TY  - JOUR
AU  - Mandić, Danijela
AU  - Nežić, Lana
AU  - Amdžić, Ljiljana
AU  - Vojinović, Nataša
AU  - Gajanin, Radoslav
AU  - Popović, Miroslav
AU  - Đeri, Jugoslav
AU  - Balint, Milena Todorović
AU  - Dumanović, Jelena
AU  - Milovanović, Zoran
AU  - Grujić-Milanović, Jelica
AU  - Škrbić, Ranko
AU  - Jaćević, Vesna
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6327
AB  - Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response. Methods: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment. Results: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups (p < 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. Conclusions: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.
PB  - MDPI
T2  - Cancers
T1  - Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment
VL  - 15
IS  - 16
SP  - 4106
DO  - 10.3390/cancers15164106
ER  - 

@article{
author = "Mandić, Danijela and Nežić, Lana and Amdžić, Ljiljana and Vojinović, Nataša and Gajanin, Radoslav and Popović, Miroslav and Đeri, Jugoslav and Balint, Milena Todorović and Dumanović, Jelena and Milovanović, Zoran and Grujić-Milanović, Jelica and Škrbić, Ranko and Jaćević, Vesna",
year = "2023",
abstract = "Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response. Methods: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment. Results: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups (p < 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. Conclusions: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.",
publisher = "MDPI",
journal = "Cancers",
title = "Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment",
volume = "15",
number = "16",
pages = "4106",
doi = "10.3390/cancers15164106"
}

Mandić, D., Nežić, L., Amdžić, L., Vojinović, N., Gajanin, R., Popović, M., Đeri, J., Balint, M. T., Dumanović, J., Milovanović, Z., Grujić-Milanović, J., Škrbić, R.,& Jaćević, V.. (2023). Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment. in Cancers
MDPI., 15(16), 4106.
https://doi.org/10.3390/cancers15164106

Mandić D, Nežić L, Amdžić L, Vojinović N, Gajanin R, Popović M, Đeri J, Balint MT, Dumanović J, Milovanović Z, Grujić-Milanović J, Škrbić R, Jaćević V. Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment. in Cancers. 2023;15(16):4106.
doi:10.3390/cancers15164106 .

Mandić, Danijela, Nežić, Lana, Amdžić, Ljiljana, Vojinović, Nataša, Gajanin, Radoslav, Popović, Miroslav, Đeri, Jugoslav, Balint, Milena Todorović, Dumanović, Jelena, Milovanović, Zoran, Grujić-Milanović, Jelica, Škrbić, Ranko, Jaćević, Vesna, "Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment" in Cancers, 15, no. 16 (2023):4106,
https://doi.org/10.3390/cancers15164106 . .

TY  - JOUR
AU  - Nežić, Lana
AU  - Amidžić, Ljiljana
AU  - Škrbić, Ranko
AU  - Gajanin, Radoslav
AU  - Mandić, Danijela
AU  - Dumanović, Jelena
AU  - Milovanović, Zoran
AU  - Jaćević, Vesna
PY  - 2022
UR  - https://www.mdpi.com/1422-0067/23/5/2596
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5208
AB  - Disruption of the alveolar–endothelial barrier caused by inflammation leads to the progression of septic acute lung injury (ALI). In the present study, we investigated the beneficial effects of simvastatin on the endotoxin lipopolysaccharide (LPS)-induced ALI and its related mechanisms. A model of ALI was induced within experimental sepsis developed by intraperitoneal injection of a single non-lethal LPS dose after short-term simvastatin pretreatment (10–40 mg/kg orally). The severity of the lung tissue inflammatory injury was expressed as pulmonary damage scores (PDS). Alveolar epithelial cell apoptosis was confirmed by TUNEL assay (DNA fragmentation) and expressed as an apoptotic index (AI), and immunohistochemically for cleaved caspase-3, cytochrome C, and anti-apoptotic Bcl-xL, an inhibitor of apoptosis, survivin, and transcriptional factor, NF-kB/p65. Severe inflammatory injury of pulmonary parenchyma (PDS 3.33 ± 0.48) was developed after the LPS challenge, whereas simvastatin significantly and dose-dependently protected lung histology after LPS (p < 0.01). Simvastatin in a dose of 40 mg/kg showed the most significant effects in amelioration alveolar epithelial cells apoptosis, demonstrating this as a marked decrease of AI (p < 0.01 vs. LPS), cytochrome C, and cleaved caspase-3 expression. Furthermore, simvastatin significantly enhanced the expression of Bcl-xL and survivin. Finally, the expression of survivin and its regulator NF-kB/p65 in the alveolar epithelium was in strong positive correlation across the groups. Simvastatin could play a protective role against LPS-induced ALI and apoptosis of the alveolar–endothelial barrier. Taken together, these effects were seemingly mediated by inhibition of caspase 3 and cytochrome C, a finding that might be associated with the up-regulation of cell-survival survivin/NF-kB/p65 pathway and Bcl-xL.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Amelioration of Endotoxin-Induced Acute Lung Injury and
Alveolar Epithelial Cells Apoptosis by Simvastatin Is
Associated with Up-Regulation of Survivin/NF-KB/p65 Pathway
VL  - 23
IS  - 5
SP  - 2596
DO  - 10.3390/ijms23052596
ER  - 

@article{
author = "Nežić, Lana and Amidžić, Ljiljana and Škrbić, Ranko and Gajanin, Radoslav and Mandić, Danijela and Dumanović, Jelena and Milovanović, Zoran and Jaćević, Vesna",
year = "2022",
abstract = "Disruption of the alveolar–endothelial barrier caused by inflammation leads to the progression of septic acute lung injury (ALI). In the present study, we investigated the beneficial effects of simvastatin on the endotoxin lipopolysaccharide (LPS)-induced ALI and its related mechanisms. A model of ALI was induced within experimental sepsis developed by intraperitoneal injection of a single non-lethal LPS dose after short-term simvastatin pretreatment (10–40 mg/kg orally). The severity of the lung tissue inflammatory injury was expressed as pulmonary damage scores (PDS). Alveolar epithelial cell apoptosis was confirmed by TUNEL assay (DNA fragmentation) and expressed as an apoptotic index (AI), and immunohistochemically for cleaved caspase-3, cytochrome C, and anti-apoptotic Bcl-xL, an inhibitor of apoptosis, survivin, and transcriptional factor, NF-kB/p65. Severe inflammatory injury of pulmonary parenchyma (PDS 3.33 ± 0.48) was developed after the LPS challenge, whereas simvastatin significantly and dose-dependently protected lung histology after LPS (p < 0.01). Simvastatin in a dose of 40 mg/kg showed the most significant effects in amelioration alveolar epithelial cells apoptosis, demonstrating this as a marked decrease of AI (p < 0.01 vs. LPS), cytochrome C, and cleaved caspase-3 expression. Furthermore, simvastatin significantly enhanced the expression of Bcl-xL and survivin. Finally, the expression of survivin and its regulator NF-kB/p65 in the alveolar epithelium was in strong positive correlation across the groups. Simvastatin could play a protective role against LPS-induced ALI and apoptosis of the alveolar–endothelial barrier. Taken together, these effects were seemingly mediated by inhibition of caspase 3 and cytochrome C, a finding that might be associated with the up-regulation of cell-survival survivin/NF-kB/p65 pathway and Bcl-xL.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Amelioration of Endotoxin-Induced Acute Lung Injury and
Alveolar Epithelial Cells Apoptosis by Simvastatin Is
Associated with Up-Regulation of Survivin/NF-KB/p65 Pathway",
volume = "23",
number = "5",
pages = "2596",
doi = "10.3390/ijms23052596"
}

Nežić, L., Amidžić, L., Škrbić, R., Gajanin, R., Mandić, D., Dumanović, J., Milovanović, Z.,& Jaćević, V.. (2022). Amelioration of Endotoxin-Induced Acute Lung Injury and
Alveolar Epithelial Cells Apoptosis by Simvastatin Is
Associated with Up-Regulation of Survivin/NF-KB/p65 Pathway. in International Journal of Molecular Sciences
MDPI., 23(5), 2596.
https://doi.org/10.3390/ijms23052596

Nežić L, Amidžić L, Škrbić R, Gajanin R, Mandić D, Dumanović J, Milovanović Z, Jaćević V. Amelioration of Endotoxin-Induced Acute Lung Injury and
Alveolar Epithelial Cells Apoptosis by Simvastatin Is
Associated with Up-Regulation of Survivin/NF-KB/p65 Pathway. in International Journal of Molecular Sciences. 2022;23(5):2596.
doi:10.3390/ijms23052596 .

Nežić, Lana, Amidžić, Ljiljana, Škrbić, Ranko, Gajanin, Radoslav, Mandić, Danijela, Dumanović, Jelena, Milovanović, Zoran, Jaćević, Vesna, "Amelioration of Endotoxin-Induced Acute Lung Injury and
Alveolar Epithelial Cells Apoptosis by Simvastatin Is
Associated with Up-Regulation of Survivin/NF-KB/p65 Pathway" in International Journal of Molecular Sciences, 23, no. 5 (2022):2596,
https://doi.org/10.3390/ijms23052596 . .