TY  - JOUR
AU  - Tumino, Salvatore
AU  - Mojić, Marija
AU  - Dinić, Svetlana
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Maksimović-Ivanić, Danijela
AU  - Grdović, Nevena
AU  - Zocca, Mai-Britt
AU  - Miljković, Đorđe
AU  - Al-Abed, Yousef
AU  - Mijatović, Sanja
AU  - McCubrey, James A
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1199
AB  - We previously reported that the NO-modified form of HIV protease inhibitor Saquinavir ( Saq) is a potent antitumoral agent efficient against numerous tumor cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO equivalent to DL100 of the parental drug were completely nontoxic. Beside direct effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL)-mediated cell death. In this study, we evaluated the effects of Saq-NO on androgen-dependent prostate cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in xenograft models. Suppression of tumor growth was accompanied with cell cycle arrest in G(0)/G(1) phase and established a persistent inhibition of proliferation. Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF. Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2. This, however, did not represent the primary mode of action of Saq-NO, as elimination with specific inhibitors did not compromise the chemotherapic efficacy of the drug. However, permanent abrogation of phosphorylation of the S6 protein, which is the downstream target of both signaling pathways, was observed. Diminished S6 phosphorylation was associated with re-established sensitivity to TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In summary, NO modification of Saq led to a new chemical entity with stronger and more pleiotropic antitumor activity than the parental drug.
T2  - Cell Cycle
T1  - Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL
IS  - 6
VL  - 11
EP  - 1182
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1199
ER  - 

@article{
author = "Tumino, Salvatore and Mojić, Marija and Dinić, Svetlana and Fagone, Paolo and Mangano, Katia and Maksimović-Ivanić, Danijela and Grdović, Nevena and Zocca, Mai-Britt and Miljković, Đorđe and Al-Abed, Yousef and Mijatović, Sanja and McCubrey, James A and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2012",
abstract = "We previously reported that the NO-modified form of HIV protease inhibitor Saquinavir ( Saq) is a potent antitumoral agent efficient against numerous tumor cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO equivalent to DL100 of the parental drug were completely nontoxic. Beside direct effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL)-mediated cell death. In this study, we evaluated the effects of Saq-NO on androgen-dependent prostate cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in xenograft models. Suppression of tumor growth was accompanied with cell cycle arrest in G(0)/G(1) phase and established a persistent inhibition of proliferation. Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF. Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2. This, however, did not represent the primary mode of action of Saq-NO, as elimination with specific inhibitors did not compromise the chemotherapic efficacy of the drug. However, permanent abrogation of phosphorylation of the S6 protein, which is the downstream target of both signaling pathways, was observed. Diminished S6 phosphorylation was associated with re-established sensitivity to TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In summary, NO modification of Saq led to a new chemical entity with stronger and more pleiotropic antitumor activity than the parental drug.",
journal = "Cell Cycle",
title = "Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL",
number = "6",
volume = "11",
pages = "1182",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1199"
}

Tumino, S., Mojić, M., Dinić, S., Fagone, P., Mangano, K., Maksimović-Ivanić, D., Grdović, N., Zocca, M., Miljković, Đ., Al-Abed, Y., Mijatović, S., McCubrey, J. A., Stošić-Grujičić, S.,& Nicoletti, F.. (2012). Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL. in Cell Cycle, 11(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1199

Tumino S, Mojić M, Dinić S, Fagone P, Mangano K, Maksimović-Ivanić D, Grdović N, Zocca M, Miljković Đ, Al-Abed Y, Mijatović S, McCubrey JA, Stošić-Grujičić S, Nicoletti F. Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL. in Cell Cycle. 2012;11(6):null-1182.
https://hdl.handle.net/21.15107/rcub_ibiss_1199 .

Tumino, Salvatore, Mojić, Marija, Dinić, Svetlana, Fagone, Paolo, Mangano, Katia, Maksimović-Ivanić, Danijela, Grdović, Nevena, Zocca, Mai-Britt, Miljković, Đorđe, Al-Abed, Yousef, Mijatović, Sanja, McCubrey, James A, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL" in Cell Cycle, 11, no. 6 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1199 .

TY  - JOUR
AU  - Mojić, Marija
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Miljković, Đorđe
AU  - Stošić-Grujičić, Stanislava
AU  - Stanković, Marija M
AU  - Mangano, Katia
AU  - Travali, Salvatore
AU  - Donia, Marco
AU  - Fagone, Paolo
AU  - Zocca, Mai-Britt
AU  - Al-Abed, Yousef
AU  - McCubrey, James A
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1099
AB  - We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-independent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death.
T2  - Molecular Pharmacology
T1  - Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells
IS  - 4
VL  - 82
SP  - 203
EP  - 710
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1099
ER  - 

@article{
author = "Mojić, Marija and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Miljković, Đorđe and Stošić-Grujičić, Stanislava and Stanković, Marija M and Mangano, Katia and Travali, Salvatore and Donia, Marco and Fagone, Paolo and Zocca, Mai-Britt and Al-Abed, Yousef and McCubrey, James A and Nicoletti, Ferdinando",
year = "2012",
abstract = "We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-independent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death.",
journal = "Molecular Pharmacology",
title = "Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells",
number = "4",
volume = "82",
pages = "203-710",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1099"
}

Mojić, M., Mijatović, S., Maksimović-Ivanić, D., Miljković, Đ., Stošić-Grujičić, S., Stanković, M. M., Mangano, K., Travali, S., Donia, M., Fagone, P., Zocca, M., Al-Abed, Y., McCubrey, J. A.,& Nicoletti, F.. (2012). Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells. in Molecular Pharmacology, 82(4), 203-710.
https://hdl.handle.net/21.15107/rcub_ibiss_1099

Mojić M, Mijatović S, Maksimović-Ivanić D, Miljković Đ, Stošić-Grujičić S, Stanković MM, Mangano K, Travali S, Donia M, Fagone P, Zocca M, Al-Abed Y, McCubrey JA, Nicoletti F. Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells. in Molecular Pharmacology. 2012;82(4):203-710.
https://hdl.handle.net/21.15107/rcub_ibiss_1099 .

Mojić, Marija, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Miljković, Đorđe, Stošić-Grujičić, Stanislava, Stanković, Marija M, Mangano, Katia, Travali, Salvatore, Donia, Marco, Fagone, Paolo, Zocca, Mai-Britt, Al-Abed, Yousef, McCubrey, James A, Nicoletti, Ferdinando, "Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells" in Molecular Pharmacology, 82, no. 4 (2012):203-710,
https://hdl.handle.net/21.15107/rcub_ibiss_1099 .

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

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

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

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

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

TY  - JOUR
AU  - 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  - McCubrey, James A
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Martelli, Alberto M
AU  - Stivala, Franca
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Mazzarino, Clorinda
AU  - Mulaponte, Graziella
AU  - Libra, Mussimo
AU  - Cervello, Melchiorre
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Steelman, Linda S
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1312
C3  - International Journal of Molecular Medicine
T1  - Novel approaches to target the prostate cancer stem cell - eliminating the root of the cancer
IS  - null
VL  - 28
EP  - S18
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1312
ER  - 

@conference{
author = "McCubrey, James A and Chappell, William H and Abrams, Stephen L and Martelli, Alberto M and Stivala, Franca and Nicoletti, Ferdinando and Fagone, Paolo and Mazzarino, Clorinda and Mulaponte, Graziella and Libra, Mussimo and Cervello, Melchiorre and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Steelman, Linda S",
year = "2011",
journal = "International Journal of Molecular Medicine",
title = "Novel approaches to target the prostate cancer stem cell - eliminating the root of the cancer",
number = "null",
volume = "28",
pages = "S18",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1312"
}

McCubrey, J. A., Chappell, W. H., Abrams, S. L., Martelli, A. M., Stivala, F., Nicoletti, F., Fagone, P., Mazzarino, C., Mulaponte, G., Libra, M., Cervello, M., Maksimović-Ivanić, D., Mijatović, S.,& Steelman, L. S.. (2011). Novel approaches to target the prostate cancer stem cell - eliminating the root of the cancer. in International Journal of Molecular Medicine, 28(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1312

McCubrey JA, Chappell WH, Abrams SL, Martelli AM, Stivala F, Nicoletti F, Fagone P, Mazzarino C, Mulaponte G, Libra M, Cervello M, Maksimović-Ivanić D, Mijatović S, Steelman LS. Novel approaches to target the prostate cancer stem cell - eliminating the root of the cancer. in International Journal of Molecular Medicine. 2011;28(null):null-S18.
https://hdl.handle.net/21.15107/rcub_ibiss_1312 .

McCubrey, James A, Chappell, William H, Abrams, Stephen L, Martelli, Alberto M, Stivala, Franca, Nicoletti, Ferdinando, Fagone, Paolo, Mazzarino, Clorinda, Mulaponte, Graziella, Libra, Mussimo, Cervello, Melchiorre, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Steelman, Linda S, "Novel approaches to target the prostate cancer stem cell - eliminating the root of the cancer" in International Journal of Molecular Medicine, 28, no. null (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1312 .

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 .