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

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

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

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

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

TY  - JOUR
AU  - Harhaji-Trajković, Ljubica
AU  - Vilimanovich, Urosh
AU  - Kravić-Stevović, Tamara
AU  - Bumbaširević, Vladimir
AU  - Trajković, Vladimir
PY  - 2009
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6547
AB  - The role of autophagy in cisplatin anticancer action was investigated using human U251 glioma, rat C6 glioma and mouse L929 fibrosarcoma cell lines. A dose- and time-dependent induction of autophagy was observed in tumour cells following cisplatin treatment, as demonstrated by up-regulation of autophagy-inducing protein beclin-1 and subsequent appearance of acridine orange-stained acidic autophagic vesicles. The presence of autophagosomes in cisplatin-treated cells was also confirmed by electron microscopy. Inhibition of autophagy with lysosomal inhibitors bafilomycin A1 and chloroquine, or a PI3 kinase inhibitor wortmannin, markedly augmented cisplatin-triggered oxidative stress and caspase activation, leading to an increase in DNA fragmentation and apoptotic cell death. The mechanisms underlying the protective effect of autophagy apparently involved the interference with cisplatin-induced modulation of Bcl-2 family proteins, as inhibition of autophagy potentiated cisplatin-mediated up-regulation of proapoptotic Bax and down-regulation of anti-apoptotic Bcl-2. Autophagy induction in cisplatin-treated cells was preceded by activation of adenosine monophosphate-activated protein kinase (AMPK) and concomitant down-regulation of mammalian target of rapamycin (mTOR)-mediated phosphorylation of p70S6 kinase. The ability of cisplatin to trigger autophagy was reduced by small interfering RNA (siRNA)-mediated AMPK silencing, while transfection with mTOR siRNA was sufficient to trigger autophagy in tumour cells. Finally, siRNA-mediated AMPK down-regulation and AMPK inhibitor compound C increased cisplatin-induced tumour cell death, while mTOR siRNA and AMPK activator metformin protected tumour cells from cisplatin. Taken together, these data suggest that cisplatin-triggered activation of AMPK and subsequent suppression of mTOR activity can induce an autophagic response that protects tumour cells from cisplatin-mediated apoptotic death.
PB  - Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
T2  - Journal of Cellular and Molecular Medicine
T1  - AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells
IS  - 9B
VL  - 13
DO  - 10.1111/j.1582-4934.2009.00663.x
SP  - 3644
EP  - 3654
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Vilimanovich, Urosh and Kravić-Stevović, Tamara and Bumbaširević, Vladimir and Trajković, Vladimir",
year = "2009",
abstract = "The role of autophagy in cisplatin anticancer action was investigated using human U251 glioma, rat C6 glioma and mouse L929 fibrosarcoma cell lines. A dose- and time-dependent induction of autophagy was observed in tumour cells following cisplatin treatment, as demonstrated by up-regulation of autophagy-inducing protein beclin-1 and subsequent appearance of acridine orange-stained acidic autophagic vesicles. The presence of autophagosomes in cisplatin-treated cells was also confirmed by electron microscopy. Inhibition of autophagy with lysosomal inhibitors bafilomycin A1 and chloroquine, or a PI3 kinase inhibitor wortmannin, markedly augmented cisplatin-triggered oxidative stress and caspase activation, leading to an increase in DNA fragmentation and apoptotic cell death. The mechanisms underlying the protective effect of autophagy apparently involved the interference with cisplatin-induced modulation of Bcl-2 family proteins, as inhibition of autophagy potentiated cisplatin-mediated up-regulation of proapoptotic Bax and down-regulation of anti-apoptotic Bcl-2. Autophagy induction in cisplatin-treated cells was preceded by activation of adenosine monophosphate-activated protein kinase (AMPK) and concomitant down-regulation of mammalian target of rapamycin (mTOR)-mediated phosphorylation of p70S6 kinase. The ability of cisplatin to trigger autophagy was reduced by small interfering RNA (siRNA)-mediated AMPK silencing, while transfection with mTOR siRNA was sufficient to trigger autophagy in tumour cells. Finally, siRNA-mediated AMPK down-regulation and AMPK inhibitor compound C increased cisplatin-induced tumour cell death, while mTOR siRNA and AMPK activator metformin protected tumour cells from cisplatin. Taken together, these data suggest that cisplatin-triggered activation of AMPK and subsequent suppression of mTOR activity can induce an autophagic response that protects tumour cells from cisplatin-mediated apoptotic death.",
publisher = "Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd",
journal = "Journal of Cellular and Molecular Medicine",
title = "AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells",
number = "9B",
volume = "13",
doi = "10.1111/j.1582-4934.2009.00663.x",
pages = "3644-3654"
}

Harhaji-Trajković, L., Vilimanovich, U., Kravić-Stevović, T., Bumbaširević, V.,& Trajković, V.. (2009). AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells. in Journal of Cellular and Molecular Medicine
Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd., 13(9B), 3644-3654.
https://doi.org/10.1111/j.1582-4934.2009.00663.x

Harhaji-Trajković L, Vilimanovich U, Kravić-Stevović T, Bumbaširević V, Trajković V. AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells. in Journal of Cellular and Molecular Medicine. 2009;13(9B):3644-3654.
doi:10.1111/j.1582-4934.2009.00663.x .

Harhaji-Trajković, Ljubica, Vilimanovich, Urosh, Kravić-Stevović, Tamara, Bumbaširević, Vladimir, Trajković, Vladimir, "AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells" in Journal of Cellular and Molecular Medicine, 13, no. 9B (2009):3644-3654,
https://doi.org/10.1111/j.1582-4934.2009.00663.x . .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
AU  - Lazaroski, Sandra
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Đorđe
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1478
AB  - Interleukin (IL)-17 is a pro-inflammatory cytokine produced by recently described T helper type 17 (Th17) cells, which have critical role in immunity to extracellular bacteria and the pathogenesis of several autoimmune disorders. IL-6 and transforming growth factor (TGF)-beta are crucial for the generation of Th17 cells in mice, while the production of IL-17 is supported by various cytokines, including IL-23, IL-1 beta, IL-21, IL-15 and tumour necrosis factor (TNF)-alpha. In this study, the influence of a multifunctional cytokine, macrophage migration inhibitory factor (MIF), on IL-17 production in mice was investigated. Treatment of lymph node cells (LNCs) with recombinant MIF up-regulated mitogen-stimulated IL-17 expression and secretion. Additionally, LNCs from MIF knockout mice (mif(-/-)) had severely impaired production of IL-17, as well as of IL-1 beta, IL-6, IL-23 and TGF-beta. When stimulated with recombinant IL-1 beta, IL-23 or TNF-alpha, mitogen-triggered mif(-/-) LNCs were fully able to achieve the IL-17 production seen in wild-type (WT) LNCs, while the addition of IL-6 and TGF-beta had no effect. Finally, after injection of mice with complete Freund's adjuvant, secretion of IL-17 as well as the number of IL-17-positive cells was significantly lower in the draining lymph nodes of mif(-/-) mice in comparison with WT mice. The effect of MIF on IL-17 production was dependent on p38, extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/STAT3), and not on nuclear factor (NF)-kappa B and nuclear factor of activated T cells (NFAT) signalling. Bearing in mind the contribution of MIF and IL-17 to the pathology of inflammatory and autoimmune disorders, from the results presented here it seems plausible that targeting MIF biological activity could be a valid therapeutic approach for the treatment of such diseases.
PB  - Hoboken: John Wiley and Sons
T2  - Immunology
T1  - Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells
IS  - 1
VL  - 126
DO  - 10.1111/j.1365-2567.2008.02879.x
SP  - 74
EP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1478
ER  - 

@article{
author = "Stojanović, Ivana D. and Saksida, Tamara and Lazaroski, Sandra and Stošić-Grujičić, Stanislava and Miljković, Đorđe",
year = "2009",
abstract = "Interleukin (IL)-17 is a pro-inflammatory cytokine produced by recently described T helper type 17 (Th17) cells, which have critical role in immunity to extracellular bacteria and the pathogenesis of several autoimmune disorders. IL-6 and transforming growth factor (TGF)-beta are crucial for the generation of Th17 cells in mice, while the production of IL-17 is supported by various cytokines, including IL-23, IL-1 beta, IL-21, IL-15 and tumour necrosis factor (TNF)-alpha. In this study, the influence of a multifunctional cytokine, macrophage migration inhibitory factor (MIF), on IL-17 production in mice was investigated. Treatment of lymph node cells (LNCs) with recombinant MIF up-regulated mitogen-stimulated IL-17 expression and secretion. Additionally, LNCs from MIF knockout mice (mif(-/-)) had severely impaired production of IL-17, as well as of IL-1 beta, IL-6, IL-23 and TGF-beta. When stimulated with recombinant IL-1 beta, IL-23 or TNF-alpha, mitogen-triggered mif(-/-) LNCs were fully able to achieve the IL-17 production seen in wild-type (WT) LNCs, while the addition of IL-6 and TGF-beta had no effect. Finally, after injection of mice with complete Freund's adjuvant, secretion of IL-17 as well as the number of IL-17-positive cells was significantly lower in the draining lymph nodes of mif(-/-) mice in comparison with WT mice. The effect of MIF on IL-17 production was dependent on p38, extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/STAT3), and not on nuclear factor (NF)-kappa B and nuclear factor of activated T cells (NFAT) signalling. Bearing in mind the contribution of MIF and IL-17 to the pathology of inflammatory and autoimmune disorders, from the results presented here it seems plausible that targeting MIF biological activity could be a valid therapeutic approach for the treatment of such diseases.",
publisher = "Hoboken: John Wiley and Sons",
journal = "Immunology",
title = "Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells",
number = "1",
volume = "126",
doi = "10.1111/j.1365-2567.2008.02879.x",
pages = "74-83",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1478"
}

Stojanović, I. D., Saksida, T., Lazaroski, S., Stošić-Grujičić, S.,& Miljković, Đ.. (2009). Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells. in Immunology
Hoboken: John Wiley and Sons., 126(1), 74-83.
https://doi.org/10.1111/j.1365-2567.2008.02879.x
https://hdl.handle.net/21.15107/rcub_ibiss_1478

Stojanović ID, Saksida T, Lazaroski S, Stošić-Grujičić S, Miljković Đ. Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells. in Immunology. 2009;126(1):74-83.
doi:10.1111/j.1365-2567.2008.02879.x
https://hdl.handle.net/21.15107/rcub_ibiss_1478 .

Stojanović, Ivana D., Saksida, Tamara, Lazaroski, Sandra, Stošić-Grujičić, Stanislava, Miljković, Đorđe, "Macrophage migration inhibitory factor stimulates interleukin-17 expression and production in lymph node cells" in Immunology, 126, no. 1 (2009):74-83,
https://doi.org/10.1111/j.1365-2567.2008.02879.x .,
https://hdl.handle.net/21.15107/rcub_ibiss_1478 .

TY  - JOUR
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Mostarica-Stojković, Marija B
PY  - 2009
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/216
AB  - Brain endothelial cells (BEC) are the major constituents of the blood-brain barrier (BBB), the structure that controls entrance of immune cells into CNS parenchyma. Our aim was to investigate the influence of BEC on production of IL-17 and IFN-γ-cytokines that are important for CNS inflammation. To that end, co-cultivations of the bEnd.3 brain endothelial cell line and lymph node cells (LNC) were performed, and gene expression and production of IL-17 and IFN-γ were determined. It was found that bEnd.3 cells inhibited expression and production of IFN-γ, but not of IL-17. Additionally, bEnd.3 cells also reduced production of the major IFN-γ-promoting cytokine - IL-12 - in LNC. The observed variation in modulation of pro-inflammatory cytokines by BEC could be of importance for the understanding of CNS inflammation.
AB  - Ćelije moždanog endotela su osnovni elementi građe krvno moždane barijere, strukture koja kontroliše ulazak ćelija imunskog sistema u parenhim CNS. Naš cilj je bio da se ispita uticaj ovih ćelija na produkciju interferona-gama i interleukina 17, kao ključnih proinflamatornih citokina u neuroinflamaciji. Zbog toga smo vršili ko-kultivaciju bEnd.3 linije moždanog endotela i ćelija limfnog čvora, i to u prisustvu ili odsustvu direktnog kontakta među navedenim populacijama, i određivali ekspresiju gena i produkciju navedenih citokina. Pokazalo se da bEnd.3 ćelije potentno inhibiraju produkciju interferona-gama, ali ne i interleukina-17. Takođe, merili smo i produkciju interleukina-12, glavnog stimulatornog citokina za produkciju interferona-gama, i pokazali da je i njegova produkcija smanjena u ko-kultivaciji bEnd.3 ćelija i ćelija limfnog čvora. Zapažena različitost u delovanju ćelija moždanog Endotela na dva osnovna proinflamatorna citokina je od Značaja za razumevanje kompleksnog procesa regulacije inflamacije u CNS.
T2  - Archives of Biological Sciences
T1  - Ćelije mišjeg moždanog endotela ostvaruju različit uticaj na produkciju interferona-γ i interleukina-17 in vitro
T1  - Murine brain endothelial cells differently modulate interferon-γ and interleukin-17 production in vitro
IS  - 1
VL  - 61
DO  - 10.2298/ABS0901029M
SP  - 29
EP  - 36
ER  - 

@article{
author = "Momčilović, Miljana and Miljković, Đorđe and Mostarica-Stojković, Marija B",
year = "2009, 2009",
abstract = "Brain endothelial cells (BEC) are the major constituents of the blood-brain barrier (BBB), the structure that controls entrance of immune cells into CNS parenchyma. Our aim was to investigate the influence of BEC on production of IL-17 and IFN-γ-cytokines that are important for CNS inflammation. To that end, co-cultivations of the bEnd.3 brain endothelial cell line and lymph node cells (LNC) were performed, and gene expression and production of IL-17 and IFN-γ were determined. It was found that bEnd.3 cells inhibited expression and production of IFN-γ, but not of IL-17. Additionally, bEnd.3 cells also reduced production of the major IFN-γ-promoting cytokine - IL-12 - in LNC. The observed variation in modulation of pro-inflammatory cytokines by BEC could be of importance for the understanding of CNS inflammation., Ćelije moždanog endotela su osnovni elementi građe krvno moždane barijere, strukture koja kontroliše ulazak ćelija imunskog sistema u parenhim CNS. Naš cilj je bio da se ispita uticaj ovih ćelija na produkciju interferona-gama i interleukina 17, kao ključnih proinflamatornih citokina u neuroinflamaciji. Zbog toga smo vršili ko-kultivaciju bEnd.3 linije moždanog endotela i ćelija limfnog čvora, i to u prisustvu ili odsustvu direktnog kontakta među navedenim populacijama, i određivali ekspresiju gena i produkciju navedenih citokina. Pokazalo se da bEnd.3 ćelije potentno inhibiraju produkciju interferona-gama, ali ne i interleukina-17. Takođe, merili smo i produkciju interleukina-12, glavnog stimulatornog citokina za produkciju interferona-gama, i pokazali da je i njegova produkcija smanjena u ko-kultivaciji bEnd.3 ćelija i ćelija limfnog čvora. Zapažena različitost u delovanju ćelija moždanog Endotela na dva osnovna proinflamatorna citokina je od Značaja za razumevanje kompleksnog procesa regulacije inflamacije u CNS.",
journal = "Archives of Biological Sciences",
title = "Ćelije mišjeg moždanog endotela ostvaruju različit uticaj na produkciju interferona-γ i interleukina-17 in vitro, Murine brain endothelial cells differently modulate interferon-γ and interleukin-17 production in vitro",
number = "1",
volume = "61",
doi = "10.2298/ABS0901029M",
pages = "29-36"
}

Momčilović, M., Miljković, Đ.,& Mostarica-Stojković, M. B.. (2009). Ćelije mišjeg moždanog endotela ostvaruju različit uticaj na produkciju interferona-γ i interleukina-17 in vitro. in Archives of Biological Sciences, 61(1), 29-36.
https://doi.org/10.2298/ABS0901029M

Momčilović M, Miljković Đ, Mostarica-Stojković MB. Ćelije mišjeg moždanog endotela ostvaruju različit uticaj na produkciju interferona-γ i interleukina-17 in vitro. in Archives of Biological Sciences. 2009;61(1):29-36.
doi:10.2298/ABS0901029M .

Momčilović, Miljana, Miljković, Đorđe, Mostarica-Stojković, Marija B, "Ćelije mišjeg moždanog endotela ostvaruju različit uticaj na produkciju interferona-γ i interleukina-17 in vitro" in Archives of Biological Sciences, 61, no. 1 (2009):29-36,
https://doi.org/10.2298/ABS0901029M . .

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  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Bjelobaba, Ivana
AU  - Peković, Sanja
AU  - Dacić, Sanja
AU  - Nedeljković, Nadežda N.
AU  - Mostarica-Stojković, Marija B.
AU  - Stošić-Grujičić, Stanislava
AU  - Rakić, Ljubisav
AU  - Stojiljković, Mirjana B.
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1141
AB  - To determine the mechanism underlying ribavirin induced amelioration of experimental autoimmune encephalomyelitis (EAE), cytokine profiles were evaluated in draining lymph node (DLN) cell culture supernatants and spinal cord obtained from EAE and/or ribavirin-treated EAE Dark Agouti rats. Administration of ribavirin to EAE rats markedly affected the production of pro-inflammatory cytokines IFN-gamma, IL-1 beta and TNF-alpha in DLN and spinal cord, thus shifting the balance towards the anti-inflammatory cytokines IL-10 and TGF-beta. These findings suggest that ribavirin attenuates EAE by limiting cytokine-mediated immunoinflammatory events leading to CNS destruction. The conducted experiments provide rationale for ribavirin to be considered as a candidate drug in the development of new therapeutic strategies for the treatment of autoimmune diseases in humans, such as multiple sclerosis. (c) 2008 Elsevier B.V. All rights reserved.
PB  - Amsterdam, Netherlands: Elsevier
T2  - International Immunopharmacology
T1  - Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production
IS  - 9
VL  - 8
DO  - 10.1016/j.intimp.2008.05.008
SP  - 1282
EP  - 1290
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1141
ER  - 

@article{
author = "Lavrnja, Irena and Savić, Danijela and Bjelobaba, Ivana and Peković, Sanja and Dacić, Sanja and Nedeljković, Nadežda N. and Mostarica-Stojković, Marija B. and Stošić-Grujičić, Stanislava and Rakić, Ljubisav and Stojiljković, Mirjana B.",
year = "2008",
abstract = "To determine the mechanism underlying ribavirin induced amelioration of experimental autoimmune encephalomyelitis (EAE), cytokine profiles were evaluated in draining lymph node (DLN) cell culture supernatants and spinal cord obtained from EAE and/or ribavirin-treated EAE Dark Agouti rats. Administration of ribavirin to EAE rats markedly affected the production of pro-inflammatory cytokines IFN-gamma, IL-1 beta and TNF-alpha in DLN and spinal cord, thus shifting the balance towards the anti-inflammatory cytokines IL-10 and TGF-beta. These findings suggest that ribavirin attenuates EAE by limiting cytokine-mediated immunoinflammatory events leading to CNS destruction. The conducted experiments provide rationale for ribavirin to be considered as a candidate drug in the development of new therapeutic strategies for the treatment of autoimmune diseases in humans, such as multiple sclerosis. (c) 2008 Elsevier B.V. All rights reserved.",
publisher = "Amsterdam, Netherlands: Elsevier",
journal = "International Immunopharmacology",
title = "Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production",
number = "9",
volume = "8",
doi = "10.1016/j.intimp.2008.05.008",
pages = "1282-1290",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1141"
}

Lavrnja, I., Savić, D., Bjelobaba, I., Peković, S., Dacić, S., Nedeljković, N. N., Mostarica-Stojković, M. B., Stošić-Grujičić, S., Rakić, L.,& Stojiljković, M. B.. (2008). Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production. in International Immunopharmacology
Amsterdam, Netherlands: Elsevier., 8(9), 1282-1290.
https://doi.org/10.1016/j.intimp.2008.05.008
https://hdl.handle.net/21.15107/rcub_ibiss_1141

Lavrnja I, Savić D, Bjelobaba I, Peković S, Dacić S, Nedeljković NN, Mostarica-Stojković MB, Stošić-Grujičić S, Rakić L, Stojiljković MB. Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production. in International Immunopharmacology. 2008;8(9):1282-1290.
doi:10.1016/j.intimp.2008.05.008
https://hdl.handle.net/21.15107/rcub_ibiss_1141 .

Lavrnja, Irena, Savić, Danijela, Bjelobaba, Ivana, Peković, Sanja, Dacić, Sanja, Nedeljković, Nadežda N., Mostarica-Stojković, Marija B., Stošić-Grujičić, Stanislava, Rakić, Ljubisav, Stojiljković, Mirjana B., "Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production" in International Immunopharmacology, 8, no. 9 (2008):1282-1290,
https://doi.org/10.1016/j.intimp.2008.05.008 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1141 .

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  - Harhaji-Trajković, Ljubica
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Popadić, Dusan
AU  - Isaković,  Aleksandra
AU  - Todorović-Marković, Biljana
AU  - Trajković, Vladimir
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3825
AB  - We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.
PB  - Amsterdam: Elsevier
T2  - European Journal of Pharmacology
T1  - Aloe emodin inhibits the cytotoxic action of tumor necrosis factor
IS  - 1-3
VL  - 568
VL  - 568
DO  - 10.1016/j.ejphar.2007.04.029
SP  - 248
EP  - 259
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Popadić, Dusan and Isaković,  Aleksandra and Todorović-Marković, Biljana and Trajković, Vladimir",
year = "2007",
abstract = "We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.",
publisher = "Amsterdam: Elsevier",
journal = "European Journal of Pharmacology",
title = "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor",
number = "1-3",
volume = "568, 568",
doi = "10.1016/j.ejphar.2007.04.029",
pages = "248-259"
}

Harhaji-Trajković, L., Mijatović, S., Maksimović-Ivanić, D., Popadić, D., Isaković,  ., Todorović-Marković, B.,& Trajković, V.. (2007). Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology
Amsterdam: Elsevier., 568(1-3), 248-259.
https://doi.org/10.1016/j.ejphar.2007.04.029

Harhaji-Trajković L, Mijatović S, Maksimović-Ivanić D, Popadić D, Isaković  , Todorović-Marković B, Trajković V. Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology. 2007;568(1-3):248-259.
doi:10.1016/j.ejphar.2007.04.029 .

Harhaji-Trajković, Ljubica, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Popadić, Dusan, Isaković,  Aleksandra, Todorović-Marković, Biljana, Trajković, Vladimir, "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor" in European Journal of Pharmacology, 568, no. 1-3 (2007):248-259,
https://doi.org/10.1016/j.ejphar.2007.04.029 . .

TY  - CONF
AU  - Savić, Danijela
AU  - Lavrnja, Irena
AU  - Peković, Sanja
AU  - Šubašić, Sanja A
AU  - Jovanović, Sasa
AU  - Nikić, Ivana
AU  - Bjelobaba, Ivana
AU  - Mostarica-Stojković, Marija B
AU  - Stošić-Grujičić, Stanislava
AU  - Rakić, Ljubisav
AU  - Stojiljković, Mirjana B
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1636
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model
of human disease multiple sclerosis (MS). Clinical signs of EAE are result of
an autoaggressive T-cell response against myelin. We have previously
shown that combined treatment with nucleoside analogues (ribavirin — R
+tiazofurin — T), inosine monophosphate dehydrogenase inhibitors,
ameliorates clinical signs and histological lesions of EAE in susceptible
rats, when they are given preventatively. The aim of this study was to
investigate the effect of combined treatment with R+T, given with the
appearance of first EAE clinical sign, on microglia and astrocytes response.
These cells of the target tissue also participate in an autoimmune process.
The disease was induced in Dark Agouti rats with rat spinal cord
homogenate and had acute monophasic course. Ribavirin and tiazofurin
were given at a dosage of 30 mg/kg/day and 10 mg/kg every other day, for
15 days, respectively. Control group was immunized and treated with saline.
Amelioration of clinical signs and faster recovery was shown in group
treated with combination of R and T in comparison to control group.
Immunohistochemical analysis of the spinal cord tissue isolated after
15 days of combined therapy revealed decrease in vimentin positive cells
and microglia compared to control group. Additionally, morphology of
GFAP positive (glial fibrillary acid protein) cells and microglia indicated to
reactive type of these cells in control group. Results of this study revealed that R and T modulate glial response and have EAE protective effects when
they are given from the onset of disease.
C3  - 8th ISNI Congress; 2006 Oct 15-19; Nagoya, Japan
T1  - Nucleoside analogues effect on glial response in experimental autoimmune encephalomyelitis
SP  - 167
EP  - 168
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1636
ER  - 

@conference{
author = "Savić, Danijela and Lavrnja, Irena and Peković, Sanja and Šubašić, Sanja A and Jovanović, Sasa and Nikić, Ivana and Bjelobaba, Ivana and Mostarica-Stojković, Marija B and Stošić-Grujičić, Stanislava and Rakić, Ljubisav and Stojiljković, Mirjana B",
year = "2006",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is an animal model
of human disease multiple sclerosis (MS). Clinical signs of EAE are result of
an autoaggressive T-cell response against myelin. We have previously
shown that combined treatment with nucleoside analogues (ribavirin — R
+tiazofurin — T), inosine monophosphate dehydrogenase inhibitors,
ameliorates clinical signs and histological lesions of EAE in susceptible
rats, when they are given preventatively. The aim of this study was to
investigate the effect of combined treatment with R+T, given with the
appearance of first EAE clinical sign, on microglia and astrocytes response.
These cells of the target tissue also participate in an autoimmune process.
The disease was induced in Dark Agouti rats with rat spinal cord
homogenate and had acute monophasic course. Ribavirin and tiazofurin
were given at a dosage of 30 mg/kg/day and 10 mg/kg every other day, for
15 days, respectively. Control group was immunized and treated with saline.
Amelioration of clinical signs and faster recovery was shown in group
treated with combination of R and T in comparison to control group.
Immunohistochemical analysis of the spinal cord tissue isolated after
15 days of combined therapy revealed decrease in vimentin positive cells
and microglia compared to control group. Additionally, morphology of
GFAP positive (glial fibrillary acid protein) cells and microglia indicated to
reactive type of these cells in control group. Results of this study revealed that R and T modulate glial response and have EAE protective effects when
they are given from the onset of disease.",
journal = "8th ISNI Congress; 2006 Oct 15-19; Nagoya, Japan",
title = "Nucleoside analogues effect on glial response in experimental autoimmune encephalomyelitis",
pages = "167-168",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1636"
}

Savić, D., Lavrnja, I., Peković, S., Šubašić, S. A., Jovanović, S., Nikić, I., Bjelobaba, I., Mostarica-Stojković, M. B., Stošić-Grujičić, S., Rakić, L.,& Stojiljković, M. B.. (2006). Nucleoside analogues effect on glial response in experimental autoimmune encephalomyelitis. in 8th ISNI Congress; 2006 Oct 15-19; Nagoya, Japan, 167-168.
https://hdl.handle.net/21.15107/rcub_ibiss_1636

Savić D, Lavrnja I, Peković S, Šubašić SA, Jovanović S, Nikić I, Bjelobaba I, Mostarica-Stojković MB, Stošić-Grujičić S, Rakić L, Stojiljković MB. Nucleoside analogues effect on glial response in experimental autoimmune encephalomyelitis. in 8th ISNI Congress; 2006 Oct 15-19; Nagoya, Japan. 2006;:167-168.
https://hdl.handle.net/21.15107/rcub_ibiss_1636 .

Savić, Danijela, Lavrnja, Irena, Peković, Sanja, Šubašić, Sanja A, Jovanović, Sasa, Nikić, Ivana, Bjelobaba, Ivana, Mostarica-Stojković, Marija B, Stošić-Grujičić, Stanislava, Rakić, Ljubisav, Stojiljković, Mirjana B, "Nucleoside analogues effect on glial response in experimental autoimmune encephalomyelitis" in 8th ISNI Congress; 2006 Oct 15-19; Nagoya, Japan (2006):167-168,
https://hdl.handle.net/21.15107/rcub_ibiss_1636 .