Effects of the Tyrosine Kinase Inhibitor Imatinib Mesylate on a Bcr-Abl-Positive Cell Line: Suppression of Autonomous Cell Growth but No Effect on Decreased Adhesive Property and Morphological Changes

2003 ◽  
Vol 78 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Toshio Nishihara ◽  
Yasuo Miura ◽  
Yumi Tohyama ◽  
Chisato Mizutani ◽  
Terutoshi Hishita ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Line ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Morphological Changes ◽  
Adhesive Property

Tyrosine Kinase Inhibitor STI571 (Imatinib) Cooperates with Wild-Type p53 on K562 Cell Line to Enhance Its Proapoptotic Effects

2005 ◽  
Vol 114 (3) ◽  
pp. 150-154 ◽  
Author(s):  
Gianluca Brusa ◽  
Manuela Mancini ◽  
Fabio Campanini ◽  
Alberto Calabrò ◽  
Elisa Zuffa ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Line ◽  
K562 Cell ◽  
Kinase Inhibitor ◽  
Wild Type ◽  
K562 Cell Line ◽  
Wild Type P53

Effects of the Tyrosine Kinase Inhibitor Imatinib on Neuroendocrine Tumor Cell Growth

Digestion ◽  
2005 ◽  
Vol 71 (3) ◽  
pp. 131-140 ◽  
Author(s):  
Brigitte Lankat-Buttgereit ◽  
Dieter Hörsch ◽  
Peter Barth ◽  
Rudolf Arnold ◽  
Silke Blöcker ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tyrosine Kinase ◽  
Tumor Cell ◽  
Tyrosine Kinase Inhibitor ◽  
Neuroendocrine Tumor ◽  
Kinase Inhibitor ◽  
Tumor Cell Growth

Cystic acne due to imatinib therapy for chronic myelocytic leukemia

2018 ◽  
Vol 25 (4) ◽  
pp. 972-974 ◽  
Author(s):  
Andrew Hwang ◽  
Andrew Iskandar ◽  
Michael del Rosario ◽  
Constantin A Dasanu
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Imatinib Mesylate ◽  
Side Effect ◽  
Medical Literature ◽  
Kinase Inhibitor ◽  
Imatinib Therapy ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Cutaneous Reactions

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of several malignancies. Its use, however, is associated with a number of toxic effects including adverse cutaneous reactions. Herein, we present a case of facial cystic acne in a patient receiving imatinib therapy for chronic myelocytic leukemia. This side effect resolved with cessation of therapy. To the best of our knowledge, this clinical entity has never been previously reported in the medical literature.

The Tyrosine Kinase Inhibitor Adaphostin (NSC 680410), but Not Imatinib Mesylate, Inhibits Survival and Src Tyrosine Kinase Family- Triggered Signaling Pathways of MM Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3352-3352
Author(s):  
Klaus Podar ◽  
Melissa Simoncini ◽  
Yu-Tzu Tai ◽  
Martin Sattler ◽  
Kenji Ishitsuka ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Signaling Pathways ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
K562 Cells ◽  
Parp Cleavage ◽  
Src Tyrosine Kinase ◽  
Kinase Family ◽  
Long Term Treatment

Abstract The tyrosine kinase inhibitor adaphostin is a member of the tyrophostin family of small molecules that interfere with peptide binding rather, than targeting the kinase ATP-binding site. Adaphostin has therefore been examined as an alternative to the 2-phenylaminopyrimidine derivate imatinib mesylate, with remarkable efficacy in the treatment of chronic myeloic leukemia (CML). Previous studies show that adaphostin induces apoptosis: (1) in Bcr/Abl+ cells more rapidly than imatinib mesylate; (2) in imatinib mesylate resistant cells; and (3) in Bcr/ Abl - cells. Imatinib mesylate has minimal, if any activity in MM; the efficacy of adaphostin in multiple myeloma (MM) is unknown. Here we compare the effects of adaphostin and imatinib mesylate against human MM cells. Our results show concentration-dependent apoptosis in MM.1S, U266, OPM-2, INA-6, RPMI8226 and RPMI-Dox40 MM cells after treatment with adaphostin, but not with imatinib mesylate. Imatinib mesylate induced more than 50% apoptosis in K562 cells using concentrations as low as 1mM, which served as a positive control. Moreover, adaphostin, but not imatinib mesylate, induced caspase-9, caspase-8, and PARP cleavage, as well as downregulation of Mcl-1, in MM cells. Further results demonstrated that adaphostin induces peroxide production and DNA strand breaks after long-term treatment. Importantly MM cell proliferation induced by MM cell binding to BMSCs was abrogated by adaphostin- treatment. IL-6 and IGF-1 signaling and sequelae triggered by these cytokines are important growth, survival, and drug resistance factors in MM; conversely, adaphostin but not imatinib mesylate, inhibited phosphorylation of Src tyrosine kinase family, Akt-1, and ERK. Taken together, our studies in MM cells show that (1) adaphostin- inhibits IGF-1- and IL-6- triggered signaling pathways as well as (2) induces reactive oxygen species and apoptosis. These studies therefore provide the preclinical framework for its clinical evaluation to improve patient outcome in MM.

Effects of AMN107, a Novel Aminopyrimidine Tyrosine Kinase Inhibitor, on Human Mast Cells Bearing Wild-Type or Mutated Codon 816 c-kit.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3528-3528 ◽  
Author(s):  
Srdan Verstovsek ◽  
Cem Akin ◽  
Giles J. Francis ◽  
Manshouri Taghi ◽  
Ly Huynh ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Line ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Kinase Inhibitor ◽  
Wild Type ◽  
Kit Mutation

Abstract Background. Majority of adult patients with systemic mastocytosis (SM) have activating mutation in codon 816 of c-kit (CD117), a receptor on the surface of mast cells. This abnormality is responsible for the pathogenesis of the disease. Methods. We investigated the effects of a newly designed tyrosine kinase inhibitor, AMN107, by comparing its in vitro inhibitory potency on c-kit mutated mast cell lines and patient samples with that of imatinib mesylate, another tyrosine kinase inhibitor, effective in some patients with SM. Two cell lines, subclones of HMC-1 cells, were used: HMC-1560 carrying juxtamembrane domain mutation in codon 560 of c-kit, and HMC-1560, 816 carrying both codon 560 mutation and tyrosine kinase domain mutation in codon 816 of c-kit. Results. In HMC-1560 mast cell line carrying wild-type codon 816, AMN107 was as potent as imatinib in inhibiting cellular proliferation, with IC50 values of 108 and 74 nM respectively, while in HMC-1560, 816 cell line carrying 816 mutation, neither medication had an effect. AMN107 was also as effective as imatinib in inhibiting phosphorylation of c-kit tyrosine kinase in HMC-1560 cells. The inhibition of cellular proliferation was associated with induction of apoptosis in HMC-1560 cells. AMN107 in concentrations up to 1 uM had no effect on bone marrow mast cells carrying D816V c-kit mutation obtained from patients with mastocytosis. Conclusions. Our results suggest similar potency of AMN107 and imatinib in mast cells that carry wild-type codon 816, but no activity against codon 816 mutation carrying cells.

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