Abstract Background Among gastrointestinal cancers, the prognosis of pancreatic cancer is one of the poorest, with a large number of patients being diagnosed with unresectable tumors at the first ...visit to a doctor. The aims of the present study were to investigate the circulating tumor cells (CTC) in peripheral blood in order to assess their clinical significance in patients with pancreatic cancer. Methods Sixty-five patients with advanced pancreatic cancer were enrolled. Borderline resectable pancreatic tumor patients were 9, and Unresectable patients were 56. The CellSearch system was used to isolate and enumerate CTCs. Results CTCs were identified in 21 out of 65 patients (32.3%) with only unresectable tumors. The overall survival rate was significantly lower in unresectable patients with than in those without CTCs ( P = 0.0051). CTC positivity was significantly higher in patients with than in those without liver metastasis. A multivariate analysis identified the presence or absence of CTCs as an independent prognostic factor. Follow-up blood specimens were obtained from 40 patients treated with chemotherapy or chemoradiotherapy. The incidences of CTC positivity at three months after beginning of treatments in patients with progressive disease and stable disease or a partial response were 45.4% and 24.1%, respectively. The overall survival rate was significantly lower in patients with than in those without CTCs even after treatments ( P = 0.045). Conclusion CTC numbers represents a useful tool for predicting prognoses and therapeutic responses to chemotherapy among patients with advanced pancreatic cancer.
Aims. The path length distribution of Galactic cosmic rays (GCRs) is the fundamental ingredient for modeling the propagation process of GCRs based on the so-called weighted slab method. We try to ...derive this distribution numerically by taking into account the discreteness in both space and time of occurrences of supernova explosions where GCRs are suspected to be born. The resultant age distribution and ratio of B/C are to be compared with recent observations. Methods. We solve numerically the stochastic differential equations equivalent to the Parker diffusion-convection equation which describes the propagation process of GCR in the Galaxy. We assume the three-dimensional diffusion is an isotropic one without any free escape boundaries. We ignore any energy change of GCRs and the existence of the Galactic wind for simplicity. We also assume axisymmetric configurations for the density distributions of the interstellar matter and for the surface density of supernovae. We have calculated age and path length of GCR protons arriving at the solar system with this stochastic method. The obtained age is not the escape time of GCRs from the Galaxy as usually assumed, but the time spent by GCRs during their journey to the solar system from the supernova remnants where they were born. Results. The derived age and path length show a distribution spread in a wide range even for GCR protons arriving at the solar system with the same energy. The distributions show a cut-off at a lower range in age or path length depending on the energy of GCRs. These cut-offs clearly come from the discreteness of occurrence of supernovae. The mean age of GeV particles obtained from the distributions is consistent with the age obtained by direct observation of radioactive secondary nuclei. The energy dependence of the B/C ratio estimated with the path length distribution reproduces reliably the energy dependence of B/C obtained by recent observations in space.
We have developed a novel low-cost gamma-ray imaging Compton camera γI that has a high detection efficiency. Our motivation for the development of this detector was to measure the arrival directions ...of gamma rays produced by radioactive nuclides that were released by the Fukushima Daiichi nuclear power plant accident in 2011. The detector comprises two arrays of inorganic scintillation detectors, which act as a scatterer and an absorber. Each array has eight scintillation detectors, each comprising a large CsI (Tl) scintillator cube of side 3.5cm, which is inexpensive and has a good energy resolution. Energies deposited by the Compton scattered electrons and subsequent photoelectric absorption, measured by each scintillation counter, are used for image reconstruction. The angular resolution was found to be 3.5° after using an image-sharpening technique. With this angular resolution, we can resolve a 1m2 radiation hot spot that is located at a distance of 10m from the detector with a wide field of view of 1sr. Moreover, the detection efficiency 0.68cps/MBq at 1m for 662keV (7.6cps/μSv/h) is sufficient for measuring low-level contamination (i.e., less than 1μSv/h) corresponding to typical values in large areas of eastern Japan. In addition to the laboratory tests, the imaging capability of our detector was verified in various regions with dose rates less than 1μSv/h (e.g., Fukushima city).
RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline ...polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we sought to determine the frequency of RETp in cutaneous melanoma and its functional responsiveness to GDNF. RETp was assessed in 71 non-desmoplastic cutaneous melanomas (non-DMs) and 70 desmoplastic melanomas (DMs). Melanoma cell lines with RETp, RET wild type (RETwt), BRAF V600E mutation (BRAFmt) or BRAF wild type (BRAFwt) were assessed for functional activity. RETp frequency was significantly higher in DMs (61%) than in non-DMs (31%, P<0.001). BRAFmt was detected in only 11% of DMs. GDNF stimulation significantly amplified cell proliferation, migration and invasion in RETp, but not in RETwt melanoma cells. GDNF stimulation of RETp cell lines enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt of the RET-RAS-RAF-ERK and RET-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. GDNF response of RETp cells in signal transduction and other functional studies were not affected by BRAFmt. The study demonstrates that RETp is frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression.
Protons with energies up to ∼1015 eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. ...Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (π0), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in γ-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from γ-rays at energies of ∼1012 eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.
Because accretion and merger shocks in clusters of galaxies may accelerate particles to high energies, clusters are candidate sites for the origin of ultra-high-energy (UHE) cosmic rays. A prediction ...was presented for gamma-ray emission from a cluster of galaxies at a detectable level with the current generation of imaging atmospheric Cherenkov telescopes. The gamma-ray emission was produced via inverse Compton upscattering of cosmic microwave background photons by electron-positron pairs generated by collisions of UHE cosmic rays in the cluster. We observed two clusters of galaxies, Abell 3667 and Abell 4038, searching for very high energy gamma-ray emission with the CANGAROO-III atmospheric Cherenkov telescope system in 2006. The analysis showed no significant excess around these clusters, yielding upper limits on the gamma-ray emission. From a comparison of the upper limit for the northwest radio relic region of Abell 3667 with a model prediction, we derive a lower limit for the magnetic field of the region of ~0.1 Delta *mG. This shows the potential of gamma-ray observations in studies of the cluster environment. We also discuss the flux upper limit from cluster center regions using a model of gamma-ray emission from neutral pions produced in hadronic collisions of cosmic-ray protons with the intracluster medium. The derived upper limit of the cosmic-ray energy density within this framework is an order of magnitude higher than that of our Galaxy.
Sub-TeV gamma-ray emission from the northwest rim of the supernova remnant RX J0852.0-4622 was detected with the CANGAROO II telescope and recently confirmed by the HESS group. In addition, the HESS ...data revealed a very wide (up to 2 in diameter), shell-like profile of the gamma-ray emission. We carried out CANGAROO III observations in 2005 January and February with three telescopes and show here the results of threefold coincidence data. We confirm the HESS results about the morphology and the energy spectrum and find that the energy spectrum in the NW rim is consistent with that of the whole remnant.
We have observed the giant radio galaxy Centaurus A and the globular cluster omega Centauri in the TeV energy region using the CANGAROO III stereoscopic system. The system has been in operation since ...2004 with an array of four Imaging Atmospheric Cerenkov Telescopes (IACT) with similar to 100 m spacings. The observations were carried out in 2004 March and April. In total, approximately 10 hr of data were obtained for each target. No statistically significant gamma-ray signal has been found above 420 GeV over a wide angular region (a 1 degree radius from the pointing center), and we derive flux upper limits using the wholefield of view. Implications for the total energy of cosmic rays and the density of the cold dark matter are considered.
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