Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs.</p> <p>Methods</p> <p>55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated.</p> <p>Results</p> <p>Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact.</p> <p>Conclusions</p> <p>Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.</p

Search for periodic signals in the dielectron and diphoton invariant mass spectra using 139 fb−1 of pp collisions at s \sqrt{s} = 13 TeV with the ATLAS detector

Acknowledgements: We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; ANID, Chile; CAS, MOST and NSFC, China; Minciencias, Colombia; MEYS CR, Czech Republic; DNRF and DNSRC, Denmark; IN2P3-CNRS and CEA-DRF/IRFU, France; SRNSFG, Georgia; BMBF, HGF and MPG, Germany; GSRI, Greece; RGC and Hong Kong SAR, China; ISF and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; NWO, Netherlands; RCN, Norway; MEiN, Poland; FCT, Portugal; MNE/IFA, Romania; MESTD, Serbia; MSSR, Slovakia; ARRS and MIZŠ, Slovenia; DSI/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SERI, SNSF and Cantons of Bern and Geneva, Switzerland; MOST, Taiwan; TENMAK, Türkiye; STFC, United Kingdom; DOE and NSF, United States of America. In addition, individual groups and members have received support from BCKDF, CANARIE, Compute Canada and CRC, Canada; PRIMUS 21/SCI/017 and UNCE SCI/013, Czech Republic; COST, ERC, ERDF, Horizon 2020 and Marie Skłodowska-Curie Actions, European Union; Investissements d’Avenir Labex, Investissements d’Avenir Idex and ANR, France; DFG and AvH Foundation, Germany; Herakleitos, Thales and Aristeia programmes co-financed by EU-ESF and the Greek NSRF, Greece; BSF-NSF and MINERVA, Israel; Norwegian Financial Mechanism 2014-2021, Norway; NCN and NAWA, Poland; La Caixa Banking Foundation, CERCA Programme Generalitat de Catalunya and PROMETEO and GenT Programmes Generalitat Valenciana, Spain; Göran Gustafssons Stiftelse, Sweden; The Royal Society and Leverhulme Trust, United Kingdom. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN, the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (U.K.) and BNL (U.S.A.), the Tier-2 facilities worldwide and large non-WLCG resource providers. Major contributors of computing resources are listed in ref. [80].Abstract A search for physics beyond the Standard Model inducing periodic signals in the dielectron and diphoton invariant mass spectra is presented using 139 fb−1 of $$\sqrt{s}$$ s = 13 TeV pp collision data collected by the ATLAS experiment at the LHC. Novel search techniques based on continuous wavelet transforms are used to infer the frequency of periodic signals from the invariant mass spectra and neural network classifiers are used to enhance the sensitivity to periodic resonances. In the absence of a signal, exclusion limits are placed at the 95% confidence level in the two-dimensional parameter space of the clockwork gravity model. Model-independent searches for deviations from the background-only hypothesis are also performed.</jats:p