95 research outputs found
Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies
Pathophysiology and treatment of rheumatic disease
FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy
An Observational Overview of Solar Flares
We present an overview of solar flares and associated phenomena, drawing upon
a wide range of observational data primarily from the RHESSI era. Following an
introductory discussion and overview of the status of observational
capabilities, the article is split into topical sections which deal with
different areas of flare phenomena (footpoints and ribbons, coronal sources,
relationship to coronal mass ejections) and their interconnections. We also
discuss flare soft X-ray spectroscopy and the energetics of the process. The
emphasis is to describe the observations from multiple points of view, while
bearing in mind the models that link them to each other and to theory. The
present theoretical and observational understanding of solar flares is far from
complete, so we conclude with a brief discussion of models, and a list of
missing but important observations.Comment: This is an article for a monograph on the physics of solar flares,
inspired by RHESSI observations. The individual articles are to appear in
Space Science Reviews (2011
Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020
We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe
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