Collective cancer invasion forms an integrin-dependent radioresistant niche

Contains fulltext : 219833.pdf (Publisher’s version ) (Open Access)Cancer fatalities result from metastatic dissemination and therapy resistance, both processes that depend on signals from the tumor microenvironment. To identify how invasion and resistance programs cooperate, we used intravital microscopy of orthotopic sarcoma and melanoma xenografts. We demonstrate that these tumors invade collectively and that, specifically, cells within the invasion zone acquire increased resistance to radiotherapy, rapidly normalize DNA damage, and preferentially survive. Using a candidate-based approach to identify effectors of invasion-associated resistance, we targeted beta1 and alphaVbeta3/beta5 integrins, essential extracellular matrix receptors in mesenchymal tumors, which mediate cancer progression and resistance. Combining radiotherapy with beta1 or alphaV integrin monotargeting in invading tumors led to relapse and metastasis in 40-60% of the cohort, in line with recently failed clinical trials individually targeting integrins. However, when combined, anti-beta1/alphaV integrin dual targeting achieved relapse-free radiosensitization and prevented metastatic escape. Collectively, invading cancer cells thus withstand radiotherapy and DNA damage by beta1/alphaVbeta3/beta5 integrin cross-talk, but efficient radiosensitization can be achieved by multiple integrin targeting

Evidence for an Excess of Soft Photons in Hadronic Decays of Z^0

Soft photons inside hadronic jets converted in front of the DELPHI main tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the experimental data as compared to the Monte Carlo predictions is observed. This excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/- 0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected level of the inner hadronic bremsstrahlung (which is not included in the Monte Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8), which is similar in strength to the anomalous soft photon signal observed in fixed target experiments with hadronic beams.Comment: 37 pages, 9 figures, Accepted by Eur. Phys. J.

Research trends in combinatorial optimization

Acknowledgments This work has been partially funded by the Spanish Ministry of Science, Innovation, and Universities through the project COGDRIVE (DPI2017-86915-C3-3-R). In this context, we would also like to thank the Karlsruhe Institute of Technology. Open access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

Measurement of the Tau Lepton Polarisation at LEP2

A first measurement of the average polarisation P_tau of tau leptons produced in e+e- annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value P_tau = -0.164 +/- 0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV.A first measurement of the average polarisation Pτ of tau leptons produced in e + e − annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value Pτ=−0.164±0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV.A first measurement of the average polarisation P_tau of tau leptons produced in e+e- annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value P_tau = -0.164 +/- 0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV

Higgs boson searches in CP-conserving and CP-violating MSSM scenarios with the DELPHI detector

n/

Production of Xi_c^0 and Xi_b in Z decays and lifetime measurement of Xi_b

The charmed strange baryon Xi_c^0 was searched for in the decay channel Xi_c^0 -> Xi- pi+, and the beauty strange baryon Xi_b in the inclusive channel Xi_b -> Xi- l- anti-nu X, using the 3.5 million hadronic Z events collected by the DELPHI experiment in the years 1992--1995. The Xi- was reconstructed through the decay Xi- -> Lambda pi-, using a constrained fit method for cascade decays. An iterative discriminant analysis was used for the Xi_c^0 and Xi_b selection. The production rates were measured to be f_{Xi_c^0} x BR(Xi_c^0 -> Xi- pi+)= (4.7 +/- 1.4 (stat.) +/- 1.1 (syst.))10^{-4} per hadronic Z decay, and BR(b -> Xi_b) x BR(Xi_b -> Xi- l- X)= (3.0 +/- 1.0 (stat.) +/- 0.3 (syst.))10^{-4} for each lepton species (electron or muon). The lifetime of the Xi_b baryon was measured to be tau_{Xi_b} = 1.45{^{+0.55}_{-0.43}} (stat.) +/- 0.13 (syst.) ps. A combination with the previous DELPHI lifetime measurement gives tau_{Xi_b} = 1.48{^{+0.40}_{-0.31}} (stat.) +/- 0.12 (syst.) ps.Comment: 21 pages, 9 figures, Accepted by Eur. Phys. J.

Masses, Lifetimes and Production Rates of Xi- and anti-Xi+ at LEP 1

Measurements of the Xi- and anti-Xi+ masses, mass differences, lifetimes and lifetime differences are presented. The anti-Xi+ sample used is much larger than those used previously for such measurements. In addition, the Xi production rates in Z -> b anti-b and Z -> q anti-q events are compared and the position xi* of the maximum of the xi distribution in Z -> q anti-q events is measured.Comment: 20 pages, 6 figures, Accepted by Phys. Lett.

Search for eta_b in two-photon collisions at LEP II with the DELPHI detector

The pseudoscalar meson eta_b has been searched for in two-photon interactions at LEP II. The data sample corresponds to a total integrated luminosity of 617 pb^{-1} at centre-of-mass energies ranging from 161 to 209 GeV. Upper limits at a confidence level of 95% on the product Gamma_{\gamma\gamma}(eta_b) x BR(eta_b) are 190, 470 and 660 eV/c^2 for the eta_b decaying into 4, 6 and 8 charged particles, respectively.Comment: 11 pages, 3 figures, Accepted by Phys. Lett.

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat