RESUMO
BACKGROUND: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. METHODS: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. RESULTS: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001). CONCLUSIONS: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.
Assuntos
Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Mesotelioma Maligno/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pleurais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imuno-Histoquímica , Imunoterapia , Masculino , Mesotelioma Maligno/genética , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/terapia , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Neoplasias Pleurais/genética , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The gamma decay from Coulomb excitation of 68Ni at 600 MeV/nucleon on a Au target was measured using the RISING setup at the fragment separator of GSI. The 68Ni beam was produced by a fragmentation reaction of 86Kr at 900 MeV/nucleon on a 9Be target and selected by the fragment separator. The gamma rays produced at the Au target were measured with HPGe detectors at forward angles and with BaF2 scintillators at backward angles. The measured spectra show a peak centered at approximately 11 MeV, whose intensity can be explained in terms of an enhanced strength of the dipole response function (pygmy resonance). Such pygmy structure has been predicted in this unstable neutron-rich nucleus by theory.
RESUMO
The gamma decay associated with the warm rotation of the superdeformed nuclei 151Tb and 196Pb has been measured with the EUROBALL IV array. Several independent quantities provide a stringent test of the population and decay dynamics in the superdeformed well. A Monte Carlo simulation of the gamma decay based on microscopic calculations gives remarkable agreement with the data only assuming a large enhancement of the B(E1) strength for 1-2 MeV gamma rays, which may be related to the evidence for octupole vibrations in both mass regions.
RESUMO
The particulate matter (PM) concentration and composition, the PM10, PM2.5, PM1 fractions, were studied in the urban area of Genoa, a coastal town in the northwest of Italy. Two instruments, the continuous monitor TEOM and the sequential sampler PARTISOL, were operated almost continuously on the same site from July 2001 to September 2004. Samples collected by PARTISOL were weighted to obtain PM concentration and then analysed by PIXE (particle induced X-ray emission) and by ED-XRF (energy dispersion X-ray fluorescence), obtaining concentrations for elements from Na to Pb. Some of the filters used in the TEOM microbalance were analysed by ED-XRF to calculate Pb concentration values averaged over 7-30 d periods.
Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Cidades , Itália , Tamanho da Partícula , Estações do AnoRESUMO
The double pi(0) photoproduction off the proton has been measured in the beam energy range of 0.65-1.5 GeV. The total and differential cross sections and the Sigma beam asymmetry were extracted. The total cross section measured for the first time in the third resonance region of the nucleon shows a prominent peak. The interpretation of these results by two independent theoretical models infers mostly the selective excitation of P11- and D13-nucleon resonances.
