127 research outputs found
Pan-cancer analysis and in vitro validation of the oncogenic and prognostic roles of AURKA in human cancers
BackgroundAurora kinase A (AURKA) plays a pivotal role in regulating cell mitosis and tumor progression. However, its prognostic significance across diverse cancer types remains relatively unexplored.MethodsWe conducted a comprehensive analysis of AURKA expression in various cancers using data from The Cancer Genome Atlas, Genotype-Tissue Expression, and The Human Protein Atlas databases. Our investigation encompassed an exploration of the associations between AURKA expression and clinical characteristics, shedding light on potential functional roles of AURKA. Additionally, we delved into the relationship between AURKA and the tumor microenvironment. To substantiate the role of AURKA, we carried out in vitro experiments in esophageal adenocarcinoma (EAC), prostate cancer (PRAD), and pancreatic cancer (PAAD) cells.ResultsOur analysis revealed that AURKA is prominently overexpressed in a majority of the cancer types under investigation. Elevated AURKA expression correlated closely with poorer prognosis and advanced tumor stages. AURKA was found to be associated with key pathways involved in the cell cycle and arachidonic acid metabolism. Moreover, AURKA expression exhibited significant correlations with immunoregulatory genes and immune cell profiles. Notably, in vitro experiments demonstrated that silencing AURKA expression resulted in reduced cell viability in EAC, PRAD, and PAAD cells, as well as a decrease in clone formation, cell cycle elongation, diminished cell invasion and reduced spheroid size in EAC cells (OE33 and OE19).ConclusionOur study elucidates the oncogenic role of AURKA and underscores its prognostic value across a spectrum of cancers, including EAC. These findings suggest that AURKA holds promise as a predictive biomarker for EAC and various other tumor types
Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer
Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Investigation of two Fermi-LAT gamma-ray blazars coincident with high-energy neutrinos detected by IceCube
After the identification of the gamma-ray blazar TXS 0506+056 as the first
compelling IceCube neutrino source candidate, we perform a systematic analysis
of all high-energy neutrino events satisfying the IceCube realtime trigger
criteria. We find one additional known gamma-ray source, the blazar GB6
J1040+0617, in spatial coincidence with a neutrino in this sample. The chance
probability of this coincidence is 30% after trial correction. For the first
time, we present a systematic study of the gamma-ray flux, spectral and optical
variability, and multi-wavelength behavior of GB6 J1040+0617 and compare it to
TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the
Fermi-LAT gamma-ray band, being in an active state around the arrival of
IceCube-170922A, but in a low state during the archival IceCube neutrino flare
in 2014/15. In both cases the spectral shape is statistically compatible () with the average spectrum showing no indication of a significant
relative increase of a high-energy component. While the association of GB6
J1040+0617 with the neutrino is consistent with background expectations, the
source appears to be a plausible neutrino source candidate based on its
energetics and multi-wavelength features, namely a bright optical flare and
modestly increased gamma-ray activity. Finding one or two neutrinos originating
from gamma-ray blazars in the given sample of high-energy neutrinos is
consistent with previously derived limits of neutrino emission from gamma-ray
blazars, indicating the sources of the majority of cosmic high-energy neutrinos
remain unknown.Comment: 22 pages, 11 figures, 2 Table
Design of an Efficient, High-Throughput Photomultiplier Tube Testing Facility for the IceCube Upgrade
Multi-messenger searches via IceCube’s high-energy neutrinos and gravitational-wave detections of LIGO/Virgo
We summarize initial results for high-energy neutrino counterpart searches coinciding with gravitational-wave events in LIGO/Virgo\u27s GWTC-2 catalog using IceCube\u27s neutrino triggers. We did not find any statistically significant high-energy neutrino counterpart and derived upper limits on the time-integrated neutrino emission on Earth as well as the isotropic equivalent energy emitted in high-energy neutrinos for each event
Non-standard neutrino interactions in IceCube
Non-standard neutrino interactions (NSI) may arise in various types of new physics. Their existence would change the potential that atmospheric neutrinos encounter when traversing Earth matter and hence alter their oscillation behavior. This imprint on coherent neutrino forward scattering can be probed using high-statistics neutrino experiments such as IceCube and its low-energy extension, DeepCore. Both provide extensive data samples that include all neutrino flavors, with oscillation baselines between tens of kilometers and the diameter of the Earth.
DeepCore event energies reach from a few GeV up to the order of 100 GeV - which marks the lower threshold for higher energy IceCube atmospheric samples, ranging up to 10 TeV.
In DeepCore data, the large sample size and energy range allow us to consider not only flavor-violating and flavor-nonuniversal NSI in the μ−τ sector, but also those involving electron flavor.
The effective parameterization used in our analyses is independent of the underlying model and the new physics mass scale. In this way, competitive limits on several NSI parameters have been set in the past. The 8 years of data available now result in significantly improved sensitivities. This improvement stems not only from the increase in statistics but also from substantial improvement in the treatment of systematic uncertainties, background rejection and event reconstruction
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