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Drug: Gleevec

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Total 75 results found since Jan 2013.

Differential and opposing effects of imatinib on LPS- and ventilator-induced lung injury
Endothelial dysfunction underlies the pathophysiology of vascular disorders such as acute lung injury (ALI) syndromes. Recent work has identified the Abl family kinases (c-Abl and Arg) as important regulators of endothelial cell (EC) barrier function and suggests that their inhibition by currently available pharmaceutical agents such as imatinib may be EC protective. Here we describe novel and differential effects of imatinib in regulating lung pathophysiology in two clinically relevant experimental models of ALI. Imatinib attenuates endotoxin (LPS)-induced vascular leak and lung inflammation in mice but exacerbates these ...
Source: AJP: Lung Cellular and Molecular Physiology - February 1, 2015 Category: Respiratory Medicine Authors: Letsiou, E., Rizzo, A. N., Sammani, S., Naureckas, P., Jacobson, J. R., Garcia, J. G. N., Dudek, S. M. Tags: CALL FOR PAPERS Source Type: research

Attenuation of fibrosis with selective inhibition of c-Abl by siRNA in systemic sclerosis dermal fibroblasts
In conclusion, specific c-Abl gene silencing using siRNA effectively reduced fibrosis-related gene expression. Inhibition of c-Abl by siRNA may be a potential therapeutic approach for fibrotic diseases such as systemic sclerosis.
Source: Archives of Dermatological Research - December 20, 2014 Category: Dermatology Source Type: research

Differential and Opposing Effects of Imatinib on LPS- and Ventilator-Induced Lung Injury.
Abstract Endothelial dysfunction underlies the pathophysiology of vascular disorders such as acute lung injury (ALI) syndromes. Recent work has identified the Abl family kinases (c-Abl and Arg) as important regulators of endothelial cell (EC) barrier function and suggests that their inhibition by currently available pharmaceutical agents such as imatinib may be EC protective. Here we describe novel and differential effects of imatinib in regulating lung pathophysiology in two clinically-relevant experimental models of ALI. Imatinib attenuates endotoxin (LPS)-induced vascular leak and lung inflammation in mice, but...
Source: Am J Physiol Lung Ce... - December 5, 2014 Category: Respiratory Medicine Authors: Letsiou E, Rizzo AN, Sammani S, Naureckas P, Jacobson JR, Garcia JG, Dudek SM Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Inhibition of STAT3-interacting protein 1 (STATIP1) promotes STAT3 transcriptional up-regulation and imatinib mesylate resistance in the chronic myeloid leukemia
Conclusions: Our data suggest that STATIP1 may be a negative regulator of STAT3 and demonstrate its involvement in IM therapy resistance in CML.
Source: BMC Cancer - November 23, 2014 Category: Cancer & Oncology Authors: André MencalhaStephany CorrêaDaniela SallesBárbara Du RocherMarcelo SantiagoEliana Abdelhay Source Type: research

A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia.
In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML. PMID: 25387678 [PubMed - in process]
Source: Braz J Med Biol Res - November 16, 2014 Category: Research Authors: Xia DY, Liu L, Hao MW, Liu Q, Chen RA, Liang YM Tags: Braz J Med Biol Res Source Type: research

MTOR inhibition enhances NVP-AUY922-induced autophagy-mediated KIT degradation and cytotoxicity in imatinib-resistant gastrointestinal stromal tumors.
Authors: Hsueh YS, Chang HH, Chiang NJ, Yen CC, Li CF, Chen LT Abstract Our previous study demonstrated NVP-AUY922, a HSP90AA1 inhibitor, could enhance mutant KIT degradation in gastrointestinal stroma tumor (GIST) cells through both proteasome- and autophagy-mediated pathways. Herein, we showed rapamycin, a MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT expression levels and enhance apoptosis in imatinib-resistant GIST cells. The involvement of autophagy in rapamycin-induced KIT downregulation was further confirmed by co-localization of KIT and autophagosome, and partial recovery of KIT e...
Source: Oncotarget - November 12, 2014 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Abstract 341: Imatinib induces expression of Bim and apoptosis in chronic myelogenous leukemia cells via p38/H2AX pathway
H2AX is a novel human tumor suppressor protein and plays an important role in apoptosis of cancer cells. Increasing published data indicate that H2AX phosphorylation (Ser139) contributes to its regulation of cancer cell apoptosis. Thus, charactering the mechanisms and signaling pathways involved in H2AX phosphorylation (Ser139) will certainly provide better understanding on H2AX function in cancer cells. Our previous report showed that caspase-3/Mst1 pathway regulates phosphorylation of H2AX at Ser139 in chronic myelogenous leukemia (CML) cells. Recently we found another pathway which regulates H2AX phosphorylation (Ser139...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Xiong, M., Niu, T., Dong, Y., Lu, C. Tags: Molecular and Cellular Biology Source Type: research

Imatinib mesylate stimulates low-density lipoprotein receptor-related protein 1-mediated ERK phosphorylation in insulin producing cells
LRP1 is an endocytic and multifunctional type I cell surface membrane protein, which is known to be phosphorylated by the activated PDGF receptor (PDGFR). The tyrosine kinase inhibitor imatinib, which inhibits PDGFR and c-Abl, and which has previously been reported to counteract beta-cell death and diabetes, has been suggested to ameliorate atherosclerosis by inhibiting PDGFR-induced LRP1 phosphorylation. The aim of this investigation was to study LRP1 function in beta-cells and to what extent imatinib modulates LRP1 activity. LRP1 and c-Abl gene knockdown was performed by RNAi using rat INS-1 832/13 and human EndoC1-bH1 c...
Source: Clinical Science - May 28, 2014 Category: Biomedical Science Authors: R Göran Fred, S Kumar Boddeti, M Lundberg, N Welsh Source Type: research

Proliferation inhibition and apoptosis induction of imatinib-resistant chronic myeloid leukemia cells via PPP2R5C down-regulation
In conclusion, the suppression of PPP2R5C by RNA interference could inhibit proliferation and effectively induce apoptosis in CML cells that were either imatinib sensitive or resistant. Down-regulating PPP2R5C gene expression might be considered as a new therapeutic target strategy for CML, particularly for imatinib-resistant CML.
Source: Journal of Hematology and Oncology - September 3, 2013 Category: Hematology Authors: Qi ShenSichu LiuYu ChenLijian YangShaohua ChenXiuli WuBo LiYuhong LuKanger ZhuYangqiu Li Source Type: research

Aberrant signalling by protein kinase CK2 in imatinib-resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic perspectives
Abstract: Chronic myeloid leukaemia (CML) is driven by the fusion protein Bcr-Abl, a constitutively active tyrosine kinase playing a crucial role in initiation and maintenance of CML phenotype. Despite the great efficacy of the Bcr-Abl-specific inhibitor imatinib, resistance to this drug is recognized as a major problem in CML treatment. We found that in LAMA84 cells, characterized by imatinib-resistance caused by BCR-ABL1 gene amplification, the pro-survival protein kinase CK2 is up-regulated as compared to the sensitive cells. CK2 exhibits a higher protein-level and a parallel enhancement of catalytic activity. Consisten...
Source: Molecular Oncology - August 28, 2013 Category: Cancer & Oncology Authors: Christian Borgo, Luca Cesaro, Valentina Salizzato, Maria Ruzzene, Maria Lina Massimino, Lorenzo A. Pinna, Arianna Donella-Deana Tags: Research Articles Source Type: research

AMPK Inhibits Oxidative Stress-induced Caveolin-1 Phosphorylation Cell Biology
Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide ...
Source: Journal of Biological Chemistry - July 12, 2013 Category: Chemistry Authors: Takeuchi, K., Morizane, Y., Kamami-Levy, C., Suzuki, J., Kayama, M., Cai, W., Miller, J. W., Vavvas, D. G. Tags: Signal Transduction Source Type: research

The role of TC-PTP (PTPN2) in modulating sensitivity to imatinib and interferon-α in CML cell line, KT-1 cells
Abstract: T-cell protein tyrosine phosphatase (TC-PTP, also known as PTPN2) is a negative regulator of the JAK/STAT pathway. STAT5 is activated by BCR-ABL kinase and STAT1 is an important transcription factor for interferon (IFN)-α-induced signaling in chronic myeloid leukemia (CML). We used siRNA to delete TC-PTP in the CML cell line, KT-1, and examined changes in the sensitivity to imatinib and IFN-α. Suppression of TC-PTP induced activation of STAT5, leading to imatinib resistance, while prolonged phosphorylation of STAT1 was induced by IFN-α, triggering cell death in KT-1 cells. These findings suggest that TC-PTP mo...
Source: Leukemia Research - June 6, 2013 Category: Hematology Authors: Yuriko Nishiyama-Fujita, Takatsune Shimizu, Morihiko Sagawa, Hideo Uchida, Masahiro Kizaki Tags: Laboratory Studies Source Type: research

Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-beta
Conclusions: The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.
Source: BMC Cancer - May 4, 2013 Category: Cancer & Oncology Authors: Jun OhishiMikiko AokiKazuki NabeshimaJunji SuzumiyaTamotsu TakeuchiAkira OgoseMichiyuki HakozakiYuichi YamashitaHiroshi Iwasaki Source Type: research

Induction of autophagy by imatinib sequesters Bcr‐Abl in autophagosomes and down‐regulates Bcr‐Abl protein
In this study, we show that following Imatinib treatment, Bcr‐Abl is sequestered into vesicular structures that co‐localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1/ATG7). Pharmacological inhibition of autophagy also reduced Bcr‐Abl/LC3 co‐localization in both K562 and CML patient cells. Bcr‐Abl protein expression was reduced with Imatinib treatment. Inhibition of both autophagy and proteasome activity in Imatinib treated cells was required to restore Bcr‐Abl protein levels to those of untreated cells. This ability to d...
Source: American Journal of Hematology - February 26, 2013 Category: Hematology Authors: Baukje M. Elzinga, Michelle J. Nyhan, Lisa C. Crowley, Tracey R. O'Donovan, Mary R. Cahill, Sharon L. McKenna Tags: Research Article Source Type: research

Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene Research Articles
Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a mitogenic factor). Therefore, enhanced SMS activity could favor cell proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we measured SMS activity in several leukemic cell lines and found that it is highly elevated in K562 chronic myelogenous leukemia (CML) cells. The increased SMS in K562 cells was caused by the presence of Bcr-abl, a hallmark of CML; stable expression of Bcr-abl elevated SMS activity in HL-60 cells while inhibition of the tyr...
Source: The Journal of Lipid Research - February 12, 2013 Category: Lipidology Authors: Burns, T. A., Subathra, M., Signorelli, P., Choi, Y., Yang, X., Wang, Y., Villani, M., Bhalla, K., Zhou, D., Luberto, C. Tags: Research Articles Source Type: research