BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1.

The bromodomain and extra terminal (BET) family protein bromodomain containing protein 4 (BRD4) is an epigenetic regulator recently identified as a therapeutic target for several hematological cancers, notably mixed lineage leukemia-fusion acute myeloid leukemia (MLL-AML). Here, we show that the BRD4 bromodomain inhibitor JQ1 is highly active against the p53-wild-type Ontario Cancer Institute (OCI)-AML3 cell line which carries mutations in nucleophosmin (NPM1) and DNA methyltransferase 3 (DNMT3A) genes commonly associated with poor prognostic disease. We find that JQ1 causes caspase 3/7-mediated apoptosis and DNA damage response in these cells.

The polo-like kinase inhibitor BI 2536 exhibits potent activity against malignant plasma cells and represents a novel therapy in multiple myeloma.

Objective: Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536.

Materials And Methods: We have used six MM cell lines and six patient-derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell viability, apoptosis, and cytokinesis.

Substrate-induced phenotypic switches of human smooth muscle cells: an in vitro study of in-stent restenosis activation pathways.

In-stent restenosis is a clinical complication following coronary angioplasty caused by the implantation of the metal device in the atherosclerotic vessel. Histological examination has shown a clear contribution of both inflammatory and smooth muscle cells (SMCs) to the deposition of an excess of neointimal tissue. However, the sequence of events leading to clinically relevant restenosis is unknown.

Galectin-1 stimulates monocyte chemotaxis via the p44/42 MAP kinase pathway and a pertussis toxin-sensitive pathway.

Galectin-1, the prototype of a family of beta-galactoside-binding proteins, has been implicated in a wide variety of biological processes. Data presented herein show that galectin-1 stimulates monocyte migration in a dose-dependent manner but is not chemotactic for macrophages. Galectin-1-induced monocyte chemotaxis is blocked by lactose and inhibited by an anti-galectin-1 antibody but not by nonspecific antibodies.

Lack of galectin-1 results in defects in myoblast fusion and muscle regeneration.

Galectin-1 has been implicated in the development of skeletal muscle, being maximally expressed at the time of myofiber formation. Furthermore, in the presence of exogenous galectin-1, mononuclear myoblasts show increased fusion in vitro. In the current study, we have used the galectin-1 null mouse to elucidate the role of galectin-1 in skeletal muscle development and regeneration.