TY  - JOUR
AU  - Stanković, Tijana
AU  - Ranđelović, Teodora
AU  - Dragoj, Miodrag
AU  - Stojković Burić, Sonja
AU  - Fernández, Luis
AU  - Ochoa, Ignacio
AU  - Pérez-García, Victor M.
AU  - Pešić, Milica
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S136876462100011X
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4242
AB  - The poor response of glioblastoma to current treatment protocols is a consequence of its intrinsic drug resistance. Resistance to chemotherapy is primarily associated with considerable cellular heterogeneity, and plasticity of glioblastoma cells, alterations in gene expression, presence of specific tumor microenvironment conditions and blood-brain barrier. In an attempt to successfully overcome chemoresistance and better understand the biological behavior of glioblastoma, numerous tri-dimensional (3D) biomimetic models were developed in the past decade. These novel advanced models are able to better recapitulate the spatial organization of glioblastoma in a real time, therefore providing more realistic and reliable evidence to the response of glioblastoma to therapy. Moreover, these models enable the fine-tuning of different tumor microenvironment conditions and facilitate studies on the effects of the tumor microenvironment on glioblastoma chemoresistance. This review outlines current knowledge on the essence of glioblastoma chemoresistance and describes the progress achieved by 3D biomimetic models. Moreover, comprehensive literature assessment regarding the influence of 3D culturing and microenvironment mimicking on glioblastoma gene expression and biological behavior is also provided. The contribution of the blood-brain barrier as well as the blood-tumor barrier to glioblastoma chemoresistance is also reviewed from the perspective of 3D biomimetic models. Finally, the role of mathematical models in predicting 3D glioblastoma behavior and drug response is elaborated. In the future, technological innovations along with mathematical simulations should create reliable 3D biomimetic systems for glioblastoma research that should facilitate the identification and possibly application in preclinical drug testing and precision medicine.
PB  - Churchill Livingstone
T2  - Drug Resistance Updates
T1  - In vitro biomimetic models for glioblastoma-a promising tool for drug response studies
VL  - 55
DO  - 10.1016/j.drup.2021.100753
SP  - 100753
ER  - 

@article{
author = "Stanković, Tijana and Ranđelović, Teodora and Dragoj, Miodrag and Stojković Burić, Sonja and Fernández, Luis and Ochoa, Ignacio and Pérez-García, Victor M. and Pešić, Milica",
year = "2021",
abstract = "The poor response of glioblastoma to current treatment protocols is a consequence of its intrinsic drug resistance. Resistance to chemotherapy is primarily associated with considerable cellular heterogeneity, and plasticity of glioblastoma cells, alterations in gene expression, presence of specific tumor microenvironment conditions and blood-brain barrier. In an attempt to successfully overcome chemoresistance and better understand the biological behavior of glioblastoma, numerous tri-dimensional (3D) biomimetic models were developed in the past decade. These novel advanced models are able to better recapitulate the spatial organization of glioblastoma in a real time, therefore providing more realistic and reliable evidence to the response of glioblastoma to therapy. Moreover, these models enable the fine-tuning of different tumor microenvironment conditions and facilitate studies on the effects of the tumor microenvironment on glioblastoma chemoresistance. This review outlines current knowledge on the essence of glioblastoma chemoresistance and describes the progress achieved by 3D biomimetic models. Moreover, comprehensive literature assessment regarding the influence of 3D culturing and microenvironment mimicking on glioblastoma gene expression and biological behavior is also provided. The contribution of the blood-brain barrier as well as the blood-tumor barrier to glioblastoma chemoresistance is also reviewed from the perspective of 3D biomimetic models. Finally, the role of mathematical models in predicting 3D glioblastoma behavior and drug response is elaborated. In the future, technological innovations along with mathematical simulations should create reliable 3D biomimetic systems for glioblastoma research that should facilitate the identification and possibly application in preclinical drug testing and precision medicine.",
publisher = "Churchill Livingstone",
journal = "Drug Resistance Updates",
title = "In vitro biomimetic models for glioblastoma-a promising tool for drug response studies",
volume = "55",
doi = "10.1016/j.drup.2021.100753",
pages = "100753"
}

Stanković, T., Ranđelović, T., Dragoj, M., Stojković Burić, S., Fernández, L., Ochoa, I., Pérez-García, V. M.,& Pešić, M.. (2021). In vitro biomimetic models for glioblastoma-a promising tool for drug response studies. in Drug Resistance Updates
Churchill Livingstone., 55, 100753.
https://doi.org/10.1016/j.drup.2021.100753

Stanković T, Ranđelović T, Dragoj M, Stojković Burić S, Fernández L, Ochoa I, Pérez-García VM, Pešić M. In vitro biomimetic models for glioblastoma-a promising tool for drug response studies. in Drug Resistance Updates. 2021;55:100753.
doi:10.1016/j.drup.2021.100753 .

Stanković, Tijana, Ranđelović, Teodora, Dragoj, Miodrag, Stojković Burić, Sonja, Fernández, Luis, Ochoa, Ignacio, Pérez-García, Victor M., Pešić, Milica, "In vitro biomimetic models for glioblastoma-a promising tool for drug response studies" in Drug Resistance Updates, 55 (2021):100753,
https://doi.org/10.1016/j.drup.2021.100753 . .

TY  - CONF
AU  - Stojković Burić, Sonja
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Jovanović, Mirna
AU  - Hadžić, Stefan
AU  - Ayuso, Jose
AU  - Virumbrales-Muñoz, María
AU  - Fernández, Luis
AU  - Ochoa, Ignacio
AU  - Pérez-García, Victor
AU  - Pešić, Milica
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6043
AB  - Development of chemoresistance and the invasion of cancer cells into surrounding brain tissue are major obstacles to successful glioma treatment. New therapeutic approaches are warranted to improve the survival of glioma patients. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) to increase sensitivity to temozolomide (TMZ) and suppress glioma cells invasion. Therefore, we have developed TMZ resistant RC6 rat glioma cell line with altered antioxidant capacity and high invasion potential. CoQ10 in combination with TMZ exerted a synergistic effect additionally confirmed in a 3D model of microfluidic devices. Co-treatment with TMZ increased
expression of mitochondrial antioxidant enzymes in RC6 cells. The anti-invasive potential was studied by gelatin degradation and 3D spheroid invasion assays. Inhibition of MMP9 gene expression as well as decreased N-cadherin and vimentin protein expression implied that CoQ10 can suppress invasiveness and the epithelial to mesenchymal transition in RC6 cells. Therefore, CoQ10 supplementation could be used with standard glioma treatment due to its potential to inhibit cancer cells invasion through modulation of the antioxidant capacity.
PB  - COST Action CA17104
C3  - Abstract book: STRATAGEM CA17104: New diagnostic and therapeutic tools against multidrug-resistant tumours: First Working-Group Meeting WG1 - WG4; 2019 Jan 30-31; Turin, Italy
T1  - The role of antioxidant, coenzyme Q10, in suppressing invasion of temozolomide resistant rat glioma
SP  - 32
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6043
ER  - 

@conference{
author = "Stojković Burić, Sonja and Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Jovanović, Mirna and Hadžić, Stefan and Ayuso, Jose and Virumbrales-Muñoz, María and Fernández, Luis and Ochoa, Ignacio and Pérez-García, Victor and Pešić, Milica",
year = "2019",
abstract = "Development of chemoresistance and the invasion of cancer cells into surrounding brain tissue are major obstacles to successful glioma treatment. New therapeutic approaches are warranted to improve the survival of glioma patients. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) to increase sensitivity to temozolomide (TMZ) and suppress glioma cells invasion. Therefore, we have developed TMZ resistant RC6 rat glioma cell line with altered antioxidant capacity and high invasion potential. CoQ10 in combination with TMZ exerted a synergistic effect additionally confirmed in a 3D model of microfluidic devices. Co-treatment with TMZ increased
expression of mitochondrial antioxidant enzymes in RC6 cells. The anti-invasive potential was studied by gelatin degradation and 3D spheroid invasion assays. Inhibition of MMP9 gene expression as well as decreased N-cadherin and vimentin protein expression implied that CoQ10 can suppress invasiveness and the epithelial to mesenchymal transition in RC6 cells. Therefore, CoQ10 supplementation could be used with standard glioma treatment due to its potential to inhibit cancer cells invasion through modulation of the antioxidant capacity.",
publisher = "COST Action CA17104",
journal = "Abstract book: STRATAGEM CA17104: New diagnostic and therapeutic tools against multidrug-resistant tumours: First Working-Group Meeting WG1 - WG4; 2019 Jan 30-31; Turin, Italy",
title = "The role of antioxidant, coenzyme Q10, in suppressing invasion of temozolomide resistant rat glioma",
pages = "32-32",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6043"
}

Stojković Burić, S., Podolski-Renić, A., Dinić, J., Stanković, T., Jovanović, M., Hadžić, S., Ayuso, J., Virumbrales-Muñoz, M., Fernández, L., Ochoa, I., Pérez-García, V.,& Pešić, M.. (2019). The role of antioxidant, coenzyme Q10, in suppressing invasion of temozolomide resistant rat glioma. in Abstract book: STRATAGEM CA17104: New diagnostic and therapeutic tools against multidrug-resistant tumours: First Working-Group Meeting WG1 - WG4; 2019 Jan 30-31; Turin, Italy
COST Action CA17104., 32-32.
https://hdl.handle.net/21.15107/rcub_ibiss_6043

Stojković Burić S, Podolski-Renić A, Dinić J, Stanković T, Jovanović M, Hadžić S, Ayuso J, Virumbrales-Muñoz M, Fernández L, Ochoa I, Pérez-García V, Pešić M. The role of antioxidant, coenzyme Q10, in suppressing invasion of temozolomide resistant rat glioma. in Abstract book: STRATAGEM CA17104: New diagnostic and therapeutic tools against multidrug-resistant tumours: First Working-Group Meeting WG1 - WG4; 2019 Jan 30-31; Turin, Italy. 2019;:32-32.
https://hdl.handle.net/21.15107/rcub_ibiss_6043 .

Stojković Burić, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Jovanović, Mirna, Hadžić, Stefan, Ayuso, Jose, Virumbrales-Muñoz, María, Fernández, Luis, Ochoa, Ignacio, Pérez-García, Victor, Pešić, Milica, "The role of antioxidant, coenzyme Q10, in suppressing invasion of temozolomide resistant rat glioma" in Abstract book: STRATAGEM CA17104: New diagnostic and therapeutic tools against multidrug-resistant tumours: First Working-Group Meeting WG1 - WG4; 2019 Jan 30-31; Turin, Italy (2019):32-32,
https://hdl.handle.net/21.15107/rcub_ibiss_6043 .

TY  - JOUR
AU  - Stojković Burić, Sonja
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Jovanović, Mirna
AU  - Hadžić, Stefan
AU  - Ayuso, Jose M.
AU  - Virumbrales-Muñoz, María
AU  - Fernández, Luis J.
AU  - Ochoa, Ignacio
AU  - Pérez-García, Victor M.
AU  - Pešić, Milica
PY  - 2019
UR  - https://www.hindawi.com/journals/omcl/2019/3061607/
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6432727
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3323
AB  - The main reasons for the inefficiency of standard glioblastoma (GBM) therapy are the occurrence of chemoresistance and the invasion of GBM cells into surrounding brain tissues. New therapeutic approaches obstructing these processes may provide substantial survival improvements. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) as a scavenger of reactive oxygen species (ROS) to increase sensitivity to temozolomide (TMZ) and suppress glioma cell invasion. To that end, we used a previously established TMZ-resistant RC6 rat glioma cell line, characterized by increased production of ROS, altered antioxidative capacity, and high invasion potential. CoQ10 in combination with TMZ exerted a synergistic antiproliferative effect. These results were confirmed in a 3D model of microfluidic devices showing that the CoQ10 and TMZ combination is more cytotoxic to RC6 cells than TMZ monotherapy. In addition, cotreatment with TMZ increased expression of mitochondrial antioxidant enzymes in RC6 cells. The anti-invasive potential of the combined treatment was shown by gelatin degradation, Matrigel invasion, and 3D spheroid invasion assays as well as in animal models. Inhibition of MMP9 gene expression as well as decreased N-cadherin and vimentin protein expression implied that CoQ10 can suppress invasiveness and the epithelial to mesenchymal transition in RC6 cells. Therefore, our data provide evidences in favor of CoQ10 supplementation to standard GBM treatment due to its potential to inhibit GBM invasion through modulation of the antioxidant capacity.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.
VL  - 2019
DO  - 10.1155/2019/3061607
SP  - 3061607
ER  - 

@article{
author = "Stojković Burić, Sonja and Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Jovanović, Mirna and Hadžić, Stefan and Ayuso, Jose M. and Virumbrales-Muñoz, María and Fernández, Luis J. and Ochoa, Ignacio and Pérez-García, Victor M. and Pešić, Milica",
year = "2019",
abstract = "The main reasons for the inefficiency of standard glioblastoma (GBM) therapy are the occurrence of chemoresistance and the invasion of GBM cells into surrounding brain tissues. New therapeutic approaches obstructing these processes may provide substantial survival improvements. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) as a scavenger of reactive oxygen species (ROS) to increase sensitivity to temozolomide (TMZ) and suppress glioma cell invasion. To that end, we used a previously established TMZ-resistant RC6 rat glioma cell line, characterized by increased production of ROS, altered antioxidative capacity, and high invasion potential. CoQ10 in combination with TMZ exerted a synergistic antiproliferative effect. These results were confirmed in a 3D model of microfluidic devices showing that the CoQ10 and TMZ combination is more cytotoxic to RC6 cells than TMZ monotherapy. In addition, cotreatment with TMZ increased expression of mitochondrial antioxidant enzymes in RC6 cells. The anti-invasive potential of the combined treatment was shown by gelatin degradation, Matrigel invasion, and 3D spheroid invasion assays as well as in animal models. Inhibition of MMP9 gene expression as well as decreased N-cadherin and vimentin protein expression implied that CoQ10 can suppress invasiveness and the epithelial to mesenchymal transition in RC6 cells. Therefore, our data provide evidences in favor of CoQ10 supplementation to standard GBM treatment due to its potential to inhibit GBM invasion through modulation of the antioxidant capacity.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.",
volume = "2019",
doi = "10.1155/2019/3061607",
pages = "3061607"
}

Stojković Burić, S., Podolski-Renić, A., Dinić, J., Stanković, T., Jovanović, M., Hadžić, S., Ayuso, J. M., Virumbrales-Muñoz, M., Fernández, L. J., Ochoa, I., Pérez-García, V. M.,& Pešić, M.. (2019). Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.. in Oxidative Medicine and Cellular Longevity, 2019, 3061607.
https://doi.org/10.1155/2019/3061607

Stojković Burić S, Podolski-Renić A, Dinić J, Stanković T, Jovanović M, Hadžić S, Ayuso JM, Virumbrales-Muñoz M, Fernández LJ, Ochoa I, Pérez-García VM, Pešić M. Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo.. in Oxidative Medicine and Cellular Longevity. 2019;2019:3061607.
doi:10.1155/2019/3061607 .

Stojković Burić, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Jovanović, Mirna, Hadžić, Stefan, Ayuso, Jose M., Virumbrales-Muñoz, María, Fernández, Luis J., Ochoa, Ignacio, Pérez-García, Victor M., Pešić, Milica, "Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma In Vitro and In Vivo." in Oxidative Medicine and Cellular Longevity, 2019 (2019):3061607,
https://doi.org/10.1155/2019/3061607 . .

TY  - JOUR
AU  - Stojković Burić, Sonja
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Pavković, Željko
AU  - Ayuso, Jose M.
AU  - Fernández, Luis J.
AU  - Ochoa, Ignacio
AU  - Pérez-Martínez, Víctor Manuel
AU  - Pešić, Vesna
AU  - Pešić, Milica
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/123456789/3872
AB  - Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.
PB  - Basel : MDPI
T2  - Molecules
T1  - Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model
IS  - 7
VL  - 21
DO  - 10.3390/molecules21070843
SP  - 843
ER  - 

@article{
author = "Stojković Burić, Sonja and Podolski-Renić, Ana and Dinić, Jelena and Pavković, Željko and Ayuso, Jose M. and Fernández, Luis J. and Ochoa, Ignacio and Pérez-Martínez, Víctor Manuel and Pešić, Vesna and Pešić, Milica",
year = "2016",
abstract = "Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.",
publisher = "Basel : MDPI",
journal = "Molecules",
title = "Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model",
number = "7",
volume = "21",
doi = "10.3390/molecules21070843",
pages = "843"
}

Stojković Burić, S., Podolski-Renić, A., Dinić, J., Pavković, Ž., Ayuso, J. M., Fernández, L. J., Ochoa, I., Pérez-Martínez, V. M., Pešić, V.,& Pešić, M.. (2016). Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model. in Molecules
Basel : MDPI., 21(7), 843.
https://doi.org/10.3390/molecules21070843

Stojković Burić S, Podolski-Renić A, Dinić J, Pavković Ž, Ayuso JM, Fernández LJ, Ochoa I, Pérez-Martínez VM, Pešić V, Pešić M. Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model. in Molecules. 2016;21(7):843.
doi:10.3390/molecules21070843 .

Stojković Burić, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Pavković, Željko, Ayuso, Jose M., Fernández, Luis J., Ochoa, Ignacio, Pérez-Martínez, Víctor Manuel, Pešić, Vesna, Pešić, Milica, "Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model" in Molecules, 21, no. 7 (2016):843,
https://doi.org/10.3390/molecules21070843 . .