUSION: Monotherapy with GaM provides a significant survival benefit in pediatric GBM, and further studies are planned to optimize the benefit of GaM in pediatric GBM.
format Online
Article
Text
id pubmed-10260053
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-102600532023-06-13 HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO Al-Gizawiy, Mona M Wujek, Robert T Zoss, Casey J Tanaka, Ryuma Mirza, Shama P Chitambar, Christopher R Schmainda, Kathleen M Neuro Oncol Final Category: High Grade Glioma/Gliomatosis Cerebri - HGG BACKGROUND: Glioblastoma (GBM) is a highly aggressive CNS tumor that is associated with poor outcome. This dire prognosis is due in part to its poor response to the limited treatment options available. Iron and iron proteins play a key role in the growth of brain tumors, with our published studies showing that the ferrobiology of adult GBM can be exploited for therapeutic purposes. Here, we further elucidate the inhibitory effects of oral gallium maltolate (GaM) in pediatric GBM in vivo. METHODS: Pediatric SJ-GBM2 cells were stereotactically implanted into the right striatum of male athymic rats. Advanced MR imaging at 9.4T was carried out weekly starting two weeks after implantation. Daily oral GaM (50mg/kg) or vehicle were provided on tumor confirmation. Longitudinal advanced MRI parameters were processed for enhancing tumor ROIs in OsiriX 8.5.1 (lite) with Imaging Biometrics Software (Imaging Biometrics LLC). Statistical analyses included Kaplan-Meier survival plots, linear mixed model comparisons, and t-statistic for slopes comparison. RESULTS: The sensitivity of the in vivo pediatric GBM xenografts to GaM was consistent with our previous in vitro work. Median overall survival was 21 days in the controls and 49 days in the treatment group (p=0.014). GaM-treated xenograft tumors grew significantly slower than control tumors (p=0.031). Histologically, xenograft tumors recapitulated the aggressive growth features of clinical specimens, such as invasive margins. Unlike adult GBM xenografts in our previous studies, pediatric GBM xenografts did not exhibit vessel normalization or a reduction in pro-angiogenic markers in response to GaM. Additionally, MIB-1% (p=0.6583) and mitotic index (p=0.7097) were not affected by treatment. Yet, transferrin receptor and H-ferritin expression patterns in GaM-treated tumors suggested cellular iron deprivation. CONCLUSION: Monotherapy with GaM provides a significant survival benefit in pediatric GBM, and further studies are planned to optimize the benefit of GaM in pediatric GBM. Oxford University Press 2023-06-12 /pmc/articles/PMC10260053/ http://dx.doi.org/10.1093/neuonc/noad073.155 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://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 Final Category: High Grade Glioma/Gliomatosis Cerebri - HGG
Al-Gizawiy, Mona M
Wujek, Robert T
Zoss, Casey J
Tanaka, Ryuma
Mirza, Shama P
Chitambar, Christopher R
Schmainda, Kathleen M
HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO
title HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO
title_full HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO
title_fullStr HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO
title_full_unstemmed HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO
title_short HGG-06. CHARACTERIZATION OF THE EFFECT OF THE ORAL IRON-MIMETIC GALLIUM MALTOLATE ON PEDIATRIC GLIOBLASTOMA GROWTH IN VIVO
title_sort hgg-06. characterization of the effect of the oral iron-mimetic gallium maltolate on pediatric glioblastoma growth in vivo
topic Final Category: High Grade Glioma/Gliomatosis Cerebri - HGG
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260053/
http://dx.doi.org/10.1093/neuonc/noad073.155
work_keys_str_mv AT algizawiymonam hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo
AT wujekrobertt hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo
AT zosscaseyj hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo
AT tanakaryuma hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo
AT mirzashamap hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo
AT chitambarchristopherr hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo
AT schmaindakathleenm hgg06characterizationoftheeffectoftheoralironmimeticgalliummaltolateonpediatricglioblastomagrowthinvivo