TY  - JOUR
AU  - Damjanović, Svetozar S
AU  - Antić, Jadranka A
AU  - Ilić, Bojana B
AU  - Beleslin-Cokić, Bojana B
AU  - Ivović, Miomira S
AU  - Ognjanović, Sanja I
AU  - Isailović, Tatjana V
AU  - Popović, Bojana M
AU  - Bozić, Ivana B
AU  - Tatić, Svetislav B
AU  - Matić, Gordana
AU  - Todorović, Vera N
AU  - Paunović, Ivan R
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1085
AB  - Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, BclI, and 9 beta) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.7-5.1; p < 0.001) and minor allele of 9 beta (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of Al. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p <= 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9 beta, are associated with Als. Their concurrent presence in patients reduces GC sensitivity Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00261
T2  - Molecular Medicine
T1  - Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids
IS  - 11
VL  - 18
SP  - 189
EP  - 1465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1085
ER  - 

@article{
author = "Damjanović, Svetozar S and Antić, Jadranka A and Ilić, Bojana B and Beleslin-Cokić, Bojana B and Ivović, Miomira S and Ognjanović, Sanja I and Isailović, Tatjana V and Popović, Bojana M and Bozić, Ivana B and Tatić, Svetislav B and Matić, Gordana and Todorović, Vera N and Paunović, Ivan R",
year = "2012",
abstract = "Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, BclI, and 9 beta) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.7-5.1; p < 0.001) and minor allele of 9 beta (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of Al. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p <= 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9 beta, are associated with Als. Their concurrent presence in patients reduces GC sensitivity Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00261",
journal = "Molecular Medicine",
title = "Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids",
number = "11",
volume = "18",
pages = "189-1465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1085"
}

Damjanović, S. S., Antić, J. A., Ilić, B. B., Beleslin-Cokić, B. B., Ivović, M. S., Ognjanović, S. I., Isailović, T. V., Popović, B. M., Bozić, I. B., Tatić, S. B., Matić, G., Todorović, V. N.,& Paunović, I. R.. (2012). Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids. in Molecular Medicine, 18(11), 189-1465.
https://hdl.handle.net/21.15107/rcub_ibiss_1085

Damjanović SS, Antić JA, Ilić BB, Beleslin-Cokić BB, Ivović MS, Ognjanović SI, Isailović TV, Popović BM, Bozić IB, Tatić SB, Matić G, Todorović VN, Paunović IR. Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids. in Molecular Medicine. 2012;18(11):189-1465.
https://hdl.handle.net/21.15107/rcub_ibiss_1085 .

Damjanović, Svetozar S, Antić, Jadranka A, Ilić, Bojana B, Beleslin-Cokić, Bojana B, Ivović, Miomira S, Ognjanović, Sanja I, Isailović, Tatjana V, Popović, Bojana M, Bozić, Ivana B, Tatić, Svetislav B, Matić, Gordana, Todorović, Vera N, Paunović, Ivan R, "Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids" in Molecular Medicine, 18, no. 11 (2012):189-1465,
https://hdl.handle.net/21.15107/rcub_ibiss_1085 .

TY  - JOUR
AU  - Kataranovski, Milena
AU  - Vlaski, Marija
AU  - Kataranovski, Dragan S.
AU  - Tosić, N
AU  - Mandić-Radić, Slavka
AU  - Todorović, Vera N
PY  - 2003
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1764
AB  - The immunotoxicity of epicutaneously administered anticoagulant rodenticide warfarin (WF) was examined in this work by using experimental contact hypersensitivity (CHS) reaction to hapten dinitrochlorobenzene (DNCB). WF (0.05 and 0.5 mg/kg) administration 24 h before the induction of CHS does not change expression of CHS evaluated by ear swelling assay. Regional draining lymph node response during sensitization phase was characterized by decreased cellularity but increased spontaneous and IL-2 stimulated proliferation of draining lymph node cells (DLC). No changes in IL-2 production and in numbers of CD25(+) cells were noted and even decreased proliferative index (ratio of IL-2 stimulated to unstimulated DLC proliferation) was detected. Increase in granulocyte activity (MTT reduction and adhesion to plastic) was noted following application of WF solely with further increase following subsequent application of DNCB, when granulocyte activation (NBT reduction) was noted also. Access of WF into general circulation might be responsible for observed changes, what was supported by ex vivo changes in DLC and granulocyte functions assessed before initiation of sensitization and by in vitro effect of exogenous WF as well. Differential effects of WF on lymphocytes and granulocytes noted in this study highlight the need for simultaneous testing of both cell type activity what might constitute a more integrated approach in immunotoxicity studies. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
T2  - Toxicology
T1  - Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats
IS  - 1
VL  - 188
EP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1764
ER  - 

@article{
author = "Kataranovski, Milena and Vlaski, Marija and Kataranovski, Dragan S. and Tosić, N and Mandić-Radić, Slavka and Todorović, Vera N",
year = "2003",
abstract = "The immunotoxicity of epicutaneously administered anticoagulant rodenticide warfarin (WF) was examined in this work by using experimental contact hypersensitivity (CHS) reaction to hapten dinitrochlorobenzene (DNCB). WF (0.05 and 0.5 mg/kg) administration 24 h before the induction of CHS does not change expression of CHS evaluated by ear swelling assay. Regional draining lymph node response during sensitization phase was characterized by decreased cellularity but increased spontaneous and IL-2 stimulated proliferation of draining lymph node cells (DLC). No changes in IL-2 production and in numbers of CD25(+) cells were noted and even decreased proliferative index (ratio of IL-2 stimulated to unstimulated DLC proliferation) was detected. Increase in granulocyte activity (MTT reduction and adhesion to plastic) was noted following application of WF solely with further increase following subsequent application of DNCB, when granulocyte activation (NBT reduction) was noted also. Access of WF into general circulation might be responsible for observed changes, what was supported by ex vivo changes in DLC and granulocyte functions assessed before initiation of sensitization and by in vitro effect of exogenous WF as well. Differential effects of WF on lymphocytes and granulocytes noted in this study highlight the need for simultaneous testing of both cell type activity what might constitute a more integrated approach in immunotoxicity studies. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.",
journal = "Toxicology",
title = "Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats",
number = "1",
volume = "188",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1764"
}

Kataranovski, M., Vlaski, M., Kataranovski, D. S., Tosić, N., Mandić-Radić, S.,& Todorović, V. N.. (2003). Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats. in Toxicology, 188(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1764

Kataranovski M, Vlaski M, Kataranovski DS, Tosić N, Mandić-Radić S, Todorović VN. Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats. in Toxicology. 2003;188(1):null-100.
https://hdl.handle.net/21.15107/rcub_ibiss_1764 .

Kataranovski, Milena, Vlaski, Marija, Kataranovski, Dragan S., Tosić, N, Mandić-Radić, Slavka, Todorović, Vera N, "Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats" in Toxicology, 188, no. 1 (2003),
https://hdl.handle.net/21.15107/rcub_ibiss_1764 .