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  - 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  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Franklin, Richard A
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Fagone, Paolo
AU  - Nicoletti, Ferdinando
AU  - Baesecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Chiarini, Francesca
AU  - Evangelisti, Camilla
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1096
AB  - The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.
T2  - Oncotarget
T1  - Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance
IS  - 10
VL  - 3
DO  - 10.18632/oncotarget.659
SP  - 389
EP  - 1111
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Chappell, William H and Abrams, Stephen L and Franklin, Richard A and Montalto, Giuseppe and Cervello, Melchiorre and Libra, Massimo and Candido, Saverio and Malaponte, Graziella and Mazzarino, Maria C and Fagone, Paolo and Nicoletti, Ferdinando and Baesecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Milella, Michele and Tafuri, Agostino and Chiarini, Francesca and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M",
year = "2012",
abstract = "The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.",
journal = "Oncotarget",
title = "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance",
number = "10",
volume = "3",
doi = "10.18632/oncotarget.659",
pages = "389-1111"
}

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Franklin, R. A., Montalto, G., Cervello, M., Libra, M., Candido, S., Malaponte, G., Mazzarino, M. C., Fagone, P., Nicoletti, F., Baesecke, J., Mijatović, S., Maksimović-Ivanić, D., Milella, M., Tafuri, A., Chiarini, F., Evangelisti, C., Cocco, L.,& Martelli, A. M.. (2012). Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance. in Oncotarget, 3(10), 389-1111.
https://doi.org/10.18632/oncotarget.659

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G, Mazzarino MC, Fagone P, Nicoletti F, Baesecke J, Mijatović S, Maksimović-Ivanić D, Milella M, Tafuri A, Chiarini F, Evangelisti C, Cocco L, Martelli AM. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance. in Oncotarget. 2012;3(10):389-1111.
doi:10.18632/oncotarget.659 .

McCubrey, James A, Steelman, Linda S, Chappell, William H, Abrams, Stephen L, Franklin, Richard A, Montalto, Giuseppe, Cervello, Melchiorre, Libra, Massimo, Candido, Saverio, Malaponte, Graziella, Mazzarino, Maria C, Fagone, Paolo, Nicoletti, Ferdinando, Baesecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Milella, Michele, Tafuri, Agostino, Chiarini, Francesca, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M, "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance" in Oncotarget, 3, no. 10 (2012):389-1111,
https://doi.org/10.18632/oncotarget.659 . .

TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Candido, Saverio
AU  - Libra, Massimo
AU  - Baesecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Cocco, Lucio
AU  - Evangelisti, Camilla
AU  - Chiarini, Francesca
AU  - Martelli, Alberto M
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1109
AB  - The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5, PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and TSC2 may also be activated/inactivated by mutations or epigenetic silencing. Upstream mutations in one signaling pathway or even in downstream components of the same pathway can alter the sensitivity of the cells to certain small molecule inhibitors. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of components of these cascades can contribute to: resistance to other pathway inhibitors, chemotherapeutic drug resistance, premature aging as well as other diseases. This review will first describe these pathways and discuss how genetic mutations and epigenetic alterations can result in resistance to various inhibitors.
T2  - Oncotarget
T1  - Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.
IS  - 9
VL  - 3
DO  - 10.18632/oncotarget.652
SP  - 153
EP  - 987
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Chappell, William H and Abrams, Stephen L and Montalto, Giuseppe and Cervello, Melchiorre and Nicoletti, Ferdinando and Fagone, Paolo and Malaponte, Graziella and Mazzarino, Maria C and Candido, Saverio and Libra, Massimo and Baesecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Milella, Michele and Tafuri, Agostino and Cocco, Lucio and Evangelisti, Camilla and Chiarini, Francesca and Martelli, Alberto M",
year = "2012",
abstract = "The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5, PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and TSC2 may also be activated/inactivated by mutations or epigenetic silencing. Upstream mutations in one signaling pathway or even in downstream components of the same pathway can alter the sensitivity of the cells to certain small molecule inhibitors. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of components of these cascades can contribute to: resistance to other pathway inhibitors, chemotherapeutic drug resistance, premature aging as well as other diseases. This review will first describe these pathways and discuss how genetic mutations and epigenetic alterations can result in resistance to various inhibitors.",
journal = "Oncotarget",
title = "Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.",
number = "9",
volume = "3",
doi = "10.18632/oncotarget.652",
pages = "153-987"
}

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Montalto, G., Cervello, M., Nicoletti, F., Fagone, P., Malaponte, G., Mazzarino, M. C., Candido, S., Libra, M., Baesecke, J., Mijatović, S., Maksimović-Ivanić, D., Milella, M., Tafuri, A., Cocco, L., Evangelisti, C., Chiarini, F.,& Martelli, A. M.. (2012). Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.. in Oncotarget, 3(9), 153-987.
https://doi.org/10.18632/oncotarget.652

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Montalto G, Cervello M, Nicoletti F, Fagone P, Malaponte G, Mazzarino MC, Candido S, Libra M, Baesecke J, Mijatović S, Maksimović-Ivanić D, Milella M, Tafuri A, Cocco L, Evangelisti C, Chiarini F, Martelli AM. Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.. in Oncotarget. 2012;3(9):153-987.
doi:10.18632/oncotarget.652 .

McCubrey, James A, Steelman, Linda S, Chappell, William H, Abrams, Stephen L, Montalto, Giuseppe, Cervello, Melchiorre, Nicoletti, Ferdinando, Fagone, Paolo, Malaponte, Graziella, Mazzarino, Maria C, Candido, Saverio, Libra, Massimo, Baesecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Milella, Michele, Tafuri, Agostino, Cocco, Lucio, Evangelisti, Camilla, Chiarini, Francesca, Martelli, Alberto M, "Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response." in Oncotarget, 3, no. 9 (2012):153-987,
https://doi.org/10.18632/oncotarget.652 . .

TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Sun, Lin
AU  - Davis, Nicole M
AU  - Abrams, Stephen L
AU  - Franklin, Richard A
AU  - Cocco, Lucio
AU  - Evangelisti, Camilla
AU  - Chiarini, Francesca
AU  - Martelli, Alberto M
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Ligresti, Giovanni
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Fagone, Paolo
AU  - Donia, Marco
AU  - Nicoletti, Ferdinando
AU  - Polesel, Jerry
AU  - Talamini, Renato
AU  - Baesecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Dulinska-Litewka, Joanna
AU  - Laidler, Piotr
AU  - D'Assoro, Antonio B
AU  - Drobot, Lyudmyla
AU  - Umezawa, Kazuo
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Demidenko, Zoya N
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1071
AB  - Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies.
T2  - Oncotarget
T1  - Advances in Targeting Signal Transduction Pathways
IS  - 12
VL  - 3
SP  - 69
EP  - 1521
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1071
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Chappell, William H and Sun, Lin and Davis, Nicole M and Abrams, Stephen L and Franklin, Richard A and Cocco, Lucio and Evangelisti, Camilla and Chiarini, Francesca and Martelli, Alberto M and Libra, Massimo and Candido, Saverio and Ligresti, Giovanni and Malaponte, Graziella and Mazzarino, Maria C and Fagone, Paolo and Donia, Marco and Nicoletti, Ferdinando and Polesel, Jerry and Talamini, Renato and Baesecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Milella, Michele and Tafuri, Agostino and Dulinska-Litewka, Joanna and Laidler, Piotr and D'Assoro, Antonio B and Drobot, Lyudmyla and Umezawa, Kazuo and Montalto, Giuseppe and Cervello, Melchiorre and Demidenko, Zoya N",
year = "2012",
abstract = "Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies.",
journal = "Oncotarget",
title = "Advances in Targeting Signal Transduction Pathways",
number = "12",
volume = "3",
pages = "69-1521",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1071"
}

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Sun, L., Davis, N. M., Abrams, S. L., Franklin, R. A., Cocco, L., Evangelisti, C., Chiarini, F., Martelli, A. M., Libra, M., Candido, S., Ligresti, G., Malaponte, G., Mazzarino, M. C., Fagone, P., Donia, M., Nicoletti, F., Polesel, J., Talamini, R., Baesecke, J., Mijatović, S., Maksimović-Ivanić, D., Milella, M., Tafuri, A., Dulinska-Litewka, J., Laidler, P., D'Assoro, A. B., Drobot, L., Umezawa, K., Montalto, G., Cervello, M.,& Demidenko, Z. N.. (2012). Advances in Targeting Signal Transduction Pathways. in Oncotarget, 3(12), 69-1521.
https://hdl.handle.net/21.15107/rcub_ibiss_1071

McCubrey JA, Steelman LS, Chappell WH, Sun L, Davis NM, Abrams SL, Franklin RA, Cocco L, Evangelisti C, Chiarini F, Martelli AM, Libra M, Candido S, Ligresti G, Malaponte G, Mazzarino MC, Fagone P, Donia M, Nicoletti F, Polesel J, Talamini R, Baesecke J, Mijatović S, Maksimović-Ivanić D, Milella M, Tafuri A, Dulinska-Litewka J, Laidler P, D'Assoro AB, Drobot L, Umezawa K, Montalto G, Cervello M, Demidenko ZN. Advances in Targeting Signal Transduction Pathways. in Oncotarget. 2012;3(12):69-1521.
https://hdl.handle.net/21.15107/rcub_ibiss_1071 .

McCubrey, James A, Steelman, Linda S, Chappell, William H, Sun, Lin, Davis, Nicole M, Abrams, Stephen L, Franklin, Richard A, Cocco, Lucio, Evangelisti, Camilla, Chiarini, Francesca, Martelli, Alberto M, Libra, Massimo, Candido, Saverio, Ligresti, Giovanni, Malaponte, Graziella, Mazzarino, Maria C, Fagone, Paolo, Donia, Marco, Nicoletti, Ferdinando, Polesel, Jerry, Talamini, Renato, Baesecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Milella, Michele, Tafuri, Agostino, Dulinska-Litewka, Joanna, Laidler, Piotr, D'Assoro, Antonio B, Drobot, Lyudmyla, Umezawa, Kazuo, Montalto, Giuseppe, Cervello, Melchiorre, Demidenko, Zoya N, "Advances in Targeting Signal Transduction Pathways" in Oncotarget, 3, no. 12 (2012):69-1521,
https://hdl.handle.net/21.15107/rcub_ibiss_1071 .

TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Abrams, Stephen L
AU  - Misaghian, Negin
AU  - Chappell, William H
AU  - Baesecke, Joerg
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Ligresti, Giovanni
AU  - Stivala, Franca
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Laidler, Piotr
AU  - Bonati, Antonio
AU  - Evangelisti, Camilla
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1183
AB  - An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models.
T2  - Current Pharmaceutical Design
T1  - Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy
IS  - 13
VL  - 18
EP  - 1795
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1183
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Abrams, Stephen L and Misaghian, Negin and Chappell, William H and Baesecke, Joerg and Nicoletti, Ferdinando and Libra, Massimo and Ligresti, Giovanni and Stivala, Franca and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Montalto, Giuseppe and Cervello, Melchiorre and Laidler, Piotr and Bonati, Antonio and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M",
year = "2012",
abstract = "An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models.",
journal = "Current Pharmaceutical Design",
title = "Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy",
number = "13",
volume = "18",
pages = "1795",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1183"
}

McCubrey, J. A., Steelman, L. S., Abrams, S. L., Misaghian, N., Chappell, W. H., Baesecke, J., Nicoletti, F., Libra, M., Ligresti, G., Stivala, F., Maksimović-Ivanić, D., Mijatović, S., Montalto, G., Cervello, M., Laidler, P., Bonati, A., Evangelisti, C., Cocco, L.,& Martelli, A. M.. (2012). Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy. in Current Pharmaceutical Design, 18(13).
https://hdl.handle.net/21.15107/rcub_ibiss_1183

McCubrey JA, Steelman LS, Abrams SL, Misaghian N, Chappell WH, Baesecke J, Nicoletti F, Libra M, Ligresti G, Stivala F, Maksimović-Ivanić D, Mijatović S, Montalto G, Cervello M, Laidler P, Bonati A, Evangelisti C, Cocco L, Martelli AM. Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy. in Current Pharmaceutical Design. 2012;18(13):null-1795.
https://hdl.handle.net/21.15107/rcub_ibiss_1183 .

McCubrey, James A, Steelman, Linda S, Abrams, Stephen L, Misaghian, Negin, Chappell, William H, Baesecke, Joerg, Nicoletti, Ferdinando, Libra, Massimo, Ligresti, Giovanni, Stivala, Franca, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Montalto, Giuseppe, Cervello, Melchiorre, Laidler, Piotr, Bonati, Antonio, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M, "Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy" in Current Pharmaceutical Design, 18, no. 13 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1183 .

TY  - CONF
AU  - McCubrey, James A
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Martelli, Alberto M
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Libra, Massimo
AU  - Cervello, Melchiorre
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Polesel, Jerry
AU  - Talamini, Renato
AU  - Maestro, Roberta
AU  - Steelman, Linda S
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1219
C3  - International Journal of Molecular Medicine
T1  - Role of NGAL (Lcn2) in prostate cancer invasion
IS  - null
VL  - 30
EP  - S25
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1219
ER  - 

@conference{
author = "McCubrey, James A and Chappell, William H and Abrams, Stephen L and Martelli, Alberto M and Nicoletti, Ferdinando and Fagone, Paolo and Libra, Massimo and Cervello, Melchiorre and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Polesel, Jerry and Talamini, Renato and Maestro, Roberta and Steelman, Linda S",
year = "2012",
journal = "International Journal of Molecular Medicine",
title = "Role of NGAL (Lcn2) in prostate cancer invasion",
number = "null",
volume = "30",
pages = "S25",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1219"
}

McCubrey, J. A., Chappell, W. H., Abrams, S. L., Martelli, A. M., Nicoletti, F., Fagone, P., Libra, M., Cervello, M., Maksimović-Ivanić, D., Mijatović, S., Polesel, J., Talamini, R., Maestro, R.,& Steelman, L. S.. (2012). Role of NGAL (Lcn2) in prostate cancer invasion. in International Journal of Molecular Medicine, 30(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1219

McCubrey JA, Chappell WH, Abrams SL, Martelli AM, Nicoletti F, Fagone P, Libra M, Cervello M, Maksimović-Ivanić D, Mijatović S, Polesel J, Talamini R, Maestro R, Steelman LS. Role of NGAL (Lcn2) in prostate cancer invasion. in International Journal of Molecular Medicine. 2012;30(null):null-S25.
https://hdl.handle.net/21.15107/rcub_ibiss_1219 .

McCubrey, James A, Chappell, William H, Abrams, Stephen L, Martelli, Alberto M, Nicoletti, Ferdinando, Fagone, Paolo, Libra, Massimo, Cervello, Melchiorre, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Polesel, Jerry, Talamini, Renato, Maestro, Roberta, Steelman, Linda S, "Role of NGAL (Lcn2) in prostate cancer invasion" in International Journal of Molecular Medicine, 30, no. null (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1219 .

TY  - CONF
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Martelli, Alberto M
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Mazzarino, Clorinda
AU  - Malaponte, 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  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1221
C3  - International Journal of Molecular Medicine
T1  - Targeting signaling pathways in prostate cancer
IS  - null
VL  - 30
EP  - S50
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1221
ER  - 

@conference{
author = "Steelman, Linda S and Chappell, William H and Abrams, Stephen L and Martelli, Alberto M and Nicoletti, Ferdinando and Fagone, Paolo and Mazzarino, Clorinda and Malaponte, 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 = "2012",
journal = "International Journal of Molecular Medicine",
title = "Targeting signaling pathways in prostate cancer",
number = "null",
volume = "30",
pages = "S50",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1221"
}

Steelman, L. S., Chappell, W. H., Abrams, S. L., Martelli, A. M., Nicoletti, F., Fagone, P., Mazzarino, C., Malaponte, G., Libra, M., Cervello, M., Montalto, G., Maksimović-Ivanić, D., Mijatović, S., Umezawa, K.,& McCubrey, J. A.. (2012). Targeting signaling pathways in prostate cancer. in International Journal of Molecular Medicine, 30(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1221

Steelman LS, Chappell WH, Abrams SL, Martelli AM, Nicoletti F, Fagone P, Mazzarino C, Malaponte G, Libra M, Cervello M, Montalto G, Maksimović-Ivanić D, Mijatović S, Umezawa K, McCubrey JA. Targeting signaling pathways in prostate cancer. in International Journal of Molecular Medicine. 2012;30(null):null-S50.
https://hdl.handle.net/21.15107/rcub_ibiss_1221 .

Steelman, Linda S, Chappell, William H, Abrams, Stephen L, Martelli, Alberto M, Nicoletti, Ferdinando, Fagone, Paolo, Mazzarino, Clorinda, Malaponte, Graziella, Libra, Massimo, Cervello, Melchiorre, Montalto, Giuseppe, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Umezawa, Kazuo, McCubrey, James A, "Targeting signaling pathways in prostate cancer" in International Journal of Molecular Medicine, 30, no. null (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1221 .

TY  - JOUR
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Kempf, C Ruth
AU  - Long, Jacquelyn M
AU  - Laidler, Piotr
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Stivala, Franca
AU  - Mazzarino, Maria C
AU  - Donia, Marco
AU  - Fagone, Paolo
AU  - Malaponte, Graziella
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Bonati, Antonio
AU  - Baesecke, Joerg
AU  - Cocco, Lucio
AU  - Evangelisti, Camilla
AU  - Martelli, Alberto M
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - McCubrey, James A
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1302
UR  - https://www.aging-us.com/article/100296
AB  - Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.
T2  - Aging-US
T1  - Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging
IS  - 3
VL  - 3
DO  - 10.18632/aging.100296
EP  - 222
ER  - 

@article{
author = "Steelman, Linda S and Chappell, William H and Abrams, Stephen L and Kempf, C Ruth and Long, Jacquelyn M and Laidler, Piotr and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Stivala, Franca and Mazzarino, Maria C and Donia, Marco and Fagone, Paolo and Malaponte, Graziella and Nicoletti, Ferdinando and Libra, Massimo and Milella, Michele and Tafuri, Agostino and Bonati, Antonio and Baesecke, Joerg and Cocco, Lucio and Evangelisti, Camilla and Martelli, Alberto M and Montalto, Giuseppe and Cervello, Melchiorre and McCubrey, James A",
year = "2011",
abstract = "Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.",
journal = "Aging-US",
title = "Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging",
number = "3",
volume = "3",
doi = "10.18632/aging.100296",
pages = "222"
}

Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C. R., Long, J. M., Laidler, P., Mijatović, S., Maksimović-Ivanić, D., Stivala, F., Mazzarino, M. C., Donia, M., Fagone, P., Malaponte, G., Nicoletti, F., Libra, M., Milella, M., Tafuri, A., Bonati, A., Baesecke, J., Cocco, L., Evangelisti, C., Martelli, A. M., Montalto, G., Cervello, M.,& McCubrey, J. A.. (2011). Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. in Aging-US, 3(3).
https://doi.org/10.18632/aging.100296

Steelman LS, Chappell WH, Abrams SL, Kempf CR, Long JM, Laidler P, Mijatović S, Maksimović-Ivanić D, Stivala F, Mazzarino MC, Donia M, Fagone P, Malaponte G, Nicoletti F, Libra M, Milella M, Tafuri A, Bonati A, Baesecke J, Cocco L, Evangelisti C, Martelli AM, Montalto G, Cervello M, McCubrey JA. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. in Aging-US. 2011;3(3):null-222.
doi:10.18632/aging.100296 .

Steelman, Linda S, Chappell, William H, Abrams, Stephen L, Kempf, C Ruth, Long, Jacquelyn M, Laidler, Piotr, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Stivala, Franca, Mazzarino, Maria C, Donia, Marco, Fagone, Paolo, Malaponte, Graziella, Nicoletti, Ferdinando, Libra, Massimo, Milella, Michele, Tafuri, Agostino, Bonati, Antonio, Baesecke, Joerg, Cocco, Lucio, Evangelisti, Camilla, Martelli, Alberto M, Montalto, Giuseppe, Cervello, Melchiorre, McCubrey, James A, "Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging" in Aging-US, 3, no. 3 (2011),
https://doi.org/10.18632/aging.100296 . .

TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Kempf, C Ruth
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Stivala, Franca
AU  - Malaponte, Graziella
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Baesecke, Joerg
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1252
AB  - Chemotherapy remains a commonly used therapeutic approach for many cancers. Indeed chemotherapy is relatively effective for treatment of certain cancers and it may be the only therapy (besides radiotherapy) that is appropriate for certain cancers. However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant patients. Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill cancer cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail PTEN regulation as this is a critical tumor suppressor gene frequently dysregulated in human cancer which contributes to therapy resistance. Controlling the expression of these pathways could improve cancer therapy and ameliorate human health.
T2  - Journal of Cellular Physiology
T1  - Therapeutic Resistance Resulting From Mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Signaling Pathways
IS  - 11
VL  - 226
DO  - 10.1002/jcp.22647
EP  - 2781
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Kempf, C Ruth and Chappell, William H and Abrams, Stephen L and Stivala, Franca and Malaponte, Graziella and Nicoletti, Ferdinando and Libra, Massimo and Baesecke, Joerg and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Montalto, Giuseppe and Cervello, Melchiorre and Cocco, Lucio and Martelli, Alberto M",
year = "2011",
abstract = "Chemotherapy remains a commonly used therapeutic approach for many cancers. Indeed chemotherapy is relatively effective for treatment of certain cancers and it may be the only therapy (besides radiotherapy) that is appropriate for certain cancers. However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant patients. Unfortunately most of these drug transporter inhibitors have not proven effective for therapy. Recently the possibilities of more specific, targeted therapies have sparked the interest of clinical and basic researchers as approaches to kill cancer cells. However, there are also problems associated with these targeted therapies. Two key signaling pathways involved in the regulation of cell growth are the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways. Dysregulated signaling through these pathways is often the result of genetic alterations in critical components in these pathways as well as mutations in upstream growth factor receptors. Furthermore, these pathways may be activated by chemotherapeutic drugs and ionizing radiation. This review documents how their abnormal expression can contribute to drug resistance as well as resistance to targeted therapy. This review will discuss in detail PTEN regulation as this is a critical tumor suppressor gene frequently dysregulated in human cancer which contributes to therapy resistance. Controlling the expression of these pathways could improve cancer therapy and ameliorate human health.",
journal = "Journal of Cellular Physiology",
title = "Therapeutic Resistance Resulting From Mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Signaling Pathways",
number = "11",
volume = "226",
doi = "10.1002/jcp.22647",
pages = "2781"
}

McCubrey, J. A., Steelman, L. S., Kempf, C. R., Chappell, W. H., Abrams, S. L., Stivala, F., Malaponte, G., Nicoletti, F., Libra, M., Baesecke, J., Maksimović-Ivanić, D., Mijatović, S., Montalto, G., Cervello, M., Cocco, L.,& Martelli, A. M.. (2011). Therapeutic Resistance Resulting From Mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Signaling Pathways. in Journal of Cellular Physiology, 226(11).
https://doi.org/10.1002/jcp.22647

McCubrey JA, Steelman LS, Kempf CR, Chappell WH, Abrams SL, Stivala F, Malaponte G, Nicoletti F, Libra M, Baesecke J, Maksimović-Ivanić D, Mijatović S, Montalto G, Cervello M, Cocco L, Martelli AM. Therapeutic Resistance Resulting From Mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Signaling Pathways. in Journal of Cellular Physiology. 2011;226(11):null-2781.
doi:10.1002/jcp.22647 .

McCubrey, James A, Steelman, Linda S, Kempf, C Ruth, Chappell, William H, Abrams, Stephen L, Stivala, Franca, Malaponte, Graziella, Nicoletti, Ferdinando, Libra, Massimo, Baesecke, Joerg, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Montalto, Giuseppe, Cervello, Melchiorre, Cocco, Lucio, Martelli, Alberto M, "Therapeutic Resistance Resulting From Mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Signaling Pathways" in Journal of Cellular Physiology, 226, no. 11 (2011),
https://doi.org/10.1002/jcp.22647 . .

TY  - JOUR
AU  - Chappell, William H
AU  - Steelman, Linda S
AU  - Long, Jacquelyn M
AU  - Kempf, Ruth C
AU  - Abrams, Stephen L
AU  - Franklin, Richard A
AU  - Baesecke, Joerg
AU  - Stivala, Franca
AU  - Donia, Marco
AU  - Fagone, Paolo
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Laidler, Piotr
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Bonati, Antonio
AU  - Evangelisti, Camilla
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
AU  - McCubrey, James A
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1300
AB  - The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.
T2  - Oncotarget
T1  - Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health
IS  - 3
VL  - 2
DO  - 10.18632/oncotarget.240
EP  - 164
ER  - 

@article{
author = "Chappell, William H and Steelman, Linda S and Long, Jacquelyn M and Kempf, Ruth C and Abrams, Stephen L and Franklin, Richard A and Baesecke, Joerg and Stivala, Franca and Donia, Marco and Fagone, Paolo and Malaponte, Graziella and Mazzarino, Maria C and Nicoletti, Ferdinando and Libra, Massimo and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Montalto, Giuseppe and Cervello, Melchiorre and Laidler, Piotr and Milella, Michele and Tafuri, Agostino and Bonati, Antonio and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M and McCubrey, James A",
year = "2011",
abstract = "The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.",
journal = "Oncotarget",
title = "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health",
number = "3",
volume = "2",
doi = "10.18632/oncotarget.240",
pages = "164"
}

Chappell, W. H., Steelman, L. S., Long, J. M., Kempf, R. C., Abrams, S. L., Franklin, R. A., Baesecke, J., Stivala, F., Donia, M., Fagone, P., Malaponte, G., Mazzarino, M. C., Nicoletti, F., Libra, M., Maksimović-Ivanić, D., Mijatović, S., Montalto, G., Cervello, M., Laidler, P., Milella, M., Tafuri, A., Bonati, A., Evangelisti, C., Cocco, L., Martelli, A. M.,& McCubrey, J. A.. (2011). Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health. in Oncotarget, 2(3).
https://doi.org/10.18632/oncotarget.240

Chappell WH, Steelman LS, Long JM, Kempf RC, Abrams SL, Franklin RA, Baesecke J, Stivala F, Donia M, Fagone P, Malaponte G, Mazzarino MC, Nicoletti F, Libra M, Maksimović-Ivanić D, Mijatović S, Montalto G, Cervello M, Laidler P, Milella M, Tafuri A, Bonati A, Evangelisti C, Cocco L, Martelli AM, McCubrey JA. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health. in Oncotarget. 2011;2(3):null-164.
doi:10.18632/oncotarget.240 .

Chappell, William H, Steelman, Linda S, Long, Jacquelyn M, Kempf, Ruth C, Abrams, Stephen L, Franklin, Richard A, Baesecke, Joerg, Stivala, Franca, Donia, Marco, Fagone, Paolo, Malaponte, Graziella, Mazzarino, Maria C, Nicoletti, Ferdinando, Libra, Massimo, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Montalto, Giuseppe, Cervello, Melchiorre, Laidler, Piotr, Milella, Michele, Tafuri, Agostino, Bonati, Antonio, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M, McCubrey, James A, "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health" in Oncotarget, 2, no. 3 (2011),
https://doi.org/10.18632/oncotarget.240 . .

TY  - CONF
AU  - Steelman, Linda S
AU  - Abrams, Stephen L
AU  - Chappell, William H
AU  - Martelli, Alberto M
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Mazzarino, Clorinda
AU  - Malaponte, Graziella
AU  - Libra, Massimo
AU  - Stivala, Franca
AU  - Cervello, Melchiorre
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - McCubrey, James A
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1313
C3  - International Journal of Molecular Medicine
T1  - Sensitization of cancer stem cells based on inhibiting key signal transduction pathways
IS  - null
VL  - 28
EP  - S18
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1313
ER  - 

@conference{
author = "Steelman, Linda S and Abrams, Stephen L and Chappell, William H and Martelli, Alberto M and Nicoletti, Ferdinando and Fagone, Paolo and Mazzarino, Clorinda and Malaponte, Graziella and Libra, Massimo and Stivala, Franca and Cervello, Melchiorre and Mijatović, Sanja and Maksimović-Ivanić, Danijela and McCubrey, James A",
year = "2011",
journal = "International Journal of Molecular Medicine",
title = "Sensitization of cancer stem cells based on inhibiting key signal transduction pathways",
number = "null",
volume = "28",
pages = "S18",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1313"
}

Steelman, L. S., Abrams, S. L., Chappell, W. H., Martelli, A. M., Nicoletti, F., Fagone, P., Mazzarino, C., Malaponte, G., Libra, M., Stivala, F., Cervello, M., Mijatović, S., Maksimović-Ivanić, D.,& McCubrey, J. A.. (2011). Sensitization of cancer stem cells based on inhibiting key signal transduction pathways. in International Journal of Molecular Medicine, 28(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1313

Steelman LS, Abrams SL, Chappell WH, Martelli AM, Nicoletti F, Fagone P, Mazzarino C, Malaponte G, Libra M, Stivala F, Cervello M, Mijatović S, Maksimović-Ivanić D, McCubrey JA. Sensitization of cancer stem cells based on inhibiting key signal transduction pathways. in International Journal of Molecular Medicine. 2011;28(null):null-S18.
https://hdl.handle.net/21.15107/rcub_ibiss_1313 .

Steelman, Linda S, Abrams, Stephen L, Chappell, William H, Martelli, Alberto M, Nicoletti, Ferdinando, Fagone, Paolo, Mazzarino, Clorinda, Malaponte, Graziella, Libra, Massimo, Stivala, Franca, Cervello, Melchiorre, Mijatović, Sanja, Maksimović-Ivanić, Danijela, McCubrey, James A, "Sensitization of cancer stem cells based on inhibiting key signal transduction pathways" in International Journal of Molecular Medicine, 28, no. null (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1313 .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Mojić, Marija
AU  - Malaponte, Graziella
AU  - Libra, Massimo
AU  - Cardile, Vera
AU  - Miljković, Đorđe
AU  - Harhaji-Trajković, Ljubica
AU  - Dabideen, Darrin
AU  - Cheng, Kai Fan
AU  - Bevelacqua, Ylenia
AU  - Donia, Marco
AU  - Garotta, Gianni
AU  - Ai-Abed, Yousef
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1517
AB  - In this study we evaluated the effects of the new NO donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) on the A375 human melanoma cell line. Treatment with the drug led to concentration-dependent reduction of mitochondrial respiration and number of viable cells in cultures. Decreased cell viability correlated with release and internalization of NO and was neutralized by the extracellular scavenger hemoglobin. GIT-27NO neither influenced cell division nor induced accidental or autophagic cell death. Early signs of apoptosis were observed upon coculture with the drug, and resulting in marked accumulation of hypodiploid cells, suggesting that the induction of apoptosis is one primary mode of action of the compound in A375 cells. GIT-27NO significantly inhibited the expression of the transcription repressor and apoptotic resistant factor YY1 and, in parallel, augmented the presence of total p53. The capacity of GIT-27NO to induce p53-mediated apoptosis along with inhibition of YY1 repressor in A375 melanoma cells indicates that GIT-27NO possesses an important anti-cancer pharmacological profile. The findings suggest the potential therapeutic use of GIT-27NO in the clinical setting. (C) 2008 Elsevier Inc. All rights reserved.
T2  - Nitric Oxide-Biology and Chemistry
T1  - Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells
IS  - 2
VL  - 19
EP  - 183
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1517
ER  - 

@article{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Mojić, Marija and Malaponte, Graziella and Libra, Massimo and Cardile, Vera and Miljković, Đorđe and Harhaji-Trajković, Ljubica and Dabideen, Darrin and Cheng, Kai Fan and Bevelacqua, Ylenia and Donia, Marco and Garotta, Gianni and Ai-Abed, Yousef and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2008",
abstract = "In this study we evaluated the effects of the new NO donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) on the A375 human melanoma cell line. Treatment with the drug led to concentration-dependent reduction of mitochondrial respiration and number of viable cells in cultures. Decreased cell viability correlated with release and internalization of NO and was neutralized by the extracellular scavenger hemoglobin. GIT-27NO neither influenced cell division nor induced accidental or autophagic cell death. Early signs of apoptosis were observed upon coculture with the drug, and resulting in marked accumulation of hypodiploid cells, suggesting that the induction of apoptosis is one primary mode of action of the compound in A375 cells. GIT-27NO significantly inhibited the expression of the transcription repressor and apoptotic resistant factor YY1 and, in parallel, augmented the presence of total p53. The capacity of GIT-27NO to induce p53-mediated apoptosis along with inhibition of YY1 repressor in A375 melanoma cells indicates that GIT-27NO possesses an important anti-cancer pharmacological profile. The findings suggest the potential therapeutic use of GIT-27NO in the clinical setting. (C) 2008 Elsevier Inc. All rights reserved.",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells",
number = "2",
volume = "19",
pages = "183",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1517"
}

Mijatović, S., Maksimović-Ivanić, D., Mojić, M., Malaponte, G., Libra, M., Cardile, V., Miljković, Đ., Harhaji-Trajković, L., Dabideen, D., Cheng, K. F., Bevelacqua, Y., Donia, M., Garotta, G., Ai-Abed, Y., Stošić-Grujičić, S.,& Nicoletti, F.. (2008). Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells. in Nitric Oxide-Biology and Chemistry, 19(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1517

Mijatović S, Maksimović-Ivanić D, Mojić M, Malaponte G, Libra M, Cardile V, Miljković Đ, Harhaji-Trajković L, Dabideen D, Cheng KF, Bevelacqua Y, Donia M, Garotta G, Ai-Abed Y, Stošić-Grujičić S, Nicoletti F. Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells. in Nitric Oxide-Biology and Chemistry. 2008;19(2):null-183.
https://hdl.handle.net/21.15107/rcub_ibiss_1517 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Mojić, Marija, Malaponte, Graziella, Libra, Massimo, Cardile, Vera, Miljković, Đorđe, Harhaji-Trajković, Ljubica, Dabideen, Darrin, Cheng, Kai Fan, Bevelacqua, Ylenia, Donia, Marco, Garotta, Gianni, Ai-Abed, Yousef, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells" in Nitric Oxide-Biology and Chemistry, 19, no. 2 (2008),
https://hdl.handle.net/21.15107/rcub_ibiss_1517 .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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