Prognostic and predictive value of MET deregulation in non-small cell lung cancer.

Recent progress in cancer biology has led to the discovery of increasing number of oncogene alterations that have dramatically changed the paradigm of lung cancer treatment. MET is a tyrosine kinase receptor for the hepatocyte growth factor (HGF) that is deregulated in several malignancies, including non-small cell lung cancer (NSCLC). Abnormal MET-HGF signaling pathway activation can occur via different mechanisms, including HGF and/or MET overexpression, MET gene amplification, mutations or rearrangements.

Search for Long-Lived Particles in e+ e- Collisions.

We present a search for a neutral, long-lived particle L that is produced in e+ e- collisions and decays at a significant distance from the e+ e- interaction point into various flavor combinations of two oppositely charged tracks. The analysis uses an e+ e- data sample with a luminosity of 489.1  fb(-1) collected by the BABAR detector at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and just below the ϒ(4S).

Cardiopulmonary responses and prognosis in hypertrophic cardiomyopathy: a potential role for comprehensive noninvasive hemodynamic assessment.

Objectives: This study sought to discover the key determinants of exercise capacity, maximal oxygen consumption (oxygen uptake [Vo2]), and ventilatory efficiency (ventilation/carbon dioxide output [VE/Vco2] slope) and assess the prognostic potential of metabolic exercise testing in hypertrophic cardiomyopathy (HCM).

Background: The intrinsic mechanisms leading to reduced functional tolerance in HCM are unclear.

Methods: The study sample included 156 HCM patients consecutively enrolled from January 1, 2007 to January 1, 2012 with a complete clinical assessment, including rest and stress echocardiography and cardiopulmonary exercise test (CPET) with impedance cardiography.

Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma.

The R132H mutation of cytosolic isocitrate dehydrogenase (IDH1) is present in the majority of low grade gliomas.Immunotherapy in these tumors has an interesting, still unexploited, therapeutic potential, as they are less immunosuppressive than glioblastomas. Using site-directed mutagenesis we introduced the R132H mutation into the murine glioma cell line GL261,creating mIDH1-GL261.

Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS).

Study of CP asymmetry in B^{0}-B[over ¯]^{0} mixing with inclusive dilepton events.

We present a measurement of the asymmetry A_{CP} between same-sign inclusive dilepton samples ℓ^{+}ℓ^{+} and ℓ^{-}ℓ^{-} (ℓ=e, μ) from semileptonic B decays in ϒ(4S)→BB[over ¯] events, using the complete data set recorded by the BABAR experiment near the ϒ(4S) resonance, corresponding to 471×10^{6} BB[over ¯] pairs. The asymmetry A_{CP} allows comparison between the mixing probabilities P(B[over ¯]^{0}→B^{0}) and P(B^{0}→B[over ¯]^{0}), and therefore probes CP and T violation. The result, A_{CP}=[-3.

Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography.

Rationale: Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting.

Objectives: To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates.

EGFR amplified and overexpressing glioblastomas and association with better response to adjuvant metronomic temozolomide.

Background: Lack of robust predictive biomarkers, other than MGMT promoter methylation, makes temozolomide responsiveness in newly diagnosed glioblastoma (GBM) patients difficult to predict. However, we identified patients with long-term survival (≥35 months) within a group of newly diagnosed GBM patients treated with standard or metronomic adjuvant temozolomide schedules. We thus investigated possible molecular profiles associated with longer survival following temozolomide treatment.

Prevalence and prognostic role of right ventricular involvement in stress-induced cardiomyopathy.

Background: Stress-induced cardiomyopathy (SCM) is a reversible cardiomyopathy observed in patients without significant coronary disease. The aim of this study was to assess the incidence and clinical significance of right ventricular (RV) involvement in SCM.

Methods And Results: We retrospectively analyzed echocardiograms from 40 consecutive patients who presented with SCM at Stanford University Medical Center from September 2000 to November 2010.

Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-type Glioma.

Purpose: Oncogenic fusions consisting of fibroblast growth factor receptor (FGFR) and TACC are present in a subgroup of glioblastoma (GBM) and other human cancers and have been proposed as new therapeutic targets. We analyzed frequency and molecular features of FGFR-TACC fusions and explored the therapeutic efficacy of inhibiting FGFR kinase in GBM and grade II and III glioma.

Experimental Design: Overall, 795 gliomas (584 GBM, 85 grades II and III with wild-type and 126 with IDH1/2 mutation) were screened for FGFR-TACC breakpoints and associated molecular profile.

Eosinophil-Specific Granules in Tumor Cell Cytoplasm: Unusual Ultrastructural Findings in a Case of Diffuse-Type Gastric Carcinoma.

A case of desmoplastic variant of diffuse-type gastric carcinoma in a 72-year-old woman is reported. Microscopic findings included poorly cohesive tumor cells, resembling mononuclear inflammatory cells, prominent diffuse desmoplasia, and tumor-associated tissue eosinophilia. Electron microscopy confirmed the undifferentiated phenotype of tumor cells and disclosed activated eosinophils in the tumor stroma.

Phase II study of afatinib, an irreversible ErbB family blocker, in EGFR FISH-positive non-small-cell lung cancer.

Introduction: Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. This phase II study investigated the activity and safety of afatinib in advanced non-small-cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation.

A subpopulation of circulating endothelial cells express CD109 and is enriched in the blood of cancer patients.

Background: The endothelium is not a homogeneous organ. Endothelial cell heterogeneity has been described at the level of cell morphology, function, gene expression, and antigen composition. As a consequence of the genetic, transcriptome and surrounding environment diversity, endothelial cells from different vascular beds have differentiated functions and phenotype.

VEGFA SNP rs2010963 is associated with vascular toxicity in recurrent glioblastomas and longer response to bevacizumab.

Although anti-VEGF therapy is widely used in high-grade gliomas, no predictor of response or toxicity has been reported yet. We investigated here the association of the functional single nucleotide polymorphism (SNP) rs2010963, located in the 5' untranslated terminal region of the VEGFA gene, with survival, response to bevacizumab (BVZ) and vascular toxicity. The rs2010963 was genotyped by Taqman assay in blood DNA from 954 glioma patients with available survival data, including 225 glioblastoma (GBM) patients treated with BVZ.

Search for a dark photon in e(+)e(-) collisions at BABAR.

Dark sectors charged under a new Abelian interaction have recently received much attention in the context of dark matter models. These models introduce a light new mediator, the so-called dark photon (A^{'}), connecting the dark sector to the standard model. We present a search for a dark photon in the reaction e^{+}e^{-}→γA^{'}, A^{'}→e^{+}e^{-}, μ^{+}μ^{-} using 514  fb^{-1} of data collected with the BABAR detector.

TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations.

Background: The role of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently further strengthened by the frequent occurrence of TERT promoter mutations (TERTp-mut) in gliomas and evidence that the TERT SNP genetic rs2736100 influences glioma risk. TERTp-mut creates a binding site for Ets/TCF transcription factors, whereas the common rs2853669 polymorphism disrupts another Ets/TCF site on TERT promoter.

Methods: We sequenced for TERTp-mut in 807 glioma DNAs and in 235 blood DNAs and analysed TERT expression by RT-PCR in 151 samples.

Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy.

Background: Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.

Prediction of sarcomere mutations in subclinical hypertrophic cardiomyopathy.

Background: Sarcomere protein mutations in hypertrophic cardiomyopathy induce subtle cardiac structural changes before the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic hypertrophic cardiomyopathy pre-LVH (genotype positive, LVH negative [G+LVH-]).

Perspectives for immunotherapy in glioblastoma treatment.

Purpose Of Review: Avoiding immune destruction is one emerging hallmark of cancer, including glioblastoma. The number of immunotherapy approaches to fight glioblastoma is growing. Here, we review the recent progress in four main areas: dendritic cell immunotherapy, peptide vaccination, chimeric antigen receptors and immune checkpoints.

Mechanisms of coagulative necrosis in malignant epithelial tumors (Review).

Histological tumor necrosis (TN) has been reported to indicate a poor prognosis for different human cancers. It is generally accepted that TN results from chronic ischemic injury due to rapid tumor growth. However, whether insufficient tumor vascularization and inadequate tumor cell oxygenation are the only factors causing TN remains controversial.

Search for CP violation in B0-B0 mixing using partial reconstruction of B0→D*- Xℓ+ νℓ and a kaon tag.

We present results of a search for CP violation in B0- B0 mixing with the BABAR detector. We select a sample of B0→D*- Xℓ+ ν decays with a partial reconstruction method and use kaon tagging to assess the flavor of the other B meson in the event. We determine the CP violating asymmetry ACP≡[N(B0B0)-N(B0B0)]/[N(B0B0)+N(B0B0)]=(0.

Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes.

Objective: To identify the prognostic significance of TERT promoter mutations (TERTp-mut) and their associations with common molecular alterations in glioblastomas (GBMs).

Methods: We sequenced the TERTp-mut in DNA from 395 GBMs and analyzed the results with their respective histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosome 10, TP53 mutation), and overall survival (OS).

Results: TERTp-mut were found in 299 of 395 GBMs (75.