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  IF of Sunitinib Malate (Sutent)
  

  Figure | PDGFR-α regulates human β-cell EZH2 expression and proliferation. a, b, Representative images showing immunostaining for PDGFR-α (a), phospho-ERK1/2 (pERK1/2), phospho-RB-Ser 780 (pRB(Ser780)), EZH2 (b) and insulin (a and b) on pancreatic sections from juvenile and adult human subjects. PDGFR-α was detected in juvenile β-cells (arrows) but not in adult β-cells (arrowheads). Scale bars, 25 μm. c–f, Assessment of effects on human juvenile or adult islets after exposure to PDGF-AA (50 ng ml^-1) for 2 days, with or without Sunitinib (2 μM) or U0126 (10 μM)co-treatment. c, Islet EZH2 mRNAlevels after the indicated treatments.

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  IF of BEZ235 (NVP-BEZ235)
  

  Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.