TY  - JOUR
AU  - Timotijević, Gordana S
AU  - Petković, Filip
AU  - Blaževski, Jana
AU  - Momčilović, Miljana
AU  - Mostarica-Stojković, Marija B
AU  - Miljković, Đorđe
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/996
AB  - CXCL12 plays a protective role in CNS autoimmunity. Expression of CXCL12-gamma, which has distinct structural and functional properties than the other isoforms of CXCL12, was determined in spinal cords of rats immunized to develop experimental autoimmune encephalomyelitis (EAE). CNS expression of CXCL12-gamma was markedly lower in EAE-prone Dark Agouti rats than in EAE-resistant Albino Oxford rats, both in spinal cord homogenates and micro-blood vessels isolated from spinal cords. Inhibition of nitric oxide (NO) synthesis in DA rats upregulated, while donation of NO in AO rats downregulated CNS expression of CXCL12-gamma. NO inhibited CXCL12-gamma expression in astrocytes in vitro. A splice variant of CXCL12-gamma which migrates into nucleolus was not detected in spinal cord or astrocytes. Thus, CXCL12-gamma is expressed in the CNS after EAE induction, but its expression is markedly suppressed in spinal cord affected with full blown inflammation. NO is an important regulator of CXCL12-gamma expression in neuroinflammation. (C) 2013 Elsevier B.V. All rights reserved.
PB  - Amsterdam: Elsevier
T2  - Brain Research
T1  - CXCL12-γ expression is inhibited in neuroinflammation
VL  - 1519
DO  - 10.1016/j.brainres.2013.04.056
SP  - 120
EP  - 126
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_996
ER  - 

@article{
author = "Timotijević, Gordana S and Petković, Filip and Blaževski, Jana and Momčilović, Miljana and Mostarica-Stojković, Marija B and Miljković, Đorđe",
year = "2013",
abstract = "CXCL12 plays a protective role in CNS autoimmunity. Expression of CXCL12-gamma, which has distinct structural and functional properties than the other isoforms of CXCL12, was determined in spinal cords of rats immunized to develop experimental autoimmune encephalomyelitis (EAE). CNS expression of CXCL12-gamma was markedly lower in EAE-prone Dark Agouti rats than in EAE-resistant Albino Oxford rats, both in spinal cord homogenates and micro-blood vessels isolated from spinal cords. Inhibition of nitric oxide (NO) synthesis in DA rats upregulated, while donation of NO in AO rats downregulated CNS expression of CXCL12-gamma. NO inhibited CXCL12-gamma expression in astrocytes in vitro. A splice variant of CXCL12-gamma which migrates into nucleolus was not detected in spinal cord or astrocytes. Thus, CXCL12-gamma is expressed in the CNS after EAE induction, but its expression is markedly suppressed in spinal cord affected with full blown inflammation. NO is an important regulator of CXCL12-gamma expression in neuroinflammation. (C) 2013 Elsevier B.V. All rights reserved.",
publisher = "Amsterdam: Elsevier",
journal = "Brain Research",
title = "CXCL12-γ expression is inhibited in neuroinflammation",
volume = "1519",
doi = "10.1016/j.brainres.2013.04.056",
pages = "120-126",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_996"
}

Timotijević, G. S., Petković, F., Blaževski, J., Momčilović, M., Mostarica-Stojković, M. B.,& Miljković, Đ.. (2013). CXCL12-γ expression is inhibited in neuroinflammation. in Brain Research
Amsterdam: Elsevier., 1519, 120-126.
https://doi.org/10.1016/j.brainres.2013.04.056
https://hdl.handle.net/21.15107/rcub_ibiss_996

Timotijević GS, Petković F, Blaževski J, Momčilović M, Mostarica-Stojković MB, Miljković Đ. CXCL12-γ expression is inhibited in neuroinflammation. in Brain Research. 2013;1519:120-126.
doi:10.1016/j.brainres.2013.04.056
https://hdl.handle.net/21.15107/rcub_ibiss_996 .

Timotijević, Gordana S, Petković, Filip, Blaževski, Jana, Momčilović, Miljana, Mostarica-Stojković, Marija B, Miljković, Đorđe, "CXCL12-γ expression is inhibited in neuroinflammation" in Brain Research, 1519 (2013):120-126,
https://doi.org/10.1016/j.brainres.2013.04.056 .,
https://hdl.handle.net/21.15107/rcub_ibiss_996 .

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  - Belij, Sandra
AU  - Miljković, Đorđe
AU  - Popov Aleksandrov, Aleksandra
AU  - Subota, Vesna S
AU  - Timotijević, Gordana S
AU  - Slavić, Marija
AU  - Mirkov, Ivana
AU  - Kataranovski, Dragan S.
AU  - Kataranovski, Milena
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1185
AB  - Warfarin affects mainly vitamin K dependent (VKD) processes, but the effects on some non-VKD-related activities such as tumor growth inhibition and mononuclear cell-mediated immune reactions were shown as well. In this study, the effect of subchronic (30 days) oral warfarin (0.35 mg/l and 3.5 mg/l) intake on peripheral blood granulocytes in rats was investigated. Increase in prothrombin and partial thromboplastin time at high warfarin dose reflected its basic activity. Priming effect for respiratory burst was noted at both warfarin doses, while only high warfarin dose resulted in priming for adhesion, the rise in intracellular myeloperoxidase content/release and stimulation of nitric oxide production. Differential effects of high warfarin dose were noted on granulocyte cytokines IL-6 (lack of the effect), TNF-alpha (decreased release and mRNA expression) and IL-12 (increase in mRNA for IL-12 subunits p35 and p40). Changes in granulocytes seems not to rely on mitogen activated kinases p38 and ERK. Warfarin intake was associated with an increase in circulating IL-6, fibrinogen and haptoglobin and with changes in the activity of erythrocyte antioxidant enzymes superoxide dismutase and catalase. The effects of oral warfarin intake on peripheral blood granulocytes demonstrated in this study might be relevant for oral anticoagulant therapy strategies in humans. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - Food and Chemical Toxicology
T1  - Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats
IS  - 5
VL  - 50
EP  - 1507
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1185
ER  - 

@article{
author = "Belij, Sandra and Miljković, Đorđe and Popov Aleksandrov, Aleksandra and Subota, Vesna S and Timotijević, Gordana S and Slavić, Marija and Mirkov, Ivana and Kataranovski, Dragan S. and Kataranovski, Milena",
year = "2012",
abstract = "Warfarin affects mainly vitamin K dependent (VKD) processes, but the effects on some non-VKD-related activities such as tumor growth inhibition and mononuclear cell-mediated immune reactions were shown as well. In this study, the effect of subchronic (30 days) oral warfarin (0.35 mg/l and 3.5 mg/l) intake on peripheral blood granulocytes in rats was investigated. Increase in prothrombin and partial thromboplastin time at high warfarin dose reflected its basic activity. Priming effect for respiratory burst was noted at both warfarin doses, while only high warfarin dose resulted in priming for adhesion, the rise in intracellular myeloperoxidase content/release and stimulation of nitric oxide production. Differential effects of high warfarin dose were noted on granulocyte cytokines IL-6 (lack of the effect), TNF-alpha (decreased release and mRNA expression) and IL-12 (increase in mRNA for IL-12 subunits p35 and p40). Changes in granulocytes seems not to rely on mitogen activated kinases p38 and ERK. Warfarin intake was associated with an increase in circulating IL-6, fibrinogen and haptoglobin and with changes in the activity of erythrocyte antioxidant enzymes superoxide dismutase and catalase. The effects of oral warfarin intake on peripheral blood granulocytes demonstrated in this study might be relevant for oral anticoagulant therapy strategies in humans. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "Food and Chemical Toxicology",
title = "Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats",
number = "5",
volume = "50",
pages = "1507",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1185"
}

Belij, S., Miljković, Đ., Popov Aleksandrov, A., Subota, V. S., Timotijević, G. S., Slavić, M., Mirkov, I., Kataranovski, D. S.,& Kataranovski, M.. (2012). Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats. in Food and Chemical Toxicology, 50(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1185

Belij S, Miljković Đ, Popov Aleksandrov A, Subota VS, Timotijević GS, Slavić M, Mirkov I, Kataranovski DS, Kataranovski M. Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats. in Food and Chemical Toxicology. 2012;50(5):null-1507.
https://hdl.handle.net/21.15107/rcub_ibiss_1185 .

Belij, Sandra, Miljković, Đorđe, Popov Aleksandrov, Aleksandra, Subota, Vesna S, Timotijević, Gordana S, Slavić, Marija, Mirkov, Ivana, Kataranovski, Dragan S., Kataranovski, Milena, "Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats" in Food and Chemical Toxicology, 50, no. 5 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1185 .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
AU  - Timotijević, Gordana S
AU  - Sandler, Stellan
AU  - Stošić-Grujičić, Stanislava
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1078
AB  - Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.
T2  - Growth Factors
T1  - Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro
IS  - 6
VL  - 30
SP  - 111
EP  - 393
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1078
ER  - 

@article{
author = "Stojanović, Ivana D. and Saksida, Tamara and Timotijević, Gordana S and Sandler, Stellan and Stošić-Grujičić, Stanislava",
year = "2012",
abstract = "Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.",
journal = "Growth Factors",
title = "Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro",
number = "6",
volume = "30",
pages = "111-393",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1078"
}

Stojanović, I. D., Saksida, T., Timotijević, G. S., Sandler, S.,& Stošić-Grujičić, S.. (2012). Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro. in Growth Factors, 30(6), 111-393.
https://hdl.handle.net/21.15107/rcub_ibiss_1078

Stojanović ID, Saksida T, Timotijević GS, Sandler S, Stošić-Grujičić S. Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro. in Growth Factors. 2012;30(6):111-393.
https://hdl.handle.net/21.15107/rcub_ibiss_1078 .

Stojanović, Ivana D., Saksida, Tamara, Timotijević, Gordana S, Sandler, Stellan, Stošić-Grujičić, Stanislava, "Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro" in Growth Factors, 30, no. 6 (2012):111-393,
https://hdl.handle.net/21.15107/rcub_ibiss_1078 .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Stošić-Grujičić, Stanislava
AU  - Timotijević, Gordana S
AU  - Sandler, Stellan
AU  - Stojanović, Ivana D.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1154
AB  - As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011
T2  - Immunology and Cell Biology
T1  - Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis
IS  - 7
VL  - 90
SP  - 619
EP  - 698
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1154
ER  - 

@article{
author = "Saksida, Tamara and Stošić-Grujičić, Stanislava and Timotijević, Gordana S and Sandler, Stellan and Stojanović, Ivana D.",
year = "2012",
abstract = "As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011",
journal = "Immunology and Cell Biology",
title = "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis",
number = "7",
volume = "90",
pages = "619-698",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1154"
}

Saksida, T., Stošić-Grujičić, S., Timotijević, G. S., Sandler, S.,& Stojanović, I. D.. (2012). Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology, 90(7), 619-698.
https://hdl.handle.net/21.15107/rcub_ibiss_1154

Saksida T, Stošić-Grujičić S, Timotijević GS, Sandler S, Stojanović ID. Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology. 2012;90(7):619-698.
https://hdl.handle.net/21.15107/rcub_ibiss_1154 .

Saksida, Tamara, Stošić-Grujičić, Stanislava, Timotijević, Gordana S, Sandler, Stellan, Stojanović, Ivana D., "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis" in Immunology and Cell Biology, 90, no. 7 (2012):619-698,
https://hdl.handle.net/21.15107/rcub_ibiss_1154 .

TY  - JOUR
AU  - Radović, Julijana M
AU  - Maksimović-Ivanić, Danijela
AU  - Timotijević, Gordana S
AU  - Popadić, S
AU  - Ramić, Zorica D.
AU  - Trajković, Vladimir S
AU  - Miljković, Đorđe
AU  - Stošić-Grujičić, Stanislava
AU  - Mijatović, Sanja
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1135
AB  - Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H2O2 production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - Food and Chemical Toxicology
T1  - Cell-type dependent response of melanoma cells to aloe emodin
IS  - 9
VL  - 50
SP  - 911
EP  - 3189
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1135
ER  - 

@article{
author = "Radović, Julijana M and Maksimović-Ivanić, Danijela and Timotijević, Gordana S and Popadić, S and Ramić, Zorica D. and Trajković, Vladimir S and Miljković, Đorđe and Stošić-Grujičić, Stanislava and Mijatović, Sanja",
year = "2012",
abstract = "Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H2O2 production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "Food and Chemical Toxicology",
title = "Cell-type dependent response of melanoma cells to aloe emodin",
number = "9",
volume = "50",
pages = "911-3189",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1135"
}

Radović, J. M., Maksimović-Ivanić, D., Timotijević, G. S., Popadić, S., Ramić, Z. D., Trajković, V. S., Miljković, Đ., Stošić-Grujičić, S.,& Mijatović, S.. (2012). Cell-type dependent response of melanoma cells to aloe emodin. in Food and Chemical Toxicology, 50(9), 911-3189.
https://hdl.handle.net/21.15107/rcub_ibiss_1135

Radović JM, Maksimović-Ivanić D, Timotijević GS, Popadić S, Ramić ZD, Trajković VS, Miljković Đ, Stošić-Grujičić S, Mijatović S. Cell-type dependent response of melanoma cells to aloe emodin. in Food and Chemical Toxicology. 2012;50(9):911-3189.
https://hdl.handle.net/21.15107/rcub_ibiss_1135 .

Radović, Julijana M, Maksimović-Ivanić, Danijela, Timotijević, Gordana S, Popadić, S, Ramić, Zorica D., Trajković, Vladimir S, Miljković, Đorđe, Stošić-Grujičić, Stanislava, Mijatović, Sanja, "Cell-type dependent response of melanoma cells to aloe emodin" in Food and Chemical Toxicology, 50, no. 9 (2012):911-3189,
https://hdl.handle.net/21.15107/rcub_ibiss_1135 .

TY  - JOUR
AU  - Timotijević, Gordana S
AU  - Mostarica-Stojković, Marija B
AU  - Miljković, Đorđe
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1179
AB  - CxCL12, also known as SDF-1 (stromal cell derived factor-1) is a small protein that belongs to the chemokine family, whose members have a crucial role in directing cell migration. CXCL12 has an essential role in neural and vascular development, hematopoiesis and in immunity. It acts through two receptors. CXCR4 and CXCR7. While the former is a classic G protein-coupled transmembrane chemokine receptor, the latter primarily function as a scavenger of CXCL12. CXCL12 has been considered as a standard proinflammatory molecule for a long time, as it attracts leukocytes to inflammatory sites and contributes to their activation. However, recent findings indicate that this chemokine has the opposite role in neuroinflammation. In this review, basic data about molecular and functional properties of CXCL12 are presented, while its role in CNS autoimmunity is addressed in details. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - International Journal of Biochemistry & Cell Biology
T1  - CXCL12: Role in neuroinflammation
IS  - 6
VL  - 44
EP  - 841
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1179
ER  - 

@article{
author = "Timotijević, Gordana S and Mostarica-Stojković, Marija B and Miljković, Đorđe",
year = "2012",
abstract = "CxCL12, also known as SDF-1 (stromal cell derived factor-1) is a small protein that belongs to the chemokine family, whose members have a crucial role in directing cell migration. CXCL12 has an essential role in neural and vascular development, hematopoiesis and in immunity. It acts through two receptors. CXCR4 and CXCR7. While the former is a classic G protein-coupled transmembrane chemokine receptor, the latter primarily function as a scavenger of CXCL12. CXCL12 has been considered as a standard proinflammatory molecule for a long time, as it attracts leukocytes to inflammatory sites and contributes to their activation. However, recent findings indicate that this chemokine has the opposite role in neuroinflammation. In this review, basic data about molecular and functional properties of CXCL12 are presented, while its role in CNS autoimmunity is addressed in details. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "International Journal of Biochemistry & Cell Biology",
title = "CXCL12: Role in neuroinflammation",
number = "6",
volume = "44",
pages = "841",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1179"
}

Timotijević, G. S., Mostarica-Stojković, M. B.,& Miljković, Đ.. (2012). CXCL12: Role in neuroinflammation. in International Journal of Biochemistry & Cell Biology, 44(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1179

Timotijević GS, Mostarica-Stojković MB, Miljković Đ. CXCL12: Role in neuroinflammation. in International Journal of Biochemistry & Cell Biology. 2012;44(6):null-841.
https://hdl.handle.net/21.15107/rcub_ibiss_1179 .

Timotijević, Gordana S, Mostarica-Stojković, Marija B, Miljković, Đorđe, "CXCL12: Role in neuroinflammation" in International Journal of Biochemistry & Cell Biology, 44, no. 6 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1179 .

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana S
AU  - Mostarica-Stojković, Marija B
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1240
AB  - Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity-related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
T2  - Febs Letters
T1  - Astrocytes in the tempest of multiple sclerosis
IS  - 23
VL  - 585
EP  - 3788
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1240
ER  - 

@article{
author = "Miljković, Đorđe and Timotijević, Gordana S and Mostarica-Stojković, Marija B",
year = "2011",
abstract = "Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity-related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",
journal = "Febs Letters",
title = "Astrocytes in the tempest of multiple sclerosis",
number = "23",
volume = "585",
pages = "3788",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1240"
}

Miljković, Đ., Timotijević, G. S.,& Mostarica-Stojković, M. B.. (2011). Astrocytes in the tempest of multiple sclerosis. in Febs Letters, 585(23).
https://hdl.handle.net/21.15107/rcub_ibiss_1240

Miljković Đ, Timotijević GS, Mostarica-Stojković MB. Astrocytes in the tempest of multiple sclerosis. in Febs Letters. 2011;585(23):null-3788.
https://hdl.handle.net/21.15107/rcub_ibiss_1240 .

Miljković, Đorđe, Timotijević, Gordana S, Mostarica-Stojković, Marija B, "Astrocytes in the tempest of multiple sclerosis" in Febs Letters, 585, no. 23 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1240 .

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Timotijević, Gordana S
AU  - Miljković, Đorđe
AU  - Radović, Julijana M
AU  - Maksimović-Ivanić, Danijela
AU  - Dekanski, Dragana P.
AU  - Stošić-Grujičić, Stanislava
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1297
AB  - Various constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno-and chemoresistant type of skin cancer-melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE-treated B16 cells were blocked in the G(0)/G(1) phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying process started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase-independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic.
T2  - International Journal of Cancer
T1  - Multiple antimelanoma potential of dry olive leaf extract
IS  - 8
VL  - 128
EP  - 1965
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1297
ER  - 

@article{
author = "Mijatović, Sanja and Timotijević, Gordana S and Miljković, Đorđe and Radović, Julijana M and Maksimović-Ivanić, Danijela and Dekanski, Dragana P. and Stošić-Grujičić, Stanislava",
year = "2011",
abstract = "Various constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno-and chemoresistant type of skin cancer-melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE-treated B16 cells were blocked in the G(0)/G(1) phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying process started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase-independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic.",
journal = "International Journal of Cancer",
title = "Multiple antimelanoma potential of dry olive leaf extract",
number = "8",
volume = "128",
pages = "1965",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1297"
}

Mijatović, S., Timotijević, G. S., Miljković, Đ., Radović, J. M., Maksimović-Ivanić, D., Dekanski, D. P.,& Stošić-Grujičić, S.. (2011). Multiple antimelanoma potential of dry olive leaf extract. in International Journal of Cancer, 128(8).
https://hdl.handle.net/21.15107/rcub_ibiss_1297

Mijatović S, Timotijević GS, Miljković Đ, Radović JM, Maksimović-Ivanić D, Dekanski DP, Stošić-Grujičić S. Multiple antimelanoma potential of dry olive leaf extract. in International Journal of Cancer. 2011;128(8):null-1965.
https://hdl.handle.net/21.15107/rcub_ibiss_1297 .

Mijatović, Sanja, Timotijević, Gordana S, Miljković, Đorđe, Radović, Julijana M, Maksimović-Ivanić, Danijela, Dekanski, Dragana P., Stošić-Grujičić, Stanislava, "Multiple antimelanoma potential of dry olive leaf extract" in International Journal of Cancer, 128, no. 8 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1297 .

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  - CONF
AU  - Stošić-Grujičić, Stanislava
AU  - Cvjetičanin, Tamara
AU  - Timotijević, Gordana S
AU  - Zdravković, Nemanja S
AU  - Lukić, M
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1348
C3  - Diabetologia
T1  - Galectin-3 deficiency reduces immune-mediated beta cell destruction in vitro
IS  - null
VL  - 53
EP  - S209
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1348
ER  - 

@conference{
author = "Stošić-Grujičić, Stanislava and Cvjetičanin, Tamara and Timotijević, Gordana S and Zdravković, Nemanja S and Lukić, M",
year = "2010",
journal = "Diabetologia",
title = "Galectin-3 deficiency reduces immune-mediated beta cell destruction in vitro",
number = "null",
volume = "53",
pages = "S209",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1348"
}

Stošić-Grujičić, S., Cvjetičanin, T., Timotijević, G. S., Zdravković, N. S.,& Lukić, M.. (2010). Galectin-3 deficiency reduces immune-mediated beta cell destruction in vitro. in Diabetologia, 53(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1348

Stošić-Grujičić S, Cvjetičanin T, Timotijević GS, Zdravković NS, Lukić M. Galectin-3 deficiency reduces immune-mediated beta cell destruction in vitro. in Diabetologia. 2010;53(null):null-S209.
https://hdl.handle.net/21.15107/rcub_ibiss_1348 .

Stošić-Grujičić, Stanislava, Cvjetičanin, Tamara, Timotijević, Gordana S, Zdravković, Nemanja S, Lukić, M, "Galectin-3 deficiency reduces immune-mediated beta cell destruction in vitro" in Diabetologia, 53, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1348 .

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

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

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

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

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

TY  - 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  - Cvjetičanin, Tamara
AU  - Stojanović, Ivana D.
AU  - Timotijević, Gordana S
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Đorđe
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1450
AB  - Background: Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction. Results: Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3(+) cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1 beta, interleukin-2, interleukin-6, interleukin-17, interferon-gamma and tumor necrosis factor-alpha. Conclusion: These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.
T2  - Bmc Immunology
T1  - T cells cooperate with palmitic acid in induction of beta cell apoptosis
IS  - null
VL  - 10
EP  - na
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1450
ER  - 

@article{
author = "Cvjetičanin, Tamara and Stojanović, Ivana D. and Timotijević, Gordana S and Stošić-Grujičić, Stanislava and Miljković, Đorđe",
year = "2009",
abstract = "Background: Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction. Results: Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3(+) cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1 beta, interleukin-2, interleukin-6, interleukin-17, interferon-gamma and tumor necrosis factor-alpha. Conclusion: These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.",
journal = "Bmc Immunology",
title = "T cells cooperate with palmitic acid in induction of beta cell apoptosis",
number = "null",
volume = "10",
pages = "na",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1450"
}

Cvjetičanin, T., Stojanović, I. D., Timotijević, G. S., Stošić-Grujičić, S.,& Miljković, Đ.. (2009). T cells cooperate with palmitic acid in induction of beta cell apoptosis. in Bmc Immunology, 10(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1450

Cvjetičanin T, Stojanović ID, Timotijević GS, Stošić-Grujičić S, Miljković Đ. T cells cooperate with palmitic acid in induction of beta cell apoptosis. in Bmc Immunology. 2009;10(null):null-na.
https://hdl.handle.net/21.15107/rcub_ibiss_1450 .

Cvjetičanin, Tamara, Stojanović, Ivana D., Timotijević, Gordana S, Stošić-Grujičić, Stanislava, Miljković, Đorđe, "T cells cooperate with palmitic acid in induction of beta cell apoptosis" in Bmc Immunology, 10, no. null (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1450 .

TY  - CONF
AU  - Mijatović, Sanja
AU  - Radović, Julijana M
AU  - Timotijević, Gordana S
AU  - Mojić, Marija
AU  - Miljković, Đorđe
AU  - Dekanski, Dragana P.
AU  - Stošić-Grujičić, Stanislava
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1443
C3  - Planta Medica
T1  - Dry olive leaf extract promotes avant-garde apoptosis in melanoma cells; switch from caspase- dependent to caspase- independent pathway
IS  - 9
VL  - 75
EP  - 903
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1443
ER  - 

@conference{
author = "Mijatović, Sanja and Radović, Julijana M and Timotijević, Gordana S and Mojić, Marija and Miljković, Đorđe and Dekanski, Dragana P. and Stošić-Grujičić, Stanislava",
year = "2009",
journal = "Planta Medica",
title = "Dry olive leaf extract promotes avant-garde apoptosis in melanoma cells; switch from caspase- dependent to caspase- independent pathway",
number = "9",
volume = "75",
pages = "903",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1443"
}

Mijatović, S., Radović, J. M., Timotijević, G. S., Mojić, M., Miljković, Đ., Dekanski, D. P.,& Stošić-Grujičić, S.. (2009). Dry olive leaf extract promotes avant-garde apoptosis in melanoma cells; switch from caspase- dependent to caspase- independent pathway. in Planta Medica, 75(9).
https://hdl.handle.net/21.15107/rcub_ibiss_1443

Mijatović S, Radović JM, Timotijević GS, Mojić M, Miljković Đ, Dekanski DP, Stošić-Grujičić S. Dry olive leaf extract promotes avant-garde apoptosis in melanoma cells; switch from caspase- dependent to caspase- independent pathway. in Planta Medica. 2009;75(9):null-903.
https://hdl.handle.net/21.15107/rcub_ibiss_1443 .

Mijatović, Sanja, Radović, Julijana M, Timotijević, Gordana S, Mojić, Marija, Miljković, Đorđe, Dekanski, Dragana P., Stošić-Grujičić, Stanislava, "Dry olive leaf extract promotes avant-garde apoptosis in melanoma cells; switch from caspase- dependent to caspase- independent pathway" in Planta Medica, 75, no. 9 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1443 .