Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis

<p>Abstract</p> <p>Background</p> <p>Epithelial mesenchymal transition (EMT) is a crucial event likely involved in dissemination of epithelial cancer cells. This process enables them to acquire migratory/invasive properties, contributing to tumor and metastatic spread. To know if this event is an early one in breast cancer, we developed a clinical trial. The aim of this protocol was to detect circulating tumor cells endowed with mesenchymal and/or stemness characteristics, at the time of initial diagnosis. Breast cancer patients (n = 61), without visceral or bone metastasis were enrolled and analysis of these dedifferentiated circulating tumor cells (ddCTC) was realized.</p> <p>Methods</p> <p><it>AdnaGen </it>method was used for enrichment cell selection. Then, ddCTC were characterized by RT-PCR study of the following genes: PI3Kα, Akt-2, Twist1 (EMT markers) and ALDH1, Bmi1 and CD44 (stemness indicators).</p> <p>Results</p> <p>Among the studied primary breast cancer cohort, presence of ddCTC was detected in 39% of cases. This positivity is independant from tumor clinicopathological factors apart from the lymph node status.</p> <p>Conclusions</p> <p>Our data uniquely demonstrated that <it>in vivo </it>EMT occurs in the primary tumors and is associated with an enhanced ability of tumor cells to intravasate in the early phase of cancer disease. These results suggest that analysis of circulating tumor cells focused on cells showing mesenchymal or stemness characteristics might facilitate assessment of new drugs in clinical trials.</p

Topological Defects in the Random-Field XY Model and the Pinned Vortex Lattice to Vortex Glass Transition in Type-II Superconductors

As a simplified model of randomly pinned vortex lattices or charge-density waves, we study the random-field XY model on square ($d=2$) and simple cubic ($d=3$) lattices. We verify in Monte Carlo simulations, that the average spacing between topological defects (vortices) diverges more strongly than the Imry-Ma pinning length as the random field strength, $H$, is reduced. We suggest that for $d=3$ the simulation data are consistent with a topological phase transition at a nonzero critical field, $H_c$, to a pinned phase that is defect-free at large length-scales. We also discuss the connection between the possible existence of this phase transition in the random-field XY model and the magnetic field driven transition from pinned vortex lattice to vortex glass in weakly disordered type-II superconductors.Comment: LATEX file; 5 Postscript figures are available from [email protected]

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Deep sub-threshold Ξ−\Xi^- production in Ar+KCl reactions at 1.76A GeV

We report first results on a deep sub-threshold production of the doubly strange hyperon $\Xi^-$ in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar+KCl was studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18/GSI. A high-statistics and high-purity $\Lambda$ sample was collected, allowing for the investigation of the decay channel $\Xi^- \to \Lambda \pi^-$. The deduced $\Xi^-/(\Lambda+\Sigma^0)$ production ratio of $(5.6 \pm 1.2 ^{+1.8}_{-1.7})\cdot 10^{-3}$ is significantly larger than available model predictions.Comment: 4 pages, including 4 figure

Study of the quasi-free np→npπ+π−np \to np \pi^+\pi^- reaction with a deuterium beam at 1.25 GeV/nucleon

The tagged quasi-free $np \to np\pi^+\pi^-$ reaction has been studied experimentally with the High Acceptance Di-Electron Spectrometer (HADES) at GSI at a deuteron incident beam energy of 1.25 GeV/nucleon ($\sqrt s \sim$ 2.42 GeV/c for the quasi-free collision). For the first time, differential distributions for $\pi^{+}\pi^{-}$ production in $np$ collisions have been collected in the region corresponding to the large transverse momenta of the secondary particles. The invariant mass and angular distributions for the $np\rightarrow np\pi^{+}\pi^{-}$ reaction are compared with different models. This comparison confirms the dominance of the $t$-channel with $\Delta\Delta$ contribution. It also validates the changes previously introduced in the Valencia model to describe two-pion production data in other isospin channels, although some deviations are observed, especially for the $\pi^{+}\pi^{-}$ invariant mass spectrum. The extracted total cross section is also in much better agreement with this model. Our new measurement puts useful constraints for the existence of the conjectured dibaryon resonance at mass M$\sim$ 2.38 GeV and with width $\Gamma\sim$ 70 MeV

Inclusive Dielectron Production in Ar+KCl Collisions at 1.76 AGeV studied with HADES

Results of the HADES measurement of inclusive dielectron production in Ar+KCl collisions at a kinetic beam energy of 1.76 AGeV are presented. For the first time, high mass resolution spectroscopy was performed. The invariant mass spectrum of dielectrons is compared with predictions of UrQMD and HSD transport codes.Comment: 4 pages, 3 figures - To appear in the conference proceedings for Quark Matter 2009, March 30 - April 4, Knoxville, Tennesse

Meson and di-electron production with HADES

The HADES experiment, installed at GSI, Darmstadt, measures di-electron production in A+A, p/pi+N and p/pi+A collisions. Here, the pi0 and eta Dalitz decays have been reconstructed in the exclusive p+p reaction at 2.2 GeV to form a reference cocktail for long-lived di-electron sources. In the C+C reaction at 1 and 2 GeV/u, these long-lived sources have been subtracted from the measured inclusive e+e- yield to exhibit the signal from the early phase of the collision. The results suggest that resonances play an important role in dense nuclear matter.Comment: Invited plenary talk at the 10th International Workshop On Meson Production, Properties And Interaction (MESON 2008) 6-10 Jun 2008, Cracow, Polan

Future perspectives at SIS-100 with HADES-at-FAIR

Currently, the HADES spectrometer undergoes un upgrade program to be prepared for measurements at the upcoming SIS-100 synchrotron at FAIR. We describe the current status of the HADES di-electron measurements at the SIS-18 and our future plans for SIS-100.Comment: Invited contribution presented at the XLVII International Winter Meeting on Nuclear Physics, Bormio (Italy), Jan. 26-30, 200

The High-Acceptance Dielectron Spectrometer HADES

HADES is a versatile magnetic spectrometer aimed at studying dielectron production in pion, proton and heavy-ion induced collisions. Its main features include a ring imaging gas Cherenkov detector for electron-hadron discrimination, a tracking system consisting of a set of 6 superconducting coils producing a toroidal field and drift chambers and a multiplicity and electron trigger array for additional electron-hadron discrimination and event characterization. A two-stage trigger system enhances events containing electrons. The physics program is focused on the investigation of hadron properties in nuclei and in the hot and dense hadronic matter. The detector system is characterized by an 85% azimuthal coverage over a polar angle interval from 18 to 85 degree, a single electron efficiency of 50% and a vector meson mass resolution of 2.5%. Identification of pions, kaons and protons is achieved combining time-of-flight and energy loss measurements over a large momentum range. This paper describes the main features and the performance of the detector system