Circulating Tumor Cell Transcriptomics as Biopsy Surrogates in Metastatic Breast Cancer

BACKGROUND Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases. METHODS We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients. CTCs were harvested using the ANGLE Parsortix microfluidics system to isolate cells based on size and deformability, independent of a priori knowledge of cell surface marker expression. RESULTS Gene expression separated CTCs, metastatic biopsies, and PB into distinct groups despite heterogeneity between patients and sample types. CTCs showed higher expression of immune oncology targets compared with corresponding metastases and PB. Predictive biomarker (n = 64) expression was highly concordant for CTCs and metastases. Repeat observation data post-treatment demonstrated changes in the activation of different biological pathways. Somatic single nucleotide variant analysis showed increasing mutational complexity over time. CONCLUSION We demonstrate that RNA-Seq of CTCs could serve as a surrogate biomarker for breast cancer macrometastasis and yield clinically relevant insights into disease biology and clinically actionable targets

Development of a PbWO4 Detector for Single-Shot Positron Annihilation Lifetime Spectroscopy at the GBAR Experiment

We have developed a PbWO4 (PWO) detector with a large dynamic range to measure the intensity of a positron beam and the absolute density of the ortho-positronium (o-Ps) cloud it creates. A simulation study shows that a setup based on such detectors may be used to determine the angular distribution of the emission and reflection of o-Ps to reduce part of the uncertainties of the measurement. These will allow to improve the precision in the measurement of the cross-section for the (anti)hydrogen formation by (anti)proton-positronium charge exchange and to optimize the yield of antihydrogen ion which is an essential parameter in the GBAR experiment

Observation of the rare decay K_S -> pi^0mu^+mu^-

A search for the decay K_S -> pi^0mu^+mu^- has been made by the NA48/1 Collaboration at the CERN SPS accelerator. The data were collected during 2002 with a high-intensity K_S beam. Six events were found with a background expectation of 0.22^+0.18_-0.11 event. Using a vector matrix element and unit form factor, the measured branching ratio is B(K_S -> pi^0mu^+mu^-)=[2.9^+1.5_-1.2(stat)+/-0.2(syst)]x10^{-9}.Comment: 19 pages, 8 figures, 4 tables. To be published in Physics Letters

First observation of the KS->pi0 gamma gamma decay

Using the NA48 detector at the CERN SPS, 31 KS->pi0 gamma gamma candidates with an estimated background of 13.7 +- 3.2 events have been observed. This first observation leads to a branching ratio of BR(KS->pi0 gamma gamma) = (4.9 +- 1.6(stat) +- 0.9(syst)) x 10^-8 in agreement with Chiral Perturbation theory predictions.Comment: 10 pages, 4 figures submitted to Phys. Lett.

Search for CP violation in K0 -> 3 pi0 decays

Using data taken during the year 2000 with the NA48 detector at the CERN SPS, a search for the CP violating decay K_S -> 3 pi0 has been performed. From a fit to the lifetime distribution of about 4.9 million reconstructed K0/K0bar -> 3 pi0 decays, the CP violating amplitude eta_000 = A(K_S -> 3 pi0)/A(K_L -> 3 pi0) has been found to be Re(eta_000) = -0.002 +- 0.011 +- 0.015 and Im(eta_000) = -0.003 +- 0.013 +- 0.017. This corresponds to an upper limit on the branching fraction of Br(K_S -> 3 pi0) < 7.4 x 10^-7 at 90% confidence level. The result is used to improve knowledge of Re(epsilon) and the CPT violating quantity Im(delta) via the Bell-Steinberger relation.Comment: 18 pages, 7 figures, submitted to Phys. Lett.

A precision measurement of direct CP violation in the decay of neutral kaons into two pions

The direct CP violation parameter Re(epsilon'/epsilon) has been measured from the decay rates of neutral kaons into two pions using the NA48 detector at the CERN SPS. The 2001 running period was devoted to collecting additional data under varied conditions compared to earlier years (1997-99). The new data yield the result: Re(epsilon'/epsilon) = (13.7 +/- 3.1) times 10^{-4}. Combining this result with that published from the 1997, 98 and 99 data, an overall value of Re(epsilon'/epsilon) = (14.7 +/- 2.2) times 10^{-4} is obtained from the NA48 experiment.Comment: 19 pages, 5 figures, to be published in Physics Letters

Measurement of the branching ratio of the decay Ξ0→Σ+μ−νˉμ\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}

From the 2002 data taking with a neutral kaon beam extracted from the CERN-SPS, the NA48/1 experiment observed 97 $\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$ candidates with a background contamination of $30.8 \pm 4.2$ events. From this sample, the BR($\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$) is measured to be $(2.17 \pm 0.32_{\mathrm{stat}}\pm 0.17_{\mathrm{syst}})\times10^{-6}$

A new measurement of direct CP violation in two pion decays of the neutral kaon

The NA48 experiment at CERN has performed a new measurement of direct CP violation, based on data taken in 1997 by simultaneously collecting K_L and K_S decays into pi0pi0 and pi+pi-. The result for the CP violating parameter Re(epsilon'/epsilon) is (18.5 +/- 4.5(stat)} +/- 5.8 (syst))x10^{-4}.Comment: 18 pages, 6 figure

Measurement of the Ratio Gamma(KL -> pi+ pi-)/Gamma(KL -> pi e nu) and Extraction of the CP Violation Parameter |eta+-|

We present a measurement of the ratio of the decay rates Gamma(KL -> pi+ pi-)/Gamma(KL -> pi e nu), denoted as Gamma(K2pi)/Gamma(Ke3). The analysis is based on data taken during a dedicated run in 1999 by the NA48 experiment at the CERN SPS. Using a sample of 47000 K2pi and five million Ke3 decays, we find Gamma(K2pi)/Gamma(Ke3) = (4.835 +- 0.022(stat) +- 0.016(syst)) x 10^-3. From this we derive the branching ratio of the CP violating decay KL -> pi+ pi- and the CP violation parameter |eta+-|. Excluding the CP conserving direct photon emission component KL -> pi+ pi- gamma, we obtain the results BR(KL -> pi+ pi-) = (1.941 +- 0.019) x 10^-3 and |eta+-| = (2.223 +- 0.012) x 10^-3.Comment: 20 pages, 7 figures, accepted by Phys. Lett.