Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus new treatment strategies are needed for this deadly disease. Poor clinical outcomes have been associated with overexpression of the anti-apoptotic Bcl-2 family proteins Bcl-2, Bcl-xL, and Mcl-1, which have garnered great interest as therapeutic targets. While the Bcl-2-selective inhibitor ABT-199 has demonstrated promising prec...

A monoclonal antibody (mAb) (T-199) of IgG1 isotype was raised against medulloblastoma by immunizations of mice with the medulloblastoma cell line TE-671. Studies of the specificity of mAb T-199 on cell lines as well as fresh frozen sections of normal and malignant tissues revealed the antigen in high amounts on the cell surface of neuroectodermally derived tumors such as medulloblastoma, neuro...

The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were...

The prepro-thyrotropin-releasing hormone (ppTRH)-derived peptide, ppTRH178-199, has been proposed to inhibit ACTH release at the level of the pituitary and attenuate prolactin and behavioral responses to stress as well. The objective of this study was to elucidate a possible link between the effects of ppTRH178-199 and glucocorticoids on the inhibition of ACTH release in corticotrophs. Compared...

Effect of drying temperatures 180 Defect categories 180 Rupture of wood tissue 180 surface checks 180 End checks and splits 182 Collapse 183 H o n e y c o m b 1 8 5 Ring failure 186 Boxed-heart splits 186 Checked knots 186 Loose knots 186 Warp 187 Uneven moisture content 188 Board rejects 188 Water pockets 188 Control measures 188 Discoloration 189 Sapwood discolorations 189 Heartwood discolora...

ABT-199, a potent and selective small-molecule antagonist of BCL-2, is being clinically vetted as pharmacotherapy for the treatment of acute myeloid leukemia (AML). However, given that prolonged monotherapy tends to beget resistance, we sought to investigate the means by which resistance to ABT-199 might arise in AML and the extent to which those mechanisms might be preempted. Here we used a pa...

........................................................................................................................................................................... 198 Introduction ...................................................................................................................................................................... 199 Material and Methods ...................