908 research outputs found
Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade
Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites
The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome
RUNX3 is believed to have tumour suppressor properties in several cancer types. Inactivation of RUNX3 has been shown to occur by methylation-induced transcriptional silencing and by mislocalization of the protein to the cytoplasm. The aim of this study was to examine the clinical significance of RUNX3 expression in a large series of colorectal cancers using immunohistochemistry and tissue arrays. With advancing tumour stage, expression of RUNX3 in the nucleus decreased, whereas expression restricted to the cytoplasmic compartment increased. Nuclear RUNX3 expression was associated with significantly better patient survival compared to tumours in which the expression of RUNX3 was restricted to the cytoplasm (P=0.025). These results support a role for RUNX3 as a tumour suppressor in colorectal cancer
Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies
We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD
Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson
We report first evidence for a fully reconstructed decay mode of the
B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to
mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in
p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider
Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background
of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a
B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability
of a peak of this magnitude occurring by random fluctuation in the search
region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR
Top quark mass measurement using the template method at CDF
We present a measurement of the top quark mass in the lepton+jets and
dilepton channels of decays using the template method. The data
sample corresponds to an integrated luminosity of 5.6 fb of
collisions at Tevatron with TeV, collected with the CDF II
detector. The measurement is performed by constructing templates of three
kinematic variables in the lepton+jets and two kinematic variables in the
dilepton channel. The variables are two reconstructed top quark masses from
different jets-to-quarks combinations and the invariant mass of two jets from
the decay in the lepton+jets channel, and a reconstructed top quark mass
and , a variable related to the transverse mass in events with two
missing particles, in the dilepton channel. The simultaneous fit of the
templates from signal and background events in the lepton+jets and dilepton
channels to the data yields a measured top quark mass of Comment: submitted to Phys. Rev.
Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays
We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using
360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector.
The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ)
charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which
the pions are from Rho0 decay. The latter case also encompasses exotic
interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho
hypotheses are compatible with our data. Since 3S1 is untenable on other
grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872).
Models for different J/Psi-Rho angular momenta L are considered. Flexibility in
the models, especially the introduction of Rho-Omega interference, enable good
descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let
Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation and copy number variants in circulating tumour DNA
Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is challenging at the genome-wide level because of lack of available input. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples. Methods: For all experiments, the Infinium HD assay for methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50 ng); eighteen blood derived specimens (lowest input 10 ng) and six matched ctDNA input (lowest input 10 ng)/fresh tumour specimens (lowest input 250 ng) were processed. Downstream analysis was performed in R/Bioconductor for quality control metrics and differential methylation analysis as well as copy number calls. Results: Correlation coefficients for CpG methylation were high at the probe level averaged R2 = 0.99 for blood derived samples and R2 > 0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared, R2 > 0.91 between the two. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample with good concordance via DQ plot. Conclusions: The Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to an input of 10 ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA. These findings demonstrate that these samples can now be accessed by methylation array technology, allowing analysis of these important sample types
Search for Higgs Boson Decaying to b-bbar and Produced in Association with W Bosons in p-pbar Collisions at sqrt{s}=1.96 TeV
We present a search for Higgs bosons decaying into b-bbar and produced in
association with W bosons in p-pbar collisions at sqrt{s}=1.96 TeV. This search
uses 320 pb-1 of the dataset accumulated by the upgraded Collider Detector at
Fermilab. Events are selected that have a high-transverse momentum electron or
muon, missing transverse energy, and two jets, one of which is consistent with
a hadronization of a b quark. Both the number of events and the dijet mass
distribution are consistent with standard model background expectations, and we
set 95% confidence level upper limits on the production cross section times
branching ratio for the Higgs boson or any new particle with similar decay
kinematics. These upper limits range from 10 pb for mH=110 GeV/c2 to 3 pb for
mH=150 GeV/c2.Comment: 7 pages, 3 figures; updated title to published versio
Search for anomalous semileptonic decay of heavy flavor hadrons produced in association with a W boson at CDF II
We present a search for anomalous semileptonic decays of heavy flavor hadrons
produced in association with a boson, in proton-antiproton collisions at
sqrt{s}=1.96 TeV. We use 162 pb-1 of data collected with the CDF II detector at
the Fermilab Tevatron Collider. We select events with one W boson and at least
one jet with an identified secondary vertex. In the jets with a secondary
vertex we look for a semileptonic decay to a muon. We compare the number of
jets with both a secondary vertex and a semileptonic decay, and the kinematic
properties of these jets, with the standard model expectation of W plus heavy
flavor production and decay. No discrepancy is seen between the observation and
the expectation, and we set limits on the production cross section of a B-like
hadron with an anomalously high semileptonic branching ratio.Comment: 8 pages, 2 figures, submitted to PRD-RC; replaced to adjust the page
forma
Search for Second-Generation Scalar Leptoquarks in Collisions at =1.96 TeV
Results on a search for pair production of second generation scalar
leptoquark in collisions at =1.96 TeV are reported. The
data analyzed were collected by the CDF detector during the 2002-2003 Tevatron
Run II and correspond to an integrated luminosity of 198 pb. Leptoquarks
(LQ) are sought through their decay into (charged) leptons and quarks, with
final state signatures represented by two muons and jets and one muon, large
transverse missing energy and jets. We observe no evidence for production
and derive 95% C.L. upper limits on the production cross sections as well
as lower limits on their mass as a function of , where is the
branching fraction for .Comment: 9 pages (3 author list) 5 figure
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