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  - JOUR
AU  - Venturelli, Leonardo
AU  - Kohler, Anne-Céline
AU  - Stupar, Petar
AU  - Villalba, Maria I.
AU  - Kalauzi, Aleksandar
AU  - Radotić, Ksenija
AU  - Bertacchi, Massimiliano
AU  - Dinarelli, Simone
AU  - Girasole, Marco
AU  - Pešić, Milica
AU  - Banković, Jasna
AU  - Vela, Maria E.
AU  - Yantorno, Osvaldo
AU  - Willaert, Ronnie
AU  - Dietler, Giovanni
AU  - Longo, Giovanni
AU  - Kasas, Sandor
PY  - 2020
UR  - http://doi.wiley.com/10.1002/jmr.2849
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3641
AB  - The insurgence of newly arising, rapidly developing health threats, such as drug-resistant bacteria and cancers, is one of the most urgent public-health issues of modern times. This menace calls for the development of sensitive and reliable diagnostic tools to monitor the response of single cells to chemical or pharmaceutical stimuli. Recently, it has been demonstrated that all living organisms oscillate at a nanometric scale and that these oscillations stop as soon as the organisms die. These nanometric scale oscillations can be detected by depositing living cells onto a micro-fabricated cantilever and by monitoring its displacements with an atomic force microscope-based electronics. Such devices, named nanomotion sensors, have been employed to determine the resistance profiles of life-threatening bacteria within minutes, to evaluate, among others, the effect of chemicals on yeast, neurons, and cancer cells. The data obtained so far demonstrate the advantages of nanomotion sensing devices in rapidly characterizing microorganism susceptibility to pharmaceutical agents. Here, we review the key aspects of this technique, presenting its major applications. and detailing its working protocols.
T2  - Journal of Molecular Recognition
T1  - A perspective view on the nanomotion detection of living organisms and its features
DO  - 10.1002/jmr.2849
SP  - e2849
ER  - 

@article{
author = "Venturelli, Leonardo and Kohler, Anne-Céline and Stupar, Petar and Villalba, Maria I. and Kalauzi, Aleksandar and Radotić, Ksenija and Bertacchi, Massimiliano and Dinarelli, Simone and Girasole, Marco and Pešić, Milica and Banković, Jasna and Vela, Maria E. and Yantorno, Osvaldo and Willaert, Ronnie and Dietler, Giovanni and Longo, Giovanni and Kasas, Sandor",
year = "2020",
abstract = "The insurgence of newly arising, rapidly developing health threats, such as drug-resistant bacteria and cancers, is one of the most urgent public-health issues of modern times. This menace calls for the development of sensitive and reliable diagnostic tools to monitor the response of single cells to chemical or pharmaceutical stimuli. Recently, it has been demonstrated that all living organisms oscillate at a nanometric scale and that these oscillations stop as soon as the organisms die. These nanometric scale oscillations can be detected by depositing living cells onto a micro-fabricated cantilever and by monitoring its displacements with an atomic force microscope-based electronics. Such devices, named nanomotion sensors, have been employed to determine the resistance profiles of life-threatening bacteria within minutes, to evaluate, among others, the effect of chemicals on yeast, neurons, and cancer cells. The data obtained so far demonstrate the advantages of nanomotion sensing devices in rapidly characterizing microorganism susceptibility to pharmaceutical agents. Here, we review the key aspects of this technique, presenting its major applications. and detailing its working protocols.",
journal = "Journal of Molecular Recognition",
title = "A perspective view on the nanomotion detection of living organisms and its features",
doi = "10.1002/jmr.2849",
pages = "e2849"
}

Venturelli, L., Kohler, A., Stupar, P., Villalba, M. I., Kalauzi, A., Radotić, K., Bertacchi, M., Dinarelli, S., Girasole, M., Pešić, M., Banković, J., Vela, M. E., Yantorno, O., Willaert, R., Dietler, G., Longo, G.,& Kasas, S.. (2020). A perspective view on the nanomotion detection of living organisms and its features. in Journal of Molecular Recognition, e2849.
https://doi.org/10.1002/jmr.2849

Venturelli L, Kohler A, Stupar P, Villalba MI, Kalauzi A, Radotić K, Bertacchi M, Dinarelli S, Girasole M, Pešić M, Banković J, Vela ME, Yantorno O, Willaert R, Dietler G, Longo G, Kasas S. A perspective view on the nanomotion detection of living organisms and its features. in Journal of Molecular Recognition. 2020;:e2849.
doi:10.1002/jmr.2849 .

Venturelli, Leonardo, Kohler, Anne-Céline, Stupar, Petar, Villalba, Maria I., Kalauzi, Aleksandar, Radotić, Ksenija, Bertacchi, Massimiliano, Dinarelli, Simone, Girasole, Marco, Pešić, Milica, Banković, Jasna, Vela, Maria E., Yantorno, Osvaldo, Willaert, Ronnie, Dietler, Giovanni, Longo, Giovanni, Kasas, Sandor, "A perspective view on the nanomotion detection of living organisms and its features" in Journal of Molecular Recognition (2020):e2849,
https://doi.org/10.1002/jmr.2849 . .

TY  - CONF
AU  - Nešović, Marija
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Tsimplouli, Chrisiida
AU  - Sereti, Evangelia
AU  - Dragoj, Miodrag
AU  - Podolski-Renić, Ana
AU  - Stanković, Tijana
AU  - Jovanović, Mirna
AU  - Dimas, Kostantinos
AU  - Pešić, Milica
AU  - Dinić, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6046
AB  - Resistance to chemotherapeutic agents represents a major issue in anticancer therapy.
Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its aggressive behavior and
resistance to treatment. Alterations in the PI3K/AKT/mTOR pathway and/or high expression
of ATP binding cassette transporters, such as P-glycoprotein and breast cancer resistance
protein (BCRP), are frequently linked to chemo-resistance. Autophagy is a key player in the
metabolic and therapeutic stress response and represents a potential target for anticancer
therapy. Autophagy induction in response to chemotherapeutics may contribute to both
drug efficacy as well as drug resistance. We assessed the therapeutic efficacy of dual mTOR
kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX) in combination in ATC cells. Rhocell line was generated from parental human thyroid carcinoma 8505C via the selection of cells with a low accumulation of rhodamine 123 (P-glycoprotein and BCRP substrate). Rhocells were 10-fold more resistant to PTX compared to 8505C cells and more tumorigenic. Both vistusertib and PTX induced autophagosome formation in the investigated cell lines. In combination, vistusertib sensitized Rho- cells to PTX via autophagy induction and proliferation inhibition, indicating a synergistic effect between the two compounds. Additionally, vistusertib and PTX combination in Rho- and 8505C cells inhibited cell migration
and invasion in vitro. Furthermore, vistusertib and PTX combination effectively suppressed
tumor growth of ATC xenografts in immunodeficient NSG mice in vivo. Considering chemoresistance and high invasive properties of ATC, described combined approach could be useful for the design of novel targeted treatment strategies in this malignancy
PB  - COST Action CA1513
C3  - Poster, Abstract Book: 3rd TRANSAutophagy CA15138 Annual Meeting 2019; 2019 Apr 23-25; Sofia, Bulgaria
T1  - Vistusertib (AZD2014), a dual mTOR kinase inhibitor, overcomes paclitaxel resistance in anaplastic thyroid carcinoma
SP  - 30
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6046
ER  - 

@conference{
author = "Nešović, Marija and Milošević, Zorica and Banković, Jasna and Tsimplouli, Chrisiida and Sereti, Evangelia and Dragoj, Miodrag and Podolski-Renić, Ana and Stanković, Tijana and Jovanović, Mirna and Dimas, Kostantinos and Pešić, Milica and Dinić, Jelena",
year = "2019",
abstract = "Resistance to chemotherapeutic agents represents a major issue in anticancer therapy.
Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its aggressive behavior and
resistance to treatment. Alterations in the PI3K/AKT/mTOR pathway and/or high expression
of ATP binding cassette transporters, such as P-glycoprotein and breast cancer resistance
protein (BCRP), are frequently linked to chemo-resistance. Autophagy is a key player in the
metabolic and therapeutic stress response and represents a potential target for anticancer
therapy. Autophagy induction in response to chemotherapeutics may contribute to both
drug efficacy as well as drug resistance. We assessed the therapeutic efficacy of dual mTOR
kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX) in combination in ATC cells. Rhocell line was generated from parental human thyroid carcinoma 8505C via the selection of cells with a low accumulation of rhodamine 123 (P-glycoprotein and BCRP substrate). Rhocells were 10-fold more resistant to PTX compared to 8505C cells and more tumorigenic. Both vistusertib and PTX induced autophagosome formation in the investigated cell lines. In combination, vistusertib sensitized Rho- cells to PTX via autophagy induction and proliferation inhibition, indicating a synergistic effect between the two compounds. Additionally, vistusertib and PTX combination in Rho- and 8505C cells inhibited cell migration
and invasion in vitro. Furthermore, vistusertib and PTX combination effectively suppressed
tumor growth of ATC xenografts in immunodeficient NSG mice in vivo. Considering chemoresistance and high invasive properties of ATC, described combined approach could be useful for the design of novel targeted treatment strategies in this malignancy",
publisher = "COST Action CA1513",
journal = "Poster, Abstract Book: 3rd TRANSAutophagy CA15138 Annual Meeting 2019; 2019 Apr 23-25; Sofia, Bulgaria",
title = "Vistusertib (AZD2014), a dual mTOR kinase inhibitor, overcomes paclitaxel resistance in anaplastic thyroid carcinoma",
pages = "30",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6046"
}

Nešović, M., Milošević, Z., Banković, J., Tsimplouli, C., Sereti, E., Dragoj, M., Podolski-Renić, A., Stanković, T., Jovanović, M., Dimas, K., Pešić, M.,& Dinić, J.. (2019). Vistusertib (AZD2014), a dual mTOR kinase inhibitor, overcomes paclitaxel resistance in anaplastic thyroid carcinoma. in Poster, Abstract Book: 3rd TRANSAutophagy CA15138 Annual Meeting 2019; 2019 Apr 23-25; Sofia, Bulgaria
COST Action CA1513., 30.
https://hdl.handle.net/21.15107/rcub_ibiss_6046

Nešović M, Milošević Z, Banković J, Tsimplouli C, Sereti E, Dragoj M, Podolski-Renić A, Stanković T, Jovanović M, Dimas K, Pešić M, Dinić J. Vistusertib (AZD2014), a dual mTOR kinase inhibitor, overcomes paclitaxel resistance in anaplastic thyroid carcinoma. in Poster, Abstract Book: 3rd TRANSAutophagy CA15138 Annual Meeting 2019; 2019 Apr 23-25; Sofia, Bulgaria. 2019;:30.
https://hdl.handle.net/21.15107/rcub_ibiss_6046 .

Nešović, Marija, Milošević, Zorica, Banković, Jasna, Tsimplouli, Chrisiida, Sereti, Evangelia, Dragoj, Miodrag, Podolski-Renić, Ana, Stanković, Tijana, Jovanović, Mirna, Dimas, Kostantinos, Pešić, Milica, Dinić, Jelena, "Vistusertib (AZD2014), a dual mTOR kinase inhibitor, overcomes paclitaxel resistance in anaplastic thyroid carcinoma" in Poster, Abstract Book: 3rd TRANSAutophagy CA15138 Annual Meeting 2019; 2019 Apr 23-25; Sofia, Bulgaria (2019):30,
https://hdl.handle.net/21.15107/rcub_ibiss_6046 .

TY  - JOUR
AU  - Dragoj, Miodrag
AU  - Banković, Jasna
AU  - Podolski-Renić, Ana
AU  - Stojković Burić, Sonja
AU  - Pešić, Milica
AU  - Tanić, Nikola
AU  - Stanković, Tijana
PY  - 2019
UR  - https://content.sciendo.com/view/journals/jomb/ahead-of-print/article-10.2478-jomb-2018-0022.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3099
AB  - Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACTR3 and E2F4. Methods: We analyzed MYC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. MYC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: MYC expression was significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed MYC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.
T2  - Journal of Medical Biochemistry
T1  - Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis
VL  - 37
DO  - 10.2478/jomb-2018-0022
SP  - 188
EP  - 195
ER  - 

@article{
author = "Dragoj, Miodrag and Banković, Jasna and Podolski-Renić, Ana and Stojković Burić, Sonja and Pešić, Milica and Tanić, Nikola and Stanković, Tijana",
year = "2019",
abstract = "Background: C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACTR3 and E2F4. Methods: We analyzed MYC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. MYC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. Results: MYC expression was significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed MYC and altered PHACTR3 or E2F4 showed trend of shorter survival. Conclusions: Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.",
journal = "Journal of Medical Biochemistry",
title = "Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis",
volume = "37",
doi = "10.2478/jomb-2018-0022",
pages = "188-195"
}

Dragoj, M., Banković, J., Podolski-Renić, A., Stojković Burić, S., Pešić, M., Tanić, N.,& Stanković, T.. (2019). Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis. in Journal of Medical Biochemistry, 37, 188-195.
https://doi.org/10.2478/jomb-2018-0022

Dragoj M, Banković J, Podolski-Renić A, Stojković Burić S, Pešić M, Tanić N, Stanković T. Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis. in Journal of Medical Biochemistry. 2019;37:188-195.
doi:10.2478/jomb-2018-0022 .

Dragoj, Miodrag, Banković, Jasna, Podolski-Renić, Ana, Stojković Burić, Sonja, Pešić, Milica, Tanić, Nikola, Stanković, Tijana, "Association of Overexpressed MYC Gene with Altered PHACTR3 and E2F4 Genes Contributes to Non-Small Cell Lung Carcinoma Pathogenesis" in Journal of Medical Biochemistry, 37 (2019):188-195,
https://doi.org/10.2478/jomb-2018-0022 . .

TY  - JOUR
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Tsimplouli, Chrisiida
AU  - Sereti, Evangelia
AU  - Dragoj, Miodrag
AU  - Paunović, Verica
AU  - Milovanović, Zorka
AU  - Nešović, Marija
AU  - Tanić, Nikola
AU  - Dimas, Kostantinos
AU  - Pešić, Milica
PY  - 2018
UR  - https://link.springer.com/article/10.1007%2Fs13402-018-0380-x
UR  - https://radar.ibiss.bg.ac.rs/123456789/3887
AB  - Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate.
Methods: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies.
Results: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth.
Conclusions: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
PB  - Basel : Springer Nature
T2  - Cellular Oncology (Dordrecht)
T1  - Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma
VL  - 41
DO  - 10.1007/s13402-018-0380-x
SP  - 409
EP  - 426
ER  - 

@article{
author = "Milošević, Zorica and Banković, Jasna and Dinić, Jelena and Tsimplouli, Chrisiida and Sereti, Evangelia and Dragoj, Miodrag and Paunović, Verica and Milovanović, Zorka and Nešović, Marija and Tanić, Nikola and Dimas, Kostantinos and Pešić, Milica",
year = "2018",
abstract = "Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate.
Methods: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies.
Results: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth.
Conclusions: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.",
publisher = "Basel : Springer Nature",
journal = "Cellular Oncology (Dordrecht)",
title = "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma",
volume = "41",
doi = "10.1007/s13402-018-0380-x",
pages = "409-426"
}

Milošević, Z., Banković, J., Dinić, J., Tsimplouli, C., Sereti, E., Dragoj, M., Paunović, V., Milovanović, Z., Nešović, M., Tanić, N., Dimas, K.,& Pešić, M.. (2018). Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. in Cellular Oncology (Dordrecht)
Basel : Springer Nature., 41, 409-426.
https://doi.org/10.1007/s13402-018-0380-x

Milošević Z, Banković J, Dinić J, Tsimplouli C, Sereti E, Dragoj M, Paunović V, Milovanović Z, Nešović M, Tanić N, Dimas K, Pešić M. Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. in Cellular Oncology (Dordrecht). 2018;41:409-426.
doi:10.1007/s13402-018-0380-x .

Milošević, Zorica, Banković, Jasna, Dinić, Jelena, Tsimplouli, Chrisiida, Sereti, Evangelia, Dragoj, Miodrag, Paunović, Verica, Milovanović, Zorka, Nešović, Marija, Tanić, Nikola, Dimas, Kostantinos, Pešić, Milica, "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma" in Cellular Oncology (Dordrecht), 41 (2018):409-426,
https://doi.org/10.1007/s13402-018-0380-x . .

TY  - JOUR
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Tsimplouli, Chrisiida
AU  - Sereti, Evangelia
AU  - Dragoj, Miodrag
AU  - Paunović, Verica
AU  - Milovanović, Zorka
AU  - Stepanović, Marija
AU  - Tanić, Nikola
AU  - Dimas, Kostantinos
AU  - Pešić, Milica
PY  - 2018
UR  - http://link.springer.com/10.1007/s13402-018-0380-x
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3128
AB  - PURPOSE Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. METHODS Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. RESULTS Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. CONCLUSIONS Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
T2  - Cellular Oncology (Dordrecht)
T1  - Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.
IS  - 4
VL  - 41
DO  - 10.1007/s13402-018-0380-x
SP  - 409
EP  - 426
ER  - 

@article{
author = "Milošević, Zorica and Banković, Jasna and Dinić, Jelena and Tsimplouli, Chrisiida and Sereti, Evangelia and Dragoj, Miodrag and Paunović, Verica and Milovanović, Zorka and Stepanović, Marija and Tanić, Nikola and Dimas, Kostantinos and Pešić, Milica",
year = "2018",
abstract = "PURPOSE Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. METHODS Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. RESULTS Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. CONCLUSIONS Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.",
journal = "Cellular Oncology (Dordrecht)",
title = "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.",
number = "4",
volume = "41",
doi = "10.1007/s13402-018-0380-x",
pages = "409-426"
}

Milošević, Z., Banković, J., Dinić, J., Tsimplouli, C., Sereti, E., Dragoj, M., Paunović, V., Milovanović, Z., Stepanović, M., Tanić, N., Dimas, K.,& Pešić, M.. (2018). Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.. in Cellular Oncology (Dordrecht), 41(4), 409-426.
https://doi.org/10.1007/s13402-018-0380-x

Milošević Z, Banković J, Dinić J, Tsimplouli C, Sereti E, Dragoj M, Paunović V, Milovanović Z, Stepanović M, Tanić N, Dimas K, Pešić M. Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma.. in Cellular Oncology (Dordrecht). 2018;41(4):409-426.
doi:10.1007/s13402-018-0380-x .

Milošević, Zorica, Banković, Jasna, Dinić, Jelena, Tsimplouli, Chrisiida, Sereti, Evangelia, Dragoj, Miodrag, Paunović, Verica, Milovanović, Zorka, Stepanović, Marija, Tanić, Nikola, Dimas, Kostantinos, Pešić, Milica, "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma." in Cellular Oncology (Dordrecht), 41, no. 4 (2018):409-426,
https://doi.org/10.1007/s13402-018-0380-x . .

TY  - JOUR
AU  - Jantsch, Michael F.
AU  - Quattrone, Alessandro
AU  - O'Connell, Mary
AU  - Helm, Mark
AU  - Frye, Michaela
AU  - Macias-Gonzales, Manuel
AU  - Ohman, Marie
AU  - Ameres, Stefan
AU  - Willems, Luc
AU  - Fuks, Francois
AU  - Oulas, Anastasis
AU  - Vanacova, Stepanka
AU  - Nielsen, Henrik
AU  - Bousquet-Antonelli, Cecile
AU  - Motorin, Yuri
AU  - Roignant, Jean-Yves
AU  - Balatsos, Nikolaos
AU  - Dinnyes, Andras
AU  - Baranov, Pavel
AU  - Kelly, Vincent
AU  - Lamm, Ayelet
AU  - Rechavi, Gideon
AU  - Pelizzola, Mattia
AU  - Liepins, Janis
AU  - Holodnuka Kholodnyuk, Irina
AU  - Zammit, Vanessa
AU  - Ayers, Duncan
AU  - Drablos, Finn
AU  - Dahl, John Arne
AU  - Bujnicki, Janusz
AU  - Jeronimo, Carmen
AU  - Almeida, Raquel
AU  - Neagu, Monica
AU  - Costache, Marieta
AU  - Banković, Jasna
AU  - Banović, Bojana
AU  - Kyselovic, Jan
AU  - Valor, Luis Miguel
AU  - Selbert, Stefan
AU  - Pir, Pinar
AU  - Demircan, Turan
AU  - Cowling, Victoria
AU  - Schäfer, Matthias
AU  - Rossmanith, Walter
AU  - Lafontaine, Denis
AU  - David, Alexandre
AU  - Carre, Clement
AU  - Lyko, Frank
AU  - Schaffrath, Raffael
AU  - Schwartz, Schraga
AU  - Verdel, Andre
AU  - Klungland, Arne
AU  - Purta, Elzbieta
AU  - Timotijevic, Gordana
AU  - Cardona, Fernando
AU  - Davalos, Alberto
AU  - Ballana, Ester
AU  - O Carroll, Donal
AU  - Ule, Jernej
AU  - Fray, Rupert
PY  - 2018
UR  - https://www.tandfonline.com/doi/full/10.1080/15476286.2018.1460996
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3063
AB  - The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.
T2  - RNA Biology
T1  - Positioning Europe for the EPITRANSCRIPTOMICS challenge.
DO  - 10.1080/15476286.2018.1460996
ER  - 

@article{
author = "Jantsch, Michael F. and Quattrone, Alessandro and O'Connell, Mary and Helm, Mark and Frye, Michaela and Macias-Gonzales, Manuel and Ohman, Marie and Ameres, Stefan and Willems, Luc and Fuks, Francois and Oulas, Anastasis and Vanacova, Stepanka and Nielsen, Henrik and Bousquet-Antonelli, Cecile and Motorin, Yuri and Roignant, Jean-Yves and Balatsos, Nikolaos and Dinnyes, Andras and Baranov, Pavel and Kelly, Vincent and Lamm, Ayelet and Rechavi, Gideon and Pelizzola, Mattia and Liepins, Janis and Holodnuka Kholodnyuk, Irina and Zammit, Vanessa and Ayers, Duncan and Drablos, Finn and Dahl, John Arne and Bujnicki, Janusz and Jeronimo, Carmen and Almeida, Raquel and Neagu, Monica and Costache, Marieta and Banković, Jasna and Banović, Bojana and Kyselovic, Jan and Valor, Luis Miguel and Selbert, Stefan and Pir, Pinar and Demircan, Turan and Cowling, Victoria and Schäfer, Matthias and Rossmanith, Walter and Lafontaine, Denis and David, Alexandre and Carre, Clement and Lyko, Frank and Schaffrath, Raffael and Schwartz, Schraga and Verdel, Andre and Klungland, Arne and Purta, Elzbieta and Timotijevic, Gordana and Cardona, Fernando and Davalos, Alberto and Ballana, Ester and O Carroll, Donal and Ule, Jernej and Fray, Rupert",
year = "2018",
abstract = "The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.",
journal = "RNA Biology",
title = "Positioning Europe for the EPITRANSCRIPTOMICS challenge.",
doi = "10.1080/15476286.2018.1460996"
}

Jantsch, M. F., Quattrone, A., O'Connell, M., Helm, M., Frye, M., Macias-Gonzales, M., Ohman, M., Ameres, S., Willems, L., Fuks, F., Oulas, A., Vanacova, S., Nielsen, H., Bousquet-Antonelli, C., Motorin, Y., Roignant, J., Balatsos, N., Dinnyes, A., Baranov, P., Kelly, V., Lamm, A., Rechavi, G., Pelizzola, M., Liepins, J., Holodnuka Kholodnyuk, I., Zammit, V., Ayers, D., Drablos, F., Dahl, J. A., Bujnicki, J., Jeronimo, C., Almeida, R., Neagu, M., Costache, M., Banković, J., Banović, B., Kyselovic, J., Valor, L. M., Selbert, S., Pir, P., Demircan, T., Cowling, V., Schäfer, M., Rossmanith, W., Lafontaine, D., David, A., Carre, C., Lyko, F., Schaffrath, R., Schwartz, S., Verdel, A., Klungland, A., Purta, E., Timotijevic, G., Cardona, F., Davalos, A., Ballana, E., O Carroll, D., Ule, J.,& Fray, R.. (2018). Positioning Europe for the EPITRANSCRIPTOMICS challenge.. in RNA Biology.
https://doi.org/10.1080/15476286.2018.1460996

Jantsch MF, Quattrone A, O'Connell M, Helm M, Frye M, Macias-Gonzales M, Ohman M, Ameres S, Willems L, Fuks F, Oulas A, Vanacova S, Nielsen H, Bousquet-Antonelli C, Motorin Y, Roignant J, Balatsos N, Dinnyes A, Baranov P, Kelly V, Lamm A, Rechavi G, Pelizzola M, Liepins J, Holodnuka Kholodnyuk I, Zammit V, Ayers D, Drablos F, Dahl JA, Bujnicki J, Jeronimo C, Almeida R, Neagu M, Costache M, Banković J, Banović B, Kyselovic J, Valor LM, Selbert S, Pir P, Demircan T, Cowling V, Schäfer M, Rossmanith W, Lafontaine D, David A, Carre C, Lyko F, Schaffrath R, Schwartz S, Verdel A, Klungland A, Purta E, Timotijevic G, Cardona F, Davalos A, Ballana E, O Carroll D, Ule J, Fray R. Positioning Europe for the EPITRANSCRIPTOMICS challenge.. in RNA Biology. 2018;.
doi:10.1080/15476286.2018.1460996 .

Jantsch, Michael F., Quattrone, Alessandro, O'Connell, Mary, Helm, Mark, Frye, Michaela, Macias-Gonzales, Manuel, Ohman, Marie, Ameres, Stefan, Willems, Luc, Fuks, Francois, Oulas, Anastasis, Vanacova, Stepanka, Nielsen, Henrik, Bousquet-Antonelli, Cecile, Motorin, Yuri, Roignant, Jean-Yves, Balatsos, Nikolaos, Dinnyes, Andras, Baranov, Pavel, Kelly, Vincent, Lamm, Ayelet, Rechavi, Gideon, Pelizzola, Mattia, Liepins, Janis, Holodnuka Kholodnyuk, Irina, Zammit, Vanessa, Ayers, Duncan, Drablos, Finn, Dahl, John Arne, Bujnicki, Janusz, Jeronimo, Carmen, Almeida, Raquel, Neagu, Monica, Costache, Marieta, Banković, Jasna, Banović, Bojana, Kyselovic, Jan, Valor, Luis Miguel, Selbert, Stefan, Pir, Pinar, Demircan, Turan, Cowling, Victoria, Schäfer, Matthias, Rossmanith, Walter, Lafontaine, Denis, David, Alexandre, Carre, Clement, Lyko, Frank, Schaffrath, Raffael, Schwartz, Schraga, Verdel, Andre, Klungland, Arne, Purta, Elzbieta, Timotijevic, Gordana, Cardona, Fernando, Davalos, Alberto, Ballana, Ester, O Carroll, Donal, Ule, Jernej, Fray, Rupert, "Positioning Europe for the EPITRANSCRIPTOMICS challenge." in RNA Biology (2018),
https://doi.org/10.1080/15476286.2018.1460996 . .

TY  - JOUR
AU  - Dragoj, Miodrag
AU  - Jovanović Stojanov, Sofija
AU  - Pešić, Milica
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Sereti, Evangelia
AU  - Dimas, Konstantinos
PY  - 2017
UR  - http://link.springer.com/10.1007/s10637-017-0494-4
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2822
AB  - Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs. In this study, we first examined the invasive characteristics of NSCLC cells with suppressed p53 and PTEN activity using wound healing, gelatin degradation and invasion assays. Further, changes in the expression of CXCR4 and FAK were evaluated by RT-qPCR and Western Blot analysis. Finally, we tested the ability of CXCR4 and FAK inhibitors (WZ811 and PF-573228, respectively) to suppress the migratory and invasive potential of p53/PTEN deficient NSCLC cells, in vitro and in vivo using metastatic models of human NSCLC. Our results showed that cells with mutually inactive p53 and PTEN have significantly increased invasive potential associated with hyperactivation of CXCR4 and FAK signaling pathways. Treatments with WZ811 and PF-573228 inhibitors significantly reduced migratory and invasive capacity in vitro and showed a trend of improved survival in vivo. Accordingly, we demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination.
T2  - Investigational New Drugs
T1  - Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors
IS  - 6
VL  - 35
DO  - 10.1007/s10637-017-0494-4
SP  - 718
EP  - 732
ER  - 

@article{
author = "Dragoj, Miodrag and Jovanović Stojanov, Sofija and Pešić, Milica and Stanković, Tijana and Banković, Jasna and Sereti, Evangelia and Dimas, Konstantinos",
year = "2017",
abstract = "Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. At the time of diagnosis, a large percentage of NSCLC patients have already developed metastasis, responsible for extremely high mortality rates. CXCR4 receptor and focal adhesion kinase (FAK) are known to regulate such invasive cancer behavior. Their expression is downregulated by p53 and PTEN tumor suppressors which are commonly co-inactivated in NSCLC patients and contribute to metastasis. Therefore, targeting CXCR4 or FAK seems to be a promising strategy in suppressing metastatic spread of p53/PTEN deficient NSCLCs. In this study, we first examined the invasive characteristics of NSCLC cells with suppressed p53 and PTEN activity using wound healing, gelatin degradation and invasion assays. Further, changes in the expression of CXCR4 and FAK were evaluated by RT-qPCR and Western Blot analysis. Finally, we tested the ability of CXCR4 and FAK inhibitors (WZ811 and PF-573228, respectively) to suppress the migratory and invasive potential of p53/PTEN deficient NSCLC cells, in vitro and in vivo using metastatic models of human NSCLC. Our results showed that cells with mutually inactive p53 and PTEN have significantly increased invasive potential associated with hyperactivation of CXCR4 and FAK signaling pathways. Treatments with WZ811 and PF-573228 inhibitors significantly reduced migratory and invasive capacity in vitro and showed a trend of improved survival in vivo. Accordingly, we demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination.",
journal = "Investigational New Drugs",
title = "Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors",
number = "6",
volume = "35",
doi = "10.1007/s10637-017-0494-4",
pages = "718-732"
}

Dragoj, M., Jovanović Stojanov, S., Pešić, M., Stanković, T., Banković, J., Sereti, E.,& Dimas, K.. (2017). Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors. in Investigational New Drugs, 35(6), 718-732.
https://doi.org/10.1007/s10637-017-0494-4

Dragoj M, Jovanović Stojanov S, Pešić M, Stanković T, Banković J, Sereti E, Dimas K. Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors. in Investigational New Drugs. 2017;35(6):718-732.
doi:10.1007/s10637-017-0494-4 .

Dragoj, Miodrag, Jovanović Stojanov, Sofija, Pešić, Milica, Stanković, Tijana, Banković, Jasna, Sereti, Evangelia, Dimas, Konstantinos, "Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors" in Investigational New Drugs, 35, no. 6 (2017):718-732,
https://doi.org/10.1007/s10637-017-0494-4 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ríos-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević-Grujičić, Nataša
AU  - Martín, Víctor S.
AU  - Padrón, José M.
AU  - Pešić, Milica
PY  - 2017
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0928098717302397
UR  - https://radar.ibiss.bg.ac.rs/123456789/3873
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
PB  - Amsterdam: Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
SP  - 159
EP  - 168
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Ríos-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević-Grujičić, Nataša and Martín, Víctor S. and Padrón, José M. and Pešić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
publisher = "Amsterdam: Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011",
pages = "159-168"
}

Podolski-Renić, A., Banković, J., Dinić, J., Ríos-Luci, C., Fernandes, M. X., Ortega, N., Kovačević-Grujičić, N., Martín, V. S., Padrón, J. M.,& Pešić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences
Amsterdam: Elsevier., 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Ríos-Luci C, Fernandes MX, Ortega N, Kovačević-Grujičić N, Martín VS, Padrón JM, Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Ríos-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević-Grujičić, Nataša, Martín, Víctor S., Padrón, José M., Pešić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ríos-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević-Grujičić, Nataša
AU  - Martín, Víctor S.
AU  - Padrón, José M.
AU  - Pešić, Milica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0928098717302397
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2762
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
SP  - 159
EP  - 168
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Ríos-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević-Grujičić, Nataša and Martín, Víctor S. and Padrón, José M. and Pešić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011",
pages = "159-168"
}

Podolski-Renić, A., Banković, J., Dinić, J., Ríos-Luci, C., Fernandes, M. X., Ortega, N., Kovačević-Grujičić, N., Martín, V. S., Padrón, J. M.,& Pešić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences, 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Ríos-Luci C, Fernandes MX, Ortega N, Kovačević-Grujičić N, Martín VS, Padrón JM, Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Ríos-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević-Grujičić, Nataša, Martín, Víctor S., Padrón, José M., Pešić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .

TY  - JOUR
AU  - Dragoj, Miodrag
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Tanić, Nikola
AU  - Pešić, Milica
AU  - Stanković, Tijana
PY  - 2017
UR  - http://link.springer.com/10.1007/s13402-016-0304-6
UR  - https://www.scopus.com/record/display.uri?eid=2-s2.0-84994434560&origin=SingleRecordEmailAlert&txGid=6CE299281CDB840158BFAC52EC5A2E1C.wsnAw8kcdt7IPYLO0V48gA:31
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2540
AB  - Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells. Methods: qRT-PCR was used for gene expression analyses in primary lung tissue samples obtained from 30 NSCLC patients and the human NSCLC-derived cell lines NCI-H460, NCI-H460/R and COR-L23. MTT, flow cytometry, cell death and β-galactosidase activity assays were used to assess the in vitro impact of CXCR4 and FAK inhibitors on DOX sensitivity. In addition, invasion and gelatin degradation assays were used to assess the in vitro impact of the respective inhibitors on metastasis-related processes in combination with DOX treatment. Results: We found that ABCB1 over-expression was significantly associated with CXCR4 and FAK over-expression, whereas ABCC1 over-expression was associated with increased FAK expression. We also found that CXCR4 and FAK inhibitors strongly synergized with DOX in reducing cell viability, arresting the cell cycle in the S or G2/M phases and inducing senescence. Additionally, we found that DOX enhanced the anti-invasive potential of CXCR4 and FAK inhibitors by reducing gelatin degradation and invasion. Conclusions: From our data we conclude that targeting of CXCR4 and FAK may overcome ABCB1 and ABCC1-dependent DOX resistance in NSCLC cells and that simultaneous treatment of these cells with DOX may potentiate the anti-invasive effects of CXCR4 and FAK inhibitors.
T2  - Cellular Oncology
T1  - Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma
IS  - 1
VL  - 40
DO  - 10.1007/s13402-016-0304-6
SP  - 47
EP  - 62
ER  - 

@article{
author = "Dragoj, Miodrag and Milošević, Zorica and Banković, Jasna and Tanić, Nikola and Pešić, Milica and Stanković, Tijana",
year = "2017",
abstract = "Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells. Methods: qRT-PCR was used for gene expression analyses in primary lung tissue samples obtained from 30 NSCLC patients and the human NSCLC-derived cell lines NCI-H460, NCI-H460/R and COR-L23. MTT, flow cytometry, cell death and β-galactosidase activity assays were used to assess the in vitro impact of CXCR4 and FAK inhibitors on DOX sensitivity. In addition, invasion and gelatin degradation assays were used to assess the in vitro impact of the respective inhibitors on metastasis-related processes in combination with DOX treatment. Results: We found that ABCB1 over-expression was significantly associated with CXCR4 and FAK over-expression, whereas ABCC1 over-expression was associated with increased FAK expression. We also found that CXCR4 and FAK inhibitors strongly synergized with DOX in reducing cell viability, arresting the cell cycle in the S or G2/M phases and inducing senescence. Additionally, we found that DOX enhanced the anti-invasive potential of CXCR4 and FAK inhibitors by reducing gelatin degradation and invasion. Conclusions: From our data we conclude that targeting of CXCR4 and FAK may overcome ABCB1 and ABCC1-dependent DOX resistance in NSCLC cells and that simultaneous treatment of these cells with DOX may potentiate the anti-invasive effects of CXCR4 and FAK inhibitors.",
journal = "Cellular Oncology",
title = "Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma",
number = "1",
volume = "40",
doi = "10.1007/s13402-016-0304-6",
pages = "47-62"
}

Dragoj, M., Milošević, Z., Banković, J., Tanić, N., Pešić, M.,& Stanković, T.. (2017). Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma. in Cellular Oncology, 40(1), 47-62.
https://doi.org/10.1007/s13402-016-0304-6

Dragoj M, Milošević Z, Banković J, Tanić N, Pešić M, Stanković T. Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma. in Cellular Oncology. 2017;40(1):47-62.
doi:10.1007/s13402-016-0304-6 .

Dragoj, Miodrag, Milošević, Zorica, Banković, Jasna, Tanić, Nikola, Pešić, Milica, Stanković, Tijana, "Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma" in Cellular Oncology, 40, no. 1 (2017):47-62,
https://doi.org/10.1007/s13402-016-0304-6 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Milošević, Zorica
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Pešić, Milica
PY  - 2016
UR  - http://xlink.rsc.org/?DOI=C6MD00391E
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2493
AB  - Cancer-initiating cells referred to as cancer stem cells (CSCs) retain the essential property of self-renewal and protection. The protective mechanisms enable tumour regrowth even after the application of chemotherapy that was believed to be successful. Among the protective mechanisms of CSCs, the overexpression of ATP binding cassette (ABC) membrane transporters is highly important. ABC transporters involved in the development of cancer multidrug resistance (MDR) such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are considered as particular features of CSCs. They provide a shield for CSCs and protect them from the adverse effects of chemotherapeutics. Hence, combating MDR would be one of the strategies for the elimination of CSCs. In order to investigate this phenomenon many model systems comprising MDR cancer cells have been established. Some of them were developed by a selection process through exposure to various anticancer drugs, others by transfection of genes for ABC transporters, while some were obtained by sorting the side population considered to possess stemness and resistant phenotypes. Herein we review the potential of cancer MDR models for studying CSCs because gaining a better insight into the mechanisms of CSC resistance to chemotherapy may lead to the discovery of new therapeutic targets and the development of better anticancer strategies.
T2  - MedChemComm
T1  - Mutual regulation and targeting of multidrug resistance and cancer stem phenotype
IS  - 12
VL  - 7
DO  - 10.1039/C6MD00391E
SP  - 2265
EP  - 2281
ER  - 

@article{
author = "Podolski-Renić, Ana and Milošević, Zorica and Dinić, Jelena and Stanković, Tijana and Banković, Jasna and Pešić, Milica",
year = "2016",
abstract = "Cancer-initiating cells referred to as cancer stem cells (CSCs) retain the essential property of self-renewal and protection. The protective mechanisms enable tumour regrowth even after the application of chemotherapy that was believed to be successful. Among the protective mechanisms of CSCs, the overexpression of ATP binding cassette (ABC) membrane transporters is highly important. ABC transporters involved in the development of cancer multidrug resistance (MDR) such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are considered as particular features of CSCs. They provide a shield for CSCs and protect them from the adverse effects of chemotherapeutics. Hence, combating MDR would be one of the strategies for the elimination of CSCs. In order to investigate this phenomenon many model systems comprising MDR cancer cells have been established. Some of them were developed by a selection process through exposure to various anticancer drugs, others by transfection of genes for ABC transporters, while some were obtained by sorting the side population considered to possess stemness and resistant phenotypes. Herein we review the potential of cancer MDR models for studying CSCs because gaining a better insight into the mechanisms of CSC resistance to chemotherapy may lead to the discovery of new therapeutic targets and the development of better anticancer strategies.",
journal = "MedChemComm",
title = "Mutual regulation and targeting of multidrug resistance and cancer stem phenotype",
number = "12",
volume = "7",
doi = "10.1039/C6MD00391E",
pages = "2265-2281"
}

Podolski-Renić, A., Milošević, Z., Dinić, J., Stanković, T., Banković, J.,& Pešić, M.. (2016). Mutual regulation and targeting of multidrug resistance and cancer stem phenotype. in MedChemComm, 7(12), 2265-2281.
https://doi.org/10.1039/C6MD00391E

Podolski-Renić A, Milošević Z, Dinić J, Stanković T, Banković J, Pešić M. Mutual regulation and targeting of multidrug resistance and cancer stem phenotype. in MedChemComm. 2016;7(12):2265-2281.
doi:10.1039/C6MD00391E .

Podolski-Renić, Ana, Milošević, Zorica, Dinić, Jelena, Stanković, Tijana, Banković, Jasna, Pešić, Milica, "Mutual regulation and targeting of multidrug resistance and cancer stem phenotype" in MedChemComm, 7, no. 12 (2016):2265-2281,
https://doi.org/10.1039/C6MD00391E . .

TY  - JOUR
AU  - Jeremić, Marko
AU  - Pešić, Milica
AU  - Dinić, Jelena
AU  - Banković, Jasna
AU  - Novaković, Irena
AU  - Šegan, Dejan
AU  - Sladić, Dušan
PY  - 2016
UR  - https://www.sciencedirect.com/science/article/pii/S0223523416302938?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/123456789/3885
AB  - In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.
PB  - Paris : Elsevier France-Editions Scientifiques Medicales Elsevier
T2  - European Journal of Medicinal Chemistry
T1  - Simple avarone mimetics as selective agents against multidrug resistant cancer cells
VL  - 118
DO  - 10.1016/j.ejmech.2016.04.011
SP  - 107
EP  - 120
ER  - 

@article{
author = "Jeremić, Marko and Pešić, Milica and Dinić, Jelena and Banković, Jasna and Novaković, Irena and Šegan, Dejan and Sladić, Dušan",
year = "2016",
abstract = "In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity.",
publisher = "Paris : Elsevier France-Editions Scientifiques Medicales Elsevier",
journal = "European Journal of Medicinal Chemistry",
title = "Simple avarone mimetics as selective agents against multidrug resistant cancer cells",
volume = "118",
doi = "10.1016/j.ejmech.2016.04.011",
pages = "107-120"
}

Jeremić, M., Pešić, M., Dinić, J., Banković, J., Novaković, I., Šegan, D.,& Sladić, D.. (2016). Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry
Paris : Elsevier France-Editions Scientifiques Medicales Elsevier., 118, 107-120.
https://doi.org/10.1016/j.ejmech.2016.04.011

Jeremić M, Pešić M, Dinić J, Banković J, Novaković I, Šegan D, Sladić D. Simple avarone mimetics as selective agents against multidrug resistant cancer cells. in European Journal of Medicinal Chemistry. 2016;118:107-120.
doi:10.1016/j.ejmech.2016.04.011 .

Jeremić, Marko, Pešić, Milica, Dinić, Jelena, Banković, Jasna, Novaković, Irena, Šegan, Dejan, Sladić, Dušan, "Simple avarone mimetics as selective agents against multidrug resistant cancer cells" in European Journal of Medicinal Chemistry, 118 (2016):107-120,
https://doi.org/10.1016/j.ejmech.2016.04.011 . .

TY  - JOUR
AU  - Savić, Danijela
AU  - Stanković, Tijana
AU  - Lavrnja, Irena
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Peković, Sanja
AU  - Stojiljković, Mirjana
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Pešić, Milica
PY  - 2015
UR  - http://www.degruyter.com/view/j/motth.2015.1.issue-1/motth-2015-0002/motth-2015-0002.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2633
AB  - Purine nucleoside analogs have been in clinical use for almost 50 years. At the beginning developed as antiviral agents, later their efficacy was demonstrated in cancer treatment, especially hematological malignances. The approval of new purine nucleoside analogs by US Food and Drug Administration (FDA) over the past decade implies that the interest for these drugs still exists. Here, we review new nucleoside analogs that are currently in preclinical or clinical development as anticancer agents. In addition, we highlight the potential for implementation of these drugs in other pathological conditions, particularly in neuroinflammation.
T2  - Molecular inhibitors in targeted therapy
T1  - Purine nucleoside analogs in the therapy of cancer and neuroinflammation
IS  - 1
VL  - 1
DO  - 10.1515/motth-2015-0002
SP  - 3
EP  - 14
ER  - 

@article{
author = "Savić, Danijela and Stanković, Tijana and Lavrnja, Irena and Podolski-Renić, Ana and Banković, Jasna and Peković, Sanja and Stojiljković, Mirjana and Rakić, Ljubisav and Ruždijić, Sabera and Pešić, Milica",
year = "2015",
abstract = "Purine nucleoside analogs have been in clinical use for almost 50 years. At the beginning developed as antiviral agents, later their efficacy was demonstrated in cancer treatment, especially hematological malignances. The approval of new purine nucleoside analogs by US Food and Drug Administration (FDA) over the past decade implies that the interest for these drugs still exists. Here, we review new nucleoside analogs that are currently in preclinical or clinical development as anticancer agents. In addition, we highlight the potential for implementation of these drugs in other pathological conditions, particularly in neuroinflammation.",
journal = "Molecular inhibitors in targeted therapy",
title = "Purine nucleoside analogs in the therapy of cancer and neuroinflammation",
number = "1",
volume = "1",
doi = "10.1515/motth-2015-0002",
pages = "3-14"
}

Savić, D., Stanković, T., Lavrnja, I., Podolski-Renić, A., Banković, J., Peković, S., Stojiljković, M., Rakić, L., Ruždijić, S.,& Pešić, M.. (2015). Purine nucleoside analogs in the therapy of cancer and neuroinflammation. in Molecular inhibitors in targeted therapy, 1(1), 3-14.
https://doi.org/10.1515/motth-2015-0002

Savić D, Stanković T, Lavrnja I, Podolski-Renić A, Banković J, Peković S, Stojiljković M, Rakić L, Ruždijić S, Pešić M. Purine nucleoside analogs in the therapy of cancer and neuroinflammation. in Molecular inhibitors in targeted therapy. 2015;1(1):3-14.
doi:10.1515/motth-2015-0002 .

Savić, Danijela, Stanković, Tijana, Lavrnja, Irena, Podolski-Renić, Ana, Banković, Jasna, Peković, Sanja, Stojiljković, Mirjana, Rakić, Ljubisav, Ruždijić, Sabera, Pešić, Milica, "Purine nucleoside analogs in the therapy of cancer and neuroinflammation" in Molecular inhibitors in targeted therapy, 1, no. 1 (2015):3-14,
https://doi.org/10.1515/motth-2015-0002 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Pešić, Milica
PY  - 2015
UR  - https://www.eurekaselect.com/135471/article
UR  - https://radar.ibiss.bg.ac.rs/123456789/3882
AB  - Resistance to chemotherapeautic drugs is one of the main obstacles to effective cancer treatment. Multidrug resistance (MDR) is defined as resistance to structurally and/or functionally unrelated drugs, and has been extensively investigated for the last three decades. There are two types of MDR: intrinsic and acquired. Tumor microenvironment selection pressure leads to the development of intrinsic MDR, while acquired resistance is a consequence of the administered chemotherapy. A central issue in chemotherapy failure is the existence of heterogeneous populations of cancer cells within one patient and patient-to-patient variability within each type of cancer.
Numerous genes and pathways contribute to the development of MDR in cancer. Point mutations, gene amplification or other genetic or epigenetic changes all affect biological functions and may lead to the occurrence of MDR phenotype. Similar to the characteristics of cancerogenesis, the main features of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and a lower susceptibility to apoptosis. In order to achieve a lethal effect on cancer cells, drugs need to reach their intracellular target molecules. The overexpression of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells leads to decreased uptake of the drug and intracellular drug accumulation, minimising drug-target interactions.
New agents being or inspired by natural products that sucessfully target these mechanisms are the main subject of this review. Two key approaches in combating MDR in cancer are discussed (i) finding agents that preserve citotoxicity toward MDR cancer cells; (ii) developing compounds that restore the cytotoxic activity of classic anticancer drugs.
PB  - Sharjah: Bentham Science Publishers
T2  - Current Pharmaceutical Design
T1  - New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer
IS  - 38
VL  - 21
DO  - 10.2174/1381612821666151002113546
SP  - 5589
EP  - 5604
ER  - 

@article{
author = "Dinić, Jelena and Podolski-Renić, Ana and Stanković, Tijana and Banković, Jasna and Pešić, Milica",
year = "2015",
abstract = "Resistance to chemotherapeautic drugs is one of the main obstacles to effective cancer treatment. Multidrug resistance (MDR) is defined as resistance to structurally and/or functionally unrelated drugs, and has been extensively investigated for the last three decades. There are two types of MDR: intrinsic and acquired. Tumor microenvironment selection pressure leads to the development of intrinsic MDR, while acquired resistance is a consequence of the administered chemotherapy. A central issue in chemotherapy failure is the existence of heterogeneous populations of cancer cells within one patient and patient-to-patient variability within each type of cancer.
Numerous genes and pathways contribute to the development of MDR in cancer. Point mutations, gene amplification or other genetic or epigenetic changes all affect biological functions and may lead to the occurrence of MDR phenotype. Similar to the characteristics of cancerogenesis, the main features of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and a lower susceptibility to apoptosis. In order to achieve a lethal effect on cancer cells, drugs need to reach their intracellular target molecules. The overexpression of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells leads to decreased uptake of the drug and intracellular drug accumulation, minimising drug-target interactions.
New agents being or inspired by natural products that sucessfully target these mechanisms are the main subject of this review. Two key approaches in combating MDR in cancer are discussed (i) finding agents that preserve citotoxicity toward MDR cancer cells; (ii) developing compounds that restore the cytotoxic activity of classic anticancer drugs.",
publisher = "Sharjah: Bentham Science Publishers",
journal = "Current Pharmaceutical Design",
title = "New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer",
number = "38",
volume = "21",
doi = "10.2174/1381612821666151002113546",
pages = "5589-5604"
}

Dinić, J., Podolski-Renić, A., Stanković, T., Banković, J.,& Pešić, M.. (2015). New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer. in Current Pharmaceutical Design
Sharjah: Bentham Science Publishers., 21(38), 5589-5604.
https://doi.org/10.2174/1381612821666151002113546

Dinić J, Podolski-Renić A, Stanković T, Banković J, Pešić M. New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer. in Current Pharmaceutical Design. 2015;21(38):5589-5604.
doi:10.2174/1381612821666151002113546 .

Dinić, Jelena, Podolski-Renić, Ana, Stanković, Tijana, Banković, Jasna, Pešić, Milica, "New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer" in Current Pharmaceutical Design, 21, no. 38 (2015):5589-5604,
https://doi.org/10.2174/1381612821666151002113546 . .

TY  - CHAP
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Pešić, Milica
PY  - 2014
UR  - https://novapublishers.com/shop/advances-in-drug-resistance-research/
UR  - https://radar.ibiss.bg.ac.rs/123456789/3883
AB  - Resistance to chemotherapy is the main obstacle to efficient cancer treatment. The problem of multi-drug resistance (MDR) has been intensively studied for the last three decades. Classically defined as resistance to structurally and/or functionally unrelated drugs, MDR is connected with aggressive, untreatable cancers. There are two types of MDR: inherent (intrinsic) and acquired. Selection pressures within the tumor microenvironment favor the development of intrinsic MDR, while the ordinary dose and schedule chemotherapy practices induce acquired MDR. In recent years, patient-to-patient variability within each type of cancer has arisen as an unsolved problem. Even more, heterogeneous populations of cancer cells within one patient must be considered as a cause of chemotherapy impediment. 
Several genes and pathways have been found to contribute to the MDR. Tentatively, MDR phenotype could develop from point mutations, gene amplification or other genetic or epigenetic changes that affect biological functions. Therefore, MDR is driven by similar mechanisms as cancerogenesis. This is also supported by the fact that important characteristics of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and an elevated apoptotic threshold. Understanding these mechanisms and developing agents to target them are important steps in the design of new therapies.
Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect due to the interaction with intracellular target molecules. Decreased activity of membrane-embedded drug uptake as well as increased activity of efflux pumps reduce the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells prompted the efforts in overcoming drug resistance by inhibition of P-gp. 
The search for nontoxic anti-cancer agents able to overcome MDR has been an imperative in the field of drug design and discovery for many years. Two main approaches in combating the problem of MDR in cancer include (i) development of agents able to preserve cytotoxic activity toward MDR cancer cells; (ii) development of compounds able to restore the cytotoxicity of classic anti-cancer drugs.
In this chapter, we discuss the new findings regarding MDR reversal strategies, the alterations obtained in our artificially developed MDR models and advantages of our different approaches in overcoming MDR.
PB  - New York : Nova Science Publishers, Inc.
T2  - Advances in Drug Resistance Research
T1  - Multi-drug Resistance in Cancer and New Approaches for Its Overcoming
SP  - 39
EP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3883
ER  - 

@inbook{
author = "Dinić, Jelena and Stanković, Tijana and Banković, Jasna and Pešić, Milica",
year = "2014",
abstract = "Resistance to chemotherapy is the main obstacle to efficient cancer treatment. The problem of multi-drug resistance (MDR) has been intensively studied for the last three decades. Classically defined as resistance to structurally and/or functionally unrelated drugs, MDR is connected with aggressive, untreatable cancers. There are two types of MDR: inherent (intrinsic) and acquired. Selection pressures within the tumor microenvironment favor the development of intrinsic MDR, while the ordinary dose and schedule chemotherapy practices induce acquired MDR. In recent years, patient-to-patient variability within each type of cancer has arisen as an unsolved problem. Even more, heterogeneous populations of cancer cells within one patient must be considered as a cause of chemotherapy impediment. 
Several genes and pathways have been found to contribute to the MDR. Tentatively, MDR phenotype could develop from point mutations, gene amplification or other genetic or epigenetic changes that affect biological functions. Therefore, MDR is driven by similar mechanisms as cancerogenesis. This is also supported by the fact that important characteristics of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and an elevated apoptotic threshold. Understanding these mechanisms and developing agents to target them are important steps in the design of new therapies.
Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect due to the interaction with intracellular target molecules. Decreased activity of membrane-embedded drug uptake as well as increased activity of efflux pumps reduce the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells prompted the efforts in overcoming drug resistance by inhibition of P-gp. 
The search for nontoxic anti-cancer agents able to overcome MDR has been an imperative in the field of drug design and discovery for many years. Two main approaches in combating the problem of MDR in cancer include (i) development of agents able to preserve cytotoxic activity toward MDR cancer cells; (ii) development of compounds able to restore the cytotoxicity of classic anti-cancer drugs.
In this chapter, we discuss the new findings regarding MDR reversal strategies, the alterations obtained in our artificially developed MDR models and advantages of our different approaches in overcoming MDR.",
publisher = "New York : Nova Science Publishers, Inc.",
journal = "Advances in Drug Resistance Research",
booktitle = "Multi-drug Resistance in Cancer and New Approaches for Its Overcoming",
pages = "39-100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3883"
}

Dinić, J., Stanković, T., Banković, J.,& Pešić, M.. (2014). Multi-drug Resistance in Cancer and New Approaches for Its Overcoming. in Advances in Drug Resistance Research
New York : Nova Science Publishers, Inc.., 39-100.
https://hdl.handle.net/21.15107/rcub_ibiss_3883

Dinić J, Stanković T, Banković J, Pešić M. Multi-drug Resistance in Cancer and New Approaches for Its Overcoming. in Advances in Drug Resistance Research. 2014;:39-100.
https://hdl.handle.net/21.15107/rcub_ibiss_3883 .

Dinić, Jelena, Stanković, Tijana, Banković, Jasna, Pešić, Milica, "Multi-drug Resistance in Cancer and New Approaches for Its Overcoming" in Advances in Drug Resistance Research (2014):39-100,
https://hdl.handle.net/21.15107/rcub_ibiss_3883 .

TY  - CHAP
AU  - Pešić, Milica
AU  - Banković, Jasna
AU  - Tanić, Nikola
AU  - Atta-ur-Rahman
AU  - Choudhary, M. Iqbal
PY  - 2014
UR  - http://ebooks.benthamscience.com/book/9781608058846/chapter/122097/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2634
AB  - Although advances have been made in reducing mortality rates and improving survival, cancer is still the second world cause of death among men and women. Such an unfavorable prognosis is a consequence of its complex genetic nature that makes it difficult to diagnose and treat. Moreover, due to inherent ability of cancer cells to acquire resistance to cytotoxic agents, most therapies eventually fail, resulting in resumption of disease progression. Therefore, the call for the discovery of less toxic, more selective, and more effective agents to treat cancer has become most urgent. At this moment, molecular targeted therapy looks most promising. Small-molecule and antibody therapeutics against targets implicated in PI3K-Akt pathway such as EGFR (e.g., cetuximab, gefitinib), erbB2 (trastuzumab, lapatinib), mTOR (sirolimus, temsirolimus), in tumor angiogenesis such as VEGFR (bevacizumab, sunitinib) and αvβ3 integrin receptors (cilengitide) as well as against other tyrosine kinases such as Abl (imatinib, nilotinib), have delivered clinical efficacy in certain disease settings. The emergence of these therapies has led to an era of treatments increasingly aimed at certain patient populations, and this has implications for the development of future novel treatments. However, cancer cells could develop the resistance to anti-cancer drugs in molecular targeted therapy, like in conventional chemotherapy, by several mechanisms. Resistance mechanisms include increased DNA damage repair, reduced apoptosis, altered drug metabolism and site of action, increased energy-dependent efflux of hydrophobic anticancer agents that enter cells. The latter refers to multi-drug resistance (MDR) which is one of the major and most common obstacles for the effective treatment of cancer. The most frequent mechanism underlying MDR is overexpression of P-glycoprotein (P-gp)/MDR1/ABCB1 which acts as an efflux pump for various hydrophobic anticancer drugs. Among them are anticancer drugs of previous generations (such as anthracyclines, Vinca alkaloids, taxanes, epipodophyllotoxins), of new generation (e.g., imatinib, nilotinib, everolimus), as well as other tumor signal transduction inhibitors currently undergoing clinical investigation (aurora B kinase inhibitor AZD1152). The most striking feature of ABCB1 is its remarkable spectrum of substrates. Namely, ABCB1 recognizes and mediates the transport of thousands of substrates without specified structural determinants. Therefore, anti-ABCB1 therapy represents a significant step forward in cancer therapy. However, many things remain to be clarified, such as how to use anti ABCB1 therapeutics, what is the biological consequence of ABCB1-blockade, etc. We know that tumors are very diverse and plastic entities, able to adapt to various conditions. Lessons that we have learned in cancer research, taught us that the diversity of signal networks underlying tumor growth could eventually overcome our efforts in finding efficient therapeutic approaches. In this chapter, we present a reflection of new anti-cancer therapeutic strategies driven toward specific molecular targets, their benefits and limitations.
PB  - Bentham Science Publishers, Sharjah
T2  - Frontiers in Anti-Cancer Drug Discovery
T1  - Targeted Anti-Cancer Therapy, Acquiring and Overcoming Multi-Drug Resistance
VL  - 3
SP  - 109
EP  - 150
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2634
ER  - 

@inbook{
author = "Pešić, Milica and Banković, Jasna and Tanić, Nikola and Atta-ur-Rahman and Choudhary, M. Iqbal",
year = "2014",
abstract = "Although advances have been made in reducing mortality rates and improving survival, cancer is still the second world cause of death among men and women. Such an unfavorable prognosis is a consequence of its complex genetic nature that makes it difficult to diagnose and treat. Moreover, due to inherent ability of cancer cells to acquire resistance to cytotoxic agents, most therapies eventually fail, resulting in resumption of disease progression. Therefore, the call for the discovery of less toxic, more selective, and more effective agents to treat cancer has become most urgent. At this moment, molecular targeted therapy looks most promising. Small-molecule and antibody therapeutics against targets implicated in PI3K-Akt pathway such as EGFR (e.g., cetuximab, gefitinib), erbB2 (trastuzumab, lapatinib), mTOR (sirolimus, temsirolimus), in tumor angiogenesis such as VEGFR (bevacizumab, sunitinib) and αvβ3 integrin receptors (cilengitide) as well as against other tyrosine kinases such as Abl (imatinib, nilotinib), have delivered clinical efficacy in certain disease settings. The emergence of these therapies has led to an era of treatments increasingly aimed at certain patient populations, and this has implications for the development of future novel treatments. However, cancer cells could develop the resistance to anti-cancer drugs in molecular targeted therapy, like in conventional chemotherapy, by several mechanisms. Resistance mechanisms include increased DNA damage repair, reduced apoptosis, altered drug metabolism and site of action, increased energy-dependent efflux of hydrophobic anticancer agents that enter cells. The latter refers to multi-drug resistance (MDR) which is one of the major and most common obstacles for the effective treatment of cancer. The most frequent mechanism underlying MDR is overexpression of P-glycoprotein (P-gp)/MDR1/ABCB1 which acts as an efflux pump for various hydrophobic anticancer drugs. Among them are anticancer drugs of previous generations (such as anthracyclines, Vinca alkaloids, taxanes, epipodophyllotoxins), of new generation (e.g., imatinib, nilotinib, everolimus), as well as other tumor signal transduction inhibitors currently undergoing clinical investigation (aurora B kinase inhibitor AZD1152). The most striking feature of ABCB1 is its remarkable spectrum of substrates. Namely, ABCB1 recognizes and mediates the transport of thousands of substrates without specified structural determinants. Therefore, anti-ABCB1 therapy represents a significant step forward in cancer therapy. However, many things remain to be clarified, such as how to use anti ABCB1 therapeutics, what is the biological consequence of ABCB1-blockade, etc. We know that tumors are very diverse and plastic entities, able to adapt to various conditions. Lessons that we have learned in cancer research, taught us that the diversity of signal networks underlying tumor growth could eventually overcome our efforts in finding efficient therapeutic approaches. In this chapter, we present a reflection of new anti-cancer therapeutic strategies driven toward specific molecular targets, their benefits and limitations.",
publisher = "Bentham Science Publishers, Sharjah",
journal = "Frontiers in Anti-Cancer Drug Discovery",
booktitle = "Targeted Anti-Cancer Therapy, Acquiring and Overcoming Multi-Drug Resistance",
volume = "3",
pages = "109-150",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2634"
}

Pešić, M., Banković, J., Tanić, N., Atta-ur-Rahman,& Choudhary, M. I.. (2014). Targeted Anti-Cancer Therapy, Acquiring and Overcoming Multi-Drug Resistance. in Frontiers in Anti-Cancer Drug Discovery
Bentham Science Publishers, Sharjah., 3, 109-150.
https://hdl.handle.net/21.15107/rcub_ibiss_2634

Pešić M, Banković J, Tanić N, Atta-ur-Rahman, Choudhary MI. Targeted Anti-Cancer Therapy, Acquiring and Overcoming Multi-Drug Resistance. in Frontiers in Anti-Cancer Drug Discovery. 2014;3:109-150.
https://hdl.handle.net/21.15107/rcub_ibiss_2634 .

Pešić, Milica, Banković, Jasna, Tanić, Nikola, Atta-ur-Rahman, Choudhary, M. Iqbal, "Targeted Anti-Cancer Therapy, Acquiring and Overcoming Multi-Drug Resistance" in Frontiers in Anti-Cancer Drug Discovery, 3 (2014):109-150,
https://hdl.handle.net/21.15107/rcub_ibiss_2634 .

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Pešić, Milica
AU  - Mojić, Marija
AU  - Banković, Jasna
AU  - Miljković, Đorđe
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Nicoletti, Ferdinando
AU  - Mccubrey, James
AU  - Tanić, Nikola
AU  - Maksimović-Ivanić, Danijela
PY  - 2013
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/508
AB  - Background: The NO-modified form of the HIV inhibitor saquinavir (Saq-NO) inhibited the growth of a variety of cancer cell lines in vitro and in vivo more potently than the original compound in a nontoxic fashion. In addition, chemo- and immunosensitizing properties were observed. The aim of the present study was to evaluate its anticancer action against non-small cell lung carcinoma cells in their doxorubicin (DOXO) sensitive and resistant phenotype (NCI-H460 and NCI-H460/R). Methods: The viability of cells was analyzed by MTT and crystal violet assays. DR5 expression was estimated by real time RT-PCR and flow cytometry. Activity of P-glycoprotein (P-gp) pumps was evaluated by the Rho123 accumulation assay. Results: Saq-NO diminished the viability of lung cancer cells through induction of cell cycle arrest in the G0/G1 phase independently of the overexpression of the P-gp pumps. In addition, Saq-NO elevated or completely reconstituted the doxorubicin efficacy in NCI-H460 and NCI-H460/R, respectively. The chemosensitizing effect in DOXO resistant cells was a consequence of P-gp inhibition which was found to be more potent than that observed with dex-verapamil, a conventional inhibitor of P-gp. Sensitization to DOXO upon Saq-NO was accompanied by elevated DR5 expression, but the resistance to TRAIL was not abrogated. Conclusions: The NO-modified HIV inhibitor saquinavir displayed equal antiproliferative and chemosensitizing properties in DOXO sensitive and resistant non-small cell lung carcinoma cells, suggesting the importance of the evaluation of this drug as an antineoplastic agent.
AB  - Uvod: Inhibitor HIV proteaze - sakvinavir nakon modifikacije kovalentnim vezivanjem NO (Saq-NO) gubi toksična svojstva dok potentnije od originalnog jedinjenja inhibira in vitro i in vivo rast brojnih ćelijskih linija kancera. Pored direktnog antitumorskog delovanja, Saq-NO povećava osetljivost ćelija kancera na antitumorski imunski odgovor i konvencionalnu hemioterapiju. Ova studija je imala za cilj ispitivanje antitumorskog potencijala Saq-NO na ćelijskim linijama nesitnoćelijskog karcinoma pluća, senzitivnim (NCI-H460), odnosno rezistentnim (NCI-H460/R) na doksorubicin. Metode: Vijabilitet ćelija je evaluiran testovima MTT i 'kristal violet'. Ekspresija receptora DR5 je procenjivana me-odom RT-PCR u realnom vremenu i protočnom citofluorimetrijom. Aktivnost P-gp pumpi određivana je akumulacionim testom Rho123. Rezultati: Saq-NO inhibira rast ćelija kancera pluća zaustavljanjem ćelija u fazi G0/G1 ćelijskog ciklusa a zapaženi efekat nije oslabljen povećanjem ekspresije P-gp pumpi. Pored toga, Saq-NO povećava osetljivost NCI-H460 ćelija, dok u slučaju rezistentne forme, NCI-H460/R, potpuno rekonstituiše njihovu osetljivost na doksorubicin. Efekat hemosenzitizacije je posledica inhibicije P-gp pumpi, što Saq-NO čini potentnijim od deksverapamila, uobičajenog inhibitora P-gp. Opisani fenomen je praćen povećanjem ekspresije receptora DR5 na genskom i membranskom nivou, ali time rezistencija na molekul TRAIL nije ukinuta. Zaključak: Saq-NO pokazuje značajan antiproliferativan i hemosenzitizujući potencijal na ćelijama nesitnoćelijskog kancera pluća nezavisno od njihove osetljivosti odnosno rezistencije na doksorubicin, ukazujući na potrebu daljeg ispitivanja ovog jedinjenja u svojstvu potencijalnog antineoplastičnog agensa.
T2  - Journal of Medical Biochemistry
T1  - Modifikovana forma sakvinavira efikasno suprimira rast ćelija nesitnoćelijskog karcinoma pluća različite osetljivosti na doksorubicin
T1  - No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells
IS  - 4
VL  - 32
DO  - 10.2478/jomb-2013-0050
SP  - 406
EP  - 416
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_508
ER  - 

@article{
author = "Mijatović, Sanja and Pešić, Milica and Mojić, Marija and Banković, Jasna and Miljković, Đorđe and Fagone, Paolo and Mangano, Katia and Nicoletti, Ferdinando and Mccubrey, James and Tanić, Nikola and Maksimović-Ivanić, Danijela",
year = "2013, 2013",
abstract = "Background: The NO-modified form of the HIV inhibitor saquinavir (Saq-NO) inhibited the growth of a variety of cancer cell lines in vitro and in vivo more potently than the original compound in a nontoxic fashion. In addition, chemo- and immunosensitizing properties were observed. The aim of the present study was to evaluate its anticancer action against non-small cell lung carcinoma cells in their doxorubicin (DOXO) sensitive and resistant phenotype (NCI-H460 and NCI-H460/R). Methods: The viability of cells was analyzed by MTT and crystal violet assays. DR5 expression was estimated by real time RT-PCR and flow cytometry. Activity of P-glycoprotein (P-gp) pumps was evaluated by the Rho123 accumulation assay. Results: Saq-NO diminished the viability of lung cancer cells through induction of cell cycle arrest in the G0/G1 phase independently of the overexpression of the P-gp pumps. In addition, Saq-NO elevated or completely reconstituted the doxorubicin efficacy in NCI-H460 and NCI-H460/R, respectively. The chemosensitizing effect in DOXO resistant cells was a consequence of P-gp inhibition which was found to be more potent than that observed with dex-verapamil, a conventional inhibitor of P-gp. Sensitization to DOXO upon Saq-NO was accompanied by elevated DR5 expression, but the resistance to TRAIL was not abrogated. Conclusions: The NO-modified HIV inhibitor saquinavir displayed equal antiproliferative and chemosensitizing properties in DOXO sensitive and resistant non-small cell lung carcinoma cells, suggesting the importance of the evaluation of this drug as an antineoplastic agent., Uvod: Inhibitor HIV proteaze - sakvinavir nakon modifikacije kovalentnim vezivanjem NO (Saq-NO) gubi toksična svojstva dok potentnije od originalnog jedinjenja inhibira in vitro i in vivo rast brojnih ćelijskih linija kancera. Pored direktnog antitumorskog delovanja, Saq-NO povećava osetljivost ćelija kancera na antitumorski imunski odgovor i konvencionalnu hemioterapiju. Ova studija je imala za cilj ispitivanje antitumorskog potencijala Saq-NO na ćelijskim linijama nesitnoćelijskog karcinoma pluća, senzitivnim (NCI-H460), odnosno rezistentnim (NCI-H460/R) na doksorubicin. Metode: Vijabilitet ćelija je evaluiran testovima MTT i 'kristal violet'. Ekspresija receptora DR5 je procenjivana me-odom RT-PCR u realnom vremenu i protočnom citofluorimetrijom. Aktivnost P-gp pumpi određivana je akumulacionim testom Rho123. Rezultati: Saq-NO inhibira rast ćelija kancera pluća zaustavljanjem ćelija u fazi G0/G1 ćelijskog ciklusa a zapaženi efekat nije oslabljen povećanjem ekspresije P-gp pumpi. Pored toga, Saq-NO povećava osetljivost NCI-H460 ćelija, dok u slučaju rezistentne forme, NCI-H460/R, potpuno rekonstituiše njihovu osetljivost na doksorubicin. Efekat hemosenzitizacije je posledica inhibicije P-gp pumpi, što Saq-NO čini potentnijim od deksverapamila, uobičajenog inhibitora P-gp. Opisani fenomen je praćen povećanjem ekspresije receptora DR5 na genskom i membranskom nivou, ali time rezistencija na molekul TRAIL nije ukinuta. Zaključak: Saq-NO pokazuje značajan antiproliferativan i hemosenzitizujući potencijal na ćelijama nesitnoćelijskog kancera pluća nezavisno od njihove osetljivosti odnosno rezistencije na doksorubicin, ukazujući na potrebu daljeg ispitivanja ovog jedinjenja u svojstvu potencijalnog antineoplastičnog agensa.",
journal = "Journal of Medical Biochemistry",
title = "Modifikovana forma sakvinavira efikasno suprimira rast ćelija nesitnoćelijskog karcinoma pluća različite osetljivosti na doksorubicin, No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells",
number = "4",
volume = "32",
doi = "10.2478/jomb-2013-0050",
pages = "406-416",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_508"
}

Mijatović, S., Pešić, M., Mojić, M., Banković, J., Miljković, Đ., Fagone, P., Mangano, K., Nicoletti, F., Mccubrey, J., Tanić, N.,& Maksimović-Ivanić, D.. (2013). Modifikovana forma sakvinavira efikasno suprimira rast ćelija nesitnoćelijskog karcinoma pluća različite osetljivosti na doksorubicin. in Journal of Medical Biochemistry, 32(4), 406-416.
https://doi.org/10.2478/jomb-2013-0050
https://hdl.handle.net/21.15107/rcub_ibiss_508

Mijatović S, Pešić M, Mojić M, Banković J, Miljković Đ, Fagone P, Mangano K, Nicoletti F, Mccubrey J, Tanić N, Maksimović-Ivanić D. Modifikovana forma sakvinavira efikasno suprimira rast ćelija nesitnoćelijskog karcinoma pluća različite osetljivosti na doksorubicin. in Journal of Medical Biochemistry. 2013;32(4):406-416.
doi:10.2478/jomb-2013-0050
https://hdl.handle.net/21.15107/rcub_ibiss_508 .

Mijatović, Sanja, Pešić, Milica, Mojić, Marija, Banković, Jasna, Miljković, Đorđe, Fagone, Paolo, Mangano, Katia, Nicoletti, Ferdinando, Mccubrey, James, Tanić, Nikola, Maksimović-Ivanić, Danijela, "Modifikovana forma sakvinavira efikasno suprimira rast ćelija nesitnoćelijskog karcinoma pluća različite osetljivosti na doksorubicin" in Journal of Medical Biochemistry, 32, no. 4 (2013):406-416,
https://doi.org/10.2478/jomb-2013-0050 .,
https://hdl.handle.net/21.15107/rcub_ibiss_508 .