TY  - CONF
AU  - Ljujić, Mila
AU  - Trifunović, Sara
AU  - Ilić, Bojan
AU  - Milovanović, Jelena
AU  - Dinić, Jelena
AU  - Divac Rankov, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6250
AB  - Introduction: Cigarette smoke exposure is a known risk factor for development of lung diseases and
electronic cigarettes (e-cigarettes) were introduced as a popular and safer alternative to combustible tobacco products. Increasing number of studies are reporting their adverse biological effects both in vivo
and in vitro. Aim of this study was to evaluate the effect of e-cigarettes on mitochondrial function in
lung bronchial epithelial cells.
Methods: Electronic cigarette vapor condensate (ECC) was generated using an e-cigarette device on a
suction trap cooled in a dry ice/ethanol bath. We used unflavoured and flavoured e-cigarette liquids with
and without nicotine. Human bronchial epithelial BEAS2B cells were seeded in 96well plates and treated
with 2% e-cigarette vapour condensate for 24h. Mitochondrial membrane potential was measured using
50nM TMRE (Tetramethyl rhodamine ethyl ester) and cells were visualized on ImageXpress® Pico Automated Cell Imaging System (Molecular Devices, San Jose, CA, USA) with a 10x objective.
Results: We found a significant reduction of TMRE fluorescence in treated cells compared to the control. Imaging of treated cells also revealed changes in cell morphology and the presence of mitochondria in TNT-like structures.
Conclusion: Mitochondrial dysfunction has been associated with various pathological conditions including lung diseases such as asthma, COPD and lung cancer. Due to their relative novelty, the role of
electronic cigarette use in development of chronic lung diseases is still relatively unknown. Our findings
contribute to the growing list of studies pointing to their adverse biological effects and imply their involvement in processes contributing to chronic lung diseases.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Electronic cigarette vapour condensate affects mitochondrial potential in BEAS2B cells
SP  - 139
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6250
ER  - 

@conference{
author = "Ljujić, Mila and Trifunović, Sara and Ilić, Bojan and Milovanović, Jelena and Dinić, Jelena and Divac Rankov, Aleksandra",
year = "2023",
abstract = "Introduction: Cigarette smoke exposure is a known risk factor for development of lung diseases and
electronic cigarettes (e-cigarettes) were introduced as a popular and safer alternative to combustible tobacco products. Increasing number of studies are reporting their adverse biological effects both in vivo
and in vitro. Aim of this study was to evaluate the effect of e-cigarettes on mitochondrial function in
lung bronchial epithelial cells.
Methods: Electronic cigarette vapor condensate (ECC) was generated using an e-cigarette device on a
suction trap cooled in a dry ice/ethanol bath. We used unflavoured and flavoured e-cigarette liquids with
and without nicotine. Human bronchial epithelial BEAS2B cells were seeded in 96well plates and treated
with 2% e-cigarette vapour condensate for 24h. Mitochondrial membrane potential was measured using
50nM TMRE (Tetramethyl rhodamine ethyl ester) and cells were visualized on ImageXpress® Pico Automated Cell Imaging System (Molecular Devices, San Jose, CA, USA) with a 10x objective.
Results: We found a significant reduction of TMRE fluorescence in treated cells compared to the control. Imaging of treated cells also revealed changes in cell morphology and the presence of mitochondria in TNT-like structures.
Conclusion: Mitochondrial dysfunction has been associated with various pathological conditions including lung diseases such as asthma, COPD and lung cancer. Due to their relative novelty, the role of
electronic cigarette use in development of chronic lung diseases is still relatively unknown. Our findings
contribute to the growing list of studies pointing to their adverse biological effects and imply their involvement in processes contributing to chronic lung diseases.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Electronic cigarette vapour condensate affects mitochondrial potential in BEAS2B cells",
pages = "139",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6250"
}

Ljujić, M., Trifunović, S., Ilić, B., Milovanović, J., Dinić, J.,& Divac Rankov, A.. (2023). Electronic cigarette vapour condensate affects mitochondrial potential in BEAS2B cells. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 139.
https://hdl.handle.net/21.15107/rcub_ibiss_6250

Ljujić M, Trifunović S, Ilić B, Milovanović J, Dinić J, Divac Rankov A. Electronic cigarette vapour condensate affects mitochondrial potential in BEAS2B cells. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:139.
https://hdl.handle.net/21.15107/rcub_ibiss_6250 .

Ljujić, Mila, Trifunović, Sara, Ilić, Bojan, Milovanović, Jelena, Dinić, Jelena, Divac Rankov, Aleksandra, "Electronic cigarette vapour condensate affects mitochondrial potential in BEAS2B cells" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):139,
https://hdl.handle.net/21.15107/rcub_ibiss_6250 .

TY  - JOUR
AU  - Divac Rankov, Aleksandra
AU  - Jovanović Stojanov, Sofija
AU  - Dragoj, Miodrag
AU  - Ljujić, Mila
PY  - 2022
UR  - https://link.springer.com/10.1007/s00418-022-02172-3
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5350
AB  - Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in therapy resistance are still insufficient. We analyzed SERPINA1 mRNA expression in three different multidrug-resistant (MDR) cell lines—U87-TxR, NCI-H460/R, and DLD1-TxR—and in U87 cells grown in alginate microfibers as a 3D cellular model of glioblastoma. Expression of IL-6 as a major modulator of SERPINA1 was also analyzed. Additionally, AAT protein expression in MDR cells was analyzed by immunofluorescence. SERPINA1 gene expression and AAT protein expression were significantly upregulated in all the tested MDR cell lines compared with their sensitive counterparts. Moreover, SERPINA1 was significantly upregulated in 3D models of glioblastoma, previously found to have upregulated drug-resistance-related gene expression compared with 2D cells. With the exception of NCI-H460/R, in all cell lines as well as in a 3D model of U87 cells, increase in SERPINA1 expression correlated with the increase in IL-6 expression. Our results indicate that AAT could be utilized as a biomarker of therapy resistance in cancer; however, further studies are needed to elucidate the mechanisms driving AAT upregulation in therapy resistance and its biological significance in this process.
T2  - Histochemistry and Cell Biology
T1  - Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells
DO  - 10.1007/s00418-022-02172-3
ER  - 

@article{
author = "Divac Rankov, Aleksandra and Jovanović Stojanov, Sofija and Dragoj, Miodrag and Ljujić, Mila",
year = "2022",
abstract = "Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in therapy resistance are still insufficient. We analyzed SERPINA1 mRNA expression in three different multidrug-resistant (MDR) cell lines—U87-TxR, NCI-H460/R, and DLD1-TxR—and in U87 cells grown in alginate microfibers as a 3D cellular model of glioblastoma. Expression of IL-6 as a major modulator of SERPINA1 was also analyzed. Additionally, AAT protein expression in MDR cells was analyzed by immunofluorescence. SERPINA1 gene expression and AAT protein expression were significantly upregulated in all the tested MDR cell lines compared with their sensitive counterparts. Moreover, SERPINA1 was significantly upregulated in 3D models of glioblastoma, previously found to have upregulated drug-resistance-related gene expression compared with 2D cells. With the exception of NCI-H460/R, in all cell lines as well as in a 3D model of U87 cells, increase in SERPINA1 expression correlated with the increase in IL-6 expression. Our results indicate that AAT could be utilized as a biomarker of therapy resistance in cancer; however, further studies are needed to elucidate the mechanisms driving AAT upregulation in therapy resistance and its biological significance in this process.",
journal = "Histochemistry and Cell Biology",
title = "Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells",
doi = "10.1007/s00418-022-02172-3"
}

Divac Rankov, A., Jovanović Stojanov, S., Dragoj, M.,& Ljujić, M.. (2022). Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. in Histochemistry and Cell Biology.
https://doi.org/10.1007/s00418-022-02172-3

Divac Rankov A, Jovanović Stojanov S, Dragoj M, Ljujić M. Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. in Histochemistry and Cell Biology. 2022;.
doi:10.1007/s00418-022-02172-3 .

Divac Rankov, Aleksandra, Jovanović Stojanov, Sofija, Dragoj, Miodrag, Ljujić, Mila, "Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells" in Histochemistry and Cell Biology (2022),
https://doi.org/10.1007/s00418-022-02172-3 . .

TY  - JOUR
AU  - Trifunović, Sara
AU  - Smiljanić, Katarina
AU  - Sickmann, Albert
AU  - Solari, Fiorella A.
AU  - Kolarević, Stoimir
AU  - Divac Rankov, Aleksandra
AU  - Ljujić, Mila
PY  - 2022
UR  - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-022-02102-w
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9285873
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5082
AB  - BACKGROUND Although still considered a safer alternative to classical cigarettes, growing body of work points to harmful effects of electronic cigarettes (e-cigarettes) affecting a range of cellular processes. The biological effect of e-cigarettes needs to be investigated in more detail considering their widespread use. METHODS In this study, we treated V79 lung fibroblasts with sub-cytotoxic concentration of e-cigarette liquids, with and without nicotine. Mutagenicity was evaluated by HPRT assay, genotoxicity by comet assay and the effect on cellular communication by metabolic cooperation assay. Additionally, comprehensive proteome analysis was performed via high resolution, parallel accumulation serial fragmentation-PASEF mass spectrometry. RESULTS E-cigarette liquid concentration used in this study showed no mutagenic or genotoxic effect, however it negatively impacted metabolic cooperation between V79 cells. Both e-cigarette liquids induced significant depletion in total number of proteins and impairment of mitochondrial function in treated cells. The focal adhesion proteins were upregulated, which is in accordance with the results of metabolic cooperation assay. Increased presence of posttranslational modifications (PTMs), including carbonylation and direct oxidative modifications, was observed. Data are available via ProteomeXchange with identifier PXD032071. CONCLUSIONS Our study revealed impairment of metabolic cooperation as well as significant proteome and PTMs alterations in V79 cells treated with e-cigarette liquid warranting future studies on e-cigarettes health impact.
PB  - London: BMC
T2  - Respiratory Research
T1  - Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells.
IS  - 1
VL  - 23
DO  - 10.1186/s12931-022-02102-w
SP  - 191
ER  - 

@article{
author = "Trifunović, Sara and Smiljanić, Katarina and Sickmann, Albert and Solari, Fiorella A. and Kolarević, Stoimir and Divac Rankov, Aleksandra and Ljujić, Mila",
year = "2022",
abstract = "BACKGROUND Although still considered a safer alternative to classical cigarettes, growing body of work points to harmful effects of electronic cigarettes (e-cigarettes) affecting a range of cellular processes. The biological effect of e-cigarettes needs to be investigated in more detail considering their widespread use. METHODS In this study, we treated V79 lung fibroblasts with sub-cytotoxic concentration of e-cigarette liquids, with and without nicotine. Mutagenicity was evaluated by HPRT assay, genotoxicity by comet assay and the effect on cellular communication by metabolic cooperation assay. Additionally, comprehensive proteome analysis was performed via high resolution, parallel accumulation serial fragmentation-PASEF mass spectrometry. RESULTS E-cigarette liquid concentration used in this study showed no mutagenic or genotoxic effect, however it negatively impacted metabolic cooperation between V79 cells. Both e-cigarette liquids induced significant depletion in total number of proteins and impairment of mitochondrial function in treated cells. The focal adhesion proteins were upregulated, which is in accordance with the results of metabolic cooperation assay. Increased presence of posttranslational modifications (PTMs), including carbonylation and direct oxidative modifications, was observed. Data are available via ProteomeXchange with identifier PXD032071. CONCLUSIONS Our study revealed impairment of metabolic cooperation as well as significant proteome and PTMs alterations in V79 cells treated with e-cigarette liquid warranting future studies on e-cigarettes health impact.",
publisher = "London: BMC",
journal = "Respiratory Research",
title = "Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells.",
number = "1",
volume = "23",
doi = "10.1186/s12931-022-02102-w",
pages = "191"
}

Trifunović, S., Smiljanić, K., Sickmann, A., Solari, F. A., Kolarević, S., Divac Rankov, A.,& Ljujić, M.. (2022). Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells.. in Respiratory Research
London: BMC., 23(1), 191.
https://doi.org/10.1186/s12931-022-02102-w

Trifunović S, Smiljanić K, Sickmann A, Solari FA, Kolarević S, Divac Rankov A, Ljujić M. Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells.. in Respiratory Research. 2022;23(1):191.
doi:10.1186/s12931-022-02102-w .

Trifunović, Sara, Smiljanić, Katarina, Sickmann, Albert, Solari, Fiorella A., Kolarević, Stoimir, Divac Rankov, Aleksandra, Ljujić, Mila, "Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells." in Respiratory Research, 23, no. 1 (2022):191,
https://doi.org/10.1186/s12931-022-02102-w . .

TY  - JOUR
AU  - Jovanović Stojanov, Sofija
AU  - Stepanović, Ana
AU  - Ljujić, Mila
AU  - Lupšić, Ema
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5043
AB  - Drug resistance presents a major obstacle to the successful treatment of glioblastoma. Autophagy plays a key role in drug resistance, particularly in relation to targeted therapy, which has prompted the use of autophagy inhibitors to increase the effectiveness of targeted therapeutics. The ability of two Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, to induce autophagy was evaluated in the human glioblastoma cell line U87 and its multidrug-resistant counterpart U87-TxR. Autophagy markers were assessed by flow cytometry, microscopy, and Western blot, and induction of autophagy by these compounds was demonstrated after 3 h as well as 48 h. The effects of Si306 and pro-Si306 on cell proliferation and cell death were examined in the presence or absence of autophagy inhibition by bafilomycin A1. Combined treatments of Si306 and pro-Si306 with bafilomycin A1 were synergistic in nature, and the inhibition of autophagy sensitized glioblastoma cells to Src tyrosine kinase inhibitors. Si306 and pro-Si306 more strongly inhibited cell proliferation and triggered necrosis in combination with bafilomycin A1. Our findings suggest that modulation of Si306- and pro-Si306-induced autophagy can be used to enhance the anticancer effects of these Src tyrosine kinase inhibitors and overcome the drug-resistant phenotype in glioblastoma cells.
PB  - Basel : MDPI
T2  - Life
T1  - Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors
IS  - 10
VL  - 12
DO  - 10.3390/life12101503
SP  - 1503
ER  - 

@article{
author = "Jovanović Stojanov, Sofija and Stepanović, Ana and Ljujić, Mila and Lupšić, Ema and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2022",
abstract = "Drug resistance presents a major obstacle to the successful treatment of glioblastoma. Autophagy plays a key role in drug resistance, particularly in relation to targeted therapy, which has prompted the use of autophagy inhibitors to increase the effectiveness of targeted therapeutics. The ability of two Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306, to induce autophagy was evaluated in the human glioblastoma cell line U87 and its multidrug-resistant counterpart U87-TxR. Autophagy markers were assessed by flow cytometry, microscopy, and Western blot, and induction of autophagy by these compounds was demonstrated after 3 h as well as 48 h. The effects of Si306 and pro-Si306 on cell proliferation and cell death were examined in the presence or absence of autophagy inhibition by bafilomycin A1. Combined treatments of Si306 and pro-Si306 with bafilomycin A1 were synergistic in nature, and the inhibition of autophagy sensitized glioblastoma cells to Src tyrosine kinase inhibitors. Si306 and pro-Si306 more strongly inhibited cell proliferation and triggered necrosis in combination with bafilomycin A1. Our findings suggest that modulation of Si306- and pro-Si306-induced autophagy can be used to enhance the anticancer effects of these Src tyrosine kinase inhibitors and overcome the drug-resistant phenotype in glioblastoma cells.",
publisher = "Basel : MDPI",
journal = "Life",
title = "Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors",
number = "10",
volume = "12",
doi = "10.3390/life12101503",
pages = "1503"
}

Jovanović Stojanov, S., Stepanović, A., Ljujić, M., Lupšić, E., Schenone, S., Pešić, M.,& Dinić, J.. (2022). Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors. in Life
Basel : MDPI., 12(10), 1503.
https://doi.org/10.3390/life12101503

Jovanović Stojanov S, Stepanović A, Ljujić M, Lupšić E, Schenone S, Pešić M, Dinić J. Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors. in Life. 2022;12(10):1503.
doi:10.3390/life12101503 .

Jovanović Stojanov, Sofija, Stepanović, Ana, Ljujić, Mila, Lupšić, Ema, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-d]pyrimidine Tyrosine Kinase Inhibitors" in Life, 12, no. 10 (2022):1503,
https://doi.org/10.3390/life12101503 . .

TY  - JOUR
AU  - Jovanović, Mirna
AU  - Stanković, Tijana
AU  - Stojković Burić, Sonja
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ljujić, Mila
AU  - Pešić, Milica
AU  - Dragoj, Miodrag
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5041
AB  - Tspan14 is a transmembrane protein of the tetraspanin (Tspan) protein family. Different members of the Tspan family can promote or suppress tumor progression. The exact role of Tspan14 in tumor cells is unknown. Earlier, mutational inactivation of the TSPAN14 gene has been proposed to coincide with a low survival rate in NSCLC patients. This study aimed to investigate the correlation of TSPAN14 lack of function with clinicopathological features of NSCLC patients, and to elucidate the role TSPAN14 might have in NSCLC progression. TSPAN14 expression was lower in tumor cells than non-tumor cells in NSCLC patients’ samples. The decreased gene expression was correlated with a low survival rate of patients and was more frequent in patients with aggressive, invasive tumor types. Additionally, the role of decreased TSPAN14 expression in the metastatic potential of cancer cells was confirmed in NSCLC cell lines. The highly invasive NSCLC cell line (NCI-H661) had the lowest TSPAN14 gene and protein expression, whereas the NSCLC cell line with the highest TSPAN14 expression (NCI-H460) had no significant metastatic potential. Finally, silencing of TSPAN14 in these non-metastatic cancer cells caused an increased expression of matrix-degrading enzymes MMP-2 and MMP-9, followed by an elevated capacity of cancer cells to degrade gelatin. The results of this study propose TSPAN14 expression as an indicator of NSCLC metastatic potential and progression.
PB  - Basel : MDPI
T2  - Life
T1  - Decreased TSPAN14 Expression Contributes to NSCLC Progression
IS  - 9
VL  - 12
DO  - 10.3390/life12091291
SP  - 1291
ER  - 

@article{
author = "Jovanović, Mirna and Stanković, Tijana and Stojković Burić, Sonja and Banković, Jasna and Dinić, Jelena and Ljujić, Mila and Pešić, Milica and Dragoj, Miodrag",
year = "2022",
abstract = "Tspan14 is a transmembrane protein of the tetraspanin (Tspan) protein family. Different members of the Tspan family can promote or suppress tumor progression. The exact role of Tspan14 in tumor cells is unknown. Earlier, mutational inactivation of the TSPAN14 gene has been proposed to coincide with a low survival rate in NSCLC patients. This study aimed to investigate the correlation of TSPAN14 lack of function with clinicopathological features of NSCLC patients, and to elucidate the role TSPAN14 might have in NSCLC progression. TSPAN14 expression was lower in tumor cells than non-tumor cells in NSCLC patients’ samples. The decreased gene expression was correlated with a low survival rate of patients and was more frequent in patients with aggressive, invasive tumor types. Additionally, the role of decreased TSPAN14 expression in the metastatic potential of cancer cells was confirmed in NSCLC cell lines. The highly invasive NSCLC cell line (NCI-H661) had the lowest TSPAN14 gene and protein expression, whereas the NSCLC cell line with the highest TSPAN14 expression (NCI-H460) had no significant metastatic potential. Finally, silencing of TSPAN14 in these non-metastatic cancer cells caused an increased expression of matrix-degrading enzymes MMP-2 and MMP-9, followed by an elevated capacity of cancer cells to degrade gelatin. The results of this study propose TSPAN14 expression as an indicator of NSCLC metastatic potential and progression.",
publisher = "Basel : MDPI",
journal = "Life",
title = "Decreased TSPAN14 Expression Contributes to NSCLC Progression",
number = "9",
volume = "12",
doi = "10.3390/life12091291",
pages = "1291"
}

Jovanović, M., Stanković, T., Stojković Burić, S., Banković, J., Dinić, J., Ljujić, M., Pešić, M.,& Dragoj, M.. (2022). Decreased TSPAN14 Expression Contributes to NSCLC Progression. in Life
Basel : MDPI., 12(9), 1291.
https://doi.org/10.3390/life12091291

Jovanović M, Stanković T, Stojković Burić S, Banković J, Dinić J, Ljujić M, Pešić M, Dragoj M. Decreased TSPAN14 Expression Contributes to NSCLC Progression. in Life. 2022;12(9):1291.
doi:10.3390/life12091291 .

Jovanović, Mirna, Stanković, Tijana, Stojković Burić, Sonja, Banković, Jasna, Dinić, Jelena, Ljujić, Mila, Pešić, Milica, Dragoj, Miodrag, "Decreased TSPAN14 Expression Contributes to NSCLC Progression" in Life, 12, no. 9 (2022):1291,
https://doi.org/10.3390/life12091291 . .

TY  - CONF
AU  - Jovanović Stojanov, Sofija
AU  - Stepanović, Ana
AU  - Ljujić, Mila
AU  - Lupšić, Ema
AU  - Podolski-Renić, Ana
AU  - Dragoj, Miodrag
AU  - Jovanović, Mirna
AU  - Schenone, Silvia
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2022
UR  - http://nwm.covr.be/EACR2022abstracts/data/HtmlApp/main.html#
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5425
AB  - Introduction:
Glioblastoma (GBM) is among the most frequent and aggressive brain tumors characterized by
infiltrating nature, high proliferation, and resistance to chemotherapy and radiation. GBM exhibit high
expression of Src tyrosine kinase which regulates proliferation, survival, and invasiveness of tumor
cells, making Src a potential target for GBM therapy. Numerous Src family kinase inhibitors (SFKI)
were reported to induce autophagy, thus protecting cells from undergoing cell death. However,
inhibition of autophagy was shown to sensitize cells to SFKI in several cancer types.
Material and Methods:
Human GBM cell line U87 and its multidrug-resistant (MDR) counterpart U87-TxR were transfected
with RFP-LC3, an autophagy marker. The ability of two SFKIs, pyrazolo[3,4-d]pyrimidines Si306 and
its prodrug pro-si306, to induce autophagy in RFP-LC3-transfected GBM cells was evaluated by flow
cytometry and fluorescent microscopy. Cell viability was assessed by MTT assay. The autophagy
induction and autophagic flux were evaluated by Acridine orange assay, immunocytochemistry and
immunoblotting. Cell proliferation rate was analyzed by CFSE assay. Cell death was detected by
Annexin/Propidium Iodide assay. PARP-1 cleavage was assessed by immunoblotting.
Results and Discussions:
SFKI treatment resulted in degradation of RFP-LC3 after 3 h treatment as well as in formation of
RFP-LC3 puncta in GBM cells demonstrating autophagy induction. The effect of SFKIs on autophagy
induction persisted after 48 h, as demonstrated by autophagy markers LC3 and p62. Inhibition of
autophagy by Bafilomycin A1 sensitized both U87 and U87-TxR cells to Si306 and its pro-drug after
48 h. The anti-proliferative effect of Si306 and pro-Si306 was additionally increased after autophagy
inhibition by Bafilomycin A1. Furthermore, while single SFKI treatments did not cause significant
cell death, combination treatments with autophagy inhibitor induced necrosis in U87 and U87-TxR
cells after 48 h. Detection of necrotic PARP-1 fragment further confirmed necrotic cell death.
Conclusion:
Taken together, these data suggest that autophagy induced by Si306 and pro-Si306 has a protective
role in GBM cells, and that autophagy modulation may be used to enhance the anticancer effects of
SFKIs. In addition, as the ability of the SFKIs to induce autophagy was not diminished by the
presence of the MDR phenotype makes these compounds promising for treatment of MDR cancers.
PB  - European Association for Cancer Research
C3  - Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain
T1  - Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug
SP  - P1-135
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5425
ER  - 

@conference{
author = "Jovanović Stojanov, Sofija and Stepanović, Ana and Ljujić, Mila and Lupšić, Ema and Podolski-Renić, Ana and Dragoj, Miodrag and Jovanović, Mirna and Schenone, Silvia and Pešić, Milica and Dinić, Jelena",
year = "2022",
abstract = "Introduction:
Glioblastoma (GBM) is among the most frequent and aggressive brain tumors characterized by
infiltrating nature, high proliferation, and resistance to chemotherapy and radiation. GBM exhibit high
expression of Src tyrosine kinase which regulates proliferation, survival, and invasiveness of tumor
cells, making Src a potential target for GBM therapy. Numerous Src family kinase inhibitors (SFKI)
were reported to induce autophagy, thus protecting cells from undergoing cell death. However,
inhibition of autophagy was shown to sensitize cells to SFKI in several cancer types.
Material and Methods:
Human GBM cell line U87 and its multidrug-resistant (MDR) counterpart U87-TxR were transfected
with RFP-LC3, an autophagy marker. The ability of two SFKIs, pyrazolo[3,4-d]pyrimidines Si306 and
its prodrug pro-si306, to induce autophagy in RFP-LC3-transfected GBM cells was evaluated by flow
cytometry and fluorescent microscopy. Cell viability was assessed by MTT assay. The autophagy
induction and autophagic flux were evaluated by Acridine orange assay, immunocytochemistry and
immunoblotting. Cell proliferation rate was analyzed by CFSE assay. Cell death was detected by
Annexin/Propidium Iodide assay. PARP-1 cleavage was assessed by immunoblotting.
Results and Discussions:
SFKI treatment resulted in degradation of RFP-LC3 after 3 h treatment as well as in formation of
RFP-LC3 puncta in GBM cells demonstrating autophagy induction. The effect of SFKIs on autophagy
induction persisted after 48 h, as demonstrated by autophagy markers LC3 and p62. Inhibition of
autophagy by Bafilomycin A1 sensitized both U87 and U87-TxR cells to Si306 and its pro-drug after
48 h. The anti-proliferative effect of Si306 and pro-Si306 was additionally increased after autophagy
inhibition by Bafilomycin A1. Furthermore, while single SFKI treatments did not cause significant
cell death, combination treatments with autophagy inhibitor induced necrosis in U87 and U87-TxR
cells after 48 h. Detection of necrotic PARP-1 fragment further confirmed necrotic cell death.
Conclusion:
Taken together, these data suggest that autophagy induced by Si306 and pro-Si306 has a protective
role in GBM cells, and that autophagy modulation may be used to enhance the anticancer effects of
SFKIs. In addition, as the ability of the SFKIs to induce autophagy was not diminished by the
presence of the MDR phenotype makes these compounds promising for treatment of MDR cancers.",
publisher = "European Association for Cancer Research",
journal = "Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain",
title = "Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug",
pages = "P1-135",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5425"
}

Jovanović Stojanov, S., Stepanović, A., Ljujić, M., Lupšić, E., Podolski-Renić, A., Dragoj, M., Jovanović, M., Schenone, S., Pešić, M.,& Dinić, J.. (2022). Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug. in Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain
European Association for Cancer Research., P1-135.
https://hdl.handle.net/21.15107/rcub_ibiss_5425

Jovanović Stojanov S, Stepanović A, Ljujić M, Lupšić E, Podolski-Renić A, Dragoj M, Jovanović M, Schenone S, Pešić M, Dinić J. Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug. in Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain. 2022;:P1-135.
https://hdl.handle.net/21.15107/rcub_ibiss_5425 .

Jovanović Stojanov, Sofija, Stepanović, Ana, Ljujić, Mila, Lupšić, Ema, Podolski-Renić, Ana, Dragoj, Miodrag, Jovanović, Mirna, Schenone, Silvia, Pešić, Milica, Dinić, Jelena, "Autophagy inhibition sensitises glioblastoma cells to Src family kinase inhibitors Si306 and its prodrug" in Congress abstracts: Annual Congress of the European Association for Cancer Research EACR 2022: Innovative Cancer Service: Translating Biology to Medicine; 2022 Jun 20-23; Seville, Spain (2022):P1-135,
https://hdl.handle.net/21.15107/rcub_ibiss_5425 .

TY  - CONF
AU  - Jovanović Stojanov, Sofija
AU  - Stepanović, Ana
AU  - Ljujić, Mila
AU  - Lupšić, Ema
AU  - Dragoj, Miodrag
AU  - Jovanović, Mirna
AU  - Dinić, Jelena
AU  - Pešić, Milica
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5394
AB  - Глиобластом је један од најагресивнијих тумора мозга који карактерише инфилтрирајућа природа, интензивна пролиферација и резистенција на терапију. Ћелије глиобластома имају високу експресију Срц тирозин-киназе која регулише пролиферацију, преживљавање и инвазивност туморских ћелија чинећи је потенцијалном метом за терапију. Инхибитори тирозин-киназа могу индуковати аутофагију која делује протективно на туморске ћелије. Способност инхибитора
Срц тирозин-киназе, деривата пиразоло[3,4-д]пиримидина Si306 и његовог пролека pro-Si306, да индукују аутофагију испитана је на ћелијској линији хуманог глиобластома U87 и њеној варијанти са вишеструком резистенцијом на лекове U87-TxR. Третман овим једињењима узроковао је појаву аутофагозома у ћелијама након 3 сата, а ефекат на индукцију аутофагије опстао је и након 48 сати што је утврђено анализом маркера аутофагије LC3 и p62. Инхибиција аутофагног флукса бафиломицином А1 значајно је увећала постојеће анти-пролиферативно дејство Si306 и pro-Si306. Такође, комбиновани третмани Срц инхибитора са бафиломицином А1 довели су до некрозе након 48 сати. Добијени резултати сугеришу да аутофагија индукована овим једињењима има заштитну улогу у ћелијама глиобластома и да се модулација аутофагије може користити за сензитизацију ћелија глиобластома на инхибиторе Срц тирозин-киназе. Поред тога, поменути ефекти Si306 и pro-Si306 нису умањени присуством вишеструкорезистентног фенотипа, што овим једињењима даје потенцијал за лечење резистентних тумора.
AB  - Glioblastom je jedan od najagresivnijih tumora mozga koji karakteriše infiltrirajuća priroda, intenzivna proliferacija i rezistencija na terapiju. Ćelije glioblastoma imaju visoku ekspresiju Src tirozin-kinaze koja reguliše proliferaciju, preživljavanje i invazivnost tumorskih ćelija čineći je potencijalnom metom za terapiju. Inhibitori tirozin-kinaza mogu indukovati autofagiju koja deluje protektivno na tumorske ćelije. Sposobnost inhibitora Src tirozin-kinaze, derivata pirazolo[3,4-d]pirimidina Si306 i njegovog proleka pro-Si306, da indukuju autofagiju ispitana je na ćelijskoj liniji humanog glioblastoma U87 i njenoj varijanti sa višestrukom rezistencijom na lekove U87-TxR. Tretman ovim jedinjenjima uzrokovao je pojavu autofagozoma u ćelijama nakon 3 sata, a efekat na indukciju autofagije opstao je i nakon 48 sati što je utvrđeno analizom markera autofagije LC3 i p62. Inhibicija autofagnog fluksa bafilomicinom A1 značajno je uvećala postojeće anti-proliferativno dejstvo Si306 i pro-Si306. Takođe, kombinovani tretmani Src inhibitora sa bafilomicinom A1 doveli su do nekroze nakon 48 sati. Dobijeni rezultati sugerišu da autofagija indukovana ovim jedinjenjima ima zaštitnu ulogu u ćelijama glioblastoma i da se modulacija autofagije može koristiti za senzitizaciju ćelija glioblastoma na inhibitore Src tirozin-kinaze. Pored toga, pomenuti efekti Si306 i pro-Si306 nisu umanjeni prisustvom višestrukorezistentnog fenotipa, što ovim jedinjenjima daje potencijal za lečenje rezistentnih tumora.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Inhibicija  autofagije  senzitizuje  ćelije  glioblastoma  na inhibitore  Src  tirozin-kinaze,  derivate  pirazolo[3,4-d]pirimidina Si306 i pro-Si306
T1  - Инхибиција аутофагије сензитизује ћелије глиобластома на инхибиторе Срц тирозин-киназе, деривате пиразоло[3,4- д]пиримидина Si306 и pro-Si306
SP  - 330
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5394
ER  - 

@conference{
author = "Jovanović Stojanov, Sofija and Stepanović, Ana and Ljujić, Mila and Lupšić, Ema and Dragoj, Miodrag and Jovanović, Mirna and Dinić, Jelena and Pešić, Milica",
year = "2022",
abstract = "Глиобластом је један од најагресивнијих тумора мозга који карактерише инфилтрирајућа природа, интензивна пролиферација и резистенција на терапију. Ћелије глиобластома имају високу експресију Срц тирозин-киназе која регулише пролиферацију, преживљавање и инвазивност туморских ћелија чинећи је потенцијалном метом за терапију. Инхибитори тирозин-киназа могу индуковати аутофагију која делује протективно на туморске ћелије. Способност инхибитора
Срц тирозин-киназе, деривата пиразоло[3,4-д]пиримидина Si306 и његовог пролека pro-Si306, да индукују аутофагију испитана је на ћелијској линији хуманог глиобластома U87 и њеној варијанти са вишеструком резистенцијом на лекове U87-TxR. Третман овим једињењима узроковао је појаву аутофагозома у ћелијама након 3 сата, а ефекат на индукцију аутофагије опстао је и након 48 сати што је утврђено анализом маркера аутофагије LC3 и p62. Инхибиција аутофагног флукса бафиломицином А1 значајно је увећала постојеће анти-пролиферативно дејство Si306 и pro-Si306. Такође, комбиновани третмани Срц инхибитора са бафиломицином А1 довели су до некрозе након 48 сати. Добијени резултати сугеришу да аутофагија индукована овим једињењима има заштитну улогу у ћелијама глиобластома и да се модулација аутофагије може користити за сензитизацију ћелија глиобластома на инхибиторе Срц тирозин-киназе. Поред тога, поменути ефекти Si306 и pro-Si306 нису умањени присуством вишеструкорезистентног фенотипа, што овим једињењима даје потенцијал за лечење резистентних тумора., Glioblastom je jedan od najagresivnijih tumora mozga koji karakteriše infiltrirajuća priroda, intenzivna proliferacija i rezistencija na terapiju. Ćelije glioblastoma imaju visoku ekspresiju Src tirozin-kinaze koja reguliše proliferaciju, preživljavanje i invazivnost tumorskih ćelija čineći je potencijalnom metom za terapiju. Inhibitori tirozin-kinaza mogu indukovati autofagiju koja deluje protektivno na tumorske ćelije. Sposobnost inhibitora Src tirozin-kinaze, derivata pirazolo[3,4-d]pirimidina Si306 i njegovog proleka pro-Si306, da indukuju autofagiju ispitana je na ćelijskoj liniji humanog glioblastoma U87 i njenoj varijanti sa višestrukom rezistencijom na lekove U87-TxR. Tretman ovim jedinjenjima uzrokovao je pojavu autofagozoma u ćelijama nakon 3 sata, a efekat na indukciju autofagije opstao je i nakon 48 sati što je utvrđeno analizom markera autofagije LC3 i p62. Inhibicija autofagnog fluksa bafilomicinom A1 značajno je uvećala postojeće anti-proliferativno dejstvo Si306 i pro-Si306. Takođe, kombinovani tretmani Src inhibitora sa bafilomicinom A1 doveli su do nekroze nakon 48 sati. Dobijeni rezultati sugerišu da autofagija indukovana ovim jedinjenjima ima zaštitnu ulogu u ćelijama glioblastoma i da se modulacija autofagije može koristiti za senzitizaciju ćelija glioblastoma na inhibitore Src tirozin-kinaze. Pored toga, pomenuti efekti Si306 i pro-Si306 nisu umanjeni prisustvom višestrukorezistentnog fenotipa, što ovim jedinjenjima daje potencijal za lečenje rezistentnih tumora.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Inhibicija  autofagije  senzitizuje  ćelije  glioblastoma  na inhibitore  Src  tirozin-kinaze,  derivate  pirazolo[3,4-d]pirimidina Si306 i pro-Si306, Инхибиција аутофагије сензитизује ћелије глиобластома на инхибиторе Срц тирозин-киназе, деривате пиразоло[3,4- д]пиримидина Si306 и pro-Si306",
pages = "330",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5394"
}

Jovanović Stojanov, S., Stepanović, A., Ljujić, M., Lupšić, E., Dragoj, M., Jovanović, M., Dinić, J.,& Pešić, M.. (2022). Inhibicija  autofagije  senzitizuje  ćelije  glioblastoma  na inhibitore  Src  tirozin-kinaze,  derivate  pirazolo[3,4-d]pirimidina Si306 i pro-Si306. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 330.
https://hdl.handle.net/21.15107/rcub_ibiss_5394

Jovanović Stojanov S, Stepanović A, Ljujić M, Lupšić E, Dragoj M, Jovanović M, Dinić J, Pešić M. Inhibicija  autofagije  senzitizuje  ćelije  glioblastoma  na inhibitore  Src  tirozin-kinaze,  derivate  pirazolo[3,4-d]pirimidina Si306 i pro-Si306. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:330.
https://hdl.handle.net/21.15107/rcub_ibiss_5394 .

Jovanović Stojanov, Sofija, Stepanović, Ana, Ljujić, Mila, Lupšić, Ema, Dragoj, Miodrag, Jovanović, Mirna, Dinić, Jelena, Pešić, Milica, "Inhibicija  autofagije  senzitizuje  ćelije  glioblastoma  na inhibitore  Src  tirozin-kinaze,  derivate  pirazolo[3,4-d]pirimidina Si306 i pro-Si306" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):330,
https://hdl.handle.net/21.15107/rcub_ibiss_5394 .

TY  - CONF
AU  - Ljujić, Mila
AU  - Divac Rankov, Aleksandra
AU  - Dragoj, Miodrag
AU  - Jovanović Stojanov, Sofija
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5713
AB  - Identification of the signature molecular factors and transcriptional profiles involved in
therapy resistance is of vital importance in developing new strategies for treatments and disease
monitoring. Tumour secretome is a set of macromolecules secreted by tumour cells into the extracellular
space as a response to changes in tumour environment that at the same time shapes the microenvironment
further promoting specific phenotypes and contributing to cellular plasticity in tumour. Protein alpha-1
antitrypsin (AAT, encoded by SERPINA1 gene) is an acute phase protein that has emerged as one of the key
components in tumour secretome involved in crucial stages of tumour development and progression, with
recent data also implicating it in therapeutic resistance. However, what exactly leads to SERPINA1
upregulation during development of therapy resistance, as well as its biological significance in this process,
is still unclear. Our aim was to analyse SERPINA1 expression in multidrug resistant cell lines and 3D cellular
models. Expression of IL-6 was also analysed, as AAT is an acute phase reactant and its levels increase in
response to inflammatory cytokines. Patients and methods: We analysed SERPINA1 and IL-6 expression in
three different cell lines - human glioblastoma U87, non-small cell lung carcinoma NCI-H460 and colorectal
carcinoma DLD1 as well as their multidrug resistant counterparts U87-TxR, NCI-H460/R and DLD1-TxR,
respectively. In addition, expression analysis was performed in long-term 3D glioblastoma model of U87
cells cultured in alginate microfibers, and compared to long-term 2D cell culture of U87. Quantitative RTPCR was performed using Taqman gene expression assays and data were normalized to GAPDH. Results:
We found that SERPINA1 expression is significantly upregulated in all the multidrug resistant cell lines
analysed compared to their sensitive counterparts. Expression of IL-6 was significantly upregulated in U87-
TxR and DLD1-TxR compared to their parental lines, however NCI-H460/R cell line had lower IL-6 expression
compared to NCI-H460. In 3D glioblastoma model of U87 cells, previously found to exhibit increased
therapy resistance compared to 2D cell culture, both SERPINA1 and IL-6 expression were significantly
upregulated. Conclusion: Our results indicate that SERPINA1 expression correlates with therapy resistance
in analysed cell lines and 3D model of glioblastoma, revealing the potential of utilizing this molecule as a
biomarker of therapy resistance. However, transcriptional profiles connected to its expression in therapy
resistance still remain to be determined.
PB  - Beograd: Srpsko društvo istraživača raka
C3  - Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event
T1  - Analysis of alpha-1 antitrypsin expression in multidrug resistant cell lines
SP  - 48
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5713
ER  - 

@conference{
author = "Ljujić, Mila and Divac Rankov, Aleksandra and Dragoj, Miodrag and Jovanović Stojanov, Sofija",
year = "2021",
abstract = "Identification of the signature molecular factors and transcriptional profiles involved in
therapy resistance is of vital importance in developing new strategies for treatments and disease
monitoring. Tumour secretome is a set of macromolecules secreted by tumour cells into the extracellular
space as a response to changes in tumour environment that at the same time shapes the microenvironment
further promoting specific phenotypes and contributing to cellular plasticity in tumour. Protein alpha-1
antitrypsin (AAT, encoded by SERPINA1 gene) is an acute phase protein that has emerged as one of the key
components in tumour secretome involved in crucial stages of tumour development and progression, with
recent data also implicating it in therapeutic resistance. However, what exactly leads to SERPINA1
upregulation during development of therapy resistance, as well as its biological significance in this process,
is still unclear. Our aim was to analyse SERPINA1 expression in multidrug resistant cell lines and 3D cellular
models. Expression of IL-6 was also analysed, as AAT is an acute phase reactant and its levels increase in
response to inflammatory cytokines. Patients and methods: We analysed SERPINA1 and IL-6 expression in
three different cell lines - human glioblastoma U87, non-small cell lung carcinoma NCI-H460 and colorectal
carcinoma DLD1 as well as their multidrug resistant counterparts U87-TxR, NCI-H460/R and DLD1-TxR,
respectively. In addition, expression analysis was performed in long-term 3D glioblastoma model of U87
cells cultured in alginate microfibers, and compared to long-term 2D cell culture of U87. Quantitative RTPCR was performed using Taqman gene expression assays and data were normalized to GAPDH. Results:
We found that SERPINA1 expression is significantly upregulated in all the multidrug resistant cell lines
analysed compared to their sensitive counterparts. Expression of IL-6 was significantly upregulated in U87-
TxR and DLD1-TxR compared to their parental lines, however NCI-H460/R cell line had lower IL-6 expression
compared to NCI-H460. In 3D glioblastoma model of U87 cells, previously found to exhibit increased
therapy resistance compared to 2D cell culture, both SERPINA1 and IL-6 expression were significantly
upregulated. Conclusion: Our results indicate that SERPINA1 expression correlates with therapy resistance
in analysed cell lines and 3D model of glioblastoma, revealing the potential of utilizing this molecule as a
biomarker of therapy resistance. However, transcriptional profiles connected to its expression in therapy
resistance still remain to be determined.",
publisher = "Beograd: Srpsko društvo istraživača raka",
journal = "Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event",
title = "Analysis of alpha-1 antitrypsin expression in multidrug resistant cell lines",
pages = "48",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5713"
}

Ljujić, M., Divac Rankov, A., Dragoj, M.,& Jovanović Stojanov, S.. (2021). Analysis of alpha-1 antitrypsin expression in multidrug resistant cell lines. in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event
Beograd: Srpsko društvo istraživača raka., 48.
https://hdl.handle.net/21.15107/rcub_ibiss_5713

Ljujić M, Divac Rankov A, Dragoj M, Jovanović Stojanov S. Analysis of alpha-1 antitrypsin expression in multidrug resistant cell lines. in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event. 2021;:48.
https://hdl.handle.net/21.15107/rcub_ibiss_5713 .

Ljujić, Mila, Divac Rankov, Aleksandra, Dragoj, Miodrag, Jovanović Stojanov, Sofija, "Analysis of alpha-1 antitrypsin expression in multidrug resistant cell lines" in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event (2021):48,
https://hdl.handle.net/21.15107/rcub_ibiss_5713 .

TY  - GEN
AU  - Divac Rankov, Aleksandra
AU  - Ljujić, Mila
AU  - Petrić, Marija
AU  - Radojković, Dragica
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2017
UR  - http://link.springer.com/10.1007/s00418-017-1590-4
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2796
AB  - Autophagy is linked to multiple cancer-related signaling pathways, and represents a defense mechanism for cancer cells under therapeutic stress. The crosstalk between apoptosis and autophagy is essential for both tumorigenesis and embryonic development. We studied the influence of autophagy on cell survival in pro-apoptotic conditions induced by anticancer drugs in three model systems: human cancer cells (NCI-H460, COR-L23 and U87), human normal cells (HaCaT and MRC-5) and zebrafish embryos (Danio rerio). Autophagy induction with AZD2014 and tamoxifen antagonized the pro-apoptotic effect of chemotherapeutics doxorubicin and cisplatin in cell lines, while autophagy inhibition by wortmannin and chloroquine synergized the action of both anticancer agents. This effect was further verified by assessing cleaved caspase-3 and PARP-1 levels. Autophagy inhibitors significantly increased both apoptotic markers when applied in combination with doxorubicin while autophagy inducers had the opposite effect. In a similar manner, autophagy induction in zebrafish embryos prevented cisplatin-induced apoptosis in the tail region while autophagy inhibition increased cell death in the tail and retina of cisplatin-treated animals. Autophagy modulation with direct inhibitors of the PI3kinase/Akt/mTOR pathway (AZD2014 and wortmannin) triggered the cellular response to anticancer drugs more effectively in NCI-H460 and zebrafish embryonic models compared to HaCaT suggesting that these modulators are selective towards rapidly proliferating cells. Therefore, evaluating the autophagic properties of chemotherapeutics could help determine more accurately the fate of different cell types under treatment. Our study underlines the importance of testing autophagic activity of potential anticancer agents in a comparative approach to develop more rational anticancer therapeutic strategies.
T2  - Histochemistry and Cell Biology
T1  - Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells
DO  - 10.1007/s00418-017-1590-4
ER  - 

@misc{
author = "Divac Rankov, Aleksandra and Ljujić, Mila and Petrić, Marija and Radojković, Dragica and Pešić, Milica and Dinić, Jelena",
year = "2017",
abstract = "Autophagy is linked to multiple cancer-related signaling pathways, and represents a defense mechanism for cancer cells under therapeutic stress. The crosstalk between apoptosis and autophagy is essential for both tumorigenesis and embryonic development. We studied the influence of autophagy on cell survival in pro-apoptotic conditions induced by anticancer drugs in three model systems: human cancer cells (NCI-H460, COR-L23 and U87), human normal cells (HaCaT and MRC-5) and zebrafish embryos (Danio rerio). Autophagy induction with AZD2014 and tamoxifen antagonized the pro-apoptotic effect of chemotherapeutics doxorubicin and cisplatin in cell lines, while autophagy inhibition by wortmannin and chloroquine synergized the action of both anticancer agents. This effect was further verified by assessing cleaved caspase-3 and PARP-1 levels. Autophagy inhibitors significantly increased both apoptotic markers when applied in combination with doxorubicin while autophagy inducers had the opposite effect. In a similar manner, autophagy induction in zebrafish embryos prevented cisplatin-induced apoptosis in the tail region while autophagy inhibition increased cell death in the tail and retina of cisplatin-treated animals. Autophagy modulation with direct inhibitors of the PI3kinase/Akt/mTOR pathway (AZD2014 and wortmannin) triggered the cellular response to anticancer drugs more effectively in NCI-H460 and zebrafish embryonic models compared to HaCaT suggesting that these modulators are selective towards rapidly proliferating cells. Therefore, evaluating the autophagic properties of chemotherapeutics could help determine more accurately the fate of different cell types under treatment. Our study underlines the importance of testing autophagic activity of potential anticancer agents in a comparative approach to develop more rational anticancer therapeutic strategies.",
journal = "Histochemistry and Cell Biology",
title = "Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells",
doi = "10.1007/s00418-017-1590-4"
}

Divac Rankov, A., Ljujić, M., Petrić, M., Radojković, D., Pešić, M.,& Dinić, J.. (2017). Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells. in Histochemistry and Cell Biology.
https://doi.org/10.1007/s00418-017-1590-4

Divac Rankov A, Ljujić M, Petrić M, Radojković D, Pešić M, Dinić J. Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells. in Histochemistry and Cell Biology. 2017;.
doi:10.1007/s00418-017-1590-4 .

Divac Rankov, Aleksandra, Ljujić, Mila, Petrić, Marija, Radojković, Dragica, Pešić, Milica, Dinić, Jelena, "Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells" in Histochemistry and Cell Biology (2017),
https://doi.org/10.1007/s00418-017-1590-4 . .

TY  - JOUR
AU  - Ljujić, Mila
AU  - Mijatović, Sanja
AU  - Bulatović, Mirna
AU  - Mojić, Marija
AU  - Maksimović-Ivanić, Danijela
AU  - Radojković, Dragica
AU  - Topić, Aleksandra
PY  - 2017
UR  - http://link.springer.com/10.1007/s12253-016-0104-3
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2729
AB  - Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.
T2  - Pathology & Oncology Research
T1  - Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines
IS  - 2
VL  - 23
DO  - 10.1007/s12253-016-0104-3
SP  - 335
EP  - 343
ER  - 

@article{
author = "Ljujić, Mila and Mijatović, Sanja and Bulatović, Mirna and Mojić, Marija and Maksimović-Ivanić, Danijela and Radojković, Dragica and Topić, Aleksandra",
year = "2017",
abstract = "Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.",
journal = "Pathology & Oncology Research",
title = "Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines",
number = "2",
volume = "23",
doi = "10.1007/s12253-016-0104-3",
pages = "335-343"
}

Ljujić, M., Mijatović, S., Bulatović, M., Mojić, M., Maksimović-Ivanić, D., Radojković, D.,& Topić, A.. (2017). Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines. in Pathology & Oncology Research, 23(2), 335-343.
https://doi.org/10.1007/s12253-016-0104-3

Ljujić M, Mijatović S, Bulatović M, Mojić M, Maksimović-Ivanić D, Radojković D, Topić A. Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines. in Pathology & Oncology Research. 2017;23(2):335-343.
doi:10.1007/s12253-016-0104-3 .

Ljujić, Mila, Mijatović, Sanja, Bulatović, Mirna, Mojić, Marija, Maksimović-Ivanić, Danijela, Radojković, Dragica, Topić, Aleksandra, "Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines" in Pathology & Oncology Research, 23, no. 2 (2017):335-343,
https://doi.org/10.1007/s12253-016-0104-3 . .