TY  - JOUR
AU  - Lazarević, Miloš
AU  - Milošević, Maja
AU  - Jelovac, Drago
AU  - Milenković, Sanja
AU  - Tepavčević, Zvezdana
AU  - Baldan, Federica
AU  - Suboticki, Tijana
AU  - Toljić, Boško
AU  - Trišić, Dijana
AU  - Dragović, Miroslav
AU  - Damante, Giuseppe
AU  - Milašin, Jelena
PY  - 2020
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2484
AB  - Epithelial to mesenchymal transition (EMT) is a feature of several types of human cancer, including oral squamous cell carcinoma (OSCC). In the present study, tumor and margin cell cultures obtained from patients with OSCC were used to determine the expression patterns of certain EMT-associated markers, including vimentin, alpha -smooth muscle actin, SLUG and SNAIL. In addition, other EMT-associated features, including clonal, proliferative and migratory potential were compared between the two cell types. Cell cultures were generated from tumor and margin tissue samples from 6 patients and cultured up to the fifth passage. EMT marker expression was assessed by reverse transcription-quantitative PCR. Cell proliferation, colony formation and scratch wound healing assays were conducted to characterize the two cell types in terms of proliferation rates, clonality and motility. All of the studied markers were expressed in tumor and margin cells. Although no significant differences were noted with regard to the aforementioned markers, their expression tended to be higher in margin cultures than in tumor cultures. The expressions of the EMT markers were also higher in the fifth passage compared with those noted at the first with a few exceptions. The rates of proliferation and cell migration were decreased during passages, while the number of colonies was increased in both types of cell culture. Tumor and margin cells indicated certain similarities with regard to EMT transition characteristics.
PB  - SPANDIDOS PUBL LTD, ATHENS
T2  - Oncology Letters
T1  - Marked epithelial to mesenchymal transition in surgical margins of oral cancer-an in vitro study
VL  - 19
IS  - 6
SP  - 3743
EP  - 3750
DO  - 10.3892/ol.2020.11494
ER  - 

@article{
author = "Lazarević, Miloš and Milošević, Maja and Jelovac, Drago and Milenković, Sanja and Tepavčević, Zvezdana and Baldan, Federica and Suboticki, Tijana and Toljić, Boško and Trišić, Dijana and Dragović, Miroslav and Damante, Giuseppe and Milašin, Jelena",
year = "2020",
abstract = "Epithelial to mesenchymal transition (EMT) is a feature of several types of human cancer, including oral squamous cell carcinoma (OSCC). In the present study, tumor and margin cell cultures obtained from patients with OSCC were used to determine the expression patterns of certain EMT-associated markers, including vimentin, alpha -smooth muscle actin, SLUG and SNAIL. In addition, other EMT-associated features, including clonal, proliferative and migratory potential were compared between the two cell types. Cell cultures were generated from tumor and margin tissue samples from 6 patients and cultured up to the fifth passage. EMT marker expression was assessed by reverse transcription-quantitative PCR. Cell proliferation, colony formation and scratch wound healing assays were conducted to characterize the two cell types in terms of proliferation rates, clonality and motility. All of the studied markers were expressed in tumor and margin cells. Although no significant differences were noted with regard to the aforementioned markers, their expression tended to be higher in margin cultures than in tumor cultures. The expressions of the EMT markers were also higher in the fifth passage compared with those noted at the first with a few exceptions. The rates of proliferation and cell migration were decreased during passages, while the number of colonies was increased in both types of cell culture. Tumor and margin cells indicated certain similarities with regard to EMT transition characteristics.",
publisher = "SPANDIDOS PUBL LTD, ATHENS",
journal = "Oncology Letters",
title = "Marked epithelial to mesenchymal transition in surgical margins of oral cancer-an in vitro study",
volume = "19",
number = "6",
pages = "3743-3750",
doi = "10.3892/ol.2020.11494"
}

Lazarević, M., Milošević, M., Jelovac, D., Milenković, S., Tepavčević, Z., Baldan, F., Suboticki, T., Toljić, B., Trišić, D., Dragović, M., Damante, G.,& Milašin, J.. (2020). Marked epithelial to mesenchymal transition in surgical margins of oral cancer-an in vitro study. in Oncology Letters
SPANDIDOS PUBL LTD, ATHENS., 19(6), 3743-3750.
https://doi.org/10.3892/ol.2020.11494

Lazarević M, Milošević M, Jelovac D, Milenković S, Tepavčević Z, Baldan F, Suboticki T, Toljić B, Trišić D, Dragović M, Damante G, Milašin J. Marked epithelial to mesenchymal transition in surgical margins of oral cancer-an in vitro study. in Oncology Letters. 2020;19(6):3743-3750.
doi:10.3892/ol.2020.11494 .

Lazarević, Miloš, Milošević, Maja, Jelovac, Drago, Milenković, Sanja, Tepavčević, Zvezdana, Baldan, Federica, Suboticki, Tijana, Toljić, Boško, Trišić, Dijana, Dragović, Miroslav, Damante, Giuseppe, Milašin, Jelena, "Marked epithelial to mesenchymal transition in surgical margins of oral cancer-an in vitro study" in Oncology Letters, 19, no. 6 (2020):3743-3750,
https://doi.org/10.3892/ol.2020.11494 . .

TY  - JOUR
AU  - Baldan, Federica
AU  - Allegri, Lorenzo
AU  - Lazarević, Miloš
AU  - Catia, Mio
AU  - Milošević, Maja
AU  - Damante, Giuseppe
AU  - Milašin, Jelena
PY  - 2019
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2457
AB  - Background Despite improvements in oral squamous cell carcinoma (OSCC) management, survival rates remain relatively low and novel anti-neoplastic agents are needed. Bromodomain and extra-terminal (BET) inhibitors proved to be promising agents for cancer treatment. We investigated the effects of three BET inhibitors (JQ1, IBET-151, IBET-762) on SCC-25 cell line and primary oral cancer cell culture. Methods Cell viability was evaluated by MTT. Protein levels of MCM5 and cleaved-PARP were estimated by Western blot. Clonogenic and migratory abilities were determined by colony forming and scratch assays. BET inhibitors effects on mRNA levels of E-Cadherin, Vimentin, SNAI1, SNAI2, CLU, SERPINI1, MCM5, c-Myc, E2F, IL7R, and PPARg were analyzed by qPCR. Results BET inhibitors significantly reduced oral cancer cell viability. JQ1 showed the greatest effect reducing cell viability to 10%, both in SCC-25 and primary OSCC cultures (P  lt  0.001), compared to control cells. Cells treated with BET inhibitors displayed a reduction to 50% in colony forming capacity compared to control cells (P  lt  0.0001) and the colonies were smaller; they also had a 50%-60% reduction in migratory capacity (P  lt  0.05) compared to untreated cells. BET inhibitors had a significant impact on genes related to epithelial to mesenchymal transition and other cancer cell markers, notably on MCM5, a gene related to cell cycle control. Conclusions BET inhibitors induce both OSCC cell death and reduction of tumor aggressiveness. Molecular mechanisms of BET inhibition involve among others, MCM5 downregulation. Importantly, this study demonstrates for the first time the anti-tumoral effect of IBET-151 and IBET-762 in oral cancer.
PB  - Wiley, Hoboken
T2  - Journal of Oral Pathology & Medicine
T1  - Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells
VL  - 48
IS  - 3
SP  - 214
EP  - 221
DO  - 10.1111/jop.12824
ER  - 

@article{
author = "Baldan, Federica and Allegri, Lorenzo and Lazarević, Miloš and Catia, Mio and Milošević, Maja and Damante, Giuseppe and Milašin, Jelena",
year = "2019",
abstract = "Background Despite improvements in oral squamous cell carcinoma (OSCC) management, survival rates remain relatively low and novel anti-neoplastic agents are needed. Bromodomain and extra-terminal (BET) inhibitors proved to be promising agents for cancer treatment. We investigated the effects of three BET inhibitors (JQ1, IBET-151, IBET-762) on SCC-25 cell line and primary oral cancer cell culture. Methods Cell viability was evaluated by MTT. Protein levels of MCM5 and cleaved-PARP were estimated by Western blot. Clonogenic and migratory abilities were determined by colony forming and scratch assays. BET inhibitors effects on mRNA levels of E-Cadherin, Vimentin, SNAI1, SNAI2, CLU, SERPINI1, MCM5, c-Myc, E2F, IL7R, and PPARg were analyzed by qPCR. Results BET inhibitors significantly reduced oral cancer cell viability. JQ1 showed the greatest effect reducing cell viability to 10%, both in SCC-25 and primary OSCC cultures (P  lt  0.001), compared to control cells. Cells treated with BET inhibitors displayed a reduction to 50% in colony forming capacity compared to control cells (P  lt  0.0001) and the colonies were smaller; they also had a 50%-60% reduction in migratory capacity (P  lt  0.05) compared to untreated cells. BET inhibitors had a significant impact on genes related to epithelial to mesenchymal transition and other cancer cell markers, notably on MCM5, a gene related to cell cycle control. Conclusions BET inhibitors induce both OSCC cell death and reduction of tumor aggressiveness. Molecular mechanisms of BET inhibition involve among others, MCM5 downregulation. Importantly, this study demonstrates for the first time the anti-tumoral effect of IBET-151 and IBET-762 in oral cancer.",
publisher = "Wiley, Hoboken",
journal = "Journal of Oral Pathology & Medicine",
title = "Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells",
volume = "48",
number = "3",
pages = "214-221",
doi = "10.1111/jop.12824"
}

Baldan, F., Allegri, L., Lazarević, M., Catia, M., Milošević, M., Damante, G.,& Milašin, J.. (2019). Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells. in Journal of Oral Pathology & Medicine
Wiley, Hoboken., 48(3), 214-221.
https://doi.org/10.1111/jop.12824

Baldan F, Allegri L, Lazarević M, Catia M, Milošević M, Damante G, Milašin J. Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells. in Journal of Oral Pathology & Medicine. 2019;48(3):214-221.
doi:10.1111/jop.12824 .

Baldan, Federica, Allegri, Lorenzo, Lazarević, Miloš, Catia, Mio, Milošević, Maja, Damante, Giuseppe, Milašin, Jelena, "Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells" in Journal of Oral Pathology & Medicine, 48, no. 3 (2019):214-221,
https://doi.org/10.1111/jop.12824 . .