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Herath N.I.,Queensland Institute of Medical Research | Spanevello M.D.,Queensland Institute of Medical Research | Doecke J.D.,Queensland Institute of Medical Research | Smith F.M.,Queensland Institute of Medical Research | And 3 more authors.
European Journal of Cancer | Year: 2012

Aberrant expression of Eph and ephrin proteins in human cancers is extensively documented. However, data are frequently limited to one gene and therefore incomplete and in some instances conflicting. We analysed expression of all Eph and ephrin genes in colorectal cancer (CRC) cell lines and 153 clinical specimens, providing for the first time a comprehensive analysis of this system in CRC. Eph/ephrin mRNA expression was assessed by quantitative real-time PCR and correlated with protein expression (flow cytometry, Western blotting and immunocytochemistry). These data show that EphA1, EphA2, EphB2 and EphB4 were significantly over expressed in CRC. In all cases, at least one Eph gene was found in normal colon (EphA1, EphA2, EphB2, EphB4), where expression was observed at high levels in most CRCs. However, other Eph gene expression was lost in individual CRCs compared to the corresponding normal, EphA7 being a striking example. Loss of expression was more common in advanced disease and thus correlated with poor survival. This is consistent with the redundant functionality of Eph receptors, such that expression of a single Eph gene is sufficient for effector function. Overall, the data suggest a progressive loss of expression of individual Eph genes suggesting that individual CRCs need to be phenotyped to determine which Eph genes are highly expressed. Targeted therapies could then be selected from a group of specific antibodies, such as those developed for EphA1. © 2011 Elsevier Ltd. All rights reserved.

Solbiati L.,General Hospital of Busto Arsizio | Ahmed M.,Beth Israel Deaconess Medical Center | Cova L.,General Hospital of Busto Arsizio | Ierace T.,General Hospital of Busto Arsizio | And 3 more authors.
Radiology | Year: 2012

Purpose: To determine the long-term (10-year) survival of patients with colorectal liver metastases treated with radiofrequency (RF) ablation and systemic chemotherapy with intention to treat. Materials and Methods: Institutional review board approval was obtained for this study. From 1997 to 2006, 99 consecutive patients with 202 small (0.8-4.0 cm; mean: 2.2 cm ± 1.1) metachronous colorectal liver metastases underwent ultrasonography-guided percutaneous RF ablation with internally-cooled electrodes in association with systemic chemotherapy. Patients ineligible for surgery (n = 80) or whose lesions were potentially resectable and who refused surgery (n = 19) were included. Patients were followed up with contrast agent-enhanced computed tomography and/ or magnetic resonance imaging for a minimum of 3 years to more than 10 years after RF ablation (n = 99, 67, 49, and 25 for 3, 5, 7, and 10 or more years, respectively). Overall local response rates and long-term survival rates were assessed. For each of these primary endpoints, Kaplan-Meier curves were generated and log-rank tests were used to assess for statistically significant differences. Results: Primary and secondary technical success rates were 93.1% (188 of 202) and 100% (14 of 14), respectively. Local tumor progression occurred in 11.9% (24 of 202) metastases, and 54.2% (13 of 24) of these were re-treated. Patient survival rates increased with re-treatment versus no re-treatment (P < .001). At follow-up, 125 new liver metastases were found, and of these 32.8% (41 of 125) were treated with RF ablation. Overall survival rates were 98.0%, 69.3%, 47.8%, 25.0%, and 18.0% (median: 53.2 months) at 1, 3, 5, 7, and 10 years, respectively. The major complication rate was 1.3% (two of 156), and there were no procedure-related deaths. At the time this article was written, 32.3% (32 of 99) of the patients were alive, and 67.7% (67 of 99) were deceased, with a median follow-up of 72 months. Conclusion: Adding RF ablation to systemic chemotherapy achieved local control in a large majority of metachronous colorectal liver metastases. The 3- to 10-year survival rates of this relatively large series of patients were essentially equivalent to those of most surgical series reported in the literature. © RSNA, 2012.

Cornet E.,University of Caen Lower Normandy | Tomowiak C.,University of Poitiers | Tanguy-Schmidt A.,University of Angers | Dupuis J.,Lymphoid haemopathy unit | And 12 more authors.
British Journal of Haematology | Year: 2014

Summary: A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34-2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90-8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable. © 2014 John Wiley & Sons Ltd.

News Article | April 15, 2016
Site: www.scientificcomputing.com

Scientists have built a single-atom magnet that is the most stable to-date. The breakthrough paves the way for the scalable production of miniature magnetic storage devices. Magnetic storage devices, such as computer hard drives or memory cards, are widespread today. But as computer technology grows smaller, there is a need to also miniaturize data storage. This is epitomized by an effort to build magnets the size of a single atom. However, a magnet that small is very hard to keep "magnetized," which means that it would be unable to retain information for a meaningful amount time. In a breakthrough study published in Science, researchers led by EPFL and ETH Zurich have now built a single-atom magnet that, although working at around 40 Kelvin (-233.15 oC), is the smallest and most stable to date. Magnets work because of electron spin, which is a complicated motion best imagined as a spinning top. Electrons can spin up or down (something like clockwise or anti-clockwise), which creates a tiny magnetic field. In an atom, electrons usually come in pairs with opposite spins, thus cancelling out each other's magnetic field. But in a magnet, atoms have unpaired electrons, and their spins create an overall magnetic field. A challenge today is to build smaller and smaller magnets that can be implemented in data storage devices. The problem is something called "magnetic remanence," which describes the ability of a magnet to remain magnetized. Remanence is very difficult to observe from a single atom, because environmental fluctuations can flip its magnetic fields. In terms of technology, a limited remanence would mean limited information storage for atom-sized magnets. A team of scientists led by Harald Brune at EPFL and Pietro Gambardella at ETH Zurich, have built a prototypical single-atom magnet based on atoms of the rare-earth element holmium. The researchers placed single holmium atoms on ultrathin films of magnesium oxide, which were previously grown on a surface of silver. This method allows the formation of single-atom magnets with robust remanence. The reason is that the electron structure of holmium atoms protects the magnetic field from being flipped. The magnetic remanence of the holmium atoms is stable at temperatures around 40 Kelvin (-233.15 oC) which, though far from room temperature, are the highest achieved ever. The scientists' calculations demonstrate that the remanence of single holmium atoms at these temperatures is much higher than the remanence seen in previous magnets, which were also made up of three to 12 atoms. This makes the new single-atom magnet a worldwide record in terms of both size and stability. This project involved a collaboration of EPFL’s Institute of Condensed Matter Physics with ETH Zurich, Swiss Light Source (PSI), Vinča Institute of Nuclear Sciences (Belgrade), the Texas A&M University at Qatar and the European Synchrotron Radiation Facility (Grenoble). It was funded by the Swiss National Science Foundation, the Swiss Competence Centre for Materials Science and Technology (CCMX), the ETH Zurich, EPFL and the Marie Curie Institute, and the Serbian Ministry of Education and Science. Citation: Donati F, Rusponi S, Stepanow S, Wäckerlin C, Singha A, Persichetti L, Baltic R, Diller K, Patthey F, Fernandes E, Dreiser J, Šljivančanin Ž, Kummer K, Nistor C, Gambardella P, Brune H. Magnetic remanence in single atoms. Science 14 April 2016. DOI: 10.1126/science.aad9898

News Article
Site: www.nanotech-now.com

Abstract: Scientists at EPFL show how a light-induced force can amplify the sensitivity and resolution of a technique used to study single molecules. When it comes to studying single molecules, scientists use a powerful technique called "surface-enhanced Raman scattering" (SERS). An extremely sensitive tool, SERS detects the vibrations within the atoms of the illuminated molecule as a change in light color. But the sensitivity of SERS is limited at room temperature because molecules vibrate too weakly. Publishing in Nature Nanotechnology, EPFL scientists now show that this obstacle can be overcome with the tools of cavity optomechanics - the interaction between light and mechanical objects. The work has significant practical applications, as it can push the capabilities of SERS even further. Raman spectroscopy and weak vibrations SERS is based on the principles of Raman spectroscopy, an old technique used to probe molecules: When laser light shines on them, it interacts with their vibrations (e.g. the stretching of a bond between two atoms). As a result, the wavelength of the light shifts, changing its color. This shift becomes the unique fingerprint of the type of molecule being probed. However, Raman spectroscopy is limited when it comes to single molecules because they interact very weakly with light. This happens mainly for two reasons: First, a single molecule is about a thousand times smaller than the wavelength of incoming light. Developed about forty years ago, SERS overcame this problem by exploiting a tiny cloud of oscillating electrons in metallic nanoparticles that were excited with laser light. The cloud is known as a "plasmon" and it can be localized to nanometer-size gaps where molecules can be placed. In other words, the metallic nanoparticles act as nano-antennas that focus light down to molecular dimensions; this approach enhanced the sensitivity of SERS by more than 10 orders of magnitude. However, the second limitation of Raman has persisted without solution: molecules vibrate very weakly at room temperature - or, in technical terms, "the relevant vibrational modes are frozen". Amplifying molecular vibrations with light Two members of Tobias J. Kippenberg's lab at EPFL have now found a theoretical solution to this problem, showing that SERS can actually be pushed even further in sensitivity and resolution. The key in overcoming the weak vibrations is the cloud of oscillating electrons, the plasmon, which can exert a force on the vibrations of the tested molecule. Researchers Philippe Roelli and Christophe Galland, were able to determine the exact conditions needed for this light-induced force to drive the molecule's vibrations to large amplitudes. As the scientific community has set specific guidelines for this field, the researchers chose laser wavelengths and properties of the plasmonic structures against these. Getting more signal out of a molecule As the light-force amplifies the vibrations of the molecule, the interaction between the molecule and the confined laser light grows stronger as well. This can dramatically increase the signal that SERS picks up, well beyond what can be reached by previously known mechanisms. "Our work offers specific guidelines for designing more efficient metallic nanostructures and excitation schemes for SERS," says Philippe Roelli. "It can push the limits of the technique in sensitivity and resolution." By doing so, the study opens new research directions in the control of molecular vibrations with light, with potential applications ranging from biology and chemistry to quantum technologies. ### This work was funded by the European Research Committee, the NCCR of Quantum Engineering (QSIT), the Swiss National Science Foundation, the Curie Institute and the Max Planck-EPFL Center for Molecular Nanoscience and Technology. Reference Roelli P, Galland C, Piro N, Kippenberg T J. Molecular cavity optomechanics: a theory of plasmon-enhanced Raman scattering. Nature Nanotechnology 23 November 2015. DOI: 10.1038/nnano.2015.264. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

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