Search

Endobronchial valves (EBVs) are a novel, minimally invasive bronchoscopic management technique for persistent air leaks that fail conservative therapy. Currently, 2 EBVs are available in the United States: the Spiration Valve System (Olympus, Redmond, WA) and the Zephyr Valve (Pulmonx, Redwood, CA). These valves are Food and Drug Administration–approved to reduce hyperinflation in emphysematous patients via bronchoscopic lung-volume reduction. However, more recently, the Spiration Valve has been granted a compassionate use exemption through the Food and Drug Administration for persistent postsurgical air leaks. Despite their popularity, these devices are not free from side effects. As an anesthesiologist, it is vital to be aware of the pathophysiology of this patient population so that safe and effective anesthetics may be provided during valve placement. Here, the use of EBVs is discussed in a patient who presented with a persistent air leak after a transthoracic needle aspiration that failed treatment due to persistent hypoxemia, warranting EBV removal. [ABSTRACT FROM AUTHOR]

Self-focused attention is an important target of intervention within Wells's (2009) metacognitive therapy and the attention training technique (ATT) is one component of metacognitive therapy that purportedly alters focus of attention. However, we do not yet fully understand whether ATT causes changes in focus of attention, the effectiveness of ATT compared to other techniques in reducing self-focused attention, and how ATT leads to its therapeutic gains. A laboratory-based component study was completed to address these gaps in the literature. Nonclinical participants were randomly assigned to one session of ATT ( n = 38) or a mindfulness-based task ( n = 38). ATT and the mindfulness-based task differentially changed focus of attention, with ATT causing greater external focus of attention and the mindfulness-based task causing greater self-focused attention from pre-to-post manipulation. ATT and the mindfulness-based task both led to reductions in anxiety. Reductions in self-focused attention were related to less anxiety following ATT, whereas increases in self-focused attention were related to less anxiety following the mindfulness-based task. Conceptual and therapeutic implications are discussed. [ABSTRACT FROM AUTHOR]

Abstract: We have identified a new series of C-5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. [Copyright &y& Elsevier]

Abstract: Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase. [Copyright &y& Elsevier]

The development and progression of cancer is controlled by gene expression, often regulated through chromatin packaging. Heterochromatin protein 1Hsα (HP1Hsα), one of three human HP1 family members, participates in heterochromatin formation and gene regulation. HP1Hsα possesses an amino-terminal chromodomain, which binds methylated lysine 9 of histone H3 (meK9 H3), and a carboxyl-terminal chromoshadow domain (CSD) that is required for dimerization and interaction with partner proteins. HP1Hsα is down-regulated in invasive metastatic breast cancer cells compared with poorly invasive nonmetastatic breast cancer cells. Expression of EGFP-HP1Hsα in highly invasive MDA-MB-231 cells causes a reduction in in vitro invasion, without affecting cell growth. Conversely, knock-down of HP1Hsα levels in the poorly invasive breast cancer cell line MCF-7 increased invasion, without affecting cell growth. To determine whether functions of the CSD were required for the regulation of invasion, mutant forms of HP1Hsα were expressed in MDA-MB-231 cells. A W174A mutation that disrupts interactions between HP1Hsα and PXVXL-containing partner proteins reduced invasion similar to that of the wild type protein. In contrast, an 1165E mutation that disrupts dimerization of HP1Hsα did not decrease invasion. No gross changes in localization and abundance of HP1Hsβ, HP1Hsγ, and meK9 H3 were observed upon expression of wild type and mutant forms of HP1Hsα in MDA-MB-231 cells. Taken together, these data demonstrate that modulation of HP1Hsα alters the invasive potential of breast cancer cells through mechanisms requiring HP1 dimerization, but not interactions with PXVXL-containing proteins. [ABSTRACT FROM AUTHOR]