45 research outputs found

    Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

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    The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

    The Red Radio Ring: a gravitationally lensed hyperluminous infrared radio galaxy at z=2.553 discovered through the citizen science project SpaceWarps

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    We report the discovery of a gravitationally lensed hyperluminous infrared galaxy (intrinsic LIR≈1013 L⊙) with strong radio emission (intrinsic L1.4 GHz≈1025WHz−1) at z=2.553. The source was identified in the citizen science project SpaceWarpsthrough the visual inspection of tens of thousands of iJKs colour composite images of luminous red galaxies (LRGs), groups and clusters of galaxies and quasars. Appearing as a partial Einstein ring (re≈3 arcsec) around an LRG at z=0.2, the galaxy is extremely bright in the sub-millimetre for a cosmological source, with the thermal dust emission approaching 1 Jy at peak. The redshift of the lensed galaxy is determined through the detection of the CO(3→2) molecular emission line with the Large Millimetre Telescope's Redshift Search Receiver and through [O iii] and Hα line detections in the near-infrared from Subaru/Infrared Camera and Spectrograph. We have resolved the radio emission with high-resolution (300-400 mas) eMERLIN L-band and Very Large Array C-band imaging. These observations are used in combination with the near-infrared imaging to construct a lens model, which indicates a lensing magnification of μ≈10. The source reconstruction appears to support a radio morphology comprised of a compact (<250 pc) core and more extended component, perhaps indicative of an active nucleus and jet or lob

    The Red Radio Ring: a gravitationally lensed hyperluminous infrared radio galaxy at z = 2.553 discovered through the citizen science project SPACE WARPS

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    This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.We report the discovery of a gravitationally lensed hyperluminous infrared galaxy (intrinsic LIR ≈ 1013 L⊙) with strong radio emission (intrinsic L1.4 GHz ≈ 1025 W Hz−1) at z = 2.553. The source was identified in the citizen science project SPACE WARPS through the visual inspection of tens of thousands of iJKs colour composite images of luminous red galaxies (LRGs), groups and clusters of galaxies and quasars. Appearing as a partial Einstein ring (re ≈ 3 arcsec) around an LRG at z = 0.2, the galaxy is extremely bright in the sub-millimetre for a cosmological source, with the thermal dust emission approaching 1 Jy at peak. The redshift of the lensed galaxy is determined through the detection of the CO(3→2) molecular emission line with the Large Millimetre Telescope's Redshift Search Receiver and through [O III] and Hα line detections in the near-infrared from Subaru/Infrared Camera and Spectrograph. We have resolved the radio emission with high-resolution (300–400 mas) eMERLIN L-band and Very Large Array C-band imaging. These observations are used in combination with the near-infrared imaging to construct a lens model, which indicates a lensing magnification of μ ≈ 10. The source reconstruction appears to support a radio morphology comprised of a compact (<250 pc) core and more extended component, perhaps indicative of an active nucleus and jet or lobe.Peer reviewedFinal Published versio

    A phase I clinical and pharmacokinetic study of capecitabine (Xeloda®) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours

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    Capecitabine is a highly active oral fluoropyrimidine that is an attractive alternative to 5-fluorouracil in colorectal cancer treatment. The current study, undertaken in 27 patients with gastrointestinal tumours, aimed to assess the toxicity and potential for significant pharmacokinetic interactions of a combination regimen incorporating capecitabine with 3-weekly irinotecan (XELIRI). Irinotecan (200 and 250 mg m−2) was administered as a 90-min infusion on day 1 in combination with escalating capecitabine doses (700–1250 mg m−2 twice daily) administered on days 2–15 of a 3-week treatment cycle. Pharmacokinetics were characterised on days 1 and 2 of the first two cycles. A total of 103 treatment cycles were administered. The principal dose-limiting toxicities were diarrhoea and neutropenia. Capecitabine 1150 mg m−2 twice daily with irinotecan 250 mg m−2 was identified as the maximum-tolerated dose and capecitabine 1000 mg m−2 with irinotecan 250 mg m−2 was identified as the recommended dose for further study. Analyses confirmed that there were no significant pharmacokinetic interactions between the two agents. The combination was clinically active, with complete and partial responses achieved in heavily pretreated patients. This study indicates that XELIRI is a potentially feasible and clinically active regimen in patients with advanced gastrointestinal cancer

    Characterization of the martensitic transformation in the superelastic Ti-24Nb-4Zr-8Sn alloy by in situ synchrotron X-ray diffraction and dynamic mechanical analysis.

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    International audienceIn this work, the martensitic transformation occurring in the superelastic Ti-24Nb-4Zr-8Sn alloy was investigated by tensile tests, in situ synchrotron X-ray diffraction (SXRD) and dynamic mech. anal. (DMA). The SXRD results clearly showed the diffraction peaks related to the α'' and β phases and their evolution, under loading and unloading conditions, have highlighted the reversible stress-induced martensitic (SIM) transformation. Consequently, a three step deformation sequence was established from both SXRD anal. and tensile test characterization. On the other hand, the characteristic temps. related to the martensitic transformation under different applied stresses have been detd. from the storage modulus and the damping curves by DMA anal. Very good accordance concerning the crit. stress inducing the martensitic transformation was obtained by comparing the results obtained from SXRD, DMA, and tensile tests
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