Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways

Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAFV600E have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAFV600E inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis

Archeologische opgraving Tienen - Kronkelweg

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Waarderend onderzoek Gouda Westergouwe, deelgebied 2 : een inventariserend veldonderzoek in de vorm van boringen en proefsleuven

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Some remarks on IBNR Evaluation Techniques

In this short note we give some comments and general remarks on the methodology of IBNR computations, as presented at the workshop on IBNR computations at the 2000 ASTIN Meeting, Porto Cervo, Sardinia

Quantifying structure of Natura 2000 heathland habitats using spectral mixture analysis and segmentation techniques on hyperspectral imagery

Monitoring of habitat types protected under the Annex I of the EU Habitats Directive requires every 6 years information to be reported on their conservation status (area, range, structure and function) in the member states. Hyperspectral imagery can be an important source of information to assist in the evaluation of the habitats’ conservation status, as it can provide continuous maps of habitat quality indicators (e.g., life forms, management activities, grass, shrub and tree encroachment) at the pixel level. Such local level information is highly needed for management purposes, e.g., the location of habitat patches and their sizes and quality within a protected site. This paper focuses on the use of continuous fraction images as derived from spectral mixture analysis of hyperspectral imagery (AHS-160), in combination with segmentation techniques, to facilitate habitat quality assessment in a heathland site in the Netherlands. This combined application of techniques on hyperspectral imagery demonstrates the usefulness of information from continuous fraction maps of grass abundance (Molinia caerulea) in heathlands – at and within the patch level – compared to traditional mapping techniques that assess grass encroachment in a limited number of abundance classes at the patch level. It therefore provides a better basis to monitor large areas for processes such as grass encroachment that largely determine the conservation status of Natura 2000 heathland areas. Timely, accurate and up-to-date spatial information on the encroachment of mosses, grasses, shrubs or trees (dominant species) can help conservation managers to take better decisions and to better evaluate the effect of taken measures. While discrepancies exist between the results of field-based vegetation surveys and the proposed remote sensing approach, we provide a discussion on the uncertainty of determining which of both methods is most accurate in relation to dominant species, which is in our case Molinia caerulea, and set forth several reasons why the remote sensing based approach might form a better basis for the monitoring of abundant species and patch evolution through time