999 resultados para 10180034 TM-58_120m
Resumo:
[Simon Frankfurt]
Resumo:
The design of upconversion phosphors with higher quantum yield requires a deeper understanding of the detailed energy transfer and upconversion processes between active ions inside the material. Rate equations can model those processes by describing the populations of the energy levels of the ions as a function of time. However, this model presents some drawbacks: energy migration is assumed to be infinitely fast, it does not determine the detailed interaction mechanism (multipolar or exchange), and it only provides the macroscopic averaged parameters of interaction. Hence, a rate equation model with the same parameters cannot correctly predict the time evolution of upconverted emission and power dependence under a wide range of concentrations of active ions. We present a model that combines information about the host material lattice, the concentration of active ions, and a microscopic rate equation system. The extent of energy migration is correctly taken into account because the energy transfer processes are described on the level of the individual ions. This model predicts the decay curves, concentration, and excitation power dependences of the emission. This detailed information can be used to predict the optimal concentration that results in the maximum upconverted emission.
Resumo:
The epidermal growth factor receptor (EGFR) and its ligands are overexpressed in many human tumors, including bladder and pancreas, correlating with a more aggressive tumor phenotype and poor patient prognosis. We initiated the present study to characterize the heterogeneity of gefitinib responsiveness in a panel of human bladder and pancreatic cancer cell lines in order to identify the biological characteristics of EGFR-dependent proliferation that could be used to prospectively identify drug-sensitive tumors. A second objective was to elucidate how to best exploit these results by utilizing gefitinib in combination therapy. To these ends, we examined the effects of the EGFR antagonist gefitinib on proliferation and apoptosis in a panel of 18 human bladder cancer cell lines and 9 human pancreatic cancer cell lines. Our data confirmed the existence of marked heterogeneity in Iressa responsiveness with less than half of the cell lines displaying significant growth inhibition by clinically relevant concentrations of the drug. Gefitinib responsiveness was found to be p27 kip1 dependent as DNA synthesis was restored following exposure to p27siRNA. Unfortunately, Iressa responsiveness was not closely linked to surface EGFR or TGF-α expression in the bladder cancer cells, however, cellular TGF-α expression correlated directly with Iressa sensitivity in the pancreatic cancer cell lines. These findings provide the potential for prospectively identifying patients with drug-sensitive tumors. ^ Further studies aimed at exploiting gefitinib-mediated cell cycle effects led us to investigate if gefitinib-mediated TRAIL sensitization correlated with increased p27kip1 accumulation. We observed that increased TRAIL sensitivity following gefitinib exposure was not dependent on p27 kip1 expression. Additional studies initiated to examine the role(s) of Akt and Erk signaling demonstrated that exposure to PI3K or MEK inhibitors significantly enhanced TRAIL-induced apoptosis at concentrations that block target phosphorylation. Furthermore, combinations of TRAIL and the PI3K or MEK inhibitors increased procaspase-8 processing above levels observed with TRAIL alone, indicating that the effects were exerted at the level of caspase-8 activation, considered the earliest step in the TRAIL pathway. ^
