758 research outputs found
Stereotactic body radiation therapy for hepatocellular carcinoma: Practice patterns, dose selection and factors impacting survival
Background Stereotactic body radiation therapy (SBRT) is an emerging option for unresectable hepatocellular carcinoma (HCC) without consensus regarding optimal dose schemas. This analysis identifies practice patterns and factors that influence dose selection and overall survival, with particular emphasis on dose and tumor size. Materials/Methods Query of the National Cancer Database (NCDB) identified patients with unresectable, nonmetastatic HCC who received SBRT from 2004 to 2013. Biological Effective Dose (BED) was calculated for each patient in order to uniformly analyze different fractionation regimens. Results A total of 456 patients met the inclusion criteria. The median BED was 100 Gy (22.5-208.0), which corresponded to the most common dose fractionation (50 Gy in five fractions). Various factors influenced dose selection including tumor size (P 2 to 4 months, HR 2.192, P < 0.001) were associated with worse survival. Conclusion SBRT use is increasing for HCC, and multiple regimens are clinically employed. Although high BED was associated with improved outcomes, multiple factors contributed to the dose selection with favorable patients receiving higher doses. Continued efforts to enhance radiation planning and delivery may help improve utilization, safety, and efficacy.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide
Glioma stem cells (GSCs) from human glioblastomas (GBMs) are resistant to radiation and chemotherapy and may drive recurrence. Treatment efficacy may depend on GSCs, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype
Modeling Astrocytoma Pathogenesis <em>In Vitro</em> and <em>In Vivo</em> Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
Current astrocytoma models are limited in their ability to define the roles of oncogenic mutations in specific brain cell types during disease pathogenesis and their utility for preclinical drug development. In order to design a better model system for these applications, phenotypically wild-type cortical astrocytes and neural stem cells (NSC) from conditional, genetically engineered mice (GEM) that harbor various combinations of floxed oncogenic alleles were harvested and grown in culture. Genetic recombination was induced in vitro using adenoviral Cre-mediated recombination, resulting in expression of mutated oncogenes and deletion of tumor suppressor genes. The phenotypic consequences of these mutations were defined by measuring proliferation, transformation, and drug response in vitro. Orthotopic allograft models, whereby transformed cells are stereotactically injected into the brains of immune-competent, syngeneic littermates, were developed to define the role of oncogenic mutations and cell type on tumorigenesis in vivo. Unlike most established human glioblastoma cell line xenografts, injection of transformed GEM-derived cortical astrocytes into the brains of immune-competent littermates produced astrocytomas, including the most aggressive subtype, glioblastoma, that recapitulated the histopathological hallmarks of human astrocytomas, including diffuse invasion of normal brain parenchyma. Bioluminescence imaging of orthotopic allografts from transformed astrocytes engineered to express luciferase was utilized to monitor in vivo tumor growth over time. Thus, astrocytoma models using astrocytes and NSC harvested from GEM with conditional oncogenic alleles provide an integrated system to study the genetics and cell biology of astrocytoma pathogenesis in vitro and in vivo and may be useful in preclinical drug development for these devastating diseases
Primordial nucleosynthesis with a varying fine structure constant: An improved estimate
We compute primordial light-element abundances for cases with fine structure
constant alpha different from the present value, including many sources of
alpha dependence neglected in previous calculations. Specifically, we consider
contributions arising from Coulomb barrier penetration, photon coupling to
nuclear currents, and the electromagnetic components of nuclear masses. We find
the primordial abundances to depend more weakly on alpha than previously
estimated, by up to a factor of 2 in the case of ^7Li. We discuss the
constraints on variations in alpha from the individual abundance measurements
and the uncertainties affecting these constraints. While the present best
measurements of primordial D/H, ^4He/H, and ^7Li/H may be reconciled pairwise
by adjusting alpha and the universal baryon density, no value of alpha allows
all three to be accommodated simultaneously without consideration of systematic
error. The combination of measured abundances with observations of acoustic
peaks in the cosmic microwave background favors no change in alpha within the
uncertainties.Comment: Phys. Rev. D accepted version; minor changes in response to refere
Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis
Glioblastoma (GBM) genomes feature recurrent genetic alterations that dysregulate core intracellular signaling pathways, including the G1/S cell cycle checkpoint and the MAPK and PI3K effector arms of receptor tyrosine kinase (RTK) signaling. Elucidation of the phenotypic consequences of activated RTK effectors is required for the design of effective therapeutic and diagnostic strategies
Generation of Bianchi type V cosmological models with varying -term
Bianchi type V perfect fluid cosmological models are investigated with
cosmological term varying with time. Using a generation technique
(Camci {\it et al.}, 2001), it is shown that the Einstein's field equations are
solvable for any arbitrary cosmic scale function. Solutions for particular
forms of cosmic scale functions are also obtained. The cosmological constant is
found to be decreasing function of time, which is supported by results from
recent type Ia supernovae observations. Some physical aspects of the models are
also discussed.Comment: 16 pages, 3 figures, submitted to CJ
A Study of Cosmic Ray Composition in the Knee Region using Multiple Muon Events in the Soudan 2 Detector
Deep underground muon events recorded by the Soudan 2 detector, located at a
depth of 2100 meters of water equivalent, have been used to infer the nuclear
composition of cosmic rays in the "knee" region of the cosmic ray energy
spectrum. The observed muon multiplicity distribution favors a composition
model with a substantial proton content in the energy region 800,000 -
13,000,000 GeV/nucleus.Comment: 38 pages including 11 figures, Latex, submitted to Physical Review
A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007
We present the results of the first search for gravitational wave bursts
associated with high energy neutrinos. Together, these messengers could reveal
new, hidden sources that are not observed by conventional photon astronomy,
particularly at high energy. Our search uses neutrinos detected by the
underwater neutrino telescope ANTARES in its 5 line configuration during the
period January - September 2007, which coincided with the fifth and first
science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed
for candidate gravitational-wave signals coincident in time and direction with
the neutrino events. No significant coincident events were observed. We place
limits on the density of joint high energy neutrino - gravitational wave
emission events in the local universe, and compare them with densities of
merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at
http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000
Standalone vertex ïŹnding in the ATLAS muon spectrometer
A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at âs = 7 TeV collected with the ATLAS detector at the LHC during 2011
Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC
Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H âÎł Îł, H â Z Zâ â4l and H âW Wâ âlÎœlÎœ. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of âs = 7 TeV and âs = 8 TeV, corresponding to an integrated luminosity of about 25 fbâ1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined ïŹts probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson
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