A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer

Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive growth inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study to determine the tolerability and efficacy of gefitinib in combination with irinotecan, infusional 5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13 patients with advanced colorectal cancer, 10 required dose reductions of irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of whom required hospitalisation, three with neutropenic fever. One patient achieved partial response and seven had disease stabilisation. The combination of this standard chemotherapy regimen with gefitinib is associated with excessive toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic level

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer

X-ray diodes for laser fusion plasma diagnostics

Photodiodes with x-ray sensitive photocathodes are commonly used as broadband x-ray detectors in fusion plasma diagnostics. We have measured the risetime of the detector system and have measured the quantum efficiency between 1 to 500 A of numerous photocathode materials of practical interest. The materials studied include aluminum, copper, nickel, gold, three forms of carbon, chromium, and cesium iodide. The results of the measurements are compared with Henke's semiempirical model of photoyield. We have studied the effects of long-term cathode aging and use as a plasma diagnostic on cathode quantum efficiency. In addition, we have measured the x-ray mass-absorption coefficient of several ultrasoft x-ray windows in energy regions where data were unavailable. Windows studied were made of aluminum, Formvar, polypropylene, and Kimfoil. Measurements between 1 to 50 A were performed with the Los Alamos Scientific Laboratory's low-energy x-ray calibration facility, and the measurements between 50 to 550 A were performed at the National Bureau of Standard's synchrotron ultraviolet radiation facility

Overview of research at NBS using synchrotron radiation at SURF-II

The National Bureau of Standards (NBS) Synchrotron Ultraviolet Radiation Facility (SURF-II) is used in conjunction with several high throughput monochromators to study the interaction of vacuum ultraviolet photons with solids and gases. Recent work has been concerned with the photon stimulated desorption of atomic and molecular ions from surfaces, with the effect of electric fields on molecular photoabsorption and with the study of molecular photoionization by angle resolved photoelectron spectroscopy. These research programs yield new information about molecular bonding at surfaces, molecular dynamics near ionization thresholds, and the coupling of the electronic and nuclear motion near resonances in molecules. In addition to these programs in basic research SURF-II is used for the calibration of transfer standard detectors over a photon energy range 20 to 250 eV. Calibration of monochromator systems is achieved over the photon energy range 5 to 250 eV by using the now calculable spectral intensity radiated by the electrons, which are confined in a nearly circular orbit