TY  - JOUR
AU  - Sudar, Emina M
AU  - Dobutović, Branislava D
AU  - Soskić, Sanja S
AU  - Mandušić, Vesna
AU  - Zakula, Zorica
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Janjetović, Kristina
AU  - Trajković, Vladimir S
AU  - Mikhailidis, Dimitri P
AU  - Isenović, Esma R
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1121
AB  - The purpose of this study was to examine the effects of ghrelin on protein kinase B (Akt) and mitogen-activated protein kinase p42/44 (ERK1/2) activation as well as ghrelin effects on inducible nitric oxide (NO) synthase (iNOS; for gene Nos2) activity/expression in rat hearts. Male Wistar rats were treated with ghrelin (0.3 nmol/5 mu l) or an equal volume of phosphate-buffered saline, injected every 24 h into the lateral cerebral ventricle for 5 days and 2 h after the last treatment the animals were sacrificed. Serum NO, l-arginine (l-Arg), and arginase activity were measured spectrophotometrically. For phosphorylation of Akt, ERK1/2, and iNOS protein expression, Western blot method was used. The expression of Nos2 mRNA was measured by the quantitative real-time polymerase chain reaction (qRT-PCR). Treatment with ghrelin significantly increased NO production in serum by 1.4-fold compared with control. The concentration of l-Arg was significantly higher in ghrelin-treated rats than in control while arginase activity was significantly lower in ghrelin-treated than in control hearts. Ghrelin treatment increased phosphorylation of Akt by 1.9-fold and ERK1/2 by 1.6-fold and increased iNOS expression by 2.5-fold compared with control. In addition, ghrelin treatment increased Nos2 gene expression by 2.2-fold as determined by qRT-PCR. These results indicate that ghrelin regulation of iNOS expression/activity is mediated via Akt/ERK1/2 signaling pathway. These results may be relevant to understanding molecular mechanisms underlying direct cardiovascular actions of ghrelin.
T2  - Journal of Physiology and Biochemistry
T1  - Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats
IS  - 2
VL  - 67
SP  - 483
EP  - 204
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1121
ER  - 

@article{
author = "Sudar, Emina M and Dobutović, Branislava D and Soskić, Sanja S and Mandušić, Vesna and Zakula, Zorica and Misirkić Marjanović, Maja and Vučićević, Ljubica and Janjetović, Kristina and Trajković, Vladimir S and Mikhailidis, Dimitri P and Isenović, Esma R",
year = "2011",
abstract = "The purpose of this study was to examine the effects of ghrelin on protein kinase B (Akt) and mitogen-activated protein kinase p42/44 (ERK1/2) activation as well as ghrelin effects on inducible nitric oxide (NO) synthase (iNOS; for gene Nos2) activity/expression in rat hearts. Male Wistar rats were treated with ghrelin (0.3 nmol/5 mu l) or an equal volume of phosphate-buffered saline, injected every 24 h into the lateral cerebral ventricle for 5 days and 2 h after the last treatment the animals were sacrificed. Serum NO, l-arginine (l-Arg), and arginase activity were measured spectrophotometrically. For phosphorylation of Akt, ERK1/2, and iNOS protein expression, Western blot method was used. The expression of Nos2 mRNA was measured by the quantitative real-time polymerase chain reaction (qRT-PCR). Treatment with ghrelin significantly increased NO production in serum by 1.4-fold compared with control. The concentration of l-Arg was significantly higher in ghrelin-treated rats than in control while arginase activity was significantly lower in ghrelin-treated than in control hearts. Ghrelin treatment increased phosphorylation of Akt by 1.9-fold and ERK1/2 by 1.6-fold and increased iNOS expression by 2.5-fold compared with control. In addition, ghrelin treatment increased Nos2 gene expression by 2.2-fold as determined by qRT-PCR. These results indicate that ghrelin regulation of iNOS expression/activity is mediated via Akt/ERK1/2 signaling pathway. These results may be relevant to understanding molecular mechanisms underlying direct cardiovascular actions of ghrelin.",
journal = "Journal of Physiology and Biochemistry",
title = "Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats",
number = "2",
volume = "67",
pages = "483-204",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1121"
}

Sudar, E. M., Dobutović, B. D., Soskić, S. S., Mandušić, V., Zakula, Z., Misirkić Marjanović, M., Vučićević, L., Janjetović, K., Trajković, V. S., Mikhailidis, D. P.,& Isenović, E. R.. (2011). Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats. in Journal of Physiology and Biochemistry, 67(2), 483-204.
https://hdl.handle.net/21.15107/rcub_ibiss_1121

Sudar EM, Dobutović BD, Soskić SS, Mandušić V, Zakula Z, Misirkić Marjanović M, Vučićević L, Janjetović K, Trajković VS, Mikhailidis DP, Isenović ER. Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats. in Journal of Physiology and Biochemistry. 2011;67(2):483-204.
https://hdl.handle.net/21.15107/rcub_ibiss_1121 .

Sudar, Emina M, Dobutović, Branislava D, Soskić, Sanja S, Mandušić, Vesna, Zakula, Zorica, Misirkić Marjanović, Maja, Vučićević, Ljubica, Janjetović, Kristina, Trajković, Vladimir S, Mikhailidis, Dimitri P, Isenović, Esma R, "Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats" in Journal of Physiology and Biochemistry, 67, no. 2 (2011):483-204,
https://hdl.handle.net/21.15107/rcub_ibiss_1121 .

TY  - JOUR
AU  - Mandušić, Vesna
AU  - Nikolić-Vukosavljević, Dragica
AU  - Tanić, Nikola T
AU  - Kanjer, Ksenija
AU  - Nešković-Konstantinović, Zora B.
AU  - Celeketić, Dusica C
AU  - Dimitrijević, Bogomir B.
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1586
AB  - Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (<= 20 mm, T1). The decrease of ER beta Delta 5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. Conclusions As far as we know, this is the first study in which ER beta Delta 5 mRNA splice variant was quantified by realtime RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ER beta 1, ER beta 2, and ER beta 5 isoforms. The higher expression of ER beta Delta 5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ER beta Delta 5 mRNA decreases in estrogen-dependent breast cancer.
T2  - Journal of Cancer Research and Clinical Oncology
T1  - Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer
IS  - 8
VL  - 133
EP  - 579
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1586
ER  - 

@article{
author = "Mandušić, Vesna and Nikolić-Vukosavljević, Dragica and Tanić, Nikola T and Kanjer, Ksenija and Nešković-Konstantinović, Zora B. and Celeketić, Dusica C and Dimitrijević, Bogomir B.",
year = "2007",
abstract = "Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (<= 20 mm, T1). The decrease of ER beta Delta 5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. Conclusions As far as we know, this is the first study in which ER beta Delta 5 mRNA splice variant was quantified by realtime RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ER beta 1, ER beta 2, and ER beta 5 isoforms. The higher expression of ER beta Delta 5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ER beta Delta 5 mRNA decreases in estrogen-dependent breast cancer.",
journal = "Journal of Cancer Research and Clinical Oncology",
title = "Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer",
number = "8",
volume = "133",
pages = "579",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1586"
}

Mandušić, V., Nikolić-Vukosavljević, D., Tanić, N. T., Kanjer, K., Nešković-Konstantinović, Z. B., Celeketić, D. C.,& Dimitrijević, B. B.. (2007). Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer. in Journal of Cancer Research and Clinical Oncology, 133(8).
https://hdl.handle.net/21.15107/rcub_ibiss_1586

Mandušić V, Nikolić-Vukosavljević D, Tanić NT, Kanjer K, Nešković-Konstantinović ZB, Celeketić DC, Dimitrijević BB. Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer. in Journal of Cancer Research and Clinical Oncology. 2007;133(8):null-579.
https://hdl.handle.net/21.15107/rcub_ibiss_1586 .

Mandušić, Vesna, Nikolić-Vukosavljević, Dragica, Tanić, Nikola T, Kanjer, Ksenija, Nešković-Konstantinović, Zora B., Celeketić, Dusica C, Dimitrijević, Bogomir B., "Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer" in Journal of Cancer Research and Clinical Oncology, 133, no. 8 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1586 .

TY  - JOUR
AU  - Mandušić, Vesna
AU  - Krtolica-Žikić, Koviljka V.
AU  - Nikolić-Vukosavljević, Dragica
AU  - Popov-Čeleketić, D.
AU  - Plećaš, D.
AU  - Boričić, I.
AU  - Dimitrijević, Bogomir B.
AU  - Tanić, N.
PY  - 2007
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/153
T2  - Archives of Biological Sciences
T1  - Transcriptional ratio of estrogen receptor β mRNAs in carcinomas and in normal tissues
IS  - 2
VL  - 59
SP  - 15
EP  - 16
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_153
ER  - 

@article{
author = "Mandušić, Vesna and Krtolica-Žikić, Koviljka V. and Nikolić-Vukosavljević, Dragica and Popov-Čeleketić, D. and Plećaš, D. and Boričić, I. and Dimitrijević, Bogomir B. and Tanić, N.",
year = "2007, 2007",
journal = "Archives of Biological Sciences",
title = "Transcriptional ratio of estrogen receptor β mRNAs in carcinomas and in normal tissues",
number = "2",
volume = "59",
pages = "15-16",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_153"
}

Mandušić, V., Krtolica-Žikić, K. V., Nikolić-Vukosavljević, D., Popov-Čeleketić, D., Plećaš, D., Boričić, I., Dimitrijević, B. B.,& Tanić, N.. (2007). Transcriptional ratio of estrogen receptor β mRNAs in carcinomas and in normal tissues. in Archives of Biological Sciences, 59(2), 15-16.
https://hdl.handle.net/21.15107/rcub_ibiss_153

Mandušić V, Krtolica-Žikić KV, Nikolić-Vukosavljević D, Popov-Čeleketić D, Plećaš D, Boričić I, Dimitrijević BB, Tanić N. Transcriptional ratio of estrogen receptor β mRNAs in carcinomas and in normal tissues. in Archives of Biological Sciences. 2007;59(2):15-16.
https://hdl.handle.net/21.15107/rcub_ibiss_153 .

Mandušić, Vesna, Krtolica-Žikić, Koviljka V., Nikolić-Vukosavljević, Dragica, Popov-Čeleketić, D., Plećaš, D., Boričić, I., Dimitrijević, Bogomir B., Tanić, N., "Transcriptional ratio of estrogen receptor β mRNAs in carcinomas and in normal tissues" in Archives of Biological Sciences, 59, no. 2 (2007):15-16,
https://hdl.handle.net/21.15107/rcub_ibiss_153 .

TY  - JOUR
AU  - Mandušić, Vesna
AU  - Nikolić-Vukosavljević, Dragica
AU  - Nešković-Konstantinović, Zora B.
AU  - Tanić, Nikola
AU  - Čeleketić, Dušica
AU  - Dimitrijević, Bogomir B.
PY  - 2006
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/374
AB  - Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ERβ isoforms correlates with ERα/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ERα and PR protein levels and for mRNA expression of two ERβ isoforms (ERβ1 and ERβΔ5). ERα and PR proteins were measured by classical biochemical techniques, and ERβ mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ERβ1 and ERβΔ5. We found that there is no correlation of ERβ1 mRNA expression with ERα and PR protein levels. We confirmed the existence of inverse correlation of ERβΔ5 with PR and of ERβΔ5 with ERα in the group of postmenopausal patients. In the subsets of tumors defined by ERα/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ERα with ERβΔ5 and PR with ERβΔ5isoform suggests that ERβΔ5 may have inhibitory effect on ERα activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ERα and ERβ isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance.
T2  - Archive of Oncology
T1  - The role of estrogen receptors isoforms in breast cancer
IS  - 3-4
VL  - 14
SP  - 106
EP  - 109
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_374
ER  - 

@article{
author = "Mandušić, Vesna and Nikolić-Vukosavljević, Dragica and Nešković-Konstantinović, Zora B. and Tanić, Nikola and Čeleketić, Dušica and Dimitrijević, Bogomir B.",
year = "2006, 2006",
abstract = "Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ERβ isoforms correlates with ERα/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ERα and PR protein levels and for mRNA expression of two ERβ isoforms (ERβ1 and ERβΔ5). ERα and PR proteins were measured by classical biochemical techniques, and ERβ mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ERβ1 and ERβΔ5. We found that there is no correlation of ERβ1 mRNA expression with ERα and PR protein levels. We confirmed the existence of inverse correlation of ERβΔ5 with PR and of ERβΔ5 with ERα in the group of postmenopausal patients. In the subsets of tumors defined by ERα/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ERα with ERβΔ5 and PR with ERβΔ5isoform suggests that ERβΔ5 may have inhibitory effect on ERα activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ERα and ERβ isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance.",
journal = "Archive of Oncology",
title = "The role of estrogen receptors isoforms in breast cancer",
number = "3-4",
volume = "14",
pages = "106-109",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_374"
}

Mandušić, V., Nikolić-Vukosavljević, D., Nešković-Konstantinović, Z. B., Tanić, N., Čeleketić, D.,& Dimitrijević, B. B.. (2006). The role of estrogen receptors isoforms in breast cancer. in Archive of Oncology, 14(3-4), 106-109.
https://hdl.handle.net/21.15107/rcub_ibiss_374

Mandušić V, Nikolić-Vukosavljević D, Nešković-Konstantinović ZB, Tanić N, Čeleketić D, Dimitrijević BB. The role of estrogen receptors isoforms in breast cancer. in Archive of Oncology. 2006;14(3-4):106-109.
https://hdl.handle.net/21.15107/rcub_ibiss_374 .

Mandušić, Vesna, Nikolić-Vukosavljević, Dragica, Nešković-Konstantinović, Zora B., Tanić, Nikola, Čeleketić, Dušica, Dimitrijević, Bogomir B., "The role of estrogen receptors isoforms in breast cancer" in Archive of Oncology, 14, no. 3-4 (2006):106-109,
https://hdl.handle.net/21.15107/rcub_ibiss_374 .