TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Krajnović, Tamara
AU  - Basile, Maria S.
AU  - Dunđerović, Duško
AU  - Cavalli, Eugenio
AU  - Mangano, Katia
AU  - Mammana, Santa
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/mc.23020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3339
AB  - The main focus of this study is exploring the effect and mechanism of two HIV-protease inhibitors: Ritonavir and Ritonavir-nitric oxide (Ritonavir-NO) on in vitro growth of melanoma cell lines. NO modification significantly improved the antitumor potential of Ritonavir, as the IC50 values of Ritonavir-NO were approximately two times lower than IC50 values of the parental compound. Our results showed for the first time, that both compounds induced senescence in primary and metastatic melanoma cell lines. This transformation was manifested as a change in cell morphology, enlargement of nuclei, increased cellular granulation, upregulation of β-galactosidase activity, lipofuscin granules appearance, higher production of reactive oxygen species and persistent inhibition of proliferation. The expression of p53, as one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir-NO treatment only in metastatic B16F10 cells, ranking it as a late-response event. The development of senescent phenotype was consistent with the alteration of the cytoskeleton-as we observed diminished expression of vinculin, α-actin, and β-tubulin. Permanent inhibition of S6 protein by Ritonavir-NO, but not Ritonavir, could be responsible for a stronger antiproliferative potential of the NO-modified compound. Taken together, induction of senescent phenotype may provide an excellent platform for developing therapeutic approaches based on selective killing of senescent cells.
T2  - Molecular Carcinogenesis
T2  - Molecular Carcinogenesis
T1  - Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.
DO  - 10.1002/mc.23020
ER  - 

@article{
author = "Paskaš, Svetlana and Krajnović, Tamara and Basile, Maria S. and Dunđerović, Duško and Cavalli, Eugenio and Mangano, Katia and Mammana, Santa and Al-Abed, Yousef and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "The main focus of this study is exploring the effect and mechanism of two HIV-protease inhibitors: Ritonavir and Ritonavir-nitric oxide (Ritonavir-NO) on in vitro growth of melanoma cell lines. NO modification significantly improved the antitumor potential of Ritonavir, as the IC50 values of Ritonavir-NO were approximately two times lower than IC50 values of the parental compound. Our results showed for the first time, that both compounds induced senescence in primary and metastatic melanoma cell lines. This transformation was manifested as a change in cell morphology, enlargement of nuclei, increased cellular granulation, upregulation of β-galactosidase activity, lipofuscin granules appearance, higher production of reactive oxygen species and persistent inhibition of proliferation. The expression of p53, as one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir-NO treatment only in metastatic B16F10 cells, ranking it as a late-response event. The development of senescent phenotype was consistent with the alteration of the cytoskeleton-as we observed diminished expression of vinculin, α-actin, and β-tubulin. Permanent inhibition of S6 protein by Ritonavir-NO, but not Ritonavir, could be responsible for a stronger antiproliferative potential of the NO-modified compound. Taken together, induction of senescent phenotype may provide an excellent platform for developing therapeutic approaches based on selective killing of senescent cells.",
journal = "Molecular Carcinogenesis, Molecular Carcinogenesis",
title = "Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.",
doi = "10.1002/mc.23020"
}

Paskaš, S., Krajnović, T., Basile, M. S., Dunđerović, D., Cavalli, E., Mangano, K., Mammana, S., Al-Abed, Y., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2019). Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.. in Molecular Carcinogenesis.
https://doi.org/10.1002/mc.23020

Paskaš S, Krajnović T, Basile MS, Dunđerović D, Cavalli E, Mangano K, Mammana S, Al-Abed Y, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.. in Molecular Carcinogenesis. 2019;.
doi:10.1002/mc.23020 .

Paskaš, Svetlana, Krajnović, Tamara, Basile, Maria S., Dunđerović, Duško, Cavalli, Eugenio, Mangano, Katia, Mammana, Santa, Al-Abed, Yousef, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma." in Molecular Carcinogenesis (2019),
https://doi.org/10.1002/mc.23020 . .

TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Krajnović, Tamara
AU  - Basile, Maria S.
AU  - Dunđerović, Duško
AU  - Cavalli, Eugenio
AU  - Mangano, Katia
AU  - Mammana, Sant
AU  - Al‐Abed, Yousef
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3780
AB  - The main focus of this study is exploring the effect and mechanism of two HIVprotease
inhibitors: Ritonavir and Ritonavir‐nitric oxide (Ritonavir‐NO) on in vitro
growth of melanoma cell lines. NO modification significantly improved the antitumor
potential of Ritonavir, as the IC50 values of Ritonavir‐NO were approximately two
times lower than IC50 values of the parental compound. Our results showed for the
first time, that both compounds induced senescence in primary and metastatic
melanoma cell lines. This transformation was manifested as a change in cell
morphology, enlargement of nuclei, increased cellular granulation, upregulation of
β‐galactosidase activity, lipofuscin granules appearance, higher production of reactive
oxygen species and persistent inhibition of proliferation. The expression of p53, as
one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir‐
NO treatment only in metastatic B16F10 cells, ranking it as a late‐response event.
The development of senescent phenotype was consistent with the alteration of
the cytoskeleton—as we observed diminished expression of vinculin, α‐actin, and
β‐tubulin. Permanent inhibition of S6 protein by Ritonavir‐NO, but not Ritonavir,
could be responsible for a stronger antiproliferative potential of the NO‐modified
compound. Taken together, induction of senescent phenotype may provide an
excellent platform for developing therapeutic approaches based on selective killing of
senescent cells.
PB  - New Jersey: Wiley-VCH Verlag GmbH & Co
T2  - Molecular Carcinogenesis
T1  - Senescence as a main mechanism of Ritonavir and Ritonavir‐NO action against melanoma
IS  - 8
VL  - 58
DO  - 10.1002/mc.23020
SP  - 1362
EP  - 1375
ER  - 

@article{
author = "Paskaš, Svetlana and Krajnović, Tamara and Basile, Maria S. and Dunđerović, Duško and Cavalli, Eugenio and Mangano, Katia and Mammana, Sant and Al‐Abed, Yousef and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "The main focus of this study is exploring the effect and mechanism of two HIVprotease
inhibitors: Ritonavir and Ritonavir‐nitric oxide (Ritonavir‐NO) on in vitro
growth of melanoma cell lines. NO modification significantly improved the antitumor
potential of Ritonavir, as the IC50 values of Ritonavir‐NO were approximately two
times lower than IC50 values of the parental compound. Our results showed for the
first time, that both compounds induced senescence in primary and metastatic
melanoma cell lines. This transformation was manifested as a change in cell
morphology, enlargement of nuclei, increased cellular granulation, upregulation of
β‐galactosidase activity, lipofuscin granules appearance, higher production of reactive
oxygen species and persistent inhibition of proliferation. The expression of p53, as
one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir‐
NO treatment only in metastatic B16F10 cells, ranking it as a late‐response event.
The development of senescent phenotype was consistent with the alteration of
the cytoskeleton—as we observed diminished expression of vinculin, α‐actin, and
β‐tubulin. Permanent inhibition of S6 protein by Ritonavir‐NO, but not Ritonavir,
could be responsible for a stronger antiproliferative potential of the NO‐modified
compound. Taken together, induction of senescent phenotype may provide an
excellent platform for developing therapeutic approaches based on selective killing of
senescent cells.",
publisher = "New Jersey: Wiley-VCH Verlag GmbH & Co",
journal = "Molecular Carcinogenesis",
title = "Senescence as a main mechanism of Ritonavir and Ritonavir‐NO action against melanoma",
number = "8",
volume = "58",
doi = "10.1002/mc.23020",
pages = "1362-1375"
}

Paskaš, S., Krajnović, T., Basile, M. S., Dunđerović, D., Cavalli, E., Mangano, K., Mammana, S., Al‐Abed, Y., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2019). Senescence as a main mechanism of Ritonavir and Ritonavir‐NO action against melanoma. in Molecular Carcinogenesis
New Jersey: Wiley-VCH Verlag GmbH & Co., 58(8), 1362-1375.
https://doi.org/10.1002/mc.23020

Paskaš S, Krajnović T, Basile MS, Dunđerović D, Cavalli E, Mangano K, Mammana S, Al‐Abed Y, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Senescence as a main mechanism of Ritonavir and Ritonavir‐NO action against melanoma. in Molecular Carcinogenesis. 2019;58(8):1362-1375.
doi:10.1002/mc.23020 .

Paskaš, Svetlana, Krajnović, Tamara, Basile, Maria S., Dunđerović, Duško, Cavalli, Eugenio, Mangano, Katia, Mammana, Sant, Al‐Abed, Yousef, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Senescence as a main mechanism of Ritonavir and Ritonavir‐NO action against melanoma" in Molecular Carcinogenesis, 58, no. 8 (2019):1362-1375,
https://doi.org/10.1002/mc.23020 . .

TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Mazzon, Emanuela
AU  - Basile, Maria Sofia
AU  - Cavalli, Eugenio
AU  - Al-Abed, Yousef
AU  - He, Mingzhu
AU  - Rakočević, Sara
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - http://link.springer.com/10.1007/s10637-019-00733-3
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3261
AB  - We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.
T2  - Investigational New Drugs
T1  - Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.
DO  - 10.1007/s10637-019-00733-3
ER  - 

@article{
author = "Paskaš, Svetlana and Mazzon, Emanuela and Basile, Maria Sofia and Cavalli, Eugenio and Al-Abed, Yousef and He, Mingzhu and Rakočević, Sara and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.",
journal = "Investigational New Drugs",
title = "Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.",
doi = "10.1007/s10637-019-00733-3"
}

Paskaš, S., Mazzon, E., Basile, M. S., Cavalli, E., Al-Abed, Y., He, M., Rakočević, S., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2019). Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.. in Investigational New Drugs.
https://doi.org/10.1007/s10637-019-00733-3

Paskaš S, Mazzon E, Basile MS, Cavalli E, Al-Abed Y, He M, Rakočević S, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.. in Investigational New Drugs. 2019;.
doi:10.1007/s10637-019-00733-3 .

Paskaš, Svetlana, Mazzon, Emanuela, Basile, Maria Sofia, Cavalli, Eugenio, Al-Abed, Yousef, He, Mingzhu, Rakočević, Sara, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo." in Investigational New Drugs (2019),
https://doi.org/10.1007/s10637-019-00733-3 . .

TY  - JOUR
AU  - Basile, Maria Sofia
AU  - Mazzon, Emanuela
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Cavalli, Eugenio
AU  - Al-Abed, Yousef
AU  - Bramanti, Placido
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2018
UR  - internal-pdf://Basile et al. - 2018 - Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.pdf
UR  - http://www.mdpi.com/1420-3049/23/10/2463
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6222694
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3216
AB  - Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of its NO-derivative Lopinavir-NO (Lopi-NO) on the in vitro growth of LN-229 and U-251 human GBM cell lines. Lopi-NO reduced the viability of LN-229 and U-251 cells at significantly lower concentrations than the parental drug. In particular, Lopi-NO inhibited tumor cell proliferation and induced the differentiation of U-251 cells toward an astrocyte-like phenotype without triggering significant cell death in both cell types. The anticancer effect of Lopi-NO was persistent even upon drug removal. Furthermore, Lopi-NO induced strong autophagy that did not appear to be related to its chemotherapeutic action. Overall, our results suggest that Lopi-NO could be a potential effective anticancer drug for GBM treatment.
T2  - Molecules (Basel, Switzerland)
T2  - Molecules (Basel, Switzerland)
T1  - Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.
IS  - 10
VL  - 23
DO  - 10.3390/molecules23102463
SP  - 2463
ER  - 

@article{
author = "Basile, Maria Sofia and Mazzon, Emanuela and Krajnović, Tamara and Drača, Dijana and Cavalli, Eugenio and Al-Abed, Yousef and Bramanti, Placido and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2018",
abstract = "Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of its NO-derivative Lopinavir-NO (Lopi-NO) on the in vitro growth of LN-229 and U-251 human GBM cell lines. Lopi-NO reduced the viability of LN-229 and U-251 cells at significantly lower concentrations than the parental drug. In particular, Lopi-NO inhibited tumor cell proliferation and induced the differentiation of U-251 cells toward an astrocyte-like phenotype without triggering significant cell death in both cell types. The anticancer effect of Lopi-NO was persistent even upon drug removal. Furthermore, Lopi-NO induced strong autophagy that did not appear to be related to its chemotherapeutic action. Overall, our results suggest that Lopi-NO could be a potential effective anticancer drug for GBM treatment.",
journal = "Molecules (Basel, Switzerland), Molecules (Basel, Switzerland)",
title = "Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.",
number = "10",
volume = "23",
doi = "10.3390/molecules23102463",
pages = "2463"
}

Basile, M. S., Mazzon, E., Krajnović, T., Drača, D., Cavalli, E., Al-Abed, Y., Bramanti, P., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2018). Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.. in Molecules (Basel, Switzerland), 23(10), 2463.
https://doi.org/10.3390/molecules23102463

Basile MS, Mazzon E, Krajnović T, Drača D, Cavalli E, Al-Abed Y, Bramanti P, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.. in Molecules (Basel, Switzerland). 2018;23(10):2463.
doi:10.3390/molecules23102463 .

Basile, Maria Sofia, Mazzon, Emanuela, Krajnović, Tamara, Drača, Dijana, Cavalli, Eugenio, Al-Abed, Yousef, Bramanti, Placido, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells." in Molecules (Basel, Switzerland), 23, no. 10 (2018):2463,
https://doi.org/10.3390/molecules23102463 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Krajnović, Tamara
AU  - Cheng, Kai-Fan
AU  - VanPatten, Sonya
AU  - He, Mingzhu
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Al-Abed, Yousef
AU  - Saksida, Tamara
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2141
AB  - Macrophage migration inhibitory factor is a multifunctional cytokine
   involved in the regulation of immune processes and also in apoptosis
   induction. Elevated MIF expression is detrimental for insulin-producing
   beta cells and MIF inhibition protected beta cells from several
   cytotoxic insults such as inflammatory cytokines, high fatty acids or
   high glucose concentrations. Therefore, the aim of this study was to
   investigate two newly synthesized small molecule MIF inhibitors (K664-1
   and K647-1) and to compare them with previously established effects of
   the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
   and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
   tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
   protection from cytokine-triggered apoptosis at significantly lower
   concentrations than LSO-1. Although all three MIF inhibitors inhibit
   caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
   expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
   MIF inhibitors operate through blockade of nitric oxide production
   stimulated by cytokines. In conclusion, two novel MIF inhibitors are
   more potent than ISO-1 and operate through inhibition of the
   mitochondria-related apoptotic pathway. We propose that these compounds
   represent a unique class of anti-MIF antagonists that should be further
   tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death
VL  - 740
DO  - 10.1016/j.ejphar.2014.06.009
SP  - 683
EP  - 689
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Krajnović, Tamara and Cheng, Kai-Fan and VanPatten, Sonya and He, Mingzhu and Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Al-Abed, Yousef and Saksida, Tamara",
year = "2014",
abstract = "Macrophage migration inhibitory factor is a multifunctional cytokine
   involved in the regulation of immune processes and also in apoptosis
   induction. Elevated MIF expression is detrimental for insulin-producing
   beta cells and MIF inhibition protected beta cells from several
   cytotoxic insults such as inflammatory cytokines, high fatty acids or
   high glucose concentrations. Therefore, the aim of this study was to
   investigate two newly synthesized small molecule MIF inhibitors (K664-1
   and K647-1) and to compare them with previously established effects of
   the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
   and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
   tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
   protection from cytokine-triggered apoptosis at significantly lower
   concentrations than LSO-1. Although all three MIF inhibitors inhibit
   caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
   expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
   MIF inhibitors operate through blockade of nitric oxide production
   stimulated by cytokines. In conclusion, two novel MIF inhibitors are
   more potent than ISO-1 and operate through inhibition of the
   mitochondria-related apoptotic pathway. We propose that these compounds
   represent a unique class of anti-MIF antagonists that should be further
   tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death",
volume = "740",
doi = "10.1016/j.ejphar.2014.06.009",
pages = "683-689"
}

Vujičić, M., Nikolić, I., Krajnović, T., Cheng, K., VanPatten, S., He, M., Stošić-Grujičić, S., Stojanović, I. D., Al-Abed, Y.,& Saksida, T.. (2014). Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death. in European Journal of Pharmacology, 740, 683-689.
https://doi.org/10.1016/j.ejphar.2014.06.009

Vujičić M, Nikolić I, Krajnović T, Cheng K, VanPatten S, He M, Stošić-Grujičić S, Stojanović ID, Al-Abed Y, Saksida T. Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death. in European Journal of Pharmacology. 2014;740:683-689.
doi:10.1016/j.ejphar.2014.06.009 .

Vujičić, Milica, Nikolić, Ivana, Krajnović, Tamara, Cheng, Kai-Fan, VanPatten, Sonya, He, Mingzhu, Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Al-Abed, Yousef, Saksida, Tamara, "Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death" in European Journal of Pharmacology, 740 (2014):683-689,
https://doi.org/10.1016/j.ejphar.2014.06.009 . .

TY  - JOUR
AU  - Tumino, Salvatore
AU  - Mojić, Marija
AU  - Dinić, Svetlana
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Maksimović-Ivanić, Danijela
AU  - Grdović, Nevena
AU  - Zocca, Mai-Britt
AU  - Miljković, Đorđe
AU  - Al-Abed, Yousef
AU  - Mijatović, Sanja
AU  - McCubrey, James A
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1199
AB  - We previously reported that the NO-modified form of HIV protease inhibitor Saquinavir ( Saq) is a potent antitumoral agent efficient against numerous tumor cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO equivalent to DL100 of the parental drug were completely nontoxic. Beside direct effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL)-mediated cell death. In this study, we evaluated the effects of Saq-NO on androgen-dependent prostate cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in xenograft models. Suppression of tumor growth was accompanied with cell cycle arrest in G(0)/G(1) phase and established a persistent inhibition of proliferation. Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF. Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2. This, however, did not represent the primary mode of action of Saq-NO, as elimination with specific inhibitors did not compromise the chemotherapic efficacy of the drug. However, permanent abrogation of phosphorylation of the S6 protein, which is the downstream target of both signaling pathways, was observed. Diminished S6 phosphorylation was associated with re-established sensitivity to TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In summary, NO modification of Saq led to a new chemical entity with stronger and more pleiotropic antitumor activity than the parental drug.
T2  - Cell Cycle
T1  - Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL
IS  - 6
VL  - 11
EP  - 1182
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1199
ER  - 

@article{
author = "Tumino, Salvatore and Mojić, Marija and Dinić, Svetlana and Fagone, Paolo and Mangano, Katia and Maksimović-Ivanić, Danijela and Grdović, Nevena and Zocca, Mai-Britt and Miljković, Đorđe and Al-Abed, Yousef and Mijatović, Sanja and McCubrey, James A and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2012",
abstract = "We previously reported that the NO-modified form of HIV protease inhibitor Saquinavir ( Saq) is a potent antitumoral agent efficient against numerous tumor cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO equivalent to DL100 of the parental drug were completely nontoxic. Beside direct effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL)-mediated cell death. In this study, we evaluated the effects of Saq-NO on androgen-dependent prostate cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in xenograft models. Suppression of tumor growth was accompanied with cell cycle arrest in G(0)/G(1) phase and established a persistent inhibition of proliferation. Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF. Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2. This, however, did not represent the primary mode of action of Saq-NO, as elimination with specific inhibitors did not compromise the chemotherapic efficacy of the drug. However, permanent abrogation of phosphorylation of the S6 protein, which is the downstream target of both signaling pathways, was observed. Diminished S6 phosphorylation was associated with re-established sensitivity to TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In summary, NO modification of Saq led to a new chemical entity with stronger and more pleiotropic antitumor activity than the parental drug.",
journal = "Cell Cycle",
title = "Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL",
number = "6",
volume = "11",
pages = "1182",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1199"
}

Tumino, S., Mojić, M., Dinić, S., Fagone, P., Mangano, K., Maksimović-Ivanić, D., Grdović, N., Zocca, M., Miljković, Đ., Al-Abed, Y., Mijatović, S., McCubrey, J. A., Stošić-Grujičić, S.,& Nicoletti, F.. (2012). Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL. in Cell Cycle, 11(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1199

Tumino S, Mojić M, Dinić S, Fagone P, Mangano K, Maksimović-Ivanić D, Grdović N, Zocca M, Miljković Đ, Al-Abed Y, Mijatović S, McCubrey JA, Stošić-Grujičić S, Nicoletti F. Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL. in Cell Cycle. 2012;11(6):null-1182.
https://hdl.handle.net/21.15107/rcub_ibiss_1199 .

Tumino, Salvatore, Mojić, Marija, Dinić, Svetlana, Fagone, Paolo, Mangano, Katia, Maksimović-Ivanić, Danijela, Grdović, Nevena, Zocca, Mai-Britt, Miljković, Đorđe, Al-Abed, Yousef, Mijatović, Sanja, McCubrey, James A, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL" in Cell Cycle, 11, no. 6 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1199 .

TY  - CONF
AU  - Mojić, Marija
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Bulatović, Mirna Z.
AU  - Radojković, Milica
AU  - Kuzmanović, Milos B
AU  - Zocca, Mai-Britt
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1117
C3  - Immunology
T1  - Therapeutic potential of Saq-NO in blood cancers
IS  - null
VL  - 137
SP  - 129
EP  - 660
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1117
ER  - 

@conference{
author = "Mojić, Marija and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Bulatović, Mirna Z. and Radojković, Milica and Kuzmanović, Milos B and Zocca, Mai-Britt and Al-Abed, Yousef and Nicoletti, Ferdinando",
year = "2012",
journal = "Immunology",
title = "Therapeutic potential of Saq-NO in blood cancers",
number = "null",
volume = "137",
pages = "129-660",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1117"
}

Mojić, M., Mijatović, S., Maksimović-Ivanić, D., Bulatović, M. Z., Radojković, M., Kuzmanović, M. B., Zocca, M., Al-Abed, Y.,& Nicoletti, F.. (2012). Therapeutic potential of Saq-NO in blood cancers. in Immunology, 137(null), 129-660.
https://hdl.handle.net/21.15107/rcub_ibiss_1117

Mojić M, Mijatović S, Maksimović-Ivanić D, Bulatović MZ, Radojković M, Kuzmanović MB, Zocca M, Al-Abed Y, Nicoletti F. Therapeutic potential of Saq-NO in blood cancers. in Immunology. 2012;137(null):129-660.
https://hdl.handle.net/21.15107/rcub_ibiss_1117 .

Mojić, Marija, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Bulatović, Mirna Z., Radojković, Milica, Kuzmanović, Milos B, Zocca, Mai-Britt, Al-Abed, Yousef, Nicoletti, Ferdinando, "Therapeutic potential of Saq-NO in blood cancers" in Immunology, 137, no. null (2012):129-660,
https://hdl.handle.net/21.15107/rcub_ibiss_1117 .

TY  - JOUR
AU  - Mojić, Marija
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Miljković, Đorđe
AU  - Stošić-Grujičić, Stanislava
AU  - Stanković, Marija M
AU  - Mangano, Katia
AU  - Travali, Salvatore
AU  - Donia, Marco
AU  - Fagone, Paolo
AU  - Zocca, Mai-Britt
AU  - Al-Abed, Yousef
AU  - McCubrey, James A
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1099
AB  - We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-independent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death.
T2  - Molecular Pharmacology
T1  - Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells
IS  - 4
VL  - 82
SP  - 203
EP  - 710
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1099
ER  - 

@article{
author = "Mojić, Marija and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Miljković, Đorđe and Stošić-Grujičić, Stanislava and Stanković, Marija M and Mangano, Katia and Travali, Salvatore and Donia, Marco and Fagone, Paolo and Zocca, Mai-Britt and Al-Abed, Yousef and McCubrey, James A and Nicoletti, Ferdinando",
year = "2012",
abstract = "We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-independent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death.",
journal = "Molecular Pharmacology",
title = "Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells",
number = "4",
volume = "82",
pages = "203-710",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1099"
}

Mojić, M., Mijatović, S., Maksimović-Ivanić, D., Miljković, Đ., Stošić-Grujičić, S., Stanković, M. M., Mangano, K., Travali, S., Donia, M., Fagone, P., Zocca, M., Al-Abed, Y., McCubrey, J. A.,& Nicoletti, F.. (2012). Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells. in Molecular Pharmacology, 82(4), 203-710.
https://hdl.handle.net/21.15107/rcub_ibiss_1099

Mojić M, Mijatović S, Maksimović-Ivanić D, Miljković Đ, Stošić-Grujičić S, Stanković MM, Mangano K, Travali S, Donia M, Fagone P, Zocca M, Al-Abed Y, McCubrey JA, Nicoletti F. Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells. in Molecular Pharmacology. 2012;82(4):203-710.
https://hdl.handle.net/21.15107/rcub_ibiss_1099 .

Mojić, Marija, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Miljković, Đorđe, Stošić-Grujičić, Stanislava, Stanković, Marija M, Mangano, Katia, Travali, Salvatore, Donia, Marco, Fagone, Paolo, Zocca, Mai-Britt, Al-Abed, Yousef, McCubrey, James A, Nicoletti, Ferdinando, "Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells" in Molecular Pharmacology, 82, no. 4 (2012):203-710,
https://hdl.handle.net/21.15107/rcub_ibiss_1099 .

TY  - JOUR
AU  - Donia, Marco
AU  - Mangano, Katia
AU  - Fagone, Paolo
AU  - De Pasquale, R
AU  - Dinotta, F
AU  - Coco, Marinella
AU  - Padron, J
AU  - Al-Abed, Yousef
AU  - Lombardo, GAG
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Zocca, Mai-Britt
AU  - Perciavalle, V
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1157
AB  - We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but also in agreement with the complex and multifaceted role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth of xenotransplants.
T2  - Oncology Reports
T1  - Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells
IS  - 2
VL  - 28
SP  - 323
EP  - 688
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1157
ER  - 

@article{
author = "Donia, Marco and Mangano, Katia and Fagone, Paolo and De Pasquale, R and Dinotta, F and Coco, Marinella and Padron, J and Al-Abed, Yousef and Lombardo, GAG and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Zocca, Mai-Britt and Perciavalle, V and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2012",
abstract = "We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but also in agreement with the complex and multifaceted role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth of xenotransplants.",
journal = "Oncology Reports",
title = "Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells",
number = "2",
volume = "28",
pages = "323-688",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1157"
}

Donia, M., Mangano, K., Fagone, P., De Pasquale, R., Dinotta, F., Coco, M., Padron, J., Al-Abed, Y., Lombardo, G., Maksimović-Ivanić, D., Mijatović, S., Zocca, M., Perciavalle, V., Stošić-Grujičić, S.,& Nicoletti, F.. (2012). Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells. in Oncology Reports, 28(2), 323-688.
https://hdl.handle.net/21.15107/rcub_ibiss_1157

Donia M, Mangano K, Fagone P, De Pasquale R, Dinotta F, Coco M, Padron J, Al-Abed Y, Lombardo G, Maksimović-Ivanić D, Mijatović S, Zocca M, Perciavalle V, Stošić-Grujičić S, Nicoletti F. Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells. in Oncology Reports. 2012;28(2):323-688.
https://hdl.handle.net/21.15107/rcub_ibiss_1157 .

Donia, Marco, Mangano, Katia, Fagone, Paolo, De Pasquale, R, Dinotta, F, Coco, Marinella, Padron, J, Al-Abed, Yousef, Lombardo, GAG, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Zocca, Mai-Britt, Perciavalle, V, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells" in Oncology Reports, 28, no. 2 (2012):323-688,
https://hdl.handle.net/21.15107/rcub_ibiss_1157 .

TY  - JOUR
AU  - Donia, Marco
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Mojić, Marija
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana S
AU  - Fagone, Paolo
AU  - Caponnetto, Salvatore
AU  - Al-Abed, Yousef
AU  - McCubrey, James A
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1309
AB  - The NO-derivative of the HIV protease inhibitor saquinavir (Saq-NO) is a nontoxic variant of the parental drug with enhanced anticancer activity on several cell lines. However, it is still unclear whether the p53 status of the target cell might influence the sensitivity to Saq-NO. In this study we evaluated the in vitro and in vivo activity of Saq-NO on the p53-deficient hormone resistant prostate cancer PC-3 cells. We demonstrate that the absence of functional p53 is not essential for the capacity of Saq-NO to reduce prostate cancer cell growth. In contrast to its previously described cytostatic action in B16 and C6 cell lines, Saq-NO exerted cytotoxic effects in PC-3 cells leading to dominant induction of apoptosis and enhanced production of proapoptotic Bim. In addition, differently from saquinavir, Saq-NO restored TRAIL sensitivity that was correlated with increased expression of DR5 independent from ROS/RNS production and YY1 repression. NF kappa B activation may be responsible of the Saq-NO induced DR5 expression. Moreover, Saq-NO but not saquinavir, exerted synergistic activity with conventional cytostatic therapy. In agreement with these in vitro studies, Saq-NO inhibited the in vivo growth of PC-3 cells xenotransplants to a greater extent than the parental compound. Taken together, these data indicate that Saq-NO possesses powerful and suitable in vitro and in vivo chemotherapeutic potential to be further studied as a novel drug for the treatment of prostate cancer in the clinical setting.
T2  - Cell Cycle
T1  - In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells
IS  - 3
VL  - 10
EP  - 499
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1309
ER  - 

@article{
author = "Donia, Marco and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Mojić, Marija and Miljković, Đorđe and Timotijević, Gordana S and Fagone, Paolo and Caponnetto, Salvatore and Al-Abed, Yousef and McCubrey, James A and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2011",
abstract = "The NO-derivative of the HIV protease inhibitor saquinavir (Saq-NO) is a nontoxic variant of the parental drug with enhanced anticancer activity on several cell lines. However, it is still unclear whether the p53 status of the target cell might influence the sensitivity to Saq-NO. In this study we evaluated the in vitro and in vivo activity of Saq-NO on the p53-deficient hormone resistant prostate cancer PC-3 cells. We demonstrate that the absence of functional p53 is not essential for the capacity of Saq-NO to reduce prostate cancer cell growth. In contrast to its previously described cytostatic action in B16 and C6 cell lines, Saq-NO exerted cytotoxic effects in PC-3 cells leading to dominant induction of apoptosis and enhanced production of proapoptotic Bim. In addition, differently from saquinavir, Saq-NO restored TRAIL sensitivity that was correlated with increased expression of DR5 independent from ROS/RNS production and YY1 repression. NF kappa B activation may be responsible of the Saq-NO induced DR5 expression. Moreover, Saq-NO but not saquinavir, exerted synergistic activity with conventional cytostatic therapy. In agreement with these in vitro studies, Saq-NO inhibited the in vivo growth of PC-3 cells xenotransplants to a greater extent than the parental compound. Taken together, these data indicate that Saq-NO possesses powerful and suitable in vitro and in vivo chemotherapeutic potential to be further studied as a novel drug for the treatment of prostate cancer in the clinical setting.",
journal = "Cell Cycle",
title = "In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells",
number = "3",
volume = "10",
pages = "499",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1309"
}

Donia, M., Maksimović-Ivanić, D., Mijatović, S., Mojić, M., Miljković, Đ., Timotijević, G. S., Fagone, P., Caponnetto, S., Al-Abed, Y., McCubrey, J. A., Stošić-Grujičić, S.,& Nicoletti, F.. (2011). In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells. in Cell Cycle, 10(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1309

Donia M, Maksimović-Ivanić D, Mijatović S, Mojić M, Miljković Đ, Timotijević GS, Fagone P, Caponnetto S, Al-Abed Y, McCubrey JA, Stošić-Grujičić S, Nicoletti F. In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells. in Cell Cycle. 2011;10(3):null-499.
https://hdl.handle.net/21.15107/rcub_ibiss_1309 .

Donia, Marco, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Mojić, Marija, Miljković, Đorđe, Timotijević, Gordana S, Fagone, Paolo, Caponnetto, Salvatore, Al-Abed, Yousef, McCubrey, James A, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells" in Cell Cycle, 10, no. 3 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1309 .

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Mojić, Marija
AU  - Timotijević, Gordana S
AU  - Miljković, Đorđe
AU  - Mangano, Katia
AU  - Donia, Marco
AU  - Di Cataldo, Antonio
AU  - Al-Abed, Yousef
AU  - Cheng, Kai Fan
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1283
AB  - We have recently shown that covalent attachment of the NO moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity. In this study we evaluated the impact of Saq-NO on the growth of A375 human melanoma cells, as a prototype of NO-dependent cancer model. The novel compound strongly affected the in vitro and in vivo progression of A375 melanoma cell growth. The mechanism of antimelanoma action comprised dual drug activity-induction of apoptotic cell death and acquisition of melanoma cell responsiveness to TRAIL. Saq-NO-triggered apoptosis was dependent on transient AKT up-regulation and reduced pERK and iNOS expression that were observed within the first 12 h of exposure to the drug. Thereafter, however, Saq-NO up-regulated both iNOS transcription and NO endogenous synthesis and sensitized A375 cells to TRAIL. Furthermore, reduced YY1 expression was observed after 24 h of Saq-NO exposure, which correlated with increased expression of DR5. The biological relevance of this complex and powerful action of Saq-NO was consistent with the marked drug-induced inhibition of the growth of A375 xenotransplants in nude mice. J. Cell. Physiol. 226: 1803-1812, 2011. (C) 2010 Wiley-Liss, Inc.
T2  - Journal of Cellular Physiology
T1  - Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells
IS  - 7
VL  - 226
EP  - 1812
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1283
ER  - 

@article{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Mojić, Marija and Timotijević, Gordana S and Miljković, Đorđe and Mangano, Katia and Donia, Marco and Di Cataldo, Antonio and Al-Abed, Yousef and Cheng, Kai Fan and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2011",
abstract = "We have recently shown that covalent attachment of the NO moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity. In this study we evaluated the impact of Saq-NO on the growth of A375 human melanoma cells, as a prototype of NO-dependent cancer model. The novel compound strongly affected the in vitro and in vivo progression of A375 melanoma cell growth. The mechanism of antimelanoma action comprised dual drug activity-induction of apoptotic cell death and acquisition of melanoma cell responsiveness to TRAIL. Saq-NO-triggered apoptosis was dependent on transient AKT up-regulation and reduced pERK and iNOS expression that were observed within the first 12 h of exposure to the drug. Thereafter, however, Saq-NO up-regulated both iNOS transcription and NO endogenous synthesis and sensitized A375 cells to TRAIL. Furthermore, reduced YY1 expression was observed after 24 h of Saq-NO exposure, which correlated with increased expression of DR5. The biological relevance of this complex and powerful action of Saq-NO was consistent with the marked drug-induced inhibition of the growth of A375 xenotransplants in nude mice. J. Cell. Physiol. 226: 1803-1812, 2011. (C) 2010 Wiley-Liss, Inc.",
journal = "Journal of Cellular Physiology",
title = "Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells",
number = "7",
volume = "226",
pages = "1812",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1283"
}

Mijatović, S., Maksimović-Ivanić, D., Mojić, M., Timotijević, G. S., Miljković, Đ., Mangano, K., Donia, M., Di Cataldo, A., Al-Abed, Y., Cheng, K. F., Stošić-Grujičić, S.,& Nicoletti, F.. (2011). Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells. in Journal of Cellular Physiology, 226(7).
https://hdl.handle.net/21.15107/rcub_ibiss_1283

Mijatović S, Maksimović-Ivanić D, Mojić M, Timotijević GS, Miljković Đ, Mangano K, Donia M, Di Cataldo A, Al-Abed Y, Cheng KF, Stošić-Grujičić S, Nicoletti F. Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells. in Journal of Cellular Physiology. 2011;226(7):null-1812.
https://hdl.handle.net/21.15107/rcub_ibiss_1283 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Mojić, Marija, Timotijević, Gordana S, Miljković, Đorđe, Mangano, Katia, Donia, Marco, Di Cataldo, Antonio, Al-Abed, Yousef, Cheng, Kai Fan, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells" in Journal of Cellular Physiology, 226, no. 7 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1283 .

TY  - CHAP
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Donia, Marco
AU  - Stošić-Grujičić, Stanislava
AU  - Garotta, Gianni
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3836
AB  - Nonsteroidal-anti-inflammatory drugs modified by covalent attachment of nitric oxide (NO) have been recognized as compounds with antitumor properties. By adopting this approach the new compound GIT-27NO was synthesized at GaNiAl Immunotherapeutics Inc. (Wilmington, Delaware, USA) on the basis of the anti-inflammatory isoxazoline derivative VGX-1027. In contrast to the usual modification, i.e., connection via a spacer molecule, GIT-27NO was generated by direct addition of a releasing NO moiety. Contrary to the parental compound which is completely inefficient as an antitumor drug, the modified compound acquired strong anticancer potential. The drug reduced the growth of various cell lines in vitro as well as some solid localized and even metastatic tumors in vivo. Decreased viability of tumor cells was caused by induction of different types of programmed cell death whereas accidental cell death was a secondary event. The outcome of the drug treatment was independent of the type of intracellular response, since the absence or inactivation of key executive mediators of apoptosis, like p53 or caspases, did not affect the death signal triggered by GIT-27NO. Furthermore, cells made resistant to apoptotic stimuli are sensitive to GIT-27NO as well. Although the drug efficacy is explicitly related to NO liberation, GIT-27NO did not function as a simple exogenous donor. Signal for NO release came from cells, and further events included the generation of ROS, RNS and subsequent nitration of tyrosine residues, caspase inhibition, or decreased activity of the YY1 repressor. The drug effect on the MAP signaling pathway was heterogeneous and defined by the cell specificity, the plasticity of the agent’s action, its high efficacy, and low toxicity and suggests that GIT-27NO is a candidate for anticancer drug of the future.
PB  - New York: Springer
T2  - Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development
T1  - (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission
DO  - 10.1007/978-1-4419-1432-3_23
SP  - 443
EP  - 457
ER  - 

@inbook{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Donia, Marco and Stošić-Grujičić, Stanislava and Garotta, Gianni and Al-Abed, Yousef and Nicoletti, Ferdinando",
year = "2010",
abstract = "Nonsteroidal-anti-inflammatory drugs modified by covalent attachment of nitric oxide (NO) have been recognized as compounds with antitumor properties. By adopting this approach the new compound GIT-27NO was synthesized at GaNiAl Immunotherapeutics Inc. (Wilmington, Delaware, USA) on the basis of the anti-inflammatory isoxazoline derivative VGX-1027. In contrast to the usual modification, i.e., connection via a spacer molecule, GIT-27NO was generated by direct addition of a releasing NO moiety. Contrary to the parental compound which is completely inefficient as an antitumor drug, the modified compound acquired strong anticancer potential. The drug reduced the growth of various cell lines in vitro as well as some solid localized and even metastatic tumors in vivo. Decreased viability of tumor cells was caused by induction of different types of programmed cell death whereas accidental cell death was a secondary event. The outcome of the drug treatment was independent of the type of intracellular response, since the absence or inactivation of key executive mediators of apoptosis, like p53 or caspases, did not affect the death signal triggered by GIT-27NO. Furthermore, cells made resistant to apoptotic stimuli are sensitive to GIT-27NO as well. Although the drug efficacy is explicitly related to NO liberation, GIT-27NO did not function as a simple exogenous donor. Signal for NO release came from cells, and further events included the generation of ROS, RNS and subsequent nitration of tyrosine residues, caspase inhibition, or decreased activity of the YY1 repressor. The drug effect on the MAP signaling pathway was heterogeneous and defined by the cell specificity, the plasticity of the agent’s action, its high efficacy, and low toxicity and suggests that GIT-27NO is a candidate for anticancer drug of the future.",
publisher = "New York: Springer",
journal = "Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development",
booktitle = "(S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission",
doi = "10.1007/978-1-4419-1432-3_23",
pages = "443-457"
}

Mijatović, S., Maksimović-Ivanić, D., Donia, M., Stošić-Grujičić, S., Garotta, G., Al-Abed, Y.,& Nicoletti, F.. (2010). (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission. in Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development
New York: Springer., 443-457.
https://doi.org/10.1007/978-1-4419-1432-3_23

Mijatović S, Maksimović-Ivanić D, Donia M, Stošić-Grujičić S, Garotta G, Al-Abed Y, Nicoletti F. (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission. in Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development. 2010;:443-457.
doi:10.1007/978-1-4419-1432-3_23 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Donia, Marco, Stošić-Grujičić, Stanislava, Garotta, Gianni, Al-Abed, Yousef, Nicoletti, Ferdinando, "(S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission" in Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development (2010):443-457,
https://doi.org/10.1007/978-1-4419-1432-3_23 . .

TY  - CONF
AU  - Timotijević, Gordana S
AU  - Maksimović-Ivanić, Danijela
AU  - Miljković, Đorđe
AU  - Mangano, Katia
AU  - Donia, Marco
AU  - Mojić, Marija
AU  - Al-Abed, Yousef
AU  - Stošić-Grujičić, Stanislava
AU  - Mijatović, Sanja
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1412
C3  - International Journal of Molecular Medicine
T1  - Anti-melanoma potential of nitric oxide-modified form of HIV inhibitor- saquinavir; cell specific mode of drug action
IS  - null
VL  - 26
EP  - S33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1412
ER  - 

@conference{
author = "Timotijević, Gordana S and Maksimović-Ivanić, Danijela and Miljković, Đorđe and Mangano, Katia and Donia, Marco and Mojić, Marija and Al-Abed, Yousef and Stošić-Grujičić, Stanislava and Mijatović, Sanja and Nicoletti, Ferdinando",
year = "2010",
journal = "International Journal of Molecular Medicine",
title = "Anti-melanoma potential of nitric oxide-modified form of HIV inhibitor- saquinavir; cell specific mode of drug action",
number = "null",
volume = "26",
pages = "S33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1412"
}

Timotijević, G. S., Maksimović-Ivanić, D., Miljković, Đ., Mangano, K., Donia, M., Mojić, M., Al-Abed, Y., Stošić-Grujičić, S., Mijatović, S.,& Nicoletti, F.. (2010). Anti-melanoma potential of nitric oxide-modified form of HIV inhibitor- saquinavir; cell specific mode of drug action. in International Journal of Molecular Medicine, 26(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1412

Timotijević GS, Maksimović-Ivanić D, Miljković Đ, Mangano K, Donia M, Mojić M, Al-Abed Y, Stošić-Grujičić S, Mijatović S, Nicoletti F. Anti-melanoma potential of nitric oxide-modified form of HIV inhibitor- saquinavir; cell specific mode of drug action. in International Journal of Molecular Medicine. 2010;26(null):null-S33.
https://hdl.handle.net/21.15107/rcub_ibiss_1412 .

Timotijević, Gordana S, Maksimović-Ivanić, Danijela, Miljković, Đorđe, Mangano, Katia, Donia, Marco, Mojić, Marija, Al-Abed, Yousef, Stošić-Grujičić, Stanislava, Mijatović, Sanja, Nicoletti, Ferdinando, "Anti-melanoma potential of nitric oxide-modified form of HIV inhibitor- saquinavir; cell specific mode of drug action" in International Journal of Molecular Medicine, 26, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1412 .

TY  - CONF
AU  - Timotijević, Gordana S
AU  - Stošić-Grujičić, Stanislava
AU  - Mojić, Marija
AU  - Mangano, Katia
AU  - Mijatović, Sanja
AU  - Donia, Marco
AU  - Miljković, Đorđe
AU  - Al-Abed, Yousef
AU  - Maksimović-Ivanić, Danijela
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1411
C3  - International Journal of Molecular Medicine
T1  - Different action of nitric oxide-modified forms of saquinavir and izoxazole dentate VGX-1027 in colon cancer cells
IS  - null
VL  - 26
EP  - S33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1411
ER  - 

@conference{
author = "Timotijević, Gordana S and Stošić-Grujičić, Stanislava and Mojić, Marija and Mangano, Katia and Mijatović, Sanja and Donia, Marco and Miljković, Đorđe and Al-Abed, Yousef and Maksimović-Ivanić, Danijela and Nicoletti, Ferdinando",
year = "2010",
journal = "International Journal of Molecular Medicine",
title = "Different action of nitric oxide-modified forms of saquinavir and izoxazole dentate VGX-1027 in colon cancer cells",
number = "null",
volume = "26",
pages = "S33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1411"
}

Timotijević, G. S., Stošić-Grujičić, S., Mojić, M., Mangano, K., Mijatović, S., Donia, M., Miljković, Đ., Al-Abed, Y., Maksimović-Ivanić, D.,& Nicoletti, F.. (2010). Different action of nitric oxide-modified forms of saquinavir and izoxazole dentate VGX-1027 in colon cancer cells. in International Journal of Molecular Medicine, 26(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1411

Timotijević GS, Stošić-Grujičić S, Mojić M, Mangano K, Mijatović S, Donia M, Miljković Đ, Al-Abed Y, Maksimović-Ivanić D, Nicoletti F. Different action of nitric oxide-modified forms of saquinavir and izoxazole dentate VGX-1027 in colon cancer cells. in International Journal of Molecular Medicine. 2010;26(null):null-S33.
https://hdl.handle.net/21.15107/rcub_ibiss_1411 .

Timotijević, Gordana S, Stošić-Grujičić, Stanislava, Mojić, Marija, Mangano, Katia, Mijatović, Sanja, Donia, Marco, Miljković, Đorđe, Al-Abed, Yousef, Maksimović-Ivanić, Danijela, Nicoletti, Ferdinando, "Different action of nitric oxide-modified forms of saquinavir and izoxazole dentate VGX-1027 in colon cancer cells" in International Journal of Molecular Medicine, 26, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1411 .

TY  - JOUR
AU  - Stošić-Grujičić, Stanislava
AU  - Timotijević, Gordana S
AU  - Donia, Marco
AU  - Miljković, Đorđe
AU  - Mijatović, Sanja
AU  - Libra, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Coco, Marinella
AU  - McCubrey, James A
AU  - Al-Abed, Yousef
AU  - Korac, Aleksandra B
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1387
AB  - The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice (C) 2010 Elsevier Inc All rights reserved
T2  - Free Radical Biology and Medicine
T1  - Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO
IS  - 8
VL  - 48
EP  - 1099
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1387
ER  - 

@article{
author = "Stošić-Grujičić, Stanislava and Timotijević, Gordana S and Donia, Marco and Miljković, Đorđe and Mijatović, Sanja and Libra, Massimo and Maksimović-Ivanić, Danijela and Coco, Marinella and McCubrey, James A and Al-Abed, Yousef and Korac, Aleksandra B and Nicoletti, Ferdinando",
year = "2010",
abstract = "The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice (C) 2010 Elsevier Inc All rights reserved",
journal = "Free Radical Biology and Medicine",
title = "Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO",
number = "8",
volume = "48",
pages = "1099",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1387"
}

Stošić-Grujičić, S., Timotijević, G. S., Donia, M., Miljković, Đ., Mijatović, S., Libra, M., Maksimović-Ivanić, D., Coco, M., McCubrey, J. A., Al-Abed, Y., Korac, A. B.,& Nicoletti, F.. (2010). Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO. in Free Radical Biology and Medicine, 48(8).
https://hdl.handle.net/21.15107/rcub_ibiss_1387

Stošić-Grujičić S, Timotijević GS, Donia M, Miljković Đ, Mijatović S, Libra M, Maksimović-Ivanić D, Coco M, McCubrey JA, Al-Abed Y, Korac AB, Nicoletti F. Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO. in Free Radical Biology and Medicine. 2010;48(8):null-1099.
https://hdl.handle.net/21.15107/rcub_ibiss_1387 .

Stošić-Grujičić, Stanislava, Timotijević, Gordana S, Donia, Marco, Miljković, Đorđe, Mijatović, Sanja, Libra, Massimo, Maksimović-Ivanić, Danijela, Coco, Marinella, McCubrey, James A, Al-Abed, Yousef, Korac, Aleksandra B, Nicoletti, Ferdinando, "Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO" in Free Radical Biology and Medicine, 48, no. 8 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1387 .

TY  - CONF
AU  - Donia, Marco
AU  - Mijatović, Sanja
AU  - Stošić-Grujičić, Stanislava
AU  - Garotta, Gianni
AU  - Maksimović-Ivanić, Danijela
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1413
C3  - International Journal of Molecular Medicine
T1  - Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?
IS  - null
VL  - 26
EP  - S65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1413
ER  - 

@conference{
author = "Donia, Marco and Mijatović, Sanja and Stošić-Grujičić, Stanislava and Garotta, Gianni and Maksimović-Ivanić, Danijela and Al-Abed, Yousef and Nicoletti, Ferdinando",
year = "2010",
journal = "International Journal of Molecular Medicine",
title = "Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?",
number = "null",
volume = "26",
pages = "S65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1413"
}

Donia, M., Mijatović, S., Stošić-Grujičić, S., Garotta, G., Maksimović-Ivanić, D., Al-Abed, Y.,& Nicoletti, F.. (2010). Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?. in International Journal of Molecular Medicine, 26(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1413

Donia M, Mijatović S, Stošić-Grujičić S, Garotta G, Maksimović-Ivanić D, Al-Abed Y, Nicoletti F. Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?. in International Journal of Molecular Medicine. 2010;26(null):null-S65.
https://hdl.handle.net/21.15107/rcub_ibiss_1413 .

Donia, Marco, Mijatović, Sanja, Stošić-Grujičić, Stanislava, Garotta, Gianni, Maksimović-Ivanić, Danijela, Al-Abed, Yousef, Nicoletti, Ferdinando, "Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?" in International Journal of Molecular Medicine, 26, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1413 .

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Miljković, Đorđe
AU  - Harhaji-Trajković, Ljubica
AU  - Timotijević, Gordana S
AU  - Mojić, Marija
AU  - Dabideen, Darrin
AU  - Cheng, Kai Fan
AU  - McCubrey, James A
AU  - Mangano, Katia
AU  - Al-Abed, Yousef
AU  - Libra, Massimo
AU  - Garotta, Gianni
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1453
AB  - Application of the HIV protease inhibitor saquinavir (Saq) to cancer chemotherapy is limited by its numerous side effects. To overcome this toxicity, we modified the original compound by covalently attaching a nitric oxide (NO) group. We compared the efficacy of the parental and NO-modified drugs in vitro and in vivo. The novel compound saquinavir-NO (Saq-NO) significantly reduced the viability of a wide spectrum of human and rodent tumor cell lines at significantly lower concentration than the unmodified drug. In contrast to Saq, Saq-NO had no effect on the viability of primary cells and drastically reduced B16 melanoma growth in syngeneic C57BL/6 mice. In addition, at the equivalent of the 100% lethal dose of Saq, Saq-NO treatment caused no apparent signs of toxicity. Saq-NO blocked the proliferation of C6 and 1316 cells, up-regulated p53 expression, and promoted the differentiation of these two cell types into oligodendrocytes or Schwann-like cells, respectively. Although it has been well documented that Saq decreases tumor cell viability by inhibiting Akt, the anticancer properties of Saq-NO were completely independent of the phosphatidylinositol 3-kinase/Akt signaling pathway. Moreover, Saq-NO transiently up-regulated Akt phosphorylation, delivering a protective signal that could be relevant for primary cell protection and the absence of drug toxicity in vivo. It was unlikely that released NO was independently responsible for these drug effects because Saq-NO treatment increased intracellular and secreted NO levels only slightly. Rather, the chemical modification seems to have produced a qualitatively new chemical entity, which may have a unique mode of action against cancer cells. [Mol Cancer Ther 2009;8(5):1169-78]
T2  - Molecular Cancer Therapeutics
T1  - The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt
IS  - 5
VL  - 8
EP  - 1178
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1453
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Miljković, Đorđe and Harhaji-Trajković, Ljubica and Timotijević, Gordana S and Mojić, Marija and Dabideen, Darrin and Cheng, Kai Fan and McCubrey, James A and Mangano, Katia and Al-Abed, Yousef and Libra, Massimo and Garotta, Gianni and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2009",
abstract = "Application of the HIV protease inhibitor saquinavir (Saq) to cancer chemotherapy is limited by its numerous side effects. To overcome this toxicity, we modified the original compound by covalently attaching a nitric oxide (NO) group. We compared the efficacy of the parental and NO-modified drugs in vitro and in vivo. The novel compound saquinavir-NO (Saq-NO) significantly reduced the viability of a wide spectrum of human and rodent tumor cell lines at significantly lower concentration than the unmodified drug. In contrast to Saq, Saq-NO had no effect on the viability of primary cells and drastically reduced B16 melanoma growth in syngeneic C57BL/6 mice. In addition, at the equivalent of the 100% lethal dose of Saq, Saq-NO treatment caused no apparent signs of toxicity. Saq-NO blocked the proliferation of C6 and 1316 cells, up-regulated p53 expression, and promoted the differentiation of these two cell types into oligodendrocytes or Schwann-like cells, respectively. Although it has been well documented that Saq decreases tumor cell viability by inhibiting Akt, the anticancer properties of Saq-NO were completely independent of the phosphatidylinositol 3-kinase/Akt signaling pathway. Moreover, Saq-NO transiently up-regulated Akt phosphorylation, delivering a protective signal that could be relevant for primary cell protection and the absence of drug toxicity in vivo. It was unlikely that released NO was independently responsible for these drug effects because Saq-NO treatment increased intracellular and secreted NO levels only slightly. Rather, the chemical modification seems to have produced a qualitatively new chemical entity, which may have a unique mode of action against cancer cells. [Mol Cancer Ther 2009;8(5):1169-78]",
journal = "Molecular Cancer Therapeutics",
title = "The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt",
number = "5",
volume = "8",
pages = "1178",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1453"
}

Maksimović-Ivanić, D., Mijatović, S., Miljković, Đ., Harhaji-Trajković, L., Timotijević, G. S., Mojić, M., Dabideen, D., Cheng, K. F., McCubrey, J. A., Mangano, K., Al-Abed, Y., Libra, M., Garotta, G., Stošić-Grujičić, S.,& Nicoletti, F.. (2009). The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt. in Molecular Cancer Therapeutics, 8(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1453

Maksimović-Ivanić D, Mijatović S, Miljković Đ, Harhaji-Trajković L, Timotijević GS, Mojić M, Dabideen D, Cheng KF, McCubrey JA, Mangano K, Al-Abed Y, Libra M, Garotta G, Stošić-Grujičić S, Nicoletti F. The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt. in Molecular Cancer Therapeutics. 2009;8(5):null-1178.
https://hdl.handle.net/21.15107/rcub_ibiss_1453 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Miljković, Đorđe, Harhaji-Trajković, Ljubica, Timotijević, Gordana S, Mojić, Marija, Dabideen, Darrin, Cheng, Kai Fan, McCubrey, James A, Mangano, Katia, Al-Abed, Yousef, Libra, Massimo, Garotta, Gianni, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt" in Molecular Cancer Therapeutics, 8, no. 5 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1453 .

TY  - JOUR
AU  - Donia, Marco
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Miljković, Đorđe
AU  - Mangano, Katia
AU  - Tumino, Salvatore
AU  - Biondi, Antonio
AU  - Basile, Francesco
AU  - Al-Abed, Yousef
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1438
AB  - We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PO and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given -24 and -1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that Grr-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis. (C) 2009 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis
IS  - 1-3
VL  - 615
EP  - 233
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1438
ER  - 

@article{
author = "Donia, Marco and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Miljković, Đorđe and Mangano, Katia and Tumino, Salvatore and Biondi, Antonio and Basile, Francesco and Al-Abed, Yousef and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2009",
abstract = "We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PO and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given -24 and -1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that Grr-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis. (C) 2009 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis",
number = "1-3",
volume = "615",
pages = "233",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1438"
}

Donia, M., Mijatović, S., Maksimović-Ivanić, D., Miljković, Đ., Mangano, K., Tumino, S., Biondi, A., Basile, F., Al-Abed, Y., Stošić-Grujičić, S.,& Nicoletti, F.. (2009). The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis. in European Journal of Pharmacology, 615(1-3).
https://hdl.handle.net/21.15107/rcub_ibiss_1438

Donia M, Mijatović S, Maksimović-Ivanić D, Miljković Đ, Mangano K, Tumino S, Biondi A, Basile F, Al-Abed Y, Stošić-Grujičić S, Nicoletti F. The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis. in European Journal of Pharmacology. 2009;615(1-3):null-233.
https://hdl.handle.net/21.15107/rcub_ibiss_1438 .

Donia, Marco, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Miljković, Đorđe, Mangano, Katia, Tumino, Salvatore, Biondi, Antonio, Basile, Francesco, Al-Abed, Yousef, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis" in European Journal of Pharmacology, 615, no. 1-3 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1438 .

TY  - JOUR
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Maksimović-Ivanić, Danijela
AU  - Momčilović, Miljana
AU  - Popadić, Dušan
AU  - Harhaji-Trajković, Ljubica
AU  - Miljković, Đorđe
AU  - Metz, Christine
AU  - Mangano, Katia
AU  - Papaccio, Gianpacilo
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1528
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine of the innate immune system that plays a major role in the induction of immunoinflammatory responses. To examine the role of endogenous MIF in the pathogenesis of type I diabetes (TID) we evaluated the effects of administration of neutralizing anti-MIF antibodies to NOD mice with accelerated forms of diabetes induced by injection of cyclophosphamide or by transfer of diabetogenic spleen cells. Both accelerated forms of diabetes were markedly reduced by anti-MIF antibody. Furthermore, MIF-deficient (MIF(-/-)) mice were less susceptible to the induction of immunoinflammatory diabetes, insulitis and apoptosis within the endocrine pancreas by multiple low doses of streptozotocin (MLD-STZ) than genetically matched wild type (WT) mice. MIF deficiency resulted in lower proliferation and lymphocyte adhesion, as well as reduced production from the spleens and peritoneal cells of a variety of inflammatory mediators typically associated with development of the disease including IL-12, IL-23, TNF-alpha, and IL-1 beta. Furthermore, MIF deletion affected the production of IL-18, TNF-alpha, IL-1 beta, and iNOS in the islets of Langerhans. These data, along with the higher expression of IL-4 and TGF-beta observed in the periphery and in the pancreas of MLD-STZ-challenged MIF(-1-) mice as compared to WT controls suggest that MIF deficiency has induced an immune deviation towards protective type 2/3 response. These results suggest that MIF participates in T1D by controlling the functional activity of monocytes/macrophages and T cells and modulating their secretory capacity of pro- and anti-inflammatory molecules.
PB  - John Wiley and Sons
T2  - Journal of Cellular Physiology
T1  - Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus
IS  - 3
VL  - 215
DO  - 10.1002/jcp.21346
SP  - 665
EP  - 675
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1528
ER  - 

@article{
author = "Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Maksimović-Ivanić, Danijela and Momčilović, Miljana and Popadić, Dušan and Harhaji-Trajković, Ljubica and Miljković, Đorđe and Metz, Christine and Mangano, Katia and Papaccio, Gianpacilo and Al-Abed, Yousef and Nicoletti, Ferdinando",
year = "2008",
abstract = "Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine of the innate immune system that plays a major role in the induction of immunoinflammatory responses. To examine the role of endogenous MIF in the pathogenesis of type I diabetes (TID) we evaluated the effects of administration of neutralizing anti-MIF antibodies to NOD mice with accelerated forms of diabetes induced by injection of cyclophosphamide or by transfer of diabetogenic spleen cells. Both accelerated forms of diabetes were markedly reduced by anti-MIF antibody. Furthermore, MIF-deficient (MIF(-/-)) mice were less susceptible to the induction of immunoinflammatory diabetes, insulitis and apoptosis within the endocrine pancreas by multiple low doses of streptozotocin (MLD-STZ) than genetically matched wild type (WT) mice. MIF deficiency resulted in lower proliferation and lymphocyte adhesion, as well as reduced production from the spleens and peritoneal cells of a variety of inflammatory mediators typically associated with development of the disease including IL-12, IL-23, TNF-alpha, and IL-1 beta. Furthermore, MIF deletion affected the production of IL-18, TNF-alpha, IL-1 beta, and iNOS in the islets of Langerhans. These data, along with the higher expression of IL-4 and TGF-beta observed in the periphery and in the pancreas of MLD-STZ-challenged MIF(-1-) mice as compared to WT controls suggest that MIF deficiency has induced an immune deviation towards protective type 2/3 response. These results suggest that MIF participates in T1D by controlling the functional activity of monocytes/macrophages and T cells and modulating their secretory capacity of pro- and anti-inflammatory molecules.",
publisher = "John Wiley and Sons",
journal = "Journal of Cellular Physiology",
title = "Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus",
number = "3",
volume = "215",
doi = "10.1002/jcp.21346",
pages = "665-675",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1528"
}

Stošić-Grujičić, S., Stojanović, I. D., Maksimović-Ivanić, D., Momčilović, M., Popadić, D., Harhaji-Trajković, L., Miljković, Đ., Metz, C., Mangano, K., Papaccio, G., Al-Abed, Y.,& Nicoletti, F.. (2008). Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus. in Journal of Cellular Physiology
John Wiley and Sons., 215(3), 665-675.
https://doi.org/10.1002/jcp.21346
https://hdl.handle.net/21.15107/rcub_ibiss_1528

Stošić-Grujičić S, Stojanović ID, Maksimović-Ivanić D, Momčilović M, Popadić D, Harhaji-Trajković L, Miljković Đ, Metz C, Mangano K, Papaccio G, Al-Abed Y, Nicoletti F. Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus. in Journal of Cellular Physiology. 2008;215(3):665-675.
doi:10.1002/jcp.21346
https://hdl.handle.net/21.15107/rcub_ibiss_1528 .

Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Maksimović-Ivanić, Danijela, Momčilović, Miljana, Popadić, Dušan, Harhaji-Trajković, Ljubica, Miljković, Đorđe, Metz, Christine, Mangano, Katia, Papaccio, Gianpacilo, Al-Abed, Yousef, Nicoletti, Ferdinando, "Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus" in Journal of Cellular Physiology, 215, no. 3 (2008):665-675,
https://doi.org/10.1002/jcp.21346 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1528 .

TY  - CONF
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Harhaji-Trajković, Ljubica
AU  - Miljković, Đorđe
AU  - Donia, Marco
AU  - Al-Abed, Yousef
AU  - Malaponte, Graziella
AU  - Libra, Massimo
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1620
C3  - Nitric Oxide-Biology and Chemistry
T1  - Tumoricidal activity of GIT-27NO depends on RNS and ROS generation
IS  - null
VL  - 17
EP  - S18
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1620
ER  - 

@conference{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Harhaji-Trajković, Ljubica and Miljković, Đorđe and Donia, Marco and Al-Abed, Yousef and Malaponte, Graziella and Libra, Massimo and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2007",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Tumoricidal activity of GIT-27NO depends on RNS and ROS generation",
number = "null",
volume = "17",
pages = "S18",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1620"
}

Mijatović, S., Maksimović-Ivanić, D., Harhaji-Trajković, L., Miljković, Đ., Donia, M., Al-Abed, Y., Malaponte, G., Libra, M., Nicoletti, F.,& Stošić-Grujičić, S.. (2007). Tumoricidal activity of GIT-27NO depends on RNS and ROS generation. in Nitric Oxide-Biology and Chemistry, 17(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1620

Mijatović S, Maksimović-Ivanić D, Harhaji-Trajković L, Miljković Đ, Donia M, Al-Abed Y, Malaponte G, Libra M, Nicoletti F, Stošić-Grujičić S. Tumoricidal activity of GIT-27NO depends on RNS and ROS generation. in Nitric Oxide-Biology and Chemistry. 2007;17(null):null-S18.
https://hdl.handle.net/21.15107/rcub_ibiss_1620 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Harhaji-Trajković, Ljubica, Miljković, Đorđe, Donia, Marco, Al-Abed, Yousef, Malaponte, Graziella, Libra, Massimo, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Tumoricidal activity of GIT-27NO depends on RNS and ROS generation" in Nitric Oxide-Biology and Chemistry, 17, no. null (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1620 .

TY  - CONF
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Harhaji-Trajković, Ljubica
AU  - Miljković, Đorđe
AU  - Donia, Marco
AU  - Al-Abed, Yousef
AU  - Stivala, Franca
AU  - Mazzarino, Clorinda
AU  - Libra, Massimo
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1618
C3  - Nitric Oxide-Biology and Chemistry
T1  - Novel NO-donation compound GIT-27NO possesses strong tumoricidal capacity in vitro and in vivo
IS  - null
VL  - 17
EP  - S25
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1618
ER  - 

@conference{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Harhaji-Trajković, Ljubica and Miljković, Đorđe and Donia, Marco and Al-Abed, Yousef and Stivala, Franca and Mazzarino, Clorinda and Libra, Massimo and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2007",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Novel NO-donation compound GIT-27NO possesses strong tumoricidal capacity in vitro and in vivo",
number = "null",
volume = "17",
pages = "S25",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1618"
}

Maksimović-Ivanić, D., Mijatović, S., Harhaji-Trajković, L., Miljković, Đ., Donia, M., Al-Abed, Y., Stivala, F., Mazzarino, C., Libra, M., Nicoletti, F.,& Stošić-Grujičić, S.. (2007). Novel NO-donation compound GIT-27NO possesses strong tumoricidal capacity in vitro and in vivo. in Nitric Oxide-Biology and Chemistry, 17(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1618

Maksimović-Ivanić D, Mijatović S, Harhaji-Trajković L, Miljković Đ, Donia M, Al-Abed Y, Stivala F, Mazzarino C, Libra M, Nicoletti F, Stošić-Grujičić S. Novel NO-donation compound GIT-27NO possesses strong tumoricidal capacity in vitro and in vivo. in Nitric Oxide-Biology and Chemistry. 2007;17(null):null-S25.
https://hdl.handle.net/21.15107/rcub_ibiss_1618 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Harhaji-Trajković, Ljubica, Miljković, Đorđe, Donia, Marco, Al-Abed, Yousef, Stivala, Franca, Mazzarino, Clorinda, Libra, Massimo, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Novel NO-donation compound GIT-27NO possesses strong tumoricidal capacity in vitro and in vivo" in Nitric Oxide-Biology and Chemistry, 17, no. null (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1618 .

TY  - JOUR
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Mangano,  Katia
AU  - Fresta, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Harhaji-Trajković, Ljubica
AU  - Popadić, Dušan
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Kim, Joseph
AU  - Al-Abed, Yousef
AU  - Nicoletti,  Ferdinando
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3824
AB  - (S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) is an isoxazole compound that exhibits various immunomodulatory properties. The capacity of VGX-1027 to prevent interleukin (IL)-1beta plus interferon-gamma-induced pancreatic islet death in vitro prompted us to evaluate its effects on the development of autoimmune diabetes in preclinical models of human type 1 diabetes mellitus (T1D). Administration of VGX-1027 to NOD mice with spontaneous or accelerated forms of diabetes induced either by injection of cyclophosphamide or by transfer of spleen cells from acutely diabetic syngeneic donors markedly reduced the cumulative incidence of diabetes and insulitis. In addition, VGX-1027 given either i.p. or p.o. to CBA/H mice made diabetic with multiple low doses of streptozotocin successfully counteracted the development of destructive insulitis and hyperglycemia. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. These results indicate that VGX-1027 probably exerts its antidiabetogenic effects by limiting cytokine-mediated immunoinflammatory events, leading to inflammation and destruction of pancreatic islets. VGX-1027 seems worthy of being considered as a candidate drug in the development of new therapeutic strategies for the prevention and early treatment of T1D.
PB  - Rockville: American Society for Pharmacology and Experimental Therapeutics (ASPET)
T2  - Journal of Pharmacology and Experimental Therapeutics
T1  - A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice
IS  - 3
VL  - 320
DO  - 10.1124/jpet.106.109272
SP  - 1038
EP  - 1049
ER  - 

@article{
author = "Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Mangano,  Katia and Fresta, Massimo and Maksimović-Ivanić, Danijela and Harhaji-Trajković, Ljubica and Popadić, Dušan and Momčilović, Miljana and Miljković, Đorđe and Kim, Joseph and Al-Abed, Yousef and Nicoletti,  Ferdinando",
year = "2007",
abstract = "(S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) is an isoxazole compound that exhibits various immunomodulatory properties. The capacity of VGX-1027 to prevent interleukin (IL)-1beta plus interferon-gamma-induced pancreatic islet death in vitro prompted us to evaluate its effects on the development of autoimmune diabetes in preclinical models of human type 1 diabetes mellitus (T1D). Administration of VGX-1027 to NOD mice with spontaneous or accelerated forms of diabetes induced either by injection of cyclophosphamide or by transfer of spleen cells from acutely diabetic syngeneic donors markedly reduced the cumulative incidence of diabetes and insulitis. In addition, VGX-1027 given either i.p. or p.o. to CBA/H mice made diabetic with multiple low doses of streptozotocin successfully counteracted the development of destructive insulitis and hyperglycemia. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. These results indicate that VGX-1027 probably exerts its antidiabetogenic effects by limiting cytokine-mediated immunoinflammatory events, leading to inflammation and destruction of pancreatic islets. VGX-1027 seems worthy of being considered as a candidate drug in the development of new therapeutic strategies for the prevention and early treatment of T1D.",
publisher = "Rockville: American Society for Pharmacology and Experimental Therapeutics (ASPET)",
journal = "Journal of Pharmacology and Experimental Therapeutics",
title = "A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice",
number = "3",
volume = "320",
doi = "10.1124/jpet.106.109272",
pages = "1038-1049"
}

Stošić-Grujičić, S., Stojanović, I. D., Mangano,  ., Fresta, M., Maksimović-Ivanić, D., Harhaji-Trajković, L., Popadić, D., Momčilović, M., Miljković, Đ., Kim, J., Al-Abed, Y.,& Nicoletti,  .. (2007). A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice. in Journal of Pharmacology and Experimental Therapeutics
Rockville: American Society for Pharmacology and Experimental Therapeutics (ASPET)., 320(3), 1038-1049.
https://doi.org/10.1124/jpet.106.109272

Stošić-Grujičić S, Stojanović ID, Mangano  , Fresta M, Maksimović-Ivanić D, Harhaji-Trajković L, Popadić D, Momčilović M, Miljković Đ, Kim J, Al-Abed Y, Nicoletti  . A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice. in Journal of Pharmacology and Experimental Therapeutics. 2007;320(3):1038-1049.
doi:10.1124/jpet.106.109272 .

Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Mangano,  Katia, Fresta, Massimo, Maksimović-Ivanić, Danijela, Harhaji-Trajković, Ljubica, Popadić, Dušan, Momčilović, Miljana, Miljković, Đorđe, Kim, Joseph, Al-Abed, Yousef, Nicoletti,  Ferdinando, "A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice" in Journal of Pharmacology and Experimental Therapeutics, 320, no. 3 (2007):1038-1049,
https://doi.org/10.1124/jpet.106.109272 . .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Cuzzocrea, S
AU  - Mangano, Katia
AU  - Mazzon, E
AU  - Miljković, Đorđe
AU  - Wang, MJ
AU  - Donia, Marco
AU  - Al-Abed, Yousef
AU  - Kim, Joseph
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
AU  - Claesson, MH
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1598
AB  - We have presently studied the in vitro, ex vivo and in vivo immunopharmacological effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This compound reduced the secretion of IL-1 beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappa B and p38 MAP kinase pathways along with up-regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4 induced in purified murine CD4(+) T cells from stimulation with either CD3(+)CD28 or ConA. These effects on macrophages may account for the capacity of VGX-1027 to markedly ameliorate the course of both acute and chronic immunoinflammatory diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and type II collagen-induced arthritis. Acute and subacute toxicological studies show that the drug is not toxic at the doses that exert biological effects in these preclinical models. These data warrant additional studies for the potential use of VGX-1027 in the clinical setting. (C) 2007 Elsevier Inc. All rights reserved.
T2  - Clinical Immunology
T1  - In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models
IS  - 3
VL  - 123
EP  - 323
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1598
ER  - 

@article{
author = "Stojanović, Ivana D. and Cuzzocrea, S and Mangano, Katia and Mazzon, E and Miljković, Đorđe and Wang, MJ and Donia, Marco and Al-Abed, Yousef and Kim, Joseph and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava and Claesson, MH",
year = "2007",
abstract = "We have presently studied the in vitro, ex vivo and in vivo immunopharmacological effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This compound reduced the secretion of IL-1 beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappa B and p38 MAP kinase pathways along with up-regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4 induced in purified murine CD4(+) T cells from stimulation with either CD3(+)CD28 or ConA. These effects on macrophages may account for the capacity of VGX-1027 to markedly ameliorate the course of both acute and chronic immunoinflammatory diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and type II collagen-induced arthritis. Acute and subacute toxicological studies show that the drug is not toxic at the doses that exert biological effects in these preclinical models. These data warrant additional studies for the potential use of VGX-1027 in the clinical setting. (C) 2007 Elsevier Inc. All rights reserved.",
journal = "Clinical Immunology",
title = "In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models",
number = "3",
volume = "123",
pages = "323",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1598"
}

Stojanović, I. D., Cuzzocrea, S., Mangano, K., Mazzon, E., Miljković, Đ., Wang, M., Donia, M., Al-Abed, Y., Kim, J., Nicoletti, F., Stošić-Grujičić, S.,& Claesson, M.. (2007). In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models. in Clinical Immunology, 123(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1598

Stojanović ID, Cuzzocrea S, Mangano K, Mazzon E, Miljković Đ, Wang M, Donia M, Al-Abed Y, Kim J, Nicoletti F, Stošić-Grujičić S, Claesson M. In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models. in Clinical Immunology. 2007;123(3):null-323.
https://hdl.handle.net/21.15107/rcub_ibiss_1598 .

Stojanović, Ivana D., Cuzzocrea, S, Mangano, Katia, Mazzon, E, Miljković, Đorđe, Wang, MJ, Donia, Marco, Al-Abed, Yousef, Kim, Joseph, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, Claesson, MH, "In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models" in Clinical Immunology, 123, no. 3 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1598 .

TY  - CONF
AU  - Malaponte, Graziella
AU  - Libra, Massimo
AU  - Cardile, Vera
AU  - Lombardo, L
AU  - Ligresti, Giovanni
AU  - Mangano, Katia
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Al-Abed, Yousef
AU  - Mazzarino, Maria C
AU  - Nicoletti, Ferdinando
AU  - Stivala, Franca
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1619
C3  - Nitric Oxide-Biology and Chemistry
T1  - GIT-27 NO may be a potential therapeutic agent for melanoma treatment by inhibition of the transcription repressor YIN-YANG
IS  - null
VL  - 17
EP  - S25
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1619
ER  - 

@conference{
author = "Malaponte, Graziella and Libra, Massimo and Cardile, Vera and Lombardo, L and Ligresti, Giovanni and Mangano, Katia and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Al-Abed, Yousef and Mazzarino, Maria C and Nicoletti, Ferdinando and Stivala, Franca",
year = "2007",
journal = "Nitric Oxide-Biology and Chemistry",
title = "GIT-27 NO may be a potential therapeutic agent for melanoma treatment by inhibition of the transcription repressor YIN-YANG",
number = "null",
volume = "17",
pages = "S25",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1619"
}

Malaponte, G., Libra, M., Cardile, V., Lombardo, L., Ligresti, G., Mangano, K., Maksimović-Ivanić, D., Mijatović, S., Al-Abed, Y., Mazzarino, M. C., Nicoletti, F.,& Stivala, F.. (2007). GIT-27 NO may be a potential therapeutic agent for melanoma treatment by inhibition of the transcription repressor YIN-YANG. in Nitric Oxide-Biology and Chemistry, 17(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1619

Malaponte G, Libra M, Cardile V, Lombardo L, Ligresti G, Mangano K, Maksimović-Ivanić D, Mijatović S, Al-Abed Y, Mazzarino MC, Nicoletti F, Stivala F. GIT-27 NO may be a potential therapeutic agent for melanoma treatment by inhibition of the transcription repressor YIN-YANG. in Nitric Oxide-Biology and Chemistry. 2007;17(null):null-S25.
https://hdl.handle.net/21.15107/rcub_ibiss_1619 .

Malaponte, Graziella, Libra, Massimo, Cardile, Vera, Lombardo, L, Ligresti, Giovanni, Mangano, Katia, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Al-Abed, Yousef, Mazzarino, Maria C, Nicoletti, Ferdinando, Stivala, Franca, "GIT-27 NO may be a potential therapeutic agent for melanoma treatment by inhibition of the transcription repressor YIN-YANG" in Nitric Oxide-Biology and Chemistry, 17, no. null (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1619 .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Al-Abed, Yousef
AU  - Miljković, Đorđe
AU  - Maksimović-Ivanić, Danijela
AU  - Roth, Jesse
AU  - Bacher, Michael
AU  - Lan, Hui Y.
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1699
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pivotal role in several immunoinflammatory and autoimmune diseases. In this study we examined the role of MIF in the development of immunoinflammatory diabetes induced in susceptible strains of mice by multiple low doses of streptozotocin. We found that MIF protein was significantly elevated in islet cells during the development of diabetes, and that targeting MIF activity with either neutralizing antibody or the pharmacological inhibitor (S, R)- 3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester, markedly reduced clinical and histopathological features of the disease, such as hyperglycemia and insulitis. Lymphocytes from mice treated with the MIF inhibitors exhibited reduction of both islet antigen-specific proliferative responses and adhesive cell-cell interactions. Neutralization of MIF also down-regulated the ex vivo secretion of the proinflammatory mediators, TNF-alpha, interferon-gamma, and nitric oxide, while augmenting that of the antiinflammatory cytokine, IL-10. This study provides the first in vivo evidence for a critical role for MIF in the immune-mediated beta-cell destruction in an animal model of human type 1 diabetes mellitus and identifies a new therapeutic strategy for the prevention and treatment of this disease in humans that is based on the selective inhibition of MIF activity.
T2  - Endocrinology
T1  - Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes
IS  - 7
VL  - 146
DO  - 10.1210/en.2004-1393
SP  - 2942
EP  - 2951
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1699
ER  - 

@article{
author = "Stojanović, Ivana D. and Al-Abed, Yousef and Miljković, Đorđe and Maksimović-Ivanić, Danijela and Roth, Jesse and Bacher, Michael and Lan, Hui Y. and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2005",
abstract = "Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pivotal role in several immunoinflammatory and autoimmune diseases. In this study we examined the role of MIF in the development of immunoinflammatory diabetes induced in susceptible strains of mice by multiple low doses of streptozotocin. We found that MIF protein was significantly elevated in islet cells during the development of diabetes, and that targeting MIF activity with either neutralizing antibody or the pharmacological inhibitor (S, R)- 3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester, markedly reduced clinical and histopathological features of the disease, such as hyperglycemia and insulitis. Lymphocytes from mice treated with the MIF inhibitors exhibited reduction of both islet antigen-specific proliferative responses and adhesive cell-cell interactions. Neutralization of MIF also down-regulated the ex vivo secretion of the proinflammatory mediators, TNF-alpha, interferon-gamma, and nitric oxide, while augmenting that of the antiinflammatory cytokine, IL-10. This study provides the first in vivo evidence for a critical role for MIF in the immune-mediated beta-cell destruction in an animal model of human type 1 diabetes mellitus and identifies a new therapeutic strategy for the prevention and treatment of this disease in humans that is based on the selective inhibition of MIF activity.",
journal = "Endocrinology",
title = "Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes",
number = "7",
volume = "146",
doi = "10.1210/en.2004-1393",
pages = "2942-2951",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1699"
}

Stojanović, I. D., Al-Abed, Y., Miljković, Đ., Maksimović-Ivanić, D., Roth, J., Bacher, M., Lan, H. Y., Nicoletti, F.,& Stošić-Grujičić, S.. (2005). Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes. in Endocrinology, 146(7), 2942-2951.
https://doi.org/10.1210/en.2004-1393
https://hdl.handle.net/21.15107/rcub_ibiss_1699

Stojanović ID, Al-Abed Y, Miljković Đ, Maksimović-Ivanić D, Roth J, Bacher M, Lan HY, Nicoletti F, Stošić-Grujičić S. Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes. in Endocrinology. 2005;146(7):2942-2951.
doi:10.1210/en.2004-1393
https://hdl.handle.net/21.15107/rcub_ibiss_1699 .

Stojanović, Ivana D., Al-Abed, Yousef, Miljković, Đorđe, Maksimović-Ivanić, Danijela, Roth, Jesse, Bacher, Michael, Lan, Hui Y., Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes" in Endocrinology, 146, no. 7 (2005):2942-2951,
https://doi.org/10.1210/en.2004-1393 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1699 .