University of South Florida

Bristol-myers Squibb Compnay

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Kapil N Bhalla

Francis Lee

Jie Wu

Zhengming Chen

A method for treating or inhibiting artery obstructive disease, such as restenosis after angioplasty and stenting procedures and stenosis after coronary artery bypass surgery, in a subject by administering to the subject a therapeutically effective amount of dasatinib or a derivative thereof. Also provided are drug-eluting medical devices, including stents, having a therapeutically effective amount of dasatinib.

Treatment of restenosis and stenosis with dasatinib

A method of inducing high anti-leukemia activity responsive to the combination of hydroxamic acid analogue histone deacetylase inhibitors and PKC412 against human acute leukemia characterized as expressing phosphorylated (p)FLT3 kinase by a novel flow cytometry-based assay.

Leukemia treatment method and composition

Here, the inventors disclose the treatment of imatinib mesylate resistant chronic myelogenous leukemia cells with a cotreatment of vorinostat (SAHA, suberoylanilide hydroxamic acid) and dasatinib, a dual Abl/Src kinase (TK) inhibitor. Combined treatment of cultured human CML and BaF3 cells with vorinostat and dasatinib induced more apoptosis than either agent alone, as well as synergistically induced loss of clonogenic survival, which was associated with greater depletion of Bcr-Abl, p-CrkL and p-STAT5 levels. Co-treatment with dasatinib and vorinostat also attenuated the levels of Bcr-AblE255K and Bcr-AblT315I and induced apoptosis of BaF3 cells with ectopic expression of the mutant forms of Bcr-Abl. Finally, co-treatment of the primary CML cells with vorinostat and dasatinib induced more loss of cell viability and depleted Bcr-Abl or Bcr-AblT315I, p-STAT5 and p-CrkL levels than either agent alone.

Method of treating chronic myelogenous leukemia cells

Due to the poor long-term clinical outcome in the adult patients with several forms of acute leukemia novel treatment strategies are needed to overcome resistance and sensitize the leukemia blasts to the extrinsic and intrinsic pathway of apoptosis. Treatment with LAQ824 and Apo-2L/TRAIL alone has been recognized to induce apoptosis of leukemia blasts but intrinsic mechanisms of resistance limit the antileukemia activity of either agent when administered alone. The inventive method overcomes the resistance to current apoptosis inducing treatments demonstrated by AML and CML-BC cells by concomitantly administering Apo-2L/TRAIL with the histone deacetylase inhibitor LAQ824.

Growing community of inventors

Tampa, FL, United States of America

Kapil N Bhalla