TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5781
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice
SP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5781
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2021",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5781"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2021). ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2021;:100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2021):100,
https://hdl.handle.net/21.15107/rcub_ibiss_5781 .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Battaglia, Giuseppe
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Bruno, Valeria
AU  - Cavalli, Eugenio
AU  - Miljković, Đorđe
AU  - Nicoletti, Ferdinando
AU  - Momčilović, Miljana
AU  - Fagone, Paolo
PY  - 2020
UR  - https://www.mdpi.com/2076-3921/9/7/608
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32664399
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3819
AB  - The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.
PB  - MDPI AG
T2  - Antioxidants (Basel, Switzerland)
T2  - Antioxidants (Basel, Switzerland)
T1  - Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.
IS  - 7
VL  - 9
DO  - 10.3390/antiox9070608
SP  - 608
ER  - 

@article{
author = "Lazarević, Milica and Battaglia, Giuseppe and Jevtić, Bojan and Nikolovski, Neda and Bruno, Valeria and Cavalli, Eugenio and Miljković, Đorđe and Nicoletti, Ferdinando and Momčilović, Miljana and Fagone, Paolo",
year = "2020",
abstract = "The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.",
publisher = "MDPI AG",
journal = "Antioxidants (Basel, Switzerland), Antioxidants (Basel, Switzerland)",
title = "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.",
number = "7",
volume = "9",
doi = "10.3390/antiox9070608",
pages = "608"
}

Lazarević, M., Battaglia, G., Jevtić, B., Nikolovski, N., Bruno, V., Cavalli, E., Miljković, Đ., Nicoletti, F., Momčilović, M.,& Fagone, P.. (2020). Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.. in Antioxidants (Basel, Switzerland)
MDPI AG., 9(7), 608.
https://doi.org/10.3390/antiox9070608

Lazarević M, Battaglia G, Jevtić B, Nikolovski N, Bruno V, Cavalli E, Miljković Đ, Nicoletti F, Momčilović M, Fagone P. Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.. in Antioxidants (Basel, Switzerland). 2020;9(7):608.
doi:10.3390/antiox9070608 .

Lazarević, Milica, Battaglia, Giuseppe, Jevtić, Bojan, Nikolovski, Neda, Bruno, Valeria, Cavalli, Eugenio, Miljković, Đorđe, Nicoletti, Ferdinando, Momčilović, Miljana, Fagone, Paolo, "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis." in Antioxidants (Basel, Switzerland), 9, no. 7 (2020):608,
https://doi.org/10.3390/antiox9070608 . .

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Savić-Radojević, Ana
AU  - Plješa-Ercegovac, Marija
AU  - Simić, Tatjana
AU  - Nicoletti, Ferdinando
AU  - Maksimović-Ivanić, Danijela
PY  - 2020
UR  - https://www.mdpi.com/2076-3921/9/5/374
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32365852
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3673
AB  - Disturbed redox homeostasis represents a hallmark of cancer phenotypes, affecting cellular metabolism and redox signaling. Since reactive oxygen and nitrogen species (ROS/RNS) are involved in regulation of proliferation and apoptosis, they may play a double-faced role in cancer, entailing protumorigenic and tumor-suppressing effects in early and later stages, respectively. In addition, ROS and RNS impact the activity and communication of all tumor constituents, mediating their reprogramming from anti- to protumorigenic phenotypes, and vice versa. An important role in this dichotomic action is played by the variable amounts of O2 in the tumor microenvironment, which dictates the ultimate outcome of the influence of ROS/RNS on carcinogenesis. Moreover, ROS/RNS levels remarkably influence the cancer response to therapy. The relevance of ROS/RNS signaling in solid tumors is witnessed by the emergence of novel targeted treatments of solid tumors with compounds that target ROS/RNS action and production, such as tyrosine kinase inhibitors and monoclonal antibodies, which might contribute to the complexity of redox regulation in cancer. Prospectively, the dual role of ROS/RNS in the different stages of tumorigenesis through different impact on oxidation and nitrosylation may also allow development of tailored diagnostic and therapeutic approaches.
PB  - MDPI AG
T2  - Antioxidants (Basel, Switzerland)
T1  - The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors.
IS  - 5
VL  - 9
DO  - 10.3390/antiox9050374
SP  - 374
ER  - 

@article{
author = "Mijatović, Sanja and Savić-Radojević, Ana and Plješa-Ercegovac, Marija and Simić, Tatjana and Nicoletti, Ferdinando and Maksimović-Ivanić, Danijela",
year = "2020",
abstract = "Disturbed redox homeostasis represents a hallmark of cancer phenotypes, affecting cellular metabolism and redox signaling. Since reactive oxygen and nitrogen species (ROS/RNS) are involved in regulation of proliferation and apoptosis, they may play a double-faced role in cancer, entailing protumorigenic and tumor-suppressing effects in early and later stages, respectively. In addition, ROS and RNS impact the activity and communication of all tumor constituents, mediating their reprogramming from anti- to protumorigenic phenotypes, and vice versa. An important role in this dichotomic action is played by the variable amounts of O2 in the tumor microenvironment, which dictates the ultimate outcome of the influence of ROS/RNS on carcinogenesis. Moreover, ROS/RNS levels remarkably influence the cancer response to therapy. The relevance of ROS/RNS signaling in solid tumors is witnessed by the emergence of novel targeted treatments of solid tumors with compounds that target ROS/RNS action and production, such as tyrosine kinase inhibitors and monoclonal antibodies, which might contribute to the complexity of redox regulation in cancer. Prospectively, the dual role of ROS/RNS in the different stages of tumorigenesis through different impact on oxidation and nitrosylation may also allow development of tailored diagnostic and therapeutic approaches.",
publisher = "MDPI AG",
journal = "Antioxidants (Basel, Switzerland)",
title = "The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors.",
number = "5",
volume = "9",
doi = "10.3390/antiox9050374",
pages = "374"
}

Mijatović, S., Savić-Radojević, A., Plješa-Ercegovac, M., Simić, T., Nicoletti, F.,& Maksimović-Ivanić, D.. (2020). The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors.. in Antioxidants (Basel, Switzerland)
MDPI AG., 9(5), 374.
https://doi.org/10.3390/antiox9050374

Mijatović S, Savić-Radojević A, Plješa-Ercegovac M, Simić T, Nicoletti F, Maksimović-Ivanić D. The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors.. in Antioxidants (Basel, Switzerland). 2020;9(5):374.
doi:10.3390/antiox9050374 .

Mijatović, Sanja, Savić-Radojević, Ana, Plješa-Ercegovac, Marija, Simić, Tatjana, Nicoletti, Ferdinando, Maksimović-Ivanić, Danijela, "The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors." in Antioxidants (Basel, Switzerland), 9, no. 5 (2020):374,
https://doi.org/10.3390/antiox9050374 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5778
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response
causes the death of pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
T1  - Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles
SP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5778
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response
causes the death of pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.",
title = "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles",
pages = "113",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5778"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
Belgrade: Faculty of Chemistry., 113.
https://hdl.handle.net/21.15107/rcub_ibiss_5778

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.. 2019;:113.
https://hdl.handle.net/21.15107/rcub_ibiss_5778 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. (2019):113,
https://hdl.handle.net/21.15107/rcub_ibiss_5778 .

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014299919306739?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3486
AB  - Type 1 diabetes (T1D) is a multifactorial autoimmune disease that develops as a consequence of macrophage- and T cell-dependent pancreatic β-cell death. Multiple approaches for induction of anti-inflammatory/regulatory mechanisms that would attenuate T1D have been utilized, with little or no beneficial effects. To achieve prolonged stimulation of regulatory immune cells, we orally introduced microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and transforming growth factor-β (TGF-β) to C57BL/6 mice treated with multiple low doses of streptozotocin (MLDS) for T1D induction. Disease incidence was significantly lower in ATRA/TGF-β MPs-treated mice, as was the degree of immune cell infiltration into the pancreatic islets. In Peyer's patches (PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDCs) (CD11c+CD11b-CD103+), while the proportion of mature dendritic cells was not altered. This was accompanied by reduced Th1 and Th17 proportions and up-regulation of regulatory T cells (Tregs - CD4+CD25highFoxP3+). The immune cell composition in the pancreatic lymph nodes was similar to PP. Further, the proportion of effector Tbet+CD25med cells was decreased, while the proportion of Tbet+ Treg cells that specifically inhibit Th1 response was increased. Moreover, ATRA/TGF-β MPs treatment resulted in increased Treg proliferation and frequency of CTLA-4+PD1+ and CD39+IL-10+ Tregs, suggestive of their higher suppressive capacity. Reduced pancreatic infiltration may have been a consequence of lower cell capacity for matrix degradation. In conclusion, oral application of ATRA/TGF-β MPs ameliorated T1D through potentiation of tolDCs and Tregs, inhibition of Th1 response and prevention of the immune cell entrance into the islets.
T2  - European Journal of Pharmacology
T1  - Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice
VL  - 864
DO  - 10.1016/j.ejphar.2019.172721
SP  - 172721
ER  - 

@article{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is a multifactorial autoimmune disease that develops as a consequence of macrophage- and T cell-dependent pancreatic β-cell death. Multiple approaches for induction of anti-inflammatory/regulatory mechanisms that would attenuate T1D have been utilized, with little or no beneficial effects. To achieve prolonged stimulation of regulatory immune cells, we orally introduced microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and transforming growth factor-β (TGF-β) to C57BL/6 mice treated with multiple low doses of streptozotocin (MLDS) for T1D induction. Disease incidence was significantly lower in ATRA/TGF-β MPs-treated mice, as was the degree of immune cell infiltration into the pancreatic islets. In Peyer's patches (PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDCs) (CD11c+CD11b-CD103+), while the proportion of mature dendritic cells was not altered. This was accompanied by reduced Th1 and Th17 proportions and up-regulation of regulatory T cells (Tregs - CD4+CD25highFoxP3+). The immune cell composition in the pancreatic lymph nodes was similar to PP. Further, the proportion of effector Tbet+CD25med cells was decreased, while the proportion of Tbet+ Treg cells that specifically inhibit Th1 response was increased. Moreover, ATRA/TGF-β MPs treatment resulted in increased Treg proliferation and frequency of CTLA-4+PD1+ and CD39+IL-10+ Tregs, suggestive of their higher suppressive capacity. Reduced pancreatic infiltration may have been a consequence of lower cell capacity for matrix degradation. In conclusion, oral application of ATRA/TGF-β MPs ameliorated T1D through potentiation of tolDCs and Tregs, inhibition of Th1 response and prevention of the immune cell entrance into the islets.",
journal = "European Journal of Pharmacology",
title = "Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice",
volume = "864",
doi = "10.1016/j.ejphar.2019.172721",
pages = "172721"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice. in European Journal of Pharmacology, 864, 172721.
https://doi.org/10.1016/j.ejphar.2019.172721

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice. in European Journal of Pharmacology. 2019;864:172721.
doi:10.1016/j.ejphar.2019.172721 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice" in European Journal of Pharmacology, 864 (2019):172721,
https://doi.org/10.1016/j.ejphar.2019.172721 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5765
AB  - Background and aims: Type 1 diabetes (T1D) is a multifactorial autoimmune
disease that develops as a consequence of macrophage and T celldependent
pancreatic β cell death. Multiple approaches have been attempted
to induce anti-inflammatory/regulatory immune mechanisms that will attenuate
disease progression, with little or no beneficial effects. To achieve
prolonged stimulation of regulatory immune cells, our aim was to introduce
microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and
transforming growth factor β (TGF-β). Both molecules are well-known synergistic
stimulators of T regulatory cell (Treg) differentiation and stabilization.
Materials and methods: Male C57BL/6 mice were treated with multiple
low doses of streptozotocin (MLDS) for 5 consecutive days to induce
T1D, and with empty MPs or ATRA and TGF-β-loaded MPs (0.1% and
0.03% w/w, respectively) for 10 days (every other day, starting from the
first streptozotocin injection). Blood glucose was monitored on a weekly
basis and ex vivo analyses of immune cells (flow cytometry, qPCR, immunoblot)
were performed and pancreas histology was evaluated 14 days
from the beginning of the T1D induction. ANOVA t test was used for
statistical analysis and significant change was considered at p<0.05.
Results: T1D incidence was significantly lower inATRA/TGF-β MP-treated
mice, as was the degree of immune cell infiltration into the pancreatic islets. In
Peyer’s patches (PP), ATRA/TGF-β MPs up-regulated the tolerogenic population
of dendritic cells (DCs) (CD11c+CD11b-CD103+), while not altering
the proportion of mature DCs (CD11c+CD11b+). Additionally, both IL-1β
expression and production were reduced in PP, as was the ratio of
iNOS/Arginase mRNA expression, reflecting a less inflammatory environment.
This was accompanied by a reduction of the proportion of Th1
(CD4+IFN-γ+) and Th17 (CD4+IL-17+) cells and up-regulation of Treg
(CD4+CD25highFoxP3+). Lower IL-17 expression within CD4+ cells from
PP was in accordance with the observed down-regulation of RORγt
mRNA expression (key transcription factor of IL-17). The situation in the
pancreatic lymph nodes (PLN) was similar to PP regarding the downregulation
of inflammatory Th1 cells. Also, the proportion of
Tbet+CD25med cells (T effector cells) was lower, while the proportion of
Treg expressing T-bet was increased in PLN, suggesting that these cells specifically
mediate the inhibition of Th1 response. Additionally, in response to
ATRA/TGF-β MP treatment, the proliferation (Ki67+) of T effector cells was
reduced in PLN while Treg proliferated more. Furthermore, ATRA/TGF-β
MP treatment favored the presence of CTLA-4+PD1+ and CD39+IL-10+
populations of Treg and thus increased their suppressive activities.
Conclusion: ATRA and TGF-β released from MPs successfully ameliorated
T1D through the potentiation of tolDC and Treg response and inhibition
of Th1 cell differentiation in the draining lymph nodes, thereby
blocking the entrance of immune cells into the pancreatic islets and
protecting β cells from further destruction.
PB  - New York: Springer Nature
C3  - 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain
T1  - Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development
DO  - 10.1007/s00125-019-4946-6
SP  - S202
ER  - 

@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Background and aims: Type 1 diabetes (T1D) is a multifactorial autoimmune
disease that develops as a consequence of macrophage and T celldependent
pancreatic β cell death. Multiple approaches have been attempted
to induce anti-inflammatory/regulatory immune mechanisms that will attenuate
disease progression, with little or no beneficial effects. To achieve
prolonged stimulation of regulatory immune cells, our aim was to introduce
microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and
transforming growth factor β (TGF-β). Both molecules are well-known synergistic
stimulators of T regulatory cell (Treg) differentiation and stabilization.
Materials and methods: Male C57BL/6 mice were treated with multiple
low doses of streptozotocin (MLDS) for 5 consecutive days to induce
T1D, and with empty MPs or ATRA and TGF-β-loaded MPs (0.1% and
0.03% w/w, respectively) for 10 days (every other day, starting from the
first streptozotocin injection). Blood glucose was monitored on a weekly
basis and ex vivo analyses of immune cells (flow cytometry, qPCR, immunoblot)
were performed and pancreas histology was evaluated 14 days
from the beginning of the T1D induction. ANOVA t test was used for
statistical analysis and significant change was considered at p<0.05.
Results: T1D incidence was significantly lower inATRA/TGF-β MP-treated
mice, as was the degree of immune cell infiltration into the pancreatic islets. In
Peyer’s patches (PP), ATRA/TGF-β MPs up-regulated the tolerogenic population
of dendritic cells (DCs) (CD11c+CD11b-CD103+), while not altering
the proportion of mature DCs (CD11c+CD11b+). Additionally, both IL-1β
expression and production were reduced in PP, as was the ratio of
iNOS/Arginase mRNA expression, reflecting a less inflammatory environment.
This was accompanied by a reduction of the proportion of Th1
(CD4+IFN-γ+) and Th17 (CD4+IL-17+) cells and up-regulation of Treg
(CD4+CD25highFoxP3+). Lower IL-17 expression within CD4+ cells from
PP was in accordance with the observed down-regulation of RORγt
mRNA expression (key transcription factor of IL-17). The situation in the
pancreatic lymph nodes (PLN) was similar to PP regarding the downregulation
of inflammatory Th1 cells. Also, the proportion of
Tbet+CD25med cells (T effector cells) was lower, while the proportion of
Treg expressing T-bet was increased in PLN, suggesting that these cells specifically
mediate the inhibition of Th1 response. Additionally, in response to
ATRA/TGF-β MP treatment, the proliferation (Ki67+) of T effector cells was
reduced in PLN while Treg proliferated more. Furthermore, ATRA/TGF-β
MP treatment favored the presence of CTLA-4+PD1+ and CD39+IL-10+
populations of Treg and thus increased their suppressive activities.
Conclusion: ATRA and TGF-β released from MPs successfully ameliorated
T1D through the potentiation of tolDC and Treg response and inhibition
of Th1 cell differentiation in the draining lymph nodes, thereby
blocking the entrance of immune cells into the pancreatic islets and
protecting β cells from further destruction.",
publisher = "New York: Springer Nature",
journal = "55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain",
title = "Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development",
doi = "10.1007/s00125-019-4946-6",
pages = "S202"
}

Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development. in 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain
New York: Springer Nature., S202.
https://doi.org/10.1007/s00125-019-4946-6

Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development. in 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain. 2019;:S202.
doi:10.1007/s00125-019-4946-6 .

Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development" in 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain (2019):S202,
https://doi.org/10.1007/s00125-019-4946-6 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Bramanti, Alessia
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Kaluđerović, Goran N.
AU  - Maksimović-Ivanić, Danijela
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0734975018300739
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29656090
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3045
AB  - Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.
T2  - Biotechnology Advances
T1  - Naturally occurring compounds in differentiation based therapy of cancer.
DO  - 10.1016/j.biotechadv.2018.04.001
ER  - 

@article{
author = "Mijatović, Sanja and Bramanti, Alessia and Nicoletti, Ferdinando and Fagone, Paolo and Kaluđerović, Goran N. and Maksimović-Ivanić, Danijela",
year = "2018",
abstract = "Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.",
journal = "Biotechnology Advances",
title = "Naturally occurring compounds in differentiation based therapy of cancer.",
doi = "10.1016/j.biotechadv.2018.04.001"
}

Mijatović, S., Bramanti, A., Nicoletti, F., Fagone, P., Kaluđerović, G. N.,& Maksimović-Ivanić, D.. (2018). Naturally occurring compounds in differentiation based therapy of cancer.. in Biotechnology Advances.
https://doi.org/10.1016/j.biotechadv.2018.04.001

Mijatović S, Bramanti A, Nicoletti F, Fagone P, Kaluđerović GN, Maksimović-Ivanić D. Naturally occurring compounds in differentiation based therapy of cancer.. in Biotechnology Advances. 2018;.
doi:10.1016/j.biotechadv.2018.04.001 .

Mijatović, Sanja, Bramanti, Alessia, Nicoletti, Ferdinando, Fagone, Paolo, Kaluđerović, Goran N., Maksimović-Ivanić, Danijela, "Naturally occurring compounds in differentiation based therapy of cancer." in Biotechnology Advances (2018),
https://doi.org/10.1016/j.biotechadv.2018.04.001 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Mazzon, Emanuela
AU  - Momčilović, Miljana
AU  - Basile, Maria Sofia
AU  - Colletti, Giuseppe
AU  - Petralia, Maria Cristina
AU  - Bramanti, Placido
AU  - Nicoletti, Ferdinando
AU  - Miljković, Đorđe
PY  - 2018
UR  - http://www.mdpi.com/1420-3049/23/11/2966
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3191
AB  - GYY4137 is a hydrogen sulfide (H₂S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H₂S donor, Na₂S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.
T2  - Molecules (Basel, Switzerland)
T1  - The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.
IS  - 11
VL  - 23
DO  - 10.3390/molecules23112966
SP  - 2966
ER  - 

@article{
author = "Lazarević, Milica and Mazzon, Emanuela and Momčilović, Miljana and Basile, Maria Sofia and Colletti, Giuseppe and Petralia, Maria Cristina and Bramanti, Placido and Nicoletti, Ferdinando and Miljković, Đorđe",
year = "2018",
abstract = "GYY4137 is a hydrogen sulfide (H₂S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H₂S donor, Na₂S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.",
journal = "Molecules (Basel, Switzerland)",
title = "The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.",
number = "11",
volume = "23",
doi = "10.3390/molecules23112966",
pages = "2966"
}

Lazarević, M., Mazzon, E., Momčilović, M., Basile, M. S., Colletti, G., Petralia, M. C., Bramanti, P., Nicoletti, F.,& Miljković, Đ.. (2018). The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.. in Molecules (Basel, Switzerland), 23(11), 2966.
https://doi.org/10.3390/molecules23112966

Lazarević M, Mazzon E, Momčilović M, Basile MS, Colletti G, Petralia MC, Bramanti P, Nicoletti F, Miljković Đ. The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.. in Molecules (Basel, Switzerland). 2018;23(11):2966.
doi:10.3390/molecules23112966 .

Lazarević, Milica, Mazzon, Emanuela, Momčilović, Miljana, Basile, Maria Sofia, Colletti, Giuseppe, Petralia, Maria Cristina, Bramanti, Placido, Nicoletti, Ferdinando, Miljković, Đorđe, "The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide." in Molecules (Basel, Switzerland), 23, no. 11 (2018):2966,
https://doi.org/10.3390/molecules23112966 . .

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Fagone, Paolo
AU  - McCubrey, James
AU  - Bendtzen, Klaus
AU  - Mijatović, Sanja
AU  - Nicoletti, Ferdinando
PY  - 2017
UR  - http://doi.wiley.com/10.1002/ijc.30529
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2553
AB  - The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this article, we discuss the current preclinical and clinical evidences for the potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the treatment of cancer.
T2  - International Journal of Cancer
T1  - HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?
DO  - 10.1002/ijc.30529
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Fagone, Paolo and McCubrey, James and Bendtzen, Klaus and Mijatović, Sanja and Nicoletti, Ferdinando",
year = "2017",
abstract = "The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this article, we discuss the current preclinical and clinical evidences for the potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the treatment of cancer.",
journal = "International Journal of Cancer",
title = "HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?",
doi = "10.1002/ijc.30529"
}

Maksimović-Ivanić, D., Fagone, P., McCubrey, J., Bendtzen, K., Mijatović, S.,& Nicoletti, F.. (2017). HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?. in International Journal of Cancer.
https://doi.org/10.1002/ijc.30529

Maksimović-Ivanić D, Fagone P, McCubrey J, Bendtzen K, Mijatović S, Nicoletti F. HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?. in International Journal of Cancer. 2017;.
doi:10.1002/ijc.30529 .

Maksimović-Ivanić, Danijela, Fagone, Paolo, McCubrey, James, Bendtzen, Klaus, Mijatović, Sanja, Nicoletti, Ferdinando, "HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?" in International Journal of Cancer (2017),
https://doi.org/10.1002/ijc.30529 . .

TY  - JOUR
AU  - Steelman, Linda S
AU  - Fitzgerald, Timothy
AU  - Lertpiriyapong, Kvin
AU  - Cocco, Lucio
AU  - Follo, Matilde Y
AU  - Martelli, Alberto M
AU  - Neri, Luca M
AU  - Marmiroli, Sandra
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Nicoletti, Ferdinando
AU  - Scalisi, Aurora
AU  - Fenga, Concettina
AU  - Drobot, Lyudmyla
AU  - Rakus, Dariusz
AU  - Gizak,  Agnieszka
AU  - Laidler, Piotr
AU  - Dulinska-Litewka, Joanna
AU  - Basecke,  Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Milella, Michelle
AU  - Tafuri, Agustino
AU  - Demidenko, Zoya
AU  - Abrams,  Stephen L
AU  - McCubrey, James A
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3822
AB  - The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses on their roles and other associated pathways in cancer stem cells (CSCs), identifying sites where therapeutic resistance may develop and the mechanisms by which microRNAs (miRs) and other RNAs regulate this pathway. This review will focus on recent advances in these fields with a specific focus on breast cancer and breast CSCs. Relatively novel areas of investigation, such as treatments for other diseases (e.g., diabetes, metabolism, and intestinal parasites), have provided new information about therapeutic resistance and CSCs.
PB  - Sharjah: Bentham Science Publishers
T2  - Current Pharmaceutical Design
T1  - Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy
IS  - 16
VL  - 22
DO  - 10.2174/1381612822666160304151011
SP  - 2358
EP  - 2388
ER  - 

@article{
author = "Steelman, Linda S and Fitzgerald, Timothy and Lertpiriyapong, Kvin and Cocco, Lucio and Follo, Matilde Y and Martelli, Alberto M and Neri, Luca M and Marmiroli, Sandra and Libra, Massimo and Candido, Saverio and Nicoletti, Ferdinando and Scalisi, Aurora and Fenga, Concettina and Drobot, Lyudmyla and Rakus, Dariusz and Gizak,  Agnieszka and Laidler, Piotr and Dulinska-Litewka, Joanna and Basecke,  Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Montalto, Giuseppe and Cervello, Melchiorre and Milella, Michelle and Tafuri, Agustino and Demidenko, Zoya and Abrams,  Stephen L and McCubrey, James A",
year = "2016",
abstract = "The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses on their roles and other associated pathways in cancer stem cells (CSCs), identifying sites where therapeutic resistance may develop and the mechanisms by which microRNAs (miRs) and other RNAs regulate this pathway. This review will focus on recent advances in these fields with a specific focus on breast cancer and breast CSCs. Relatively novel areas of investigation, such as treatments for other diseases (e.g., diabetes, metabolism, and intestinal parasites), have provided new information about therapeutic resistance and CSCs.",
publisher = "Sharjah: Bentham Science Publishers",
journal = "Current Pharmaceutical Design",
title = "Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy",
number = "16",
volume = "22",
doi = "10.2174/1381612822666160304151011",
pages = "2358-2388"
}

Steelman, L. S., Fitzgerald, T., Lertpiriyapong, K., Cocco, L., Follo, M. Y., Martelli, A. M., Neri, L. M., Marmiroli, S., Libra, M., Candido, S., Nicoletti, F., Scalisi, A., Fenga, C., Drobot, L., Rakus, D., Gizak,  ., Laidler, P., Dulinska-Litewka, J., Basecke,  ., Mijatović, S., Maksimović-Ivanić, D., Montalto, G., Cervello, M., Milella, M., Tafuri, A., Demidenko, Z., Abrams,  . L.,& McCubrey, J. A.. (2016). Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy. in Current Pharmaceutical Design
Sharjah: Bentham Science Publishers., 22(16), 2358-2388.
https://doi.org/10.2174/1381612822666160304151011

Steelman LS, Fitzgerald T, Lertpiriyapong K, Cocco L, Follo MY, Martelli AM, Neri LM, Marmiroli S, Libra M, Candido S, Nicoletti F, Scalisi A, Fenga C, Drobot L, Rakus D, Gizak  , Laidler P, Dulinska-Litewka J, Basecke  , Mijatović S, Maksimović-Ivanić D, Montalto G, Cervello M, Milella M, Tafuri A, Demidenko Z, Abrams  L, McCubrey JA. Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy. in Current Pharmaceutical Design. 2016;22(16):2358-2388.
doi:10.2174/1381612822666160304151011 .

Steelman, Linda S, Fitzgerald, Timothy, Lertpiriyapong, Kvin, Cocco, Lucio, Follo, Matilde Y, Martelli, Alberto M, Neri, Luca M, Marmiroli, Sandra, Libra, Massimo, Candido, Saverio, Nicoletti, Ferdinando, Scalisi, Aurora, Fenga, Concettina, Drobot, Lyudmyla, Rakus, Dariusz, Gizak,  Agnieszka, Laidler, Piotr, Dulinska-Litewka, Joanna, Basecke,  Joerg, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Montalto, Giuseppe, Cervello, Melchiorre, Milella, Michelle, Tafuri, Agustino, Demidenko, Zoya, Abrams,  Stephen L, McCubrey, James A, "Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy" in Current Pharmaceutical Design, 22, no. 16 (2016):2358-2388,
https://doi.org/10.2174/1381612822666160304151011 . .

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Mojić, Marija
AU  - Bulatović, Mirna Z.
AU  - Radojkovic, Milica
AU  - Kuzmanovic, Milos
AU  - Ristic, Slobodan
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Đorđe
AU  - Cavalli, Eugenio
AU  - Libra, Massimo
AU  - Fagone, Paolo
AU  - McCubrey, James
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2353
AB  - Covalent attachment of NO to the first approved HIV protease inhibitor
   Saquinavir (Saq-NO) expands the therapeutic potential of the original
   drug. Apart from retained antiviral activity, the modified drug exerts
   strong antitumor effects and lower toxicity. In the present study, we
   have evaluated the sensitivity of different hematological malignancies
   to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji,
   HL-60 and K562 cells. While Jurkat and Raji cells (established from
   pediatric patients) displayed abrogated proliferative potential, HL-60
   and K652 cells (originated from adults) exposed to Saq-NO treatment
   underwent caspase dependent apoptosis. In addition, similar sensitivity
   to Saq-NO was observed in mononuclear blood cells obtained from
   pediatric patients with acute lymphoblastic leukemia (ALL) and adult
   patients with acute myeloid leukemia (AML). Western blot analysis
   indicated p70S6 kinase as a possible intracellular target of Saq-NO
   action. Moreover, the addition of a NO moiety to Lopinavir resulted in
   improved antitumor potential as compared to the parental compound,
   suggesting that NO-derived HIV protease inhibitors are a potential new
   source of anticancer drugs with unique mode of action. (C) 2015 Elsevier
   Ltd. All rights reserved.
T2  - Leukemia Research
T1  - The NO-modified HIV protease inhibitor as a valuable drug for
 hematological malignancies: Role of p70S6K
IS  - 10
VL  - 39
DO  - 10.1016/j.leukres.2015.06.013
SP  - 1088
EP  - 1095
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mojić, Marija and Bulatović, Mirna Z. and Radojkovic, Milica and Kuzmanovic, Milos and Ristic, Slobodan and Stošić-Grujičić, Stanislava and Miljković, Đorđe and Cavalli, Eugenio and Libra, Massimo and Fagone, Paolo and McCubrey, James and Nicoletti, Ferdinando and Mijatović, Sanja",
year = "2015",
abstract = "Covalent attachment of NO to the first approved HIV protease inhibitor
   Saquinavir (Saq-NO) expands the therapeutic potential of the original
   drug. Apart from retained antiviral activity, the modified drug exerts
   strong antitumor effects and lower toxicity. In the present study, we
   have evaluated the sensitivity of different hematological malignancies
   to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji,
   HL-60 and K562 cells. While Jurkat and Raji cells (established from
   pediatric patients) displayed abrogated proliferative potential, HL-60
   and K652 cells (originated from adults) exposed to Saq-NO treatment
   underwent caspase dependent apoptosis. In addition, similar sensitivity
   to Saq-NO was observed in mononuclear blood cells obtained from
   pediatric patients with acute lymphoblastic leukemia (ALL) and adult
   patients with acute myeloid leukemia (AML). Western blot analysis
   indicated p70S6 kinase as a possible intracellular target of Saq-NO
   action. Moreover, the addition of a NO moiety to Lopinavir resulted in
   improved antitumor potential as compared to the parental compound,
   suggesting that NO-derived HIV protease inhibitors are a potential new
   source of anticancer drugs with unique mode of action. (C) 2015 Elsevier
   Ltd. All rights reserved.",
journal = "Leukemia Research",
title = "The NO-modified HIV protease inhibitor as a valuable drug for
 hematological malignancies: Role of p70S6K",
number = "10",
volume = "39",
doi = "10.1016/j.leukres.2015.06.013",
pages = "1088-1095"
}

Maksimović-Ivanić, D., Mojić, M., Bulatović, M. Z., Radojkovic, M., Kuzmanovic, M., Ristic, S., Stošić-Grujičić, S., Miljković, Đ., Cavalli, E., Libra, M., Fagone, P., McCubrey, J., Nicoletti, F.,& Mijatović, S.. (2015). The NO-modified HIV protease inhibitor as a valuable drug for
 hematological malignancies: Role of p70S6K. in Leukemia Research, 39(10), 1088-1095.
https://doi.org/10.1016/j.leukres.2015.06.013

Maksimović-Ivanić D, Mojić M, Bulatović MZ, Radojkovic M, Kuzmanovic M, Ristic S, Stošić-Grujičić S, Miljković Đ, Cavalli E, Libra M, Fagone P, McCubrey J, Nicoletti F, Mijatović S. The NO-modified HIV protease inhibitor as a valuable drug for
 hematological malignancies: Role of p70S6K. in Leukemia Research. 2015;39(10):1088-1095.
doi:10.1016/j.leukres.2015.06.013 .

Maksimović-Ivanić, Danijela, Mojić, Marija, Bulatović, Mirna Z., Radojkovic, Milica, Kuzmanovic, Milos, Ristic, Slobodan, Stošić-Grujičić, Stanislava, Miljković, Đorđe, Cavalli, Eugenio, Libra, Massimo, Fagone, Paolo, McCubrey, James, Nicoletti, Ferdinando, Mijatović, Sanja, "The NO-modified HIV protease inhibitor as a valuable drug for
 hematological malignancies: Role of p70S6K" in Leukemia Research, 39, no. 10 (2015):1088-1095,
https://doi.org/10.1016/j.leukres.2015.06.013 . .

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Davis, Nicole M.
AU  - Sokolosky, Melissa
AU  - Stadelman, Kristin
AU  - Abrams, Stephen L.
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Nicoletti, Ferdinando
AU  - Polesel, Jerry
AU  - Maestro, Roberta
AU  - D'Assoro, Antonino
AU  - Drobot, Lyudmyla
AU  - Rakus, Dariusz
AU  - Gizak, Agnieszka
AU  - Laidler, Piotr
AU  - Dulinska-Litewka, Joanna
AU  - Basecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Fitzgerald, Timothy L.
AU  - Demidenko, Zoya N.
AU  - Martelli, Alberto M.
AU  - Cocco, Lucio
AU  - Steelman, Linda S.
AU  - McCubrey, James A.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2188
AB  - The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in
   malignant transformation, prevention of apoptosis, drug resistance and
   metastasis. The expression of this pathway is frequently altered in
   breast cancer due to mutations at or aberrant expression of: HER2,
   ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other
   oncogenes and tumor suppressor genes. In some breast cancer cases,
   mutations at certain components of this pathway (e.g., PIK3CA) are
   associated with a better prognosis than breast cancers lacking these
   mutations. The expression of this pathway and upstream HER2 has been
   associated with breast cancer initiating cells (CICs) and in some cases
   resistance to treatment. The anti-diabetes drug metformin can suppress
   the growth of breast CICs and herceptin-resistant HER2+ cells. This
   review will discuss the importance of the
   EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but
   will also include relevant examples from other cancer types. The
   targeting of this pathway will be discussed as well as clinical trials
   with novel small molecule inhibitors. The targeting of the hormone
   receptor, HER2 and EGFR1 in breast cancer will be reviewed in
   association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3
   pathway.
T2  - Oncotarget
T1  - Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer:
 possibilities for therapeutic intervention
IS  - 13
VL  - 5
DO  - 10.18632/oncotarget.2209
SP  - 4603
EP  - 4650
ER  - 

@article{
author = "Davis, Nicole M. and Sokolosky, Melissa and Stadelman, Kristin and Abrams, Stephen L. and Libra, Massimo and Candido, Saverio and Nicoletti, Ferdinando and Polesel, Jerry and Maestro, Roberta and D'Assoro, Antonino and Drobot, Lyudmyla and Rakus, Dariusz and Gizak, Agnieszka and Laidler, Piotr and Dulinska-Litewka, Joanna and Basecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Montalto, Giuseppe and Cervello, Melchiorre and Fitzgerald, Timothy L. and Demidenko, Zoya N. and Martelli, Alberto M. and Cocco, Lucio and Steelman, Linda S. and McCubrey, James A.",
year = "2014",
abstract = "The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in
   malignant transformation, prevention of apoptosis, drug resistance and
   metastasis. The expression of this pathway is frequently altered in
   breast cancer due to mutations at or aberrant expression of: HER2,
   ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other
   oncogenes and tumor suppressor genes. In some breast cancer cases,
   mutations at certain components of this pathway (e.g., PIK3CA) are
   associated with a better prognosis than breast cancers lacking these
   mutations. The expression of this pathway and upstream HER2 has been
   associated with breast cancer initiating cells (CICs) and in some cases
   resistance to treatment. The anti-diabetes drug metformin can suppress
   the growth of breast CICs and herceptin-resistant HER2+ cells. This
   review will discuss the importance of the
   EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but
   will also include relevant examples from other cancer types. The
   targeting of this pathway will be discussed as well as clinical trials
   with novel small molecule inhibitors. The targeting of the hormone
   receptor, HER2 and EGFR1 in breast cancer will be reviewed in
   association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3
   pathway.",
journal = "Oncotarget",
title = "Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer:
 possibilities for therapeutic intervention",
number = "13",
volume = "5",
doi = "10.18632/oncotarget.2209",
pages = "4603-4650"
}

Davis, N. M., Sokolosky, M., Stadelman, K., Abrams, S. L., Libra, M., Candido, S., Nicoletti, F., Polesel, J., Maestro, R., D'Assoro, A., Drobot, L., Rakus, D., Gizak, A., Laidler, P., Dulinska-Litewka, J., Basecke, J., Mijatović, S., Maksimović-Ivanić, D., Montalto, G., Cervello, M., Fitzgerald, T. L., Demidenko, Z. N., Martelli, A. M., Cocco, L., Steelman, L. S.,& McCubrey, J. A.. (2014). Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer:
 possibilities for therapeutic intervention. in Oncotarget, 5(13), 4603-4650.
https://doi.org/10.18632/oncotarget.2209

Davis NM, Sokolosky M, Stadelman K, Abrams SL, Libra M, Candido S, Nicoletti F, Polesel J, Maestro R, D'Assoro A, Drobot L, Rakus D, Gizak A, Laidler P, Dulinska-Litewka J, Basecke J, Mijatović S, Maksimović-Ivanić D, Montalto G, Cervello M, Fitzgerald TL, Demidenko ZN, Martelli AM, Cocco L, Steelman LS, McCubrey JA. Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer:
 possibilities for therapeutic intervention. in Oncotarget. 2014;5(13):4603-4650.
doi:10.18632/oncotarget.2209 .

Davis, Nicole M., Sokolosky, Melissa, Stadelman, Kristin, Abrams, Stephen L., Libra, Massimo, Candido, Saverio, Nicoletti, Ferdinando, Polesel, Jerry, Maestro, Roberta, D'Assoro, Antonino, Drobot, Lyudmyla, Rakus, Dariusz, Gizak, Agnieszka, Laidler, Piotr, Dulinska-Litewka, Joanna, Basecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Montalto, Giuseppe, Cervello, Melchiorre, Fitzgerald, Timothy L., Demidenko, Zoya N., Martelli, Alberto M., Cocco, Lucio, Steelman, Linda S., McCubrey, James A., "Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer:
 possibilities for therapeutic intervention" in Oncotarget, 5, no. 13 (2014):4603-4650,
https://doi.org/10.18632/oncotarget.2209 . .

TY  - CONF
AU  - McCubrey, James A.
AU  - Chappell, William H.
AU  - Abrams, Stephen L.
AU  - Davis, Nicole
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Nicoletti, Ferdinando
AU  - Polesel, Jerry
AU  - Talamini, Renato
AU  - Maestro, Roberta
AU  - Martelli, Alberto M.
AU  - Cervello, Melchiorre
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Steelman, Linda S.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2277
C3  - International Journal of Molecular Medicine
T1  - Suppressing prostate cancer by targeting NGAL
IS  - 1
VL  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2277
ER  - 

@conference{
author = "McCubrey, James A. and Chappell, William H. and Abrams, Stephen L. and Davis, Nicole and Libra, Massimo and Candido, Saverio and Nicoletti, Ferdinando and Polesel, Jerry and Talamini, Renato and Maestro, Roberta and Martelli, Alberto M. and Cervello, Melchiorre and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Steelman, Linda S.",
year = "2014",
journal = "International Journal of Molecular Medicine",
title = "Suppressing prostate cancer by targeting NGAL",
number = "1",
volume = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2277"
}

McCubrey, J. A., Chappell, W. H., Abrams, S. L., Davis, N., Libra, M., Candido, S., Nicoletti, F., Polesel, J., Talamini, R., Maestro, R., Martelli, A. M., Cervello, M., Maksimović-Ivanić, D., Mijatović, S.,& Steelman, L. S.. (2014). Suppressing prostate cancer by targeting NGAL. in International Journal of Molecular Medicine, 34(1).
https://hdl.handle.net/21.15107/rcub_ibiss_2277

McCubrey JA, Chappell WH, Abrams SL, Davis N, Libra M, Candido S, Nicoletti F, Polesel J, Talamini R, Maestro R, Martelli AM, Cervello M, Maksimović-Ivanić D, Mijatović S, Steelman LS. Suppressing prostate cancer by targeting NGAL. in International Journal of Molecular Medicine. 2014;34(1).
https://hdl.handle.net/21.15107/rcub_ibiss_2277 .

McCubrey, James A., Chappell, William H., Abrams, Stephen L., Davis, Nicole, Libra, Massimo, Candido, Saverio, Nicoletti, Ferdinando, Polesel, Jerry, Talamini, Renato, Maestro, Roberta, Martelli, Alberto M., Cervello, Melchiorre, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Steelman, Linda S., "Suppressing prostate cancer by targeting NGAL" in International Journal of Molecular Medicine, 34, no. 1 (2014),
https://hdl.handle.net/21.15107/rcub_ibiss_2277 .

TY  - CONF
AU  - Steelman, Linda S.
AU  - Davis, Nicole M.
AU  - Sokolosky, Melissa
AU  - Abrams, Stephen L.
AU  - Martelli, Alberto M.
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Mazzarino, Clorinda
AU  - Malponte, Graziella
AU  - Libra, Massimo
AU  - Cervello, Melchiorre
AU  - Montalto, Giuseppe
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Umezawa, Kazuo
AU  - McCubrey, James A.
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2278
C3  - International Journal of Molecular Medicine
T1  - Inhibition of GSK-3 beta activity can result in drug and hormonal
 resistance and alter sensitivity to targeted therapy in breast cancer
IS  - 1
VL  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2278
ER  - 

@conference{
author = "Steelman, Linda S. and Davis, Nicole M. and Sokolosky, Melissa and Abrams, Stephen L. and Martelli, Alberto M. and Nicoletti, Ferdinando and Fagone, Paolo and Mazzarino, Clorinda and Malponte, Graziella and Libra, Massimo and Cervello, Melchiorre and Montalto, Giuseppe and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Umezawa, Kazuo and McCubrey, James A.",
year = "2014",
journal = "International Journal of Molecular Medicine",
title = "Inhibition of GSK-3 beta activity can result in drug and hormonal
 resistance and alter sensitivity to targeted therapy in breast cancer",
number = "1",
volume = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2278"
}

Steelman, L. S., Davis, N. M., Sokolosky, M., Abrams, S. L., Martelli, A. M., Nicoletti, F., Fagone, P., Mazzarino, C., Malponte, G., Libra, M., Cervello, M., Montalto, G., Maksimović-Ivanić, D., Mijatović, S., Umezawa, K.,& McCubrey, J. A.. (2014). Inhibition of GSK-3 beta activity can result in drug and hormonal
 resistance and alter sensitivity to targeted therapy in breast cancer. in International Journal of Molecular Medicine, 34(1).
https://hdl.handle.net/21.15107/rcub_ibiss_2278

Steelman LS, Davis NM, Sokolosky M, Abrams SL, Martelli AM, Nicoletti F, Fagone P, Mazzarino C, Malponte G, Libra M, Cervello M, Montalto G, Maksimović-Ivanić D, Mijatović S, Umezawa K, McCubrey JA. Inhibition of GSK-3 beta activity can result in drug and hormonal
 resistance and alter sensitivity to targeted therapy in breast cancer. in International Journal of Molecular Medicine. 2014;34(1).
https://hdl.handle.net/21.15107/rcub_ibiss_2278 .

Steelman, Linda S., Davis, Nicole M., Sokolosky, Melissa, Abrams, Stephen L., Martelli, Alberto M., Nicoletti, Ferdinando, Fagone, Paolo, Mazzarino, Clorinda, Malponte, Graziella, Libra, Massimo, Cervello, Melchiorre, Montalto, Giuseppe, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Umezawa, Kazuo, McCubrey, James A., "Inhibition of GSK-3 beta activity can result in drug and hormonal
 resistance and alter sensitivity to targeted therapy in breast cancer" in International Journal of Molecular Medicine, 34, no. 1 (2014),
https://hdl.handle.net/21.15107/rcub_ibiss_2278 .

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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Vujičić, Milica
AU  - Stojanović, Ivana D.
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/966
C3  - Diabetologia
T1  - Carbon monoxide-releasing molecule CORM-A1 ameliorates islet-directed autoimmunity in mice
IS  - null
VL  - 56
SP  - 39
EP  - S228
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_966
ER  - 

@conference{
author = "Nikolić, Ivana and Saksida, Tamara and Vujičić, Milica and Stojanović, Ivana D. and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2013",
journal = "Diabetologia",
title = "Carbon monoxide-releasing molecule CORM-A1 ameliorates islet-directed autoimmunity in mice",
number = "null",
volume = "56",
pages = "39-S228",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_966"
}

Nikolić, I., Saksida, T., Vujičić, M., Stojanović, I. D., Nicoletti, F.,& Stošić-Grujičić, S.. (2013). Carbon monoxide-releasing molecule CORM-A1 ameliorates islet-directed autoimmunity in mice. in Diabetologia, 56(null), 39-S228.
https://hdl.handle.net/21.15107/rcub_ibiss_966

Nikolić I, Saksida T, Vujičić M, Stojanović ID, Nicoletti F, Stošić-Grujičić S. Carbon monoxide-releasing molecule CORM-A1 ameliorates islet-directed autoimmunity in mice. in Diabetologia. 2013;56(null):39-S228.
https://hdl.handle.net/21.15107/rcub_ibiss_966 .

Nikolić, Ivana, Saksida, Tamara, Vujičić, Milica, Stojanović, Ivana D., Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Carbon monoxide-releasing molecule CORM-A1 ameliorates islet-directed autoimmunity in mice" in Diabetologia, 56, no. null (2013):39-S228,
https://hdl.handle.net/21.15107/rcub_ibiss_966 .

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 .