4,843 research outputs found
Unexpected frequency of genomic alterations in histologically normal colonic tissue from colon cancer patients
As shown by genomic studies, colorectal cancer (CRC) is a highly heterogeneous disease, where copy number alterations (CNAs) may greatly vary among different patients. To explore whether CNAs may be present also in histologically normal tissues from patients affected by CRC, we performed CGH + SNP Microarray on 15 paired tumoral and normal samples. Here, we report for the first time the occurrence of CNAs as a common feature of the histologically normal tissue from CRC patients, particularly CNAs affecting different oncogenes and tumor-suppressor genes, including some not previously reported in CRC and others known as being involved in tumor progression. Moreover, from the comparison of normal vs paired tumoral tissue, we were able to identify three groups: samples with an increased number of CNAs in tumoral vs normal tissue, samples with a similar number of CNAs in both tissues, and samples with a decrease of CNAs in tumoral vs normal tissue, which may be likely due to a selection of the cell population within the tumor. In conclusion, our approach allowed us to uncover for the first time an unexpected frequency of genetic alteration in normal tissue, suggesting that tumorigenic genetic lesions are already present in histologically normal colonic tissue and that the use in array comparative genomic hybridization (CGH) studies of normal samples as reference for the paired tumors can lead to misrepresented genomic data, which may be incomplete or limited, especially if used for the research of target molecules for personalized therapy and for the possible correlation with clinical outcome
Scales of Fermion Mass Generation and Electroweak Symmetry Breaking
The scale of mass generation for fermions (including neutrinos) and the scale
for electroweak symmetry breaking (EWSB) can be bounded from above by the
unitarity of scattering involving longitudinal weak gauge bosons or their
corresponding would-be Goldstone bosons. Including the exact n-body phase space
we analyze the 2 --> n () processes for the fermion-(anti)fermion
scattering into multiple gauge boson final states. Contrary to naive energy
power counting, we demonstrate that as becomes large, the competition
between an increasing energy factor and a phase-space suppression leads to a
{\it strong new upper bound} on the scale of fermion mass generation at a
finite value , which is {\it independent of the EWSB scale,} . For quarks, leptons and Majorana neutrinos, the
strongest 2 --> n limits range from about 3TeV to 130-170TeV (with ), depending on the measured fermion masses. Strikingly, given
the tiny neutrino masses as constrained by the neutrino oscillations,
neutrinoless double-beta decays and astrophysical observations, the unitarity
violation of scattering actually occurs at a scale no
higher than ~170 TeV. Implications for various mechanisms of neutrino mass
generation are analyzed. On the other hand, for the 2 --> n pure
Goldstone-boson scattering, we find that the decreasing phase space factor
always dominates over the growing overall energy factor when becomes large,
so that the best unitarity bound on the scale of EWSB remains at n=2.Comment: 67pp, to match PRD (minor typos fixed
Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine
Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs
A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation
20siBruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5'-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach.openopenGrassilli, Emanuela; Pisano, Fabio; Cialdella, Annamaria; Bonomo, Sara; Missaglia, Carola; Cerrito, Maria Grazia; Masiero, Laura; Ianzano, Leonarda; Giordano, Federica; Cicirelli, Vittoria; Narloch, Robert; D'Amato, Filomena; Noli, Barbara; Ferri, Gian Luca; Leone, Biagio; Stanta, Giorgio; Bonin, Serena; Helin, Kristian; Giovannoni, Roberto; Lavitrano, MarialuisaGrassilli, Emanuela; Pisano, Fabio; Cialdella, Annamaria; Bonomo, Sara; Missaglia, Carola; Cerrito, Maria Grazia; Masiero, Laura; Ianzano, Leonarda; Giordano, Federica; Cicirelli, Vittoria; Narloch, Robert; D'Amato, Filomena; Noli, Barbara; Ferri, Gian Luca; Leone, Biagio; Stanta, Giorgio; Bonin, Serena; Helin, Kristian; Giovannoni, Roberto; Lavitrano, Marialuis
A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation
Bruton’s tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumor tissue samples. p65BTK protein is expressed, through hnRNPK-dependent and IRES-driven translation, from a transcript containing an alternative first exon in the 5’UTR, and is post-transcriptionally regulated, via hnRNPK, by the MAPK pathway. p65BTK is endowed with strong transforming activity that depends on active ERK1/2 and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approac
Combined search for the standard model Higgs boson decaying to a bb pair using the full CDF data set
We combine the results of searches for the standard model Higgs boson based
on the full CDF Run II data set obtained from sqrt(s) = 1.96 TeV p-pbar
collisions at the Fermilab Tevatron corresponding to an integrated luminosity
of 9.45/fb. The searches are conducted for Higgs bosons that are produced in
association with a W or Z boson, have masses in the range 90-150 GeV/c^2, and
decay into bb pairs. An excess of data is present that is inconsistent with the
background prediction at the level of 2.5 standard deviations (the most
significant local excess is 2.7 standard deviations).Comment: To be published in Phys. Rev. Lett (v2 contains minor updates based
on comments from PRL
Evidence for t\bar{t}\gamma Production and Measurement of \sigma_t\bar{t}\gamma / \sigma_t\bar{t}
Using data corresponding to 6.0/fb of ppbar collisions at sqrt(s) = 1.96 TeV
collected by the CDF II detector, we present a cross section measurement of
top-quark pair production with an additional radiated photon. The events are
selected by looking for a lepton, a photon, significant transverse momentum
imbalance, large total transverse energy, and three or more jets, with at least
one identified as containing a b quark. The ttbar+photon sample requires the
photon to have 10 GeV or more of transverse energy, and to be in the central
region. Using an event selection optimized for the ttbar+photon candidate
sample we measure the production cross section of, and the ratio of cross
sections of the two samples. Control samples in the dilepton+photon and
lepton+photon+\met, channels are constructed to aid in decay product
identification and background measurements. We observe 30 ttbar+photon
candidate events compared to the standard model expectation of 26.9 +/- 3.4
events. We measure the ttbar+photon cross section to be 0.18+0.08 pb, and the
ratio of the cross section of ttbar+photon to ttbar to be 0.024 +/- 0.009.
Assuming no ttbar+photon production, we observe a probability of 0.0015 of the
background events alone producing 30 events or more, corresponding to 3.0
standard deviations.Comment: 9 pages, 3 figure
Precision Top-Quark Mass Measurements at CDF
We present a precision measurement of the top-quark mass using the full
sample of Tevatron TeV proton-antiproton collisions collected
by the CDF II detector, corresponding to an integrated luminosity of 8.7
. Using a sample of candidate events decaying into the
lepton+jets channel, we obtain distributions of the top-quark masses and the
invariant mass of two jets from the boson decays from data. We then compare
these distributions to templates derived from signal and background samples to
extract the top-quark mass and the energy scale of the calorimeter jets with
{\it in situ} calibration. The likelihood fit of the templates from signal and
background events to the data yields the single most-precise measurement of the
top-quark mass, \mtop = 172.85 \pm\pmComment: submitted to Phys. Rev. Let
A search for resonant production of pairs in $4.8\ \rm{fb}^{-1}p\bar{p}\sqrt{s}=1.96\ \rm{TeV}$
We search for resonant production of tt pairs in 4.8 fb^{-1} integrated
luminosity of ppbar collision data at sqrt{s}=1.96 TeV in the lepton+jets decay
channel, where one top quark decays leptonically and the other hadronically. A
matrix element reconstruction technique is used; for each event a probability
density function (pdf) of the ttbar candidate invariant mass is sampled. These
pdfs are used to construct a likelihood function, whereby the cross section for
resonant ttbar production is estimated, given a hypothetical resonance mass and
width. The data indicate no evidence of resonant production of ttbar pairs. A
benchmark model of leptophobic Z \rightarrow ttbar is excluded with m_{Z'} <
900 GeV at 95% confidence level.Comment: accepted for publication in Physical Review D Sep 21, 201
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