The proteins of the B-cell lymphoma 2 (Bcl-2) family are important regulators of apoptosis under normal and pathological conditions. Chemical compounds that block the antiapoptotic proteins of this family have been introduced, such as 4-[4-[(4'-Chloro[1,1'-biphenyl]-2-yl)methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl]amino]-3-nitrophenyl]sulfonyl]benzamide (A...

Stat6 and IRS-2 are two important signaling proteins that associate with the cytoplasmic tail of the interleukin 4 (IL-4) receptor. Data from numerous in vitro experiments have led to a model for IL-4 signal transduction in which the Stat6 signaling pathway is responsible for the IL-4 induced changes in gene expression and differentiation events, while the IRS-2 signaling pathway provides mitog...

PURPOSE Chronic lymphocytic leukemia (CLL) cells in lymph nodes (LN), from which relapses are postulated to originate, display an antiapoptotic profile in contrast to CLL cells from peripheral blood (PB). The BH3 mimetic ABT-737 antagonizes the antiapoptotic proteins Bcl-X(L) and Bcl-2 but not Mcl-1 or Bfl-1. Previously, it was shown that CD40-stimulated CLL cells were resistant to ABT-737. We ...

The natural product gambogic acid (GA) has been reported to have cytotoxic activity against tumor cells in culture and was identified as an active compound in a cell-based high-throughput screening assay for activators of caspases, proteases involved in apoptosis. Using the antiapoptotic Bcl-2 family protein, Bfl-1, as a target for screening of a library of natural products, we identified GA as...

Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+) T cells caused by the human T-cell leukemia virus type 1 (HTLV-1). The viral leukemogenesis is critically dependent on its oncoprotein Tax because the protein as well as the virus can immortalize primary human lymphocytes to permanent growth. As a transcriptional transactivator, Tax can stimulate the expression of distinct cellul...

Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synovioc...

This study tested the hypothesis that certain secretory phospholipase A(2) (sPLA(2)) isotypes act in a cytokine-like fashion through cell surface receptors to influence mast cell survival. Initial experiments revealed that sPLA(2) activity and sPLA(2) receptor expression are increased, and mast cells lost their capacity to maintain membrane asymmetry upon cytokine depletion. Groups IB and III, ...

The future of safe cell-based therapy rests on overcoming teratoma/tumor formation, in particular when using human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Because the presence of a few remaining undifferentiated hPSCs can cause undesirable teratomas after transplantation, complete removal of these cells with n...

The neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester DHEA sulfate (DHEAS), and allopregnanolone (Allo), produced by the CNS and the adrenals, appear to exert a protective effect in hippocampal and cortical neuron ischemia- and excitotoxicity-induced injury. We hypothesized that they may also play a protective role on the adrenal medulla, an important part of the sympathetic...