4,026 research outputs found

    Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease

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    Background The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment. Methods Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed. Results The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28-61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08-1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08-11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities. Conclusion The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population. © 2012 The Author(s).published_or_final_versio

    Identifying landslides from continuous seismic surface waves: a case study of multiple small-scale landslides triggered by Typhoon Talas, 2011

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    Landslides can cause devastating damage. In particular, heavy rainfall-triggered landslides pose a chain of natural hazards. However, such events are often difficult to detect, leaving the physical processes poorly understood. Here we apply a novel surface-wave detector to detect and locate landslides during the transit of Typhoon Talas 2011. We identify multiple landslides triggered by Typhoon Talas, including a landslide in the Tenryu Ward, Shizuoka prefecture, Japan, ∼400 km east from the typhoon track. The Tenryu landslide displaced a total volume of 1.2 − −1.5 × 106 m. The landslide is much smaller than those detected by using globally recorded surface waves, yet the event generated coherent seismic signals propagating up to 3000 km away. Our observations show that attributes of small and large landslides may follow the same empirical scaling relationships, indicating possible invariant failure mechanisms. Our results also suggest an alerting technology to detect and locate landslides with a sparse seismic network

    A Stealth Supersymmetry Sampler

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    The LHC has strongly constrained models of supersymmetry with traditional missing energy signatures. We present a variety of models that realize the concept of Stealth Supersymmetry, i.e. models with R-parity in which one or more nearly-supersymmetric particles (a "stealth sector") lead to collider signatures with only a small amount of missing energy. The simplest realization involves low-scale supersymmetry breaking, with an R-odd particle decaying to its superpartner and a soft gravitino. We clarify the stealth mechanism and its differences from compressed supersymmetry and explain the requirements for stealth models with high-scale supersymmetry breaking, in which the soft invisible particle is not a gravitino. We also discuss new and distinctive classes of stealth models that couple through a baryon portal or Z' gauge interactions. Finally, we present updated limits on stealth supersymmetry in light of current LHC searches.Comment: 45 pages, 16 figure

    Clear cell odontogenic carcinoma: a diagnostic and therapeutic dilemma

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    BACKGROUND: Clear cell odontogenic carcinoma is a rare odontogenic tumor occurring in the anterior region of the mandible in 5(th)–7(th )decades and shows a female preponderance. It is potentially aggressive, capable of frequent recurrences and loco-regional and distant metastases. CASE PRESENTATION: A 45- year- old woman presented with a radiolucent left mandibular swelling associated with loss of teeth. Left cervical lymph nodes were enlarged on palpation. The patient underwent resection of the tumor but consequent to resected margins being positive for tumor cells underwent left hemimandibulectomy with ipsilateral functional neck dissection and was free of recurrence at 8 months follow-up. CONCLUSION: Clear cell odontogenic carcinoma should be considered in the differential diagnosis of jaw tumors with conspicuous clear cell component. Curettage or conservative resection inevitably results in recurrences and/or metastasis and more radical resection is warranted in these tumors, especially when they are large and show soft tissue invasion

    Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip

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    Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics

    A Collective Breaking of R-Parity

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    Supersymmetric theories with an R-parity generally yield a striking missing energy signature, with cascade decays concluding in a neutralino that escapes the detector. In theories where R-parity is broken the missing energy is replaced with additional jets or leptons, often making traditional search strategies ineffective. Such R-parity violation is very constrained, however, by resulting B and L violating signals, requiring couplings so small that LSPs will decay outside the detector in all but a few scenarios. In theories with additional matter fields, R-parity can be broken collectively, such that R-parity is not broken by any single coupling, but only by an ensemble of couplings. Cascade decays can proceed normally, with each step only sensitive to one or two couplings at a time, but B and L violation requires the full set, yielding a highly suppressed constraint. s-channel production of new scalar states, typically small for standard RPV, can be large when RPV is broken collectively. While missing energy is absent, making these models difficult to discover by traditional SUSY searches, they produce complicated many object resonances (MORes), with many different possible numbers of jets and leptons. We outline a simple model and discuss its discoverability at the LHC.Comment: 28 pages, 10 figure

    Supersymmetry in the shadow of photini

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    Additional neutral gauge fermions -- "photini" -- arise in string compactifications as superpartners of U(1) gauge fields. Unlike their vector counterparts, the photini can acquire weak-scale masses from soft SUSY breaking and lead to observable signatures at the LHC through mass mixing with the bino. In this work we investigate the collider consequences of adding photini to the neutralino sector of the MSSM. Relatively large mixing of one or more photini with the bino can lead to prompt decays of the lightest ordinary supersymmetric particle; these extra cascades transfer most of the energy of SUSY decay chains into Standard Model particles, diminishing the power of missing energy as an experimental handle for signal discrimination. We demonstrate that the missing energy in SUSY events with photini is reduced dramatically for supersymmetric spectra with MSSM neutralinos near the weak scale, and study the effects on limits set by the leading hadronic SUSY searches at ATLAS and CMS. We find that in the presence of even one light photino the limits on squark masses from hadronic searches can be reduced by 400 GeV, with comparable (though more modest) reduction of gluino mass limits. We also consider potential discovery channels such as dilepton and multilepton searches, which remain sensitive to SUSY spectra with photini and can provide an unexpected route to the discovery of supersymmetry. Although presented in the context of photini, our results apply in general to theories in which additional light neutral fermions mix with MSSM gauginos.Comment: 23 pages, 8 figures, references adde

    TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

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    Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

    Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

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    <p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported.</p> <p>Methods</p> <p>Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation.</p> <p>Results</p> <p>In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (<it>P </it>< 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC).</p> <p>Conclusion</p> <p>Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms.</p
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