Possible quenching of static neutron pairing near the N=98 deformed shell gap: Rotational structures in Gd-160,Gd-161

A Gd160 beam was accelerated to an energy of 1000 MeV and, separately, bombarded thick targets of Sm154 and Dy164 in order to observe neutron-rich, rare-earth nuclei via deep-inelastic collision processes. Gammasphere was utilized to observe ?-ray emissions. Many new states and transitions were observed in Gd160 as a result of so-called unsafe Coulomb excitation. The ground-state band in Gd160 has been extended to Ip=20+ and a rotational band based on the Kp=4+ state, previously associated with a hexadecapole vibration, was observed up to 18+. The quasiparticle configuration of the Kp=4+ band has been determined, and its unusual alignment behavior may result from a possible quenching of static neutron pairing. In addition, the band based on the [523]5/2 quasineutron orbital in Gd161 was extended from 11/2- to 33/2- and also displays the same unusual alignment behavior

Immunotherapy biomarkers 2016: overcoming the barriers

This report summarizes the symposium, ‘Immunotherapy Biomarkers 2016: Overcoming the Barriers’, which was held on April 1, 2016 at the National Institutes of Health in Bethesda, Maryland. The symposium, cosponsored by the Society for Immunotherapy of Cancer (SITC) and the National Cancer Institute (NCI), focused on emerging immunotherapy biomarkers, new technologies, current hurdles to further progress, and recommendations for advancing the field of biomarker development

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade >/= 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC

Brachyury Is associated with glioma differentiation and response to temozolomide

Glioblastomas (GBMs) are the most aggressive tumor type of the central nervous system, mainly due to their high invasiveness and innate resistance to radiotherapy and chemotherapy, with temozolomide (TMZ) being the current standard therapy. Recently, brachyury was described as a novel tumor suppressor gene in gliomas, and its loss was associated with increased gliomagenesis. Here, we aimed to explore the role of brachyury as a suppressor of glioma invasion, stem cell features, and resistance to TMZ. Using gene-edited glioma cells to overexpress brachyury, we found that brachyury-positive cells exhibit reduced invasive and migratory capabilities and stem cell features. Importantly, these brachyury-expressing cells have increased expression of differentiation markers, which corroborates the results from human glioma samples andin vivotumors. Glioma cells treated with retinoic acid increased the differentiation status with concomitant increased expression of brachyury. We then selected TMZ-resistant (SNB-19) and TMZ-responsive (A172 and U373) cell lines to evaluate the role of brachyury in the response to TMZ treatment. We observed that both exogenous and endogenous brachyury activation, through overexpression and retinoic acid treatment, are associated with TMZ sensitization in glioma-resistant cell lines. In this study, we demonstrate that brachyury expression can impair aggressive glioma features associated with treatment resistance. Finally, we provide the first evidence that brachyury can be a potential therapeutic target in GBM patients who do not respond to conventional chemotherapeutic drugs.ICVSBarretos Cancer Hospital internal research foundsPortuguese FundacAo para a Ciencia e a Tecnologia (FCT)Portuguese Foundation for Science and Technology [PTDC/BEX-BID/5410/2014, UID/BIM/04773/2013 CBMR, PTDC/SAU-TOX/114549/2009-FCOMP-01-0124-FEDER-016057, PTDC/SAU-ONC/115513/2009-FCOMP-01-0124-FEDER-015949, PTDC/MED-ONC/31423/2017-POCI-01-0145-FEDER-031423]Project ON.2 SR&TD Integrated Program [NORTE-07-0124-FEDER-000017]Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER)Brazilian FAPESP grant [2012/19590-0]FCTPortuguese Foundation for Science and TechnologyEuropean CommissionFundo Social Europeu-FSEEuropean Social Fund (ESF) [SFRH/BD/81369/2011, SFRH/BPD/115730/2016][PTDC/SAU-TOX/114549/2009]info:eu-repo/semantics/publishedVersio