Curr Drug Targets
August 2010
Here we review phospho-specific, quantitative flow cytometry approach as a rapid and reliable tool for measuring intracellular signaling proteins with potential applications in monitoring efficacy of targeted therapy. The single cell, multiparameter nature of flow cytometry allows simultaneous investigation of specific cell type and the corresponding intracellular markers. Peripheral blood can be directly stained with surface markers to delineate cell populations of interest, followed by fixation, permeabilization, and immunostaining with specific antibodies to the cellular targets.
View Article and Find Full Text PDFPurpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice.
Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.
The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent stimulator of differentiation and apoptosis in myeloid leukemia cells. In the present study, we investigated the role of the transcription factor NF-kappaB in TPA-induced growth inhibition and apoptosis in the myeloid leukemia HL-60 cell line and its TPA-resistant cell variant HL-525. Unlike the parental cell line, HL-525 cells are protein kinase C (PKC)-beta deficient and resistant to TPA-induced differentiation and apoptosis.
View Article and Find Full Text PDFOur previous studies demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) had pharmacological activity for the treatment of myeloid leukemia patients. In the present study, we investigated the effects of TPA alone or in combination with capsaicin (8-methyl-N-vanillyl-6-nonenamide) on growth and differentiation in myeloid leukemia HL-60 cells and in a TPA-resistant HL-60 variant cell line termed HL-525. Treatment of HL-60 cells with TPA (0.
View Article and Find Full Text PDFClinically achievable concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA; 0.16-0.32 nM) and all-trans-retinoic acid (ATRA; 0.
View Article and Find Full Text PDF12-O-Tetradecanoylphorbol-13-acetate (TPA) is a potent stimulator of differentiation in myelocytic leukemia cells, and it has been shown to have activity in patients with acute myelocytic leukemia. Because attempts to develop a suitable mass spectrometry assay for TPA were unsuccessful (because of the lack of sufficient sensitivity), we developed a novel and highly sensitive blood level bioassay for TPA that measures ethyl acetate-extractable differentiating activity in blood. Differentiating activity in ethyl acetate extracts of blood was measured in HL-60 cells by measuring the formation of adherent cells.
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