TY  - JOUR
AU  - Ostojić, Marija
AU  - Jevrić, Marko
AU  - Mitrović-Ajtić, Olivera
AU  - Živić, Kristina
AU  - Tanić, Miljana
AU  - Čavić, Milena
AU  - Srdić-Rajić, Tatjana
AU  - Grahovac, Jelena
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1396
AB  - Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motility and invasion. The aim of this study was to examine the expression and potential role of nischarin in melanoma. We found that nischarin expression was decreased in melanoma tissues compared to the uninvolved skin, and this was attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue. In addition to the previously reported cytoplasmic and membranous localization, we observed nischarin in the nuclei in melanoma patients’ tissues. NISCH expression in primary melanoma had favorable prognostic value for female patients, but, unexpectedly, high NISCH expression predicted worse prognosis for males. Gene set enrichment analysis suggested significant sex-related disparities in predicted association of NISCH with several signaling pathways, as well as with different tumor immune infiltrate composition in male and female patients. Taken together, our results imply that nischarin may have a role in melanoma progression, but that fine-tuning of the pathways it regulates is sex-dependent.
T2  - Research Square
T1  - Nischarin expression may have differing roles in male and female melanoma patients
DO  - 10.21203/rs.3.rs-1576440/v2
ER  - 

@article{
author = "Ostojić, Marija and Jevrić, Marko and Mitrović-Ajtić, Olivera and Živić, Kristina and Tanić, Miljana and Čavić, Milena and Srdić-Rajić, Tatjana and Grahovac, Jelena",
year = "2023",
abstract = "Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motility and invasion. The aim of this study was to examine the expression and potential role of nischarin in melanoma. We found that nischarin expression was decreased in melanoma tissues compared to the uninvolved skin, and this was attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue. In addition to the previously reported cytoplasmic and membranous localization, we observed nischarin in the nuclei in melanoma patients’ tissues. NISCH expression in primary melanoma had favorable prognostic value for female patients, but, unexpectedly, high NISCH expression predicted worse prognosis for males. Gene set enrichment analysis suggested significant sex-related disparities in predicted association of NISCH with several signaling pathways, as well as with different tumor immune infiltrate composition in male and female patients. Taken together, our results imply that nischarin may have a role in melanoma progression, but that fine-tuning of the pathways it regulates is sex-dependent.",
journal = "Research Square",
title = "Nischarin expression may have differing roles in male and female melanoma patients",
doi = "10.21203/rs.3.rs-1576440/v2"
}

Ostojić, M., Jevrić, M., Mitrović-Ajtić, O., Živić, K., Tanić, M., Čavić, M., Srdić-Rajić, T.,& Grahovac, J.. (2023). Nischarin expression may have differing roles in male and female melanoma patients. in Research Square.
https://doi.org/10.21203/rs.3.rs-1576440/v2

Ostojić M, Jevrić M, Mitrović-Ajtić O, Živić K, Tanić M, Čavić M, Srdić-Rajić T, Grahovac J. Nischarin expression may have differing roles in male and female melanoma patients. in Research Square. 2023;.
doi:10.21203/rs.3.rs-1576440/v2 .

Ostojić, Marija, Jevrić, Marko, Mitrović-Ajtić, Olivera, Živić, Kristina, Tanić, Miljana, Čavić, Milena, Srdić-Rajić, Tatjana, Grahovac, Jelena, "Nischarin expression may have differing roles in male and female melanoma patients" in Research Square (2023),
https://doi.org/10.21203/rs.3.rs-1576440/v2 . .

TY  - CONF
AU  - Vidosavljević, Marija
AU  - Srdić-Rajić, Tatjana
AU  - Mitrović-Ajtić, Olivera
AU  - Jevrić, Marko
AU  - Grahovac, Jelena
PY  - 2020
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1399
AB  - Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted 
BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still 
have poor prognosis with a median survival of 9 months and a long-term survival rate 
of 10%. There is an urgent need for novel treatment modalities that target metastatic 
melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that 
has been shown to be a tumor suppressor in breast cancer through regulation of 
cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has 
not been investigated to date. Of importance, several IR1 agonists are clinically 
approved for treatment of hypertension. The aim of this study was to examine the 
IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell 
viability. To confirm the target expression, we first determined IR1 levels in primary 
and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. 
We found that it is expressed in primary tumors and liver metastases and, to a lesser 
extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists 
– rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell 
lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently 
inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts 
and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced 
cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that 
imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already 
clinically approved agents have promising anti-cancer activity.
PB  - European Association for Cancer Research
C3  - 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy
T1  - Potential anti-melanoma activity of Imidazoline I1 receptor agonists
EP  - 92
SP  - 92
UR  - https://hdl.handle.net/21.15107/rcub_rimi_1399
ER  - 

@conference{
author = "Vidosavljević, Marija and Srdić-Rajić, Tatjana and Mitrović-Ajtić, Olivera and Jevrić, Marko and Grahovac, Jelena",
year = "2020",
abstract = "Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted 
BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still 
have poor prognosis with a median survival of 9 months and a long-term survival rate 
of 10%. There is an urgent need for novel treatment modalities that target metastatic 
melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that 
has been shown to be a tumor suppressor in breast cancer through regulation of 
cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has 
not been investigated to date. Of importance, several IR1 agonists are clinically 
approved for treatment of hypertension. The aim of this study was to examine the 
IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell 
viability. To confirm the target expression, we first determined IR1 levels in primary 
and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. 
We found that it is expressed in primary tumors and liver metastases and, to a lesser 
extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists 
– rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell 
lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently 
inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts 
and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced 
cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that 
imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already 
clinically approved agents have promising anti-cancer activity.",
publisher = "European Association for Cancer Research",
journal = "5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy",
title = "Potential anti-melanoma activity of Imidazoline I1 receptor agonists",
pages = "92-92",
url = "https://hdl.handle.net/21.15107/rcub_rimi_1399"
}

Vidosavljević, M., Srdić-Rajić, T., Mitrović-Ajtić, O., Jevrić, M.,& Grahovac, J.. (2020). Potential anti-melanoma activity of Imidazoline I1 receptor agonists. in 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy
European Association for Cancer Research., 92-92.
https://hdl.handle.net/21.15107/rcub_rimi_1399

Vidosavljević M, Srdić-Rajić T, Mitrović-Ajtić O, Jevrić M, Grahovac J. Potential anti-melanoma activity of Imidazoline I1 receptor agonists. in 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy. 2020;:92-92.
https://hdl.handle.net/21.15107/rcub_rimi_1399 .

Vidosavljević, Marija, Srdić-Rajić, Tatjana, Mitrović-Ajtić, Olivera, Jevrić, Marko, Grahovac, Jelena, "Potential anti-melanoma activity of Imidazoline I1 receptor agonists" in 5th EACR Conference A Matter of Life or Death Mechanisms, Models and Therapeutic Opportunities, 12-14 February 2020, Bergamo, Italy (2020):92-92,
https://hdl.handle.net/21.15107/rcub_rimi_1399 .

TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Santibanez, Juan F.
AU  - Kanjer, Ksenija
AU  - Tišma-Miletić, Nevena
AU  - Cavić, Milena
AU  - Galun, Daniel
AU  - Jevrić, Marko
AU  - Kardum, Nevena Đ.
AU  - Konić-Ristić, Aleksandra
AU  - Zoranović, Tamara
PY  - 2018
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/859
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells (vol 7, 3763, 2017)
VL  - 8
DO  - 10.1038/s41598-018-31450-1
ER  - 

@article{
author = "Srdić-Rajić, Tatjana and Santibanez, Juan F. and Kanjer, Ksenija and Tišma-Miletić, Nevena and Cavić, Milena and Galun, Daniel and Jevrić, Marko and Kardum, Nevena Đ. and Konić-Ristić, Aleksandra and Zoranović, Tamara",
year = "2018",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells (vol 7, 3763, 2017)",
volume = "8",
doi = "10.1038/s41598-018-31450-1"
}

Srdić-Rajić, T., Santibanez, J. F., Kanjer, K., Tišma-Miletić, N., Cavić, M., Galun, D., Jevrić, M., Kardum, N. Đ., Konić-Ristić, A.,& Zoranović, T.. (2018). Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells (vol 7, 3763, 2017). in Scientific Reports
Nature Publishing Group, London., 8.
https://doi.org/10.1038/s41598-018-31450-1

Srdić-Rajić T, Santibanez JF, Kanjer K, Tišma-Miletić N, Cavić M, Galun D, Jevrić M, Kardum NĐ, Konić-Ristić A, Zoranović T. Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells (vol 7, 3763, 2017). in Scientific Reports. 2018;8.
doi:10.1038/s41598-018-31450-1 .

Srdić-Rajić, Tatjana, Santibanez, Juan F., Kanjer, Ksenija, Tišma-Miletić, Nevena, Cavić, Milena, Galun, Daniel, Jevrić, Marko, Kardum, Nevena Đ., Konić-Ristić, Aleksandra, Zoranović, Tamara, "Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells (vol 7, 3763, 2017)" in Scientific Reports, 8 (2018),
https://doi.org/10.1038/s41598-018-31450-1 . .

TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Santibanez, Juan F.
AU  - Kanjer, Ksenija
AU  - Tišma-Miletić, Nevena
AU  - Cavić, Milena
AU  - Galun, Daniel
AU  - Jevrić, Marko
AU  - Kardum, Nevena Đ.
AU  - Konić-Ristić, Aleksandra
AU  - Zoranović, Tamara
PY  - 2017
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/819
AB  - Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells. We report that cotreatment of MCF7 with Viscum album and Dox abrogates G2/M cycle arrest replacing senescence with intrinsic apoptotic program. Mechanistically, this switch was associated with down-regulation of p21, p53/p73 as well as Erk1/2 and p38 activation. Our findings, therefore, identify a novel mechanistic axis of additive antitumor activity of Viscum album and low dose-Dox. In conclusion, ER + breast cancer patients may benefit from addition of Viscum album to low-dose Dox chemotherapy due to suppression of cancer cell senescence and induction of apoptosis.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells
SP  - 3763
VL  - 7
DO  - 10.1038/s41598-017-03898-0
ER  - 

@article{
author = "Srdić-Rajić, Tatjana and Santibanez, Juan F. and Kanjer, Ksenija and Tišma-Miletić, Nevena and Cavić, Milena and Galun, Daniel and Jevrić, Marko and Kardum, Nevena Đ. and Konić-Ristić, Aleksandra and Zoranović, Tamara",
year = "2017",
abstract = "Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells. We report that cotreatment of MCF7 with Viscum album and Dox abrogates G2/M cycle arrest replacing senescence with intrinsic apoptotic program. Mechanistically, this switch was associated with down-regulation of p21, p53/p73 as well as Erk1/2 and p38 activation. Our findings, therefore, identify a novel mechanistic axis of additive antitumor activity of Viscum album and low dose-Dox. In conclusion, ER + breast cancer patients may benefit from addition of Viscum album to low-dose Dox chemotherapy due to suppression of cancer cell senescence and induction of apoptosis.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells",
pages = "3763",
volume = "7",
doi = "10.1038/s41598-017-03898-0"
}

Srdić-Rajić, T., Santibanez, J. F., Kanjer, K., Tišma-Miletić, N., Cavić, M., Galun, D., Jevrić, M., Kardum, N. Đ., Konić-Ristić, A.,& Zoranović, T.. (2017). Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells. in Scientific Reports
Nature Publishing Group, London., 7, 3763.
https://doi.org/10.1038/s41598-017-03898-0

Srdić-Rajić T, Santibanez JF, Kanjer K, Tišma-Miletić N, Cavić M, Galun D, Jevrić M, Kardum NĐ, Konić-Ristić A, Zoranović T. Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells. in Scientific Reports. 2017;7:3763.
doi:10.1038/s41598-017-03898-0 .

Srdić-Rajić, Tatjana, Santibanez, Juan F., Kanjer, Ksenija, Tišma-Miletić, Nevena, Cavić, Milena, Galun, Daniel, Jevrić, Marko, Kardum, Nevena Đ., Konić-Ristić, Aleksandra, Zoranović, Tamara, "Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells" in Scientific Reports, 7 (2017):3763,
https://doi.org/10.1038/s41598-017-03898-0 . .