TY  - JOUR
AU  - Mandić, Danijela
AU  - Nežić, Lana
AU  - Amdžić, Ljiljana
AU  - Vojinović, Nataša
AU  - Gajanin, Radoslav
AU  - Popović, Miroslav
AU  - Đeri, Jugoslav
AU  - Todorović Balint, Milena
AU  - Dumanović, Jelena
AU  - Milovanović, Zoran
AU  - Grujić-Milanović, Jelica
AU  - Škrbić, Ranko
AU  - Jaćević, Vesna
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1343
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 (Multidisciplinary Digital Publishing Institute)
T2  - Cancers
T2  - Cancers
T1  - Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment
IS  - 16
SP  - 4106
VL  - 15
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 Todorović Balint, Milena 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 (Multidisciplinary Digital Publishing Institute)",
journal = "Cancers, Cancers",
title = "Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment",
number = "16",
pages = "4106",
volume = "15",
doi = "10.3390/cancers15164106"
}

Mandić, D., Nežić, L., Amdžić, L., Vojinović, N., Gajanin, R., Popović, M., Đeri, J., Todorović Balint, M., 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 (Multidisciplinary Digital Publishing Institute)., 15(16), 4106.
https://doi.org/10.3390/cancers15164106

Mandić D, Nežić L, Amdžić L, Vojinović N, Gajanin R, Popović M, Đeri J, Todorović Balint M, 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, Todorović Balint, Milena, 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  - Jaćević, Vesna
AU  - Dumanović, Jelena
AU  - Grujić-Milanović, Jelica
AU  - Milovanović, Zoran
AU  - Amidžić, Ljiljana
AU  - Vojinović, Nataša
AU  - Nežić, Lana
AU  - Marković, Bojan
AU  - Dobričić, Vladimir
AU  - Milosavljević, Petar
AU  - Nepovimova, Eugenie
AU  - Kuča, Kamil
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1342
AB  - Oxidative stress status and morphological injuries in the brain of Wistar rats induced by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, glutathione reductase, GR, and glutathione peroxidase, GPx), were estimated in the brain tissue homogenates on day 35 of the study. Brain alterations were carefully quantified by semiquantitative grading scales - brain damage score (BDS). Oxidative stress parameters, MDA and AOPP were significantly highest in the asoxime-, obidoxime- and K075-treated groups (p < 0.001). The activity of SOD and CAT was significantly elevated in the obidoxime-, K048-, and K075-treated groups (p < 0.001). Besides, GR was markedly decreased in the obidoxime- and K074-treated groups (p < 0.01), while treatment with K048, K074 and K075 induced extremely high elevation in GPx levels (p < 0.001). In the same groups of rats, brain alterations associated with polymorphonuclear cell infiltrate were significantly more severe than those observed in animals receiving only asoxime or K027 (p < 0.001). The presented results confirmed that treatment with different oximes significantly improved the oxidative status and attenuated signs of inflammation in rats' brains. Presented results, together with our previously published data can help to predict likely adverse systemic toxic effects, and target organ systems, which are crucial for establishing risk categories, as well as in dose selection of K-oximes as drug candidates.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T2  - Chemico-Biological InteractionsChem Biol Interact
T1  - Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes
SP  - 110658
VL  - 383
DO  - 10.1016/j.cbi.2023.110658
ER  - 

@article{
author = "Jaćević, Vesna and Dumanović, Jelena and Grujić-Milanović, Jelica and Milovanović, Zoran and Amidžić, Ljiljana and Vojinović, Nataša and Nežić, Lana and Marković, Bojan and Dobričić, Vladimir and Milosavljević, Petar and Nepovimova, Eugenie and Kuča, Kamil",
year = "2023",
abstract = "Oxidative stress status and morphological injuries in the brain of Wistar rats induced by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, glutathione reductase, GR, and glutathione peroxidase, GPx), were estimated in the brain tissue homogenates on day 35 of the study. Brain alterations were carefully quantified by semiquantitative grading scales - brain damage score (BDS). Oxidative stress parameters, MDA and AOPP were significantly highest in the asoxime-, obidoxime- and K075-treated groups (p < 0.001). The activity of SOD and CAT was significantly elevated in the obidoxime-, K048-, and K075-treated groups (p < 0.001). Besides, GR was markedly decreased in the obidoxime- and K074-treated groups (p < 0.01), while treatment with K048, K074 and K075 induced extremely high elevation in GPx levels (p < 0.001). In the same groups of rats, brain alterations associated with polymorphonuclear cell infiltrate were significantly more severe than those observed in animals receiving only asoxime or K027 (p < 0.001). The presented results confirmed that treatment with different oximes significantly improved the oxidative status and attenuated signs of inflammation in rats' brains. Presented results, together with our previously published data can help to predict likely adverse systemic toxic effects, and target organ systems, which are crucial for establishing risk categories, as well as in dose selection of K-oximes as drug candidates.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions, Chemico-Biological InteractionsChem Biol Interact",
title = "Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes",
pages = "110658",
volume = "383",
doi = "10.1016/j.cbi.2023.110658"
}

Jaćević, V., Dumanović, J., Grujić-Milanović, J., Milovanović, Z., Amidžić, L., Vojinović, N., Nežić, L., Marković, B., Dobričić, V., Milosavljević, P., Nepovimova, E.,& Kuča, K.. (2023). Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-Biological Interactions
Elsevier., 383, 110658.
https://doi.org/10.1016/j.cbi.2023.110658

Jaćević V, Dumanović J, Grujić-Milanović J, Milovanović Z, Amidžić L, Vojinović N, Nežić L, Marković B, Dobričić V, Milosavljević P, Nepovimova E, Kuča K. Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-Biological Interactions. 2023;383:110658.
doi:10.1016/j.cbi.2023.110658 .

Jaćević, Vesna, Dumanović, Jelena, Grujić-Milanović, Jelica, Milovanović, Zoran, Amidžić, Ljiljana, Vojinović, Nataša, Nežić, Lana, Marković, Bojan, Dobričić, Vladimir, Milosavljević, Petar, Nepovimova, Eugenie, Kuča, Kamil, "Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes" in Chemico-Biological Interactions, 383 (2023):110658,
https://doi.org/10.1016/j.cbi.2023.110658 . .