Disability weights for the burden of oral disease in South Australia

BACKGROUND: Australian burden of disease estimates appeared inconsistent with the reported repetitive and ubiquitous nature of dental problems. The aims of the study were to measure the nature, severity and duration of symptoms for specific oral conditions, and calculate disability weights from these measures. METHODS: Data were collected in 2001–02 from a random sample of South Australian dentists using mailed self-complete questionnaires. Dentists recorded the diagnosis of dental problems and provided patients with self-complete questionnaires to record the nature, severity and duration of symptoms using the EuroQol instrument. Data were available from 378 dentists (response rate = 60%). RESULTS: Disability weights were highest for pulpal infection (0.069), caries (0.044) and dentinal sensitivity (0.040), followed by denture problems (0.026), periodontal disease (0.023), failed restorations (0.019), tooth fractures (0.014) and tooth wear (0.011). Aesthetic problems had a low disability weight (0.002), and both recall/maintenance care and oral hygiene had adjusted weights of zero. CONCLUSIONS: Disability weights for caries (0.044), periodontal disease (0.023) and denture problems (0.026) in this study were higher than comparable oral health conditions in the Australian Burden of Disease and Injury Study (0.005 for caries involving a filling and 0.014 for caries involving an extraction, 0.007 for periodontal disease, and 0.004 for edentulism). A range of common problems such as pulpal infection, failed restorations and tooth fracture that were not included in the Australian Burden of Disease and Injury Study had relatively high disability weights. The inclusion of a fuller range of oral health problems along with revised disability weights would result in oral health accounting for a larger amount of disability than originally estimated

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

CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer

CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.Oncogene advance online publication, 10 April 2017; doi:10.1038/onc.2017.87

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