Establishment of a glioblastoma in vitro (in)complete resection dual co-culture model suitable for drug testing.
AT101
Glioma co-culture in vitro model
R-(−)-gossypol
Resection grade
Sequential treatment
Temozolomide
Tumor microenvironment
Journal
Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft
ISSN: 1618-0402
Titre abrégé: Ann Anat
Pays: Germany
ID NLM: 100963897
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
08
07
2019
revised:
25
10
2019
accepted:
01
11
2019
pubmed:
15
11
2019
medline:
17
2
2021
entrez:
15
11
2019
Statut:
ppublish
Résumé
The treatment of glioblastomas (GBM) is still a clinical challenge. Current GBM therapeutic plans focus on the development of new strategies for local drug administration in the tumor cavity to realize an efficient long-term treatment with small side-effects. Here, different amounts of residual GBM cells and healthy brain cells define the microenvironment of the tumor cavity after individual surgical GBM resection (complete or incomplete). We evaluated available in vivo data and determined the required amounts and numerical ratios of GBM and healthy brain cells for our in vitro (in)complete resection dual co-culture model. We applied a generic two-drug treatment [Temozolomide (TMZ) in combination with AT101, followed by single AT101 treatment] strategy and analyzed the results in comparison with appropriate mono-culture systems to prove the applicability of our model. We established a suitable GBM dual co-culture model, mimicking the complete and incomplete resection in vitro, giving stable and reliable results on drug testing. Both dual co-culture conditions protectively influenced on cell death and growth rates of primary GBMs when treated with TMZ+AT101/AT101, although the treatment strategy per se was still efficient. Cell death of astrocytes correlated with amounts of increasing GBM cell numbers in the incomplete resection model upon drug treatment, and probably GBM-released chemokine and cytokines were involved in this interplay. Our results suggest that this dual co-culture model provides a biologically relevant platform for the discovery and compound screening of local GBM treatment strategies.
Sections du résumé
BACKGROUND
BACKGROUND
The treatment of glioblastomas (GBM) is still a clinical challenge. Current GBM therapeutic plans focus on the development of new strategies for local drug administration in the tumor cavity to realize an efficient long-term treatment with small side-effects. Here, different amounts of residual GBM cells and healthy brain cells define the microenvironment of the tumor cavity after individual surgical GBM resection (complete or incomplete).
METHODS
METHODS
We evaluated available in vivo data and determined the required amounts and numerical ratios of GBM and healthy brain cells for our in vitro (in)complete resection dual co-culture model. We applied a generic two-drug treatment [Temozolomide (TMZ) in combination with AT101, followed by single AT101 treatment] strategy and analyzed the results in comparison with appropriate mono-culture systems to prove the applicability of our model.
RESULTS
RESULTS
We established a suitable GBM dual co-culture model, mimicking the complete and incomplete resection in vitro, giving stable and reliable results on drug testing. Both dual co-culture conditions protectively influenced on cell death and growth rates of primary GBMs when treated with TMZ+AT101/AT101, although the treatment strategy per se was still efficient. Cell death of astrocytes correlated with amounts of increasing GBM cell numbers in the incomplete resection model upon drug treatment, and probably GBM-released chemokine and cytokines were involved in this interplay.
CONCLUSIONS
CONCLUSIONS
Our results suggest that this dual co-culture model provides a biologically relevant platform for the discovery and compound screening of local GBM treatment strategies.
Identifiants
pubmed: 31726206
pii: S0940-9602(19)30144-X
doi: 10.1016/j.aanat.2019.151440
pii:
doi:
Substances chimiques
Antineoplastic Agents, Alkylating
0
Antineoplastic Agents, Phytogenic
0
Gossypol
KAV15B369O
gossypol acetic acid
S7RL72610R
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
151440Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier GmbH.. All rights reserved.