TGLI1 transcription factor mediates breast cancer brain metastasis via activating metastasis-initiating cancer stem cells and astrocytes in the tumor microenvironment

Mechanisms for breast cancer metastasis remain unclear. Whether truncated glioma-associated oncogene homolog 1 (TGLI1), a transcription factor known to promote angiogenesis, migration and invasion, plays any role in metastasis of any tumor type has never been investigated. In this study, results of two mouse models of breast cancer metastasis showed that ectopic expression of TGLI1, but not GLI1, promoted preferential metastasis to the brain. Conversely, selective TGLI1 knockdown using antisense oligonucleotides led to decreased breast cancer brain metastasis (BCBM) in vivo. Immunohistochemical staining showed that TGLI1, but not GLI1, was increased in lymph node metastases compared to matched primary tumors, and that TGLI1 was expressed at higher levels in BCBM specimens compared to primary tumors. TGLI1 activation is associated with a shortened time to develop BCBM and enriched in HER2-enriched and triple-negative breast cancers. Radioresistant BCBM cell lines and specimens expressed higher levels of TGLI1, but not GLI1, than radiosensitive counterparts. Since cancer stem cells (CSCs) are radioresistant and metastasis-initiating cells, we examined TGLI1 for its involvement in breast CSCs and found TGLI1 to transcriptionally activate stemness genes CD44, Nanog, Sox2, and OCT4 leading to CSC renewal, and TGLI1 outcompetes with GLI1 for binding to target promoters. We next examined whether astrocyte-priming underlies TGLI1-mediated brain tropism and found that TGLI1-positive CSCs strongly activated and interacted with astrocytes in vitro and in vivo. These findings demonstrate, for the first time, that TGLI1 mediates breast cancer metastasis to the brain, in part, through promoting metastasis-initiating CSCs and activating astrocytes in BCBM microenvironment

Prevalence of sexual harassment among Norwegian female elite athletes in relation to sport type

Although it is often assumed that the prevalence of sexual harassment is different in different sports, this assumption has not been empirically tested. This study considers whether the experience of sexual harassment varies by sport. The female elite athletes (N = 553) in the study participated in 56 different sport disciplines. These were grouped as follows :1) team or individual sports; 2) extent to which clothing required for competition is revealing ; 3) gender structure (male-or female dominated membership statistics); and 4) gender culture (masculine, gender-neutral, or feminine). The data show that sexual harassment occurs in every sport group. Female elite athletes who participated in ‘masculine’ sports appear to experience more harassment than women in the other groups. We conclude that, when it comes to female athletes’ experiences of sexual harassment, sport type matters far less than sport participation per se

Monitoring Feeding Tube Placement

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141133/1/ncp0487.pd

Atomic mass dependence of \Xi^- and \overline{\Xi}^+ production in central 250 GeV \pi^- nucleon interactions

We present the first measurement of the atomic mass dependence of central \Xi^- and \overline{\Xi}^+ production. It is measured using a sample of 22,459 \Xi^-'s and \overline{\Xi}^+'s produced in collisions between a 250 GeV \pi^- beam and targets of beryllium, aluminum, copper, and tungsten. The relative cross sections are fit to the two parameter function \sigma_0 A^\alpha, where A is the atomic mass. We measure \alpha = 0.924+-0.020+-0.025, for Feynman-x in the range -0.09 < x_F < 0.15.Comment: 10 pages, revtex, 2 figures, submitted to Phys. Rev.

Stabilization of breast cancer xenograft tumour neovasculature by angiopoietin-1

Angiopoietin-1 is a promoter of physiological vasculogenesis and angiogenesis because it induces vascular branching and smooth muscle recruitment to newly formed blood vessels. However, angiopoietin-1 expression in tumours appears to be uncommon, and angiopoietin-1 overexpression in cancer cells has been reported to lead to inhibition of xenograft tumour growth. We report here that angiopoietin-1 overexpression resulted in stabilization of tumour edge-associated blood vessels, as it prevented vessel dilation and dissociation of smooth muscle cells from existing vessels. In addition, angiopoietin-1 stimulated an infiltration of mesenchymal cells into the tumours, such that the coverage of microvessels by pericytes increased markedly, and the cancer cells were separated into small masses by the host stroma. The rates of both cancer cell proliferation and apoptosis decreased significantly in the presence of angiopoietin-1. Tie2, the receptor for angiopoietin-1, was found to be present in vascular smooth muscle cells in culture in addition to endothelial cells. These findings suggest that a vascular stabilization effect of angiopoietin-1 accounts for the inhibition of tumour growth

The incidence of ventilator-associated pneumonia using the PneuX System with or without elective endotracheal tube exchange: A pilot study

<p>Abstract</p> <p>Background</p> <p>The PneuX System is a novel endotracheal tube and tracheal seal monitor, which has been designed to minimise the aspiration of oropharyngeal secretions. We aimed to determine the incidence of ventilator-associated pneumonia (VAP) in patients who were intubated with the PneuX System and to establish whether intermittent subglottic secretion drainage could be performed reliably and safely using the PneuX System.</p> <p>Findings</p> <p>In this retrospective observational study, data was collected from 53 sequential patients. Nine (17%) patients were initially intubated with the PneuX System and 44 (83%) patients underwent elective exchange to the PneuX System. There were no episodes of VAP while the PneuX System was <it>in situ</it>. On an intention to treat basis, the incidence VAP was 1.8%. There were no complications from, or failure of, subglottic secretion drainage during the study.</p> <p>Conclusions</p> <p>Our study demonstrates that a low incidence of VAP is possible using the PneuX System. Our study also demonstrates that elective exchange and intermittent subglottic secretion drainage can be performed reliably and safely using the PneuX System.</p

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, wit

Endotracheal tubes and fluid aspiration: An in vitro evaluation of new cuff technologies

© 2017 The Author(s). Background: Aspiration of subglottic secretions past the endotracheal tube (ETT) cuff is a prerequisite for developing ventilator-associated pneumonia (VAP). Subglottic secretion drainage (SSD) ETTs reduce aspiration of subglottic secretions and have demonstrated lower VAP rates. We compared the performance of seven SSD ETTs against a non-SSD ETT in preventing aspiration below inflated cuffs. Methods: ETTs were positioned vertically in 2 cm diameter cylinders. Four ml of a standard microbial suspension was added above inflated cuffs. After 1 h, aspiration was measured and ETTs demonstrating no leakage were subjected to rotational movement and evaluation over 24 h. Collected aspirated fluid was used to inoculate agar media and incubated aerobically at 37 °C for 24 h. The aspiration rate, volume and number of microorganisms that leaked past the cuff was measured. Experiments were repeated (×10) for each type of ETT, with new ETTs used for each repeat. Best performing ETTs were then tested in five different cylinder diameters (1.6, 1.8, 2.0, 2.2 and 2.4 cm). Experiments were repeated as above using sterile water. Volume and time taken for aspiration past the cuff was measured. Experiments were repeated (×10) for each type of ETT. Results were analysed using non-parametric tests for repeated measures. Results: The PneuX ETT prevented aspiration past the cuff in all experiments. All other ETTs allowed aspiration, with considerable variability in performance. The PneuX ETT was statistically superior in reducing aspiration compared to the SealGuard (p < 0.009), KimVent (p < 0.002), TaperGuard (p < 0.004), Lanz (p < 0.001), ISIS (p < 0.001), SACETT (p < 0.001) and Soft Seal (p < 0.001) ETTs. Of the 4 ETTs tested in differing cylinder sizes, the PneuX significantly reduced aspiration across the range of diameters compared to the SealGuard (p < 0.0001), TaperGuard (p < 0.0001) and KimVent (p < 0.0001) ETTs. Conclusions: ETTs showed substantial variation in fluid aspiration, relating to cuff material and design. Variability in performance was likely due to the random manner in which involutional folds form in the inflated ETT cuff. The PneuX ETT was the only ETT able to consistently prevent aspiration past the cuff in all experiments