TY  - JOUR
AU  - Ivanović, Vesna
AU  - Demajo, Miroslav
AU  - Todorović-Raković, N
AU  - Nikolić-Vukosavljević, Dragica
AU  - Nešković-Konstantinović, Zora
AU  - Krtolica-Žikić, Koviljka
AU  - Veljković, Veljko
AU  - Prljić, Jelena
AU  - Dimitrijević, Bogomir B.
PY  - 2004
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2769
AB  - Although overexpression of TGF-beta(1) protein has been demonstrated in advanced breast cancer(BC) patients, as well as in other solid tumours, the molecular mechanism of this process remains obscure. This paper proposes that a genetic/epigenetic alteration might occur in the TGF-beta(1) gene, within the region coding for the recognition site with TGF(beta) receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta(1) cascade-related BC progression. To establish the operational framework for this hypothesis, in the present study, this recognition site was identified by the Informational Spectrum Method (ISM) to comprise two TGF-beta(1) peptides (positions 47-66 as and 83-112 aa) and one receptor peptide at positions 112-151 as of the extracellular domain of the receptor (TbetaRII(M)). The TbetaRII(M) locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta(1) analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta(1) MAb (MAb) and other with TbetaRII(M) as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta(1) elevation. In MAb-profile, the TGF-beta(1) increase was detected in 7 of 8 patients, whereas analogous TbetaRII(M)-profile revealed the elevation in 3 of 8 patients, taking a 50% of maximal elevation as the cut-off value. These findings are consistent with the proposed aberration of TGF-beta(1) ligand within the TbetaRII recognition site. Summarizing, this model system is a good starting point for further genetic studies, particularly on genetic/epigenetic alterations of sequences involved in TGF-beta(1) and TbetaRII(M) interaction, with putative prognostic value for breast cancer. (C) 2004 Elsevier Ltd. All rights reserved.
T2  - Medical Hypotheses
T1  - Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer
VL  - 62
IS  - 5
SP  - 727
EP  - 732
DO  - 10.1016/j.mehy.2003.11.027
ER  - 

@article{
author = "Ivanović, Vesna and Demajo, Miroslav and Todorović-Raković, N and Nikolić-Vukosavljević, Dragica and Nešković-Konstantinović, Zora and Krtolica-Žikić, Koviljka and Veljković, Veljko and Prljić, Jelena and Dimitrijević, Bogomir B.",
year = "2004",
abstract = "Although overexpression of TGF-beta(1) protein has been demonstrated in advanced breast cancer(BC) patients, as well as in other solid tumours, the molecular mechanism of this process remains obscure. This paper proposes that a genetic/epigenetic alteration might occur in the TGF-beta(1) gene, within the region coding for the recognition site with TGF(beta) receptor type II, leading to a disruption of the ligand-receptor interaction and triggering the TGF-beta(1) cascade-related BC progression. To establish the operational framework for this hypothesis, in the present study, this recognition site was identified by the Informational Spectrum Method (ISM) to comprise two TGF-beta(1) peptides (positions 47-66 as and 83-112 aa) and one receptor peptide at positions 112-151 as of the extracellular domain of the receptor (TbetaRII(M)). The TbetaRII(M) locus was further evaluated by ISM-derived deletion analysis of the TbetaRII sequences. To provide experimental support for the proposed model, a pilot study of plasma TGF-beta(1) analysis was performed in advanced BC patients (n = 8). Two commercial ELISA assays, one with specific alphaTGF-beta(1) MAb (MAb) and other with TbetaRII(M) as the immobilized phase, revealed pronounced differences in the pattern of plasma TGF-beta(1) elevation. In MAb-profile, the TGF-beta(1) increase was detected in 7 of 8 patients, whereas analogous TbetaRII(M)-profile revealed the elevation in 3 of 8 patients, taking a 50% of maximal elevation as the cut-off value. These findings are consistent with the proposed aberration of TGF-beta(1) ligand within the TbetaRII recognition site. Summarizing, this model system is a good starting point for further genetic studies, particularly on genetic/epigenetic alterations of sequences involved in TGF-beta(1) and TbetaRII(M) interaction, with putative prognostic value for breast cancer. (C) 2004 Elsevier Ltd. All rights reserved.",
journal = "Medical Hypotheses",
title = "Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer",
volume = "62",
number = "5",
pages = "727-732",
doi = "10.1016/j.mehy.2003.11.027"
}

Ivanović, V., Demajo, M., Todorović-Raković, N., Nikolić-Vukosavljević, D., Nešković-Konstantinović, Z., Krtolica-Žikić, K., Veljković, V., Prljić, J.,& Dimitrijević, B. B.. (2004). Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer. in Medical Hypotheses, 62(5), 727-732.
https://doi.org/10.1016/j.mehy.2003.11.027

Ivanović V, Demajo M, Todorović-Raković N, Nikolić-Vukosavljević D, Nešković-Konstantinović Z, Krtolica-Žikić K, Veljković V, Prljić J, Dimitrijević BB. Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer. in Medical Hypotheses. 2004;62(5):727-732.
doi:10.1016/j.mehy.2003.11.027 .

Ivanović, Vesna, Demajo, Miroslav, Todorović-Raković, N, Nikolić-Vukosavljević, Dragica, Nešković-Konstantinović, Zora, Krtolica-Žikić, Koviljka, Veljković, Veljko, Prljić, Jelena, Dimitrijević, Bogomir B., "Localization of recognition site between transforming growth factor-beta(1) (TGF-beta(1)) and TGF beta receptor type II: possible implications in breast cancer" in Medical Hypotheses, 62, no. 5 (2004):727-732,
https://doi.org/10.1016/j.mehy.2003.11.027 . .

TY  - JOUR
AU  - Nikolić-Vukosavljević, Dragica
AU  - Todorović-Raković, N
AU  - Demajo, Miroslav
AU  - Ivanović, Vesna
AU  - Neskovic, B
AU  - Markicevic, M
AU  - Nešković-Konstantinović, Zora
PY  - 2004
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2869
AB  - A pilot study was conducted to assess whether plasma levels of transforming growth factor-beta 1 (TGF-beta 1) might facilitate biological subgrouping of postmenopausal metastatic breast cancer patients, and, accordingly, its applicability in clinical oncology. This study included 29 postmenopausal metastatic breast cancer patients. Plasma TGF-beta 1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Estrogen and progesterone receptors were assayed by radioligand binding, in accordance with the recommendation of the EORTC. Concentrations of 17-beta estradiol were determined by using ELISA-microwell method (DIALAB). Overall survival was followed for 24 months for each individual patient. Stratification of the patients by ER/PR status showed that 14 patients with estrogen receptor-negative, progesterone receptor-negative carcinomas displayed a statistically significant increase in plasma TGF-beta 1 levels when compared to plasma TGF-beta 1 levels of 6 patients with ER-positive, PR-positive carcinomas (P=0.04). In this study, 7 out of 14 patients with negative receptors status had no plasma TGF-beta 1 values overlapping with patients having positive receptors status. The TGF-beta 1 cut-off value was defined as the highest plasma TGF-beta 1 level of ER-positive, PR-positive patients: 3.28 ng/ml. This plasma TGF-beta 1 cut-off value defined low-risk subgroup of 19 patients (! 3.28 ng/ml) and high-risk subgroup of 10 patients ( GT 3.28 ng/ml) (P=0.047). Plasma TGF-beta 1-related survival was independent of the classical prognostic factors of metastatic breast cancer. Accordingly, a clinical significance of elevated plasma TGF-beta 1 levels may be suggested.
T2  - Clinical and Experimental Metastasis
T1  - Plasma TGF-beta 1-related survival of postmenopausal metastatic breast cancer patients
VL  - 21
IS  - 7
SP  - 581
EP  - 585
UR  - https://hdl.handle.net/21.15107/rcub_vinar_2869
ER  - 

@article{
author = "Nikolić-Vukosavljević, Dragica and Todorović-Raković, N and Demajo, Miroslav and Ivanović, Vesna and Neskovic, B and Markicevic, M and Nešković-Konstantinović, Zora",
year = "2004",
abstract = "A pilot study was conducted to assess whether plasma levels of transforming growth factor-beta 1 (TGF-beta 1) might facilitate biological subgrouping of postmenopausal metastatic breast cancer patients, and, accordingly, its applicability in clinical oncology. This study included 29 postmenopausal metastatic breast cancer patients. Plasma TGF-beta 1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Estrogen and progesterone receptors were assayed by radioligand binding, in accordance with the recommendation of the EORTC. Concentrations of 17-beta estradiol were determined by using ELISA-microwell method (DIALAB). Overall survival was followed for 24 months for each individual patient. Stratification of the patients by ER/PR status showed that 14 patients with estrogen receptor-negative, progesterone receptor-negative carcinomas displayed a statistically significant increase in plasma TGF-beta 1 levels when compared to plasma TGF-beta 1 levels of 6 patients with ER-positive, PR-positive carcinomas (P=0.04). In this study, 7 out of 14 patients with negative receptors status had no plasma TGF-beta 1 values overlapping with patients having positive receptors status. The TGF-beta 1 cut-off value was defined as the highest plasma TGF-beta 1 level of ER-positive, PR-positive patients: 3.28 ng/ml. This plasma TGF-beta 1 cut-off value defined low-risk subgroup of 19 patients (! 3.28 ng/ml) and high-risk subgroup of 10 patients ( GT 3.28 ng/ml) (P=0.047). Plasma TGF-beta 1-related survival was independent of the classical prognostic factors of metastatic breast cancer. Accordingly, a clinical significance of elevated plasma TGF-beta 1 levels may be suggested.",
journal = "Clinical and Experimental Metastasis",
title = "Plasma TGF-beta 1-related survival of postmenopausal metastatic breast cancer patients",
volume = "21",
number = "7",
pages = "581-585",
url = "https://hdl.handle.net/21.15107/rcub_vinar_2869"
}

Nikolić-Vukosavljević, D., Todorović-Raković, N., Demajo, M., Ivanović, V., Neskovic, B., Markicevic, M.,& Nešković-Konstantinović, Z.. (2004). Plasma TGF-beta 1-related survival of postmenopausal metastatic breast cancer patients. in Clinical and Experimental Metastasis, 21(7), 581-585.
https://hdl.handle.net/21.15107/rcub_vinar_2869

Nikolić-Vukosavljević D, Todorović-Raković N, Demajo M, Ivanović V, Neskovic B, Markicevic M, Nešković-Konstantinović Z. Plasma TGF-beta 1-related survival of postmenopausal metastatic breast cancer patients. in Clinical and Experimental Metastasis. 2004;21(7):581-585.
https://hdl.handle.net/21.15107/rcub_vinar_2869 .

Nikolić-Vukosavljević, Dragica, Todorović-Raković, N, Demajo, Miroslav, Ivanović, Vesna, Neskovic, B, Markicevic, M, Nešković-Konstantinović, Zora, "Plasma TGF-beta 1-related survival of postmenopausal metastatic breast cancer patients" in Clinical and Experimental Metastasis, 21, no. 7 (2004):581-585,
https://hdl.handle.net/21.15107/rcub_vinar_2869 .

TY  - JOUR
AU  - Ivanović, Vesna
AU  - Todorović-Raković, N
AU  - Demajo, Miroslav
AU  - Nešković-Konstantinović, Zora
AU  - Subota, Vesna
AU  - Ivanišević-Milovanović, Olivera
AU  - Nikolić-Vukosavljević, Dragica
PY  - 2003
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2617
AB  - We examined the association between an elevated plasma TGF-beta(1) level and the disease progression of advanced breast cancer (BC) patients (n = 44). TGF-beta(1) levels were detected by an enzyme-linked immunosorbent assay (ELISA). Platelet carryover and in vitro platelet activation in our plasma samples was assessed and found to be insignificant. Plasma TGF-beta(1) values were significantly elevated (P LT 0.05) in stage IIIB/IV patients (median value: 2.40 ng/ml, range: 0.13-8.48 ng/ml, n=44) compared with healthy donors (median value: 1.30 ng/ml, range: 0.41-4.93 ng/ml, n=36). Although pronounced in metastatic patients, especially those who had been newly diagnosed, TGF- and beta;(1) elevation was independent of tumour mass, site of distant metastases, histopathological type, steroid receptor (SR) content and age of the BC patients. Follow-up of 6 patients indicated a relationship between the plasma TGF- and beta;(1) and the patients response. This suggests that TGF- and beta;(1), may be a promising prognostic marker for breast cancer patients with advanced disease. Confirmatory large-scale studies are needed, particularly given the overlap of values between our different subgroups analysed.
T2  - European Journal of Cancer
T1  - Elevated plasma levels of transforming growth factor-beta(1) (TGF-beta(1)) in patients with advanced breast cancer: association with disease progression
VL  - 39
IS  - 4
SP  - 454
EP  - 461
DO  - 10.1016/S0959-8049(02)00502-6
ER  - 

@article{
author = "Ivanović, Vesna and Todorović-Raković, N and Demajo, Miroslav and Nešković-Konstantinović, Zora and Subota, Vesna and Ivanišević-Milovanović, Olivera and Nikolić-Vukosavljević, Dragica",
year = "2003",
abstract = "We examined the association between an elevated plasma TGF-beta(1) level and the disease progression of advanced breast cancer (BC) patients (n = 44). TGF-beta(1) levels were detected by an enzyme-linked immunosorbent assay (ELISA). Platelet carryover and in vitro platelet activation in our plasma samples was assessed and found to be insignificant. Plasma TGF-beta(1) values were significantly elevated (P LT 0.05) in stage IIIB/IV patients (median value: 2.40 ng/ml, range: 0.13-8.48 ng/ml, n=44) compared with healthy donors (median value: 1.30 ng/ml, range: 0.41-4.93 ng/ml, n=36). Although pronounced in metastatic patients, especially those who had been newly diagnosed, TGF- and beta;(1) elevation was independent of tumour mass, site of distant metastases, histopathological type, steroid receptor (SR) content and age of the BC patients. Follow-up of 6 patients indicated a relationship between the plasma TGF- and beta;(1) and the patients response. This suggests that TGF- and beta;(1), may be a promising prognostic marker for breast cancer patients with advanced disease. Confirmatory large-scale studies are needed, particularly given the overlap of values between our different subgroups analysed.",
journal = "European Journal of Cancer",
title = "Elevated plasma levels of transforming growth factor-beta(1) (TGF-beta(1)) in patients with advanced breast cancer: association with disease progression",
volume = "39",
number = "4",
pages = "454-461",
doi = "10.1016/S0959-8049(02)00502-6"
}

Ivanović, V., Todorović-Raković, N., Demajo, M., Nešković-Konstantinović, Z., Subota, V., Ivanišević-Milovanović, O.,& Nikolić-Vukosavljević, D.. (2003). Elevated plasma levels of transforming growth factor-beta(1) (TGF-beta(1)) in patients with advanced breast cancer: association with disease progression. in European Journal of Cancer, 39(4), 454-461.
https://doi.org/10.1016/S0959-8049(02)00502-6

Ivanović V, Todorović-Raković N, Demajo M, Nešković-Konstantinović Z, Subota V, Ivanišević-Milovanović O, Nikolić-Vukosavljević D. Elevated plasma levels of transforming growth factor-beta(1) (TGF-beta(1)) in patients with advanced breast cancer: association with disease progression. in European Journal of Cancer. 2003;39(4):454-461.
doi:10.1016/S0959-8049(02)00502-6 .

Ivanović, Vesna, Todorović-Raković, N, Demajo, Miroslav, Nešković-Konstantinović, Zora, Subota, Vesna, Ivanišević-Milovanović, Olivera, Nikolić-Vukosavljević, Dragica, "Elevated plasma levels of transforming growth factor-beta(1) (TGF-beta(1)) in patients with advanced breast cancer: association with disease progression" in European Journal of Cancer, 39, no. 4 (2003):454-461,
https://doi.org/10.1016/S0959-8049(02)00502-6 . .

TY  - JOUR
AU  - Ivanović, Vesna
AU  - Todorović-Raković, N
AU  - Demajo, Miroslav
AU  - Nešković-Konstantinović, Zora
AU  - Nikolić-Vukosavljević, Dragica
AU  - Ivanišević-Milovanović, Olivera
AU  - Mitrovic, L
PY  - 2001
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2438
AB  - There has been much controversy concerning the detection of plasma TGF-beta (1) levels in breast cancer patients. The present study provides preliminary evidence on underestimated plasma TGF-beta (1) levels due to ex vivo proteolysis and previous therapeutic treatment of breast cancer patients, as detected by a commercial ELISA immunoassay. Our results revealed that the addition of protease inhibitors: phenylmethylsulfonyl fluoride and aprotinin, to the plasma preparation of healthy volunteers, has increased TGF-beta (1) median Value from 3.1 ng/mL to 33.9 ng/mL. Relative to that, in protease-inhibited plasma of locally advanced/metastatic breast cancer patients, significantly elevated TGF-beta (1) was observed (median value: 65.5 ng/mL), which included untreated and previously treated patients with median values of: 74.2 ng/mL and 58.1 ng/mL, respectively. These findings indicate to the potential usefulness of this plasma marker in breast cancer prognosis, thus deserving future clinical attention.
T2  - Jugoslovenska Medicinska Biohemija
T1  - Detection of transforming growth factor-beta 1 in human plasma - A pilot study on breast cancer patients
VL  - 20
IS  - 2
SP  - 81
EP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_vinar_2438
ER  - 

@article{
author = "Ivanović, Vesna and Todorović-Raković, N and Demajo, Miroslav and Nešković-Konstantinović, Zora and Nikolić-Vukosavljević, Dragica and Ivanišević-Milovanović, Olivera and Mitrovic, L",
year = "2001",
abstract = "There has been much controversy concerning the detection of plasma TGF-beta (1) levels in breast cancer patients. The present study provides preliminary evidence on underestimated plasma TGF-beta (1) levels due to ex vivo proteolysis and previous therapeutic treatment of breast cancer patients, as detected by a commercial ELISA immunoassay. Our results revealed that the addition of protease inhibitors: phenylmethylsulfonyl fluoride and aprotinin, to the plasma preparation of healthy volunteers, has increased TGF-beta (1) median Value from 3.1 ng/mL to 33.9 ng/mL. Relative to that, in protease-inhibited plasma of locally advanced/metastatic breast cancer patients, significantly elevated TGF-beta (1) was observed (median value: 65.5 ng/mL), which included untreated and previously treated patients with median values of: 74.2 ng/mL and 58.1 ng/mL, respectively. These findings indicate to the potential usefulness of this plasma marker in breast cancer prognosis, thus deserving future clinical attention.",
journal = "Jugoslovenska Medicinska Biohemija",
title = "Detection of transforming growth factor-beta 1 in human plasma - A pilot study on breast cancer patients",
volume = "20",
number = "2",
pages = "81-87",
url = "https://hdl.handle.net/21.15107/rcub_vinar_2438"
}

Ivanović, V., Todorović-Raković, N., Demajo, M., Nešković-Konstantinović, Z., Nikolić-Vukosavljević, D., Ivanišević-Milovanović, O.,& Mitrovic, L.. (2001). Detection of transforming growth factor-beta 1 in human plasma - A pilot study on breast cancer patients. in Jugoslovenska Medicinska Biohemija, 20(2), 81-87.
https://hdl.handle.net/21.15107/rcub_vinar_2438

Ivanović V, Todorović-Raković N, Demajo M, Nešković-Konstantinović Z, Nikolić-Vukosavljević D, Ivanišević-Milovanović O, Mitrovic L. Detection of transforming growth factor-beta 1 in human plasma - A pilot study on breast cancer patients. in Jugoslovenska Medicinska Biohemija. 2001;20(2):81-87.
https://hdl.handle.net/21.15107/rcub_vinar_2438 .

Ivanović, Vesna, Todorović-Raković, N, Demajo, Miroslav, Nešković-Konstantinović, Zora, Nikolić-Vukosavljević, Dragica, Ivanišević-Milovanović, Olivera, Mitrovic, L, "Detection of transforming growth factor-beta 1 in human plasma - A pilot study on breast cancer patients" in Jugoslovenska Medicinska Biohemija, 20, no. 2 (2001):81-87,
https://hdl.handle.net/21.15107/rcub_vinar_2438 .