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  - Nikolić, Ivana
AU  - Stojanović, Ivana D.
AU  - Vujičić, Milica
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Saksida, Tamara
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0171298516303746
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2484
AB  - Bovine colostrum is a rich source of nutrients and immunologically active components that play a role in conveying passive immunity to the offspring, protection and maturation of new-born's gastrointestinal tract. Colostrum has exerted positive effects in diseases affecting gastrointestinal tract, as well as type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have not been reported. The aim of this study was to investigate therapeutic value of oral administration of standardized bovine colostrum derivative (SBCD) in three models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB-DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of streptozotocin (MLDS). SBCD was administered per os and the disease development was evaluated by weekly measurement of blood glucose and by histological analyses of the pancreas. SBCD administration prevented diabetes development in all three models, as indicated by euglicaemia. Ex vivo analysis of cytokine expression and production in the spleen and mesenteric lymph nodes (MLN) in MLDS challenged mice revealed a strong modulation of the immune response. In the MLN cells SBCD disrupted harmful Th17 response induced by MLDS. Expression of Th1 signature cytokine IFN-γ was down-regulated in MLN cells of SBCD-treated mice, while IL-4 secretion (Th2 cytokine) was up-regulated in comparison to diabetic group. Modulation of the immune response seen in the MLN protruded to the spleen, giving overall less infiltration of immune cells to the pancreas. SBCD acted on immune cells and halted (auto) aggression towards pancreatic beta cells. Moreover, SBCD induced beta cell proliferation. Hence, this derivative could be tested in diabetes and other similar diseases with aberrant immune response.
T2  - Immunobiology
T1  - Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents
IS  - 2
VL  - 222
DO  - 10.1016/j.imbio.2016.09.013
SP  - 272
EP  - 279
ER  - 

@article{
author = "Nikolić, Ivana and Stojanović, Ivana D. and Vujičić, Milica and Fagone, Paolo and Mangano, Katia and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Saksida, Tamara",
year = "2017",
abstract = "Bovine colostrum is a rich source of nutrients and immunologically active components that play a role in conveying passive immunity to the offspring, protection and maturation of new-born's gastrointestinal tract. Colostrum has exerted positive effects in diseases affecting gastrointestinal tract, as well as type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have not been reported. The aim of this study was to investigate therapeutic value of oral administration of standardized bovine colostrum derivative (SBCD) in three models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB-DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of streptozotocin (MLDS). SBCD was administered per os and the disease development was evaluated by weekly measurement of blood glucose and by histological analyses of the pancreas. SBCD administration prevented diabetes development in all three models, as indicated by euglicaemia. Ex vivo analysis of cytokine expression and production in the spleen and mesenteric lymph nodes (MLN) in MLDS challenged mice revealed a strong modulation of the immune response. In the MLN cells SBCD disrupted harmful Th17 response induced by MLDS. Expression of Th1 signature cytokine IFN-γ was down-regulated in MLN cells of SBCD-treated mice, while IL-4 secretion (Th2 cytokine) was up-regulated in comparison to diabetic group. Modulation of the immune response seen in the MLN protruded to the spleen, giving overall less infiltration of immune cells to the pancreas. SBCD acted on immune cells and halted (auto) aggression towards pancreatic beta cells. Moreover, SBCD induced beta cell proliferation. Hence, this derivative could be tested in diabetes and other similar diseases with aberrant immune response.",
journal = "Immunobiology",
title = "Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents",
number = "2",
volume = "222",
doi = "10.1016/j.imbio.2016.09.013",
pages = "272-279"
}

Nikolić, I., Stojanović, I. D., Vujičić, M., Fagone, P., Mangano, K., Stošić-Grujičić, S., Nicoletti, F.,& Saksida, T.. (2017). Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents. in Immunobiology, 222(2), 272-279.
https://doi.org/10.1016/j.imbio.2016.09.013

Nikolić I, Stojanović ID, Vujičić M, Fagone P, Mangano K, Stošić-Grujičić S, Nicoletti F, Saksida T. Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents. in Immunobiology. 2017;222(2):272-279.
doi:10.1016/j.imbio.2016.09.013 .

Nikolić, Ivana, Stojanović, Ivana D., Vujičić, Milica, Fagone, Paolo, Mangano, Katia, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Saksida, Tamara, "Standardized bovine colostrum derivative impedes development of type 1 diabetes in rodents" in Immunobiology, 222, no. 2 (2017):272-279,
https://doi.org/10.1016/j.imbio.2016.09.013 . .

TY  - JOUR
AU  - Momčilović, Miljana
AU  - Mangano, Katia
AU  - Jevtić, Bojan
AU  - Mammana, Santa
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Miljković, Đorđe
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2118
AB  - Covalent attachment of the nitric oxide (NO) moiety to the HIV protease
   inhibitor Saquinavir (Saq) produced a new chemical entity, named
   Saquinavir-NO, (Saq-NO) with reduced toxicity and potent
   immunoregulatory influence on T lymphocytes. In this study, we have
   compared head-to-head the effects of Saq-NO and Saq on mouse and rat
   peritoneal macrophage cytokine secretion and NO production upon in
   vitro, ex vivo and in vivo conditions. The results demonstrate that
   Saq-NO, but not Saq, potently decreased interleukin (IL)-10, IL-6 and
   nitrite accumulation and increased the levels of IL-1 and tumour
   necrosis factor (TNF) in supernatants of mouse and rat macrophage
   cultures in vitro. Treatment of mice with Saq-NO, but not Saq, inhibited
   ex vivo secretion of IL-6 from macrophages. Consistent with these
   findings, Saq-NO also reduced blood levels of IL-6 in
   lipopolysaccharide-treated mice. The observed inhibitory influence of
   Saq-NO on IL-6 generation in macrophages may be involved in the observed
   antitumour and immunomodulatory effects of the drug.
T2  - Basic & Clinical Pharmacology & Toxicology
T1  - Saquinavir-NO Inhibits IL-6 Production in Macrophages
IS  - 6
VL  - 115
DO  - 10.1111/bcpt.12268
SP  - 499
EP  - 506
ER  - 

@article{
author = "Momčilović, Miljana and Mangano, Katia and Jevtić, Bojan and Mammana, Santa and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Miljković, Đorđe",
year = "2014",
abstract = "Covalent attachment of the nitric oxide (NO) moiety to the HIV protease
   inhibitor Saquinavir (Saq) produced a new chemical entity, named
   Saquinavir-NO, (Saq-NO) with reduced toxicity and potent
   immunoregulatory influence on T lymphocytes. In this study, we have
   compared head-to-head the effects of Saq-NO and Saq on mouse and rat
   peritoneal macrophage cytokine secretion and NO production upon in
   vitro, ex vivo and in vivo conditions. The results demonstrate that
   Saq-NO, but not Saq, potently decreased interleukin (IL)-10, IL-6 and
   nitrite accumulation and increased the levels of IL-1 and tumour
   necrosis factor (TNF) in supernatants of mouse and rat macrophage
   cultures in vitro. Treatment of mice with Saq-NO, but not Saq, inhibited
   ex vivo secretion of IL-6 from macrophages. Consistent with these
   findings, Saq-NO also reduced blood levels of IL-6 in
   lipopolysaccharide-treated mice. The observed inhibitory influence of
   Saq-NO on IL-6 generation in macrophages may be involved in the observed
   antitumour and immunomodulatory effects of the drug.",
journal = "Basic & Clinical Pharmacology & Toxicology",
title = "Saquinavir-NO Inhibits IL-6 Production in Macrophages",
number = "6",
volume = "115",
doi = "10.1111/bcpt.12268",
pages = "499-506"
}

Momčilović, M., Mangano, K., Jevtić, B., Mammana, S., Stošić-Grujičić, S., Nicoletti, F.,& Miljković, Đ.. (2014). Saquinavir-NO Inhibits IL-6 Production in Macrophages. in Basic & Clinical Pharmacology & Toxicology, 115(6), 499-506.
https://doi.org/10.1111/bcpt.12268

Momčilović M, Mangano K, Jevtić B, Mammana S, Stošić-Grujičić S, Nicoletti F, Miljković Đ. Saquinavir-NO Inhibits IL-6 Production in Macrophages. in Basic & Clinical Pharmacology & Toxicology. 2014;115(6):499-506.
doi:10.1111/bcpt.12268 .

Momčilović, Miljana, Mangano, Katia, Jevtić, Bojan, Mammana, Santa, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Miljković, Đorđe, "Saquinavir-NO Inhibits IL-6 Production in Macrophages" in Basic & Clinical Pharmacology & Toxicology, 115, no. 6 (2014):499-506,
https://doi.org/10.1111/bcpt.12268 . .

TY  - JOUR
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Mangano, Katia
AU  - Vujičić, Milica
AU  - Stojanović, Ivana D.
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2221
AB  - Aims/hypothesis Recent studies have identified carbon monoxide (CO) as a
   potential therapeutic molecule for the treatment of autoimmune diseases
   owing to its anti-inflammatory and anti-apoptotic properties. We
   explored the efficacy and the mechanisms of action of the CO-releasing
   molecule (CORM)-A1 in preclinical models of type 1 diabetes.
   Methods The impact of CORM-A1 on diabetes development was evaluated in
   models of spontaneous diabetes in NOD mice and in diabetes induced in
   C57BL/6 mice by multiple low-dose streptozotocin (MLDS). Ex vivo
   analysis was performed to determine the impact of CORM-A1 both on T
   helper (Th) cell and macrophage differentiation and on their production
   of soluble mediators in peripheral tissues and in infiltrates of
   pancreatic islets. The potential effect of CORM-A1 on cytokine-induced
   apoptosis in pancreatic islets or beta cells was evaluated in vitro.
   Results CORM-A1 conferred protection from diabetes in MLDS-induced mice
   and reduced diabetes incidence in NOD mice as confirmed by preserved
   insulin secretion and improved histological signs of the disease. In
   MLDS-challenged mice, CORM-A1 attenuated Th1, Th17, and M1 macrophage
   response and facilitated Th2 cell differentiation. In addition, CORM-A1
   treatment in NOD mice upregulated the regulatory arm of the immune
   response (M2 macrophages and FoxP3(+) regulatory T cells). Importantly,
   CORM-A1 interfered with in vitro cytokine-induced beta cell apoptosis
   through the reduction of cytochrome c and caspase 3 levels.
   Conclusions/interpretation The ability of CORM-A1 to protect mice from
   developing type 1 diabetes provides a valuable proof of concept for the
   potential exploitation of controlled CO delivery in clinical settings
   for the treatment of autoimmune diabetes.
T2  - Diabetologia
T1  - Pharmacological application of carbon monoxide ameliorates
 islet-directed autoimmunity in mice via anti-inflammatory and
 anti-apoptotic effects
IS  - 5
VL  - 57
DO  - 10.1007/s00125-014-3170-7
SP  - 980
EP  - 990
ER  - 

@article{
author = "Nikolić, Ivana and Saksida, Tamara and Mangano, Katia and Vujičić, Milica and Stojanović, Ivana D. and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2014",
abstract = "Aims/hypothesis Recent studies have identified carbon monoxide (CO) as a
   potential therapeutic molecule for the treatment of autoimmune diseases
   owing to its anti-inflammatory and anti-apoptotic properties. We
   explored the efficacy and the mechanisms of action of the CO-releasing
   molecule (CORM)-A1 in preclinical models of type 1 diabetes.
   Methods The impact of CORM-A1 on diabetes development was evaluated in
   models of spontaneous diabetes in NOD mice and in diabetes induced in
   C57BL/6 mice by multiple low-dose streptozotocin (MLDS). Ex vivo
   analysis was performed to determine the impact of CORM-A1 both on T
   helper (Th) cell and macrophage differentiation and on their production
   of soluble mediators in peripheral tissues and in infiltrates of
   pancreatic islets. The potential effect of CORM-A1 on cytokine-induced
   apoptosis in pancreatic islets or beta cells was evaluated in vitro.
   Results CORM-A1 conferred protection from diabetes in MLDS-induced mice
   and reduced diabetes incidence in NOD mice as confirmed by preserved
   insulin secretion and improved histological signs of the disease. In
   MLDS-challenged mice, CORM-A1 attenuated Th1, Th17, and M1 macrophage
   response and facilitated Th2 cell differentiation. In addition, CORM-A1
   treatment in NOD mice upregulated the regulatory arm of the immune
   response (M2 macrophages and FoxP3(+) regulatory T cells). Importantly,
   CORM-A1 interfered with in vitro cytokine-induced beta cell apoptosis
   through the reduction of cytochrome c and caspase 3 levels.
   Conclusions/interpretation The ability of CORM-A1 to protect mice from
   developing type 1 diabetes provides a valuable proof of concept for the
   potential exploitation of controlled CO delivery in clinical settings
   for the treatment of autoimmune diabetes.",
journal = "Diabetologia",
title = "Pharmacological application of carbon monoxide ameliorates
 islet-directed autoimmunity in mice via anti-inflammatory and
 anti-apoptotic effects",
number = "5",
volume = "57",
doi = "10.1007/s00125-014-3170-7",
pages = "980-990"
}

Nikolić, I., Saksida, T., Mangano, K., Vujičić, M., Stojanović, I. D., Nicoletti, F.,& Stošić-Grujičić, S.. (2014). Pharmacological application of carbon monoxide ameliorates
 islet-directed autoimmunity in mice via anti-inflammatory and
 anti-apoptotic effects. in Diabetologia, 57(5), 980-990.
https://doi.org/10.1007/s00125-014-3170-7

Nikolić I, Saksida T, Mangano K, Vujičić M, Stojanović ID, Nicoletti F, Stošić-Grujičić S. Pharmacological application of carbon monoxide ameliorates
 islet-directed autoimmunity in mice via anti-inflammatory and
 anti-apoptotic effects. in Diabetologia. 2014;57(5):980-990.
doi:10.1007/s00125-014-3170-7 .

Nikolić, Ivana, Saksida, Tamara, Mangano, Katia, Vujičić, Milica, Stojanović, Ivana D., Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Pharmacological application of carbon monoxide ameliorates
 islet-directed autoimmunity in mice via anti-inflammatory and
 anti-apoptotic effects" in Diabetologia, 57, no. 5 (2014):980-990,
https://doi.org/10.1007/s00125-014-3170-7 . .

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

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

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

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

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

TY  - JOUR
AU  - Petković, Filip
AU  - Blaževski, Jana
AU  - Momčilović, Miljana
AU  - Timotijević, Gordana
AU  - Zocca, Mai-Britt
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Mangano, Katia
AU  - Fagone, Paolo
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Miljković, Đorđe
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/998
AB  - NO-hybridization of the HIV protease inhibitor Saquinavir generates a new chemical entity named Saq-NO, that retains the anti-viral activity and exerts lower toxicity. We show that Saq-NO inhibited the generation of various cytokines in ConA-stimulated unfractionated murine spleen cells and rat lymph nodes stimulated with ConA as well as in purified CD4(+) T cells in vitro and reduced the circulating levels of cytokines in mice challenged with anti-CD3 antibody. Furthermore, Saq-NO reduced IL-17 and IFN-gamma production in myelin basic protein (MBP)-specific cells isolated from rats immunized with MBP. These findings translated well into the in vivo setting as Saq-NO ameliorated the course of the disease in two preclinical models of multiple sclerosis. Our results demonstrate that Saq-NO exerts immunomodulatory effects that warrant studies on its application in autoimmune diseases. (c) 2013 Elsevier B.V. All rights reserved.
PB  - Amsterdam: Elsevier
T2  - Journal of Neuroimmunology
T1  - Saquinavir-NO inhibits S6 kinase activity, impairs secretion of the encephalytogenic cytokines interleukin-17 and interferon-gamma and ameliorates experimental autoimmune encephalomyelitis
IS  - 1-2
VL  - 259
DO  - 10.1016/j.jneuroim.2013.03.010
SP  - 55
EP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_998
ER  - 

@article{
author = "Petković, Filip and Blaževski, Jana and Momčilović, Miljana and Timotijević, Gordana and Zocca, Mai-Britt and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Mangano, Katia and Fagone, Paolo and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Miljković, Đorđe",
year = "2013",
abstract = "NO-hybridization of the HIV protease inhibitor Saquinavir generates a new chemical entity named Saq-NO, that retains the anti-viral activity and exerts lower toxicity. We show that Saq-NO inhibited the generation of various cytokines in ConA-stimulated unfractionated murine spleen cells and rat lymph nodes stimulated with ConA as well as in purified CD4(+) T cells in vitro and reduced the circulating levels of cytokines in mice challenged with anti-CD3 antibody. Furthermore, Saq-NO reduced IL-17 and IFN-gamma production in myelin basic protein (MBP)-specific cells isolated from rats immunized with MBP. These findings translated well into the in vivo setting as Saq-NO ameliorated the course of the disease in two preclinical models of multiple sclerosis. Our results demonstrate that Saq-NO exerts immunomodulatory effects that warrant studies on its application in autoimmune diseases. (c) 2013 Elsevier B.V. All rights reserved.",
publisher = "Amsterdam: Elsevier",
journal = "Journal of Neuroimmunology",
title = "Saquinavir-NO inhibits S6 kinase activity, impairs secretion of the encephalytogenic cytokines interleukin-17 and interferon-gamma and ameliorates experimental autoimmune encephalomyelitis",
number = "1-2",
volume = "259",
doi = "10.1016/j.jneuroim.2013.03.010",
pages = "55-65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_998"
}

Petković, F., Blaževski, J., Momčilović, M., Timotijević, G., Zocca, M., Mijatović, S., Maksimović-Ivanić, D., Mangano, K., Fagone, P., Stošić-Grujičić, S., Nicoletti, F.,& Miljković, Đ.. (2013). Saquinavir-NO inhibits S6 kinase activity, impairs secretion of the encephalytogenic cytokines interleukin-17 and interferon-gamma and ameliorates experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology
Amsterdam: Elsevier., 259(1-2), 55-65.
https://doi.org/10.1016/j.jneuroim.2013.03.010
https://hdl.handle.net/21.15107/rcub_ibiss_998

Petković F, Blaževski J, Momčilović M, Timotijević G, Zocca M, Mijatović S, Maksimović-Ivanić D, Mangano K, Fagone P, Stošić-Grujičić S, Nicoletti F, Miljković Đ. Saquinavir-NO inhibits S6 kinase activity, impairs secretion of the encephalytogenic cytokines interleukin-17 and interferon-gamma and ameliorates experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2013;259(1-2):55-65.
doi:10.1016/j.jneuroim.2013.03.010
https://hdl.handle.net/21.15107/rcub_ibiss_998 .

Petković, Filip, Blaževski, Jana, Momčilović, Miljana, Timotijević, Gordana, Zocca, Mai-Britt, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Mangano, Katia, Fagone, Paolo, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Miljković, Đorđe, "Saquinavir-NO inhibits S6 kinase activity, impairs secretion of the encephalytogenic cytokines interleukin-17 and interferon-gamma and ameliorates experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 259, no. 1-2 (2013):55-65,
https://doi.org/10.1016/j.jneuroim.2013.03.010 .,
https://hdl.handle.net/21.15107/rcub_ibiss_998 .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana S
AU  - Stojanović, Ivana D.
AU  - Mijatović, Sanja
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Mammana, Santa
AU  - Farina, Claudio
AU  - Ascione, Ester
AU  - Maiello, Valentina
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/965
AB  - Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1 beta, TNF, INF-gamma, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3(+) T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NF kappa B signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis. (C) 2013 Elsevier B.V. All rights reserved.
T2  - Journal of Neuroimmunology
T1  - Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis
IS  - 1-2
VL  - 262
SP  - 63
EP  - 78
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_965
ER  - 

@article{
author = "Saksida, Tamara and Miljković, Đorđe and Timotijević, Gordana S and Stojanović, Ivana D. and Mijatović, Sanja and Fagone, Paolo and Mangano, Katia and Mammana, Santa and Farina, Claudio and Ascione, Ester and Maiello, Valentina and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2013",
abstract = "Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1 beta, TNF, INF-gamma, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3(+) T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NF kappa B signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis. (C) 2013 Elsevier B.V. All rights reserved.",
journal = "Journal of Neuroimmunology",
title = "Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis",
number = "1-2",
volume = "262",
pages = "63-78",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_965"
}

Saksida, T., Miljković, Đ., Timotijević, G. S., Stojanović, I. D., Mijatović, S., Fagone, P., Mangano, K., Mammana, S., Farina, C., Ascione, E., Maiello, V., Nicoletti, F.,& Stošić-Grujičić, S.. (2013). Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology, 262(1-2), 63-78.
https://hdl.handle.net/21.15107/rcub_ibiss_965

Saksida T, Miljković Đ, Timotijević GS, Stojanović ID, Mijatović S, Fagone P, Mangano K, Mammana S, Farina C, Ascione E, Maiello V, Nicoletti F, Stošić-Grujičić S. Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2013;262(1-2):63-78.
https://hdl.handle.net/21.15107/rcub_ibiss_965 .

Saksida, Tamara, Miljković, Đorđe, Timotijević, Gordana S, Stojanović, Ivana D., Mijatović, Sanja, Fagone, Paolo, Mangano, Katia, Mammana, Santa, Farina, Claudio, Ascione, Ester, Maiello, Valentina, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 262, no. 1-2 (2013):63-78,
https://hdl.handle.net/21.15107/rcub_ibiss_965 .

TY  - JOUR
AU  - Mangano, Katia
AU  - Fagone, Paolo
AU  - Di Mauro, M
AU  - Ascione, E
AU  - Maiello, V
AU  - Milicić, Tanja
AU  - Jotić, Aleksandra Z
AU  - Lalić, Nebojsa M
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
AU  - Selmi, C
AU  - Farina, C
AU  - Stošić-Grujičić, Stanislava
AU  - Meroni, P
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1119
AB  - The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology.
T2  - Clinical and Experimental Immunology
T1  - The immunobiology of apotransferrin in type 1 diabetes
IS  - 3
VL  - 169
SP  - 5
EP  - 252
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1119
ER  - 

@article{
author = "Mangano, Katia and Fagone, Paolo and Di Mauro, M and Ascione, E and Maiello, V and Milicić, Tanja and Jotić, Aleksandra Z and Lalić, Nebojsa M and Saksida, Tamara and Stojanović, Ivana D. and Selmi, C and Farina, C and Stošić-Grujičić, Stanislava and Meroni, P and Nicoletti, Ferdinando",
year = "2012",
abstract = "The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology.",
journal = "Clinical and Experimental Immunology",
title = "The immunobiology of apotransferrin in type 1 diabetes",
number = "3",
volume = "169",
pages = "5-252",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1119"
}

Mangano, K., Fagone, P., Di Mauro, M., Ascione, E., Maiello, V., Milicić, T., Jotić, A. Z., Lalić, N. M., Saksida, T., Stojanović, I. D., Selmi, C., Farina, C., Stošić-Grujičić, S., Meroni, P.,& Nicoletti, F.. (2012). The immunobiology of apotransferrin in type 1 diabetes. in Clinical and Experimental Immunology, 169(3), 5-252.
https://hdl.handle.net/21.15107/rcub_ibiss_1119

Mangano K, Fagone P, Di Mauro M, Ascione E, Maiello V, Milicić T, Jotić AZ, Lalić NM, Saksida T, Stojanović ID, Selmi C, Farina C, Stošić-Grujičić S, Meroni P, Nicoletti F. The immunobiology of apotransferrin in type 1 diabetes. in Clinical and Experimental Immunology. 2012;169(3):5-252.
https://hdl.handle.net/21.15107/rcub_ibiss_1119 .

Mangano, Katia, Fagone, Paolo, Di Mauro, M, Ascione, E, Maiello, V, Milicić, Tanja, Jotić, Aleksandra Z, Lalić, Nebojsa M, Saksida, Tamara, Stojanović, Ivana D., Selmi, C, Farina, C, Stošić-Grujičić, Stanislava, Meroni, P, Nicoletti, Ferdinando, "The immunobiology of apotransferrin in type 1 diabetes" in Clinical and Experimental Immunology, 169, no. 3 (2012):5-252,
https://hdl.handle.net/21.15107/rcub_ibiss_1119 .

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  - 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  - 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  - 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  - CONF
AU  - Donia, Marco
AU  - Mijatović, Sanja
AU  - Timotijević, Gordana S
AU  - Miljković, Đorđe
AU  - Stošić-Grujičić, Stanislava
AU  - Caponnetto, Salvatore
AU  - Fagone, Paolo
AU  - Mojić, Marija
AU  - Libra, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Mangano, Katia
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1410
C3  - International Journal of Molecular Medicine
T1  - The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines
IS  - null
VL  - 26
EP  - S69
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1410
ER  - 

@conference{
author = "Donia, Marco and Mijatović, Sanja and Timotijević, Gordana S and Miljković, Đorđe and Stošić-Grujičić, Stanislava and Caponnetto, Salvatore and Fagone, Paolo and Mojić, Marija and Libra, Massimo and Maksimović-Ivanić, Danijela and Mangano, Katia and Nicoletti, Ferdinando",
year = "2010",
journal = "International Journal of Molecular Medicine",
title = "The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines",
number = "null",
volume = "26",
pages = "S69",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1410"
}

Donia, M., Mijatović, S., Timotijević, G. S., Miljković, Đ., Stošić-Grujičić, S., Caponnetto, S., Fagone, P., Mojić, M., Libra, M., Maksimović-Ivanić, D., Mangano, K.,& Nicoletti, F.. (2010). The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines. in International Journal of Molecular Medicine, 26(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1410

Donia M, Mijatović S, Timotijević GS, Miljković Đ, Stošić-Grujičić S, Caponnetto S, Fagone P, Mojić M, Libra M, Maksimović-Ivanić D, Mangano K, Nicoletti F. The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines. in International Journal of Molecular Medicine. 2010;26(null):null-S69.
https://hdl.handle.net/21.15107/rcub_ibiss_1410 .

Donia, Marco, Mijatović, Sanja, Timotijević, Gordana S, Miljković, Đorđe, Stošić-Grujičić, Stanislava, Caponnetto, Salvatore, Fagone, Paolo, Mojić, Marija, Libra, Massimo, Maksimović-Ivanić, Danijela, Mangano, Katia, Nicoletti, Ferdinando, "The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines" in International Journal of Molecular Medicine, 26, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1410 .

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  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Harhaji-Trajković, Ljubica
AU  - Miljković, Đorđe
AU  - Dabideen, Darrin
AU  - Cheng, Kai Fan
AU  - Mangano, Katia
AU  - Malaponte, Graziella
AU  - Ai-Abed, Yousef
AU  - Libra, Massimo
AU  - Garotta, Gianni
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1543
AB  - Preclinical studies have shown that nitric oxide (NO)donating nonsteroidal anti-inflammatory drugs possess anticancer activities. Here, we report in vitro and in vivo studies showing the antitumor effect of the NO-donating isoxazole derivative (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not the NO-deprived parental compound VGX-1027, significantly affected viability of both rodent (L929, B16, and C6) and human (U1251, BT20, HeLa, and LS174) tumor cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the viability of cisplatin-resistant B16 cells. NO scavenger hemoglobin completely prevented GIT-27NO-induced death, indicating that NO release mediated the tumoricidal effect of the compound. Increase in intracellular NO upon on the treatment was associated with intensified production of reactive oxygen species, whereas their neutralization by antioxidant N-acetylcysteine resulted in partial recovery of cell viability. The antitumor activity of the drug was mediated by the selective activation of mitogen-activated protein kinases in a cell-specific manner and was neutralized by their specific inhibitors. In vivo treatment with GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice. The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT-27NO five times higher than that found effective in the melanoma model was well tolerated by the mice when administered for 4 consecutive weeks. These data warrant additional studies to evaluate the possible translation of these findings to the clinical setting.
T2  - Molecular Cancer Therapeutics
T1  - Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo
IS  - 3
VL  - 7
DO  - 10.1158/1535-7163.MCT-07-2037
SP  - 510
EP  - 520
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Harhaji-Trajković, Ljubica and Miljković, Đorđe and Dabideen, Darrin and Cheng, Kai Fan and Mangano, Katia and Malaponte, Graziella and Ai-Abed, Yousef and Libra, Massimo and Garotta, Gianni and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2008",
abstract = "Preclinical studies have shown that nitric oxide (NO)donating nonsteroidal anti-inflammatory drugs possess anticancer activities. Here, we report in vitro and in vivo studies showing the antitumor effect of the NO-donating isoxazole derivative (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not the NO-deprived parental compound VGX-1027, significantly affected viability of both rodent (L929, B16, and C6) and human (U1251, BT20, HeLa, and LS174) tumor cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the viability of cisplatin-resistant B16 cells. NO scavenger hemoglobin completely prevented GIT-27NO-induced death, indicating that NO release mediated the tumoricidal effect of the compound. Increase in intracellular NO upon on the treatment was associated with intensified production of reactive oxygen species, whereas their neutralization by antioxidant N-acetylcysteine resulted in partial recovery of cell viability. The antitumor activity of the drug was mediated by the selective activation of mitogen-activated protein kinases in a cell-specific manner and was neutralized by their specific inhibitors. In vivo treatment with GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice. The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT-27NO five times higher than that found effective in the melanoma model was well tolerated by the mice when administered for 4 consecutive weeks. These data warrant additional studies to evaluate the possible translation of these findings to the clinical setting.",
journal = "Molecular Cancer Therapeutics",
title = "Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo",
number = "3",
volume = "7",
doi = "10.1158/1535-7163.MCT-07-2037",
pages = "510-520"
}

Maksimović-Ivanić, D., Mijatović, S., Harhaji-Trajković, L., Miljković, Đ., Dabideen, D., Cheng, K. F., Mangano, K., Malaponte, G., Ai-Abed, Y., Libra, M., Garotta, G., Nicoletti, F.,& Stošić-Grujičić, S.. (2008). Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo. in Molecular Cancer Therapeutics, 7(3), 510-520.
https://doi.org/10.1158/1535-7163.MCT-07-2037

Maksimović-Ivanić D, Mijatović S, Harhaji-Trajković L, Miljković Đ, Dabideen D, Cheng KF, Mangano K, Malaponte G, Ai-Abed Y, Libra M, Garotta G, Nicoletti F, Stošić-Grujičić S. Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo. in Molecular Cancer Therapeutics. 2008;7(3):510-520.
doi:10.1158/1535-7163.MCT-07-2037 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Harhaji-Trajković, Ljubica, Miljković, Đorđe, Dabideen, Darrin, Cheng, Kai Fan, Mangano, Katia, Malaponte, Graziella, Ai-Abed, Yousef, Libra, Massimo, Garotta, Gianni, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo" in Molecular Cancer Therapeutics, 7, no. 3 (2008):510-520,
https://doi.org/10.1158/1535-7163.MCT-07-2037 . .

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  - 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 .