tbuckley/cabot-search huggingface dataset:
Abstract P4-06-16: TWEAK/Fn14 Signaling Axis as a Driver of Breast Cancer Cell Invasion and Metastasis
Authors: AE Stone, AL Willis, JR Niska, MA Black, P Ramos, CM Mancini, HE. Cunliffe
Journal: Cancer Research (2010)

Abstract The molecular events associated with the multi-step process of cell invasion and metastasis are poorly understood. Tumor necrosis factor receptor family member fibroblast growth factor-inducible 14 (Fn14) and its ligand TWEAK (tumor necrosis factor-like weak inducer of apoptosis) have recently emerged as a pro-invasive signaling mechanism and indicator of poor prognosis in breast cancer. Our laboratory has recently reported enhanced Fn14 expression in a significant proportion of breast tumor samples, but not in normal breast epithelium. Analysis of publicly available breast cancer data indicates that high Fn14 expression positively correlates with HER2/neu positivity, estrogen receptor negativity, high tumor grade, positive lymph nodes, and metastasis. Modulation of Fn14 expression in breast cancer cell lines either by exogenous overexpression or siRNA-mediated blockade is sufficient to regulate breast cancer cell invasive behavior in vitro. However, the mechanisms leading to Fn14 overexpression, and how activation of the TWEAK/Fn14 signaling axis contributes to breast tumor malignant progression remain unclear. We hypothesized that genomic alterations and inappropriate autocrine or paracrine growth factor signaling may play a role in aberrant Fn14 regulation. Using array genomic hybridization and fluorescence in situ hybridization, we found increased Fn14 gene copy number relative to centromere 16 in two out of four Fn14-expressing, invasive breast cancer cell lines and in 28% of primary breast tumors. We also investigated the role of exogenous growth factors known to play important roles in the breast tumor microenvironment in stimulating Fn14 expression in vitro. TWEAK, EGF, IGF1, HRG and HGF/SF were sufficient to stimulate Fn14 expression de novo in a variety of biologic contexts. Many of these growth factors converge on the MAPK signaling axis. We have confirmed a functional role for the MAPK pathway in facilitating Fn14-mediated invasion. Consistent with this observation, Fn14 expression in primary breast tumors is high in the context of K-RAS mutation. We are currently evaluating the presence of important key regulatory regions within the Fn14 promoter that may be contributing Fn14 over expression in breast cancer cells. To define mechanisms by which Fn14 contributes to a malignant cell phenotype we have identified an Fn14-specific invasion signature using gene expression microarray profiling. Analysis of this data points to key malignant mechanisms likely to be impacted by Fn14 activation within different biologic contexts that warrants further investigation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-16.
Circle applies for 3.5m government loan to invest in services at Hinchingbrooke
Authors: I. Torjesen
Journal: BMJ (2013)

The private company Circle, which runs the financially challenged Hinchingbrooke Health Care NHS Trust for the NHS in Cambridgeshire, has applied for a £3.5m (€4.1m; $5.4m) “working capital loan” from the government to help fund its hospital investment plans.

If the loan is approved the trust will be the first to qualify for such funding from the NHS Trust Development Authority.

The minutes of Hinchingbrooke’s April board meeting, published in July, show that the board has approved a £7.8m Capital …
Abstract 4103: Ptprz gene encoding a transmembrane-type protein phosphatase is up-regulated by Sox-2 in glioma.
Authors: Yoji Yamashita, Nobuhiro Tanuma, Toshihiro Kumabe, Teiji Tominaga, Hiroshi Shima, Ryuichi Katakura
Journal: Cancer Research (2013)

Abstract Ptprz is a receptor-like protein-tyrosine phosphatase (PTP) abundantly expressed in neuronal and glial cells in the central nervous system. To date, several potential substrates of Ptprz such as p190RhoGAP, ErbB4, and Git-1, have been identified. In terms of its biological functions, for example, it was shown that Ptprz regulates differentiation of glial cells, but its role(s) in gliomagenesis remains obscue. In this study, expression of Ptprz mRNA in human glioma samples were analyzed. Ptprz mRNA was up-regulated in glioma when compared to normal brain. We found that the levels of Ptprz mRNA in specimens are correlated with those of Sox-2, a transcription factor associating with glioma stemness. Knock-down of Sox-2 by siRNA decreased Ptprz mRNA of several glioma cell-lines. ChIP analysis showed the physical association of Sox2 to the putative promoter region of Ptprz gene, suggesting that Ptprz is a direct transcriptional target of Sox-2. Up-regulation of Ptprz expression may be a part of transcriptional program elicited by Sox-2, which may contribute to glioma stemness Citation Format: Yoji Yamashita, Nobuhiro Tanuma, Toshihiro Kumabe, Teiji Tominaga, Hiroshi Shima, Ryuichi Katakura. Ptprz gene encoding a transmembrane-type protein phosphatase is up-regulated by Sox-2 in glioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4103. doi:10.1158/1538-7445.AM2013-4103
Retrieval of a bread bag clip from the duodenum
Authors: N. Ding, A. Ting, D. Loh, M. Leong, C. Hair
Journal: Endoscopy (2013)

A 73-year-old woman presented with iron deficiency anemia and melena. Biochemical parameters revealed a hemoglobin of 77 g/L and urea 8.5 mmol/L with normal renal indices. She was transfused with 2 units of red blood cells. Gastroscopy revealed a bread clip embedded in D1 (showing the date Friday, 13 April; [Fig. 1]), pinching the distal and proximal duodenal roof fold and dangling like an earring. Attempts to remove the clip by crushing with grasping forceps, cutting with a needle-knife device, and snapping with snare were unsuccessful. A gastric band cutter (Endotherapeutics, Sydney, Australia) was employed endoscopically. The cutting wire was threaded between the bread clip and the duodenum ([Fig. 2]), and the free end was retrieved and locked into the racheting device, forming a loop. Tightening of the loop resulted in the wire snapping the clip, which was then retrieved orally ([Fig. 3]).
AB1249 The situation of ultrasound in the spanish rheumatology
Authors: E. de Miguel, J.L. Andreu, E. Naredo, I. Möller
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasonography has been recently introduced in rheumatology. Since 1996 the Spanish Society Rheumatology has developed a training program and today, 15 years later, we feel that it is time to analyze its impact in clinical practice. <h3>Objectives</h3> To know the situation of ultrasonography in Spanish rheumatology and to sound out the opinion of Spanish rheumatologist about it. <h3>Methods</h3> A National survey was addressed to every rheumatology units in hospitals with at least 200 beds. The questionnaire studied: a) the availability and the model of the ultrasound equipment b) the degree of training, c) the purpose and areas of ultrasound examination, d) the usefulness of the technique, and e) the relevance of ultrasonography in the training of residents. <h3>Results</h3> 169 units of the 234 surveyed answered the questionnaire (72%). The availability of ultrasound equipment was high. In fact, 90% of the rheumatology units had ultrasound. The mean number of rheumatologist doing ultrasound in the respondent units was 1.2. Half of the units had a rheumatologist especially dedicated to performing ultrasound, in the other half there were several rheumatologists doing it. Training plans have enabled the incorporation of ultrasound to clinical practice, but there are points which could be improved and people with advanced o intermediate skill are still low, 34% of ultrasonographers. The utility in routine clinical practice was valued at 7.8 (scale 0-10), and ultrasound was integrated in taking diagnostic decisions as shows Figure 1. There is a broad consensus on the need to include ultrasonography in the official training of residents. The Health Administration is adding ultrasound to the portfolio of rheumatology specialty services. Figure 1. Answers about use of ultrasound (%) in clinical practice. <h3>Conclusions</h3> In just 15 years, ultrasonography has become available in 90% of rheumatology units from previous inexistence.Its use isextensive, integrated into clinical practice and linked to decision making processes. Training plans have been effective, but areas for improvement were identified, and there is a broad consensus on the need to integrate ultrasound in residents' training program. <h3>Disclosure of Interest</h3> E. De Miguel Grant/Research support from: The study was supported by an unrestricted grant for Abbott., J. Andreu: None Declared, E. Naredo: None Declared, I. Möller: None Declared
S87 The effect of on patient comfort and neural respiratory drive (NRD) of ventilator trigger delay during non-invasive ventilation (NIV)
Authors: MC Ramsay, S Mandal, E-S Suh, J Steier, A Simonds, N Hart
Journal: Thorax (2013)

<h3>Introduction</h3> Optimising patient-ventilator interaction (PVI) has been shown to enhance patient comfort and respiratory muscle unloading. A major cause of poor PVI is ventilator trigger delay, defined as an extended response time in the delivery of airway pressure following initiation of inspiratory effort by the patient. Although bench tests of ventilators have demonstrated variation in trigger response times (120–500ms), there are limited data reporting the effect of trigger delay on a subject’s NRD and comfort. We therefore investigated the relationship between ventilator trigger delay, NRD and comfort perception. <h3>Methods</h3> A custom-made NIPPY3 + ventilator (B&amp;D Electromedical, Stratford-upon-Avon, UK) with modifiable trigger delay was used. A standardised protocol of 10cm H20 inspiratory positive airway pressure, 4cm H20 expiratory positive airway pressure and back up rate of 6 breaths per minute was utilised in healthy subjects familiarised with NIV. Subjects were blinded to the settings and asked to assess perceived comfort using a visual analogue score (VAS) at 20 randomised trigger delay timings ranging from 10ms to 1000ms following a 2 minute assessment period. Second intercostal space electromyography (EMGpara%max), as a marker of NRD, mask pressure and flow were used to assess PVI. Transcutaneous carbon dioxide and oxygen saturations were controlled within limits of 0.5 kPa and 4% respectively of the subject’s baseline values to minimise changes in the biochemical drive to breathe. <h3>Results</h3> 5 subjects (1 male) were enrolled to date with a mean age of 34 ± 8years, BMI 22 ± 3kgm<sup>2</sup>, FEV<sub>1</sub> 105 ± 11%predicted and FVC 114 ± 13%predicted. 500 breaths were analysed. The EMGpara%max was lowest at a trigger delay setting of 400ms 5.9%(4.8–8.0) and largest at a trigger delay of 800ms 10.1%(6.0–16.5). (Figure 1). There was a corresponding decrease in the VAS score from 78cm (63.5–92.5) at 400ms trigger delay to 47cm (30–66) at 1000ms trigger delay. The highest comfort score was 89cm (52–92) observed at 170ms trigger delay. <h3>Conclusion</h3> This is the first study to comprehensively investigate NIV trigger delay in healthy subjects. Based on NRD, these data suggest that the optimal NIV trigger response time was up to 400ms. This challenges previous bench studies that reported ventilators with response times over 100–150ms have limited clinical utility.
P4-11-14: Number Needed To Treat (NNT) as a Measure of Incremental Drug Benefit: Denosumab vs. Zoledronic Acid for the Prevention of Skeletal Related Events (SREs) in Advanced Breast Cancer.
Authors: G Dranitsaris, S Kaura
Journal: Cancer Research (2011)

Abstract Background Intravenous zoledronic acid (ZOL) is the standard of care for the prevention of SREs in advanced breast cancer. However, monthly subcutaneous denosumab (Dmab) was recently approved in the US, as an alternative to ZOL based on the results of a large randomized trial which demonstrated a prolongation in median time to first SRE (HR = 0.82, p = 0.01) and a 5.8% (p = 0.01) absolute reduction in SREs in favour of Dmab over the 34 month study period. The challenge for clinicians and payers is how to reconcile the modest benefits of Dmab with the cost, which is approximately twice that of ZOL. NNT represents the number of patients that need to be treated with a new intervention in order to avoid one additional event, and is a widely accepted approach used to make sense of numerical results from clinical trials. In this analysis, the NNT approach was used to assess the incremental benefit of Dmab over ZOL for the prevention of SREs in advanced breast cancer. Methods: The pivotal randomized trial for Dmab vs. ZOL in breast cancer (Stopeck, JCO 2010 &amp; US PI 2010) was reviewed. As an alternative to ZOL, the NNT with Dmab to avoid any SRE at 12 and 34 months (trial end) was determined. NNT by type of SRE was also estimated. These consisted of pathologic fractures, radiation to bone, spinal cord compressions and surgery to bone. The calculated NNT represents the incremental benefit provided by Dmab above and beyond Zometa therapy. Results: To avoid a single SRE after 12 months of treatment of continuous therapy with Dmab, approximately 36 patients need to be treated. To avoid a single fracture and radiation to bone, approximately 39 and 27 patients need to be treated with Dmab over a 34 month period. Dmab was unable to offer any incremental benefit over ZOL in terms of avoiding spinal cord compressions or surgery to bone after 34 months of treatment. Discussion: The NNT approach is a simple and effective method to express the findings in a clinically meaningful way. In this analysis, the incremental benefit of Dmab would only be realized when a minimum of 36 patients are treated for 12 months. For the more severe skeletal-related events, in terms of clinical and economic burden to patients and society, such as spinal cord compression and surgery to bone, Dmab did not offer any incremental benefit over ZOL in terms of SRE avoidance. This marginal incremental benefit needs to be considered alongside the high cost of Dmab. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-14.
Abstract 1892: Identification of differentially methylated genes associated with cetuximab and erlotinib resistance
Authors: Takenori Ogawa, Xiaofei Chang, Wayne Koch, David Sidransky
Journal: Cancer Research (2012)

Abstract Anti-EGFR therapy is among the most promising molecular targeted therapies against cancer developed in the past decade. Two classes of EGFR-directed therapeutic inhibitors are currently in clinical use: anti-EGFR monoclonal antibodies, such as cetuximab, and small-molecule tyrosine kinase inhibitors (TKIs) of EGFR, such as erlotinib. Although both classes of drugs are capable of inducing an initial therapeutic response, primary as well as acquired drug resistance is frequently observed. Emerging evidence has linked epigenetic changes, such as DNA methylation at CpG islands, to the development of cytotoxic chemotherapeutic drug resistance. To identify genes that are specifically methylated during the evolution of resistance to anti-EGFR therapeutic agents, we employed two parental NSCLC and HNSCC cell lines and their resistant derivatives to either erlotinib or cetuximab. DNA from each pair was used for methylation-specific array containing a panel of 64 genes that are commonly known to be regulated through promoter methylation. We found that death-associated protein kinase 1 (DAPK1) was hypermethylated in drug resistant cells generated from both parental cell lines. Restoration of DAPK1 into the resistant cells by stable transfection re-sensitized the cells to both erlotinib and cetuximab. Conversely, siRNA-mediated knockdown of DAPK1 induced resistance in the parental sensitive cells. These results demonstrate that DAPK1 plays an important role in both cetuximab and erlotinib resistance in NSCLC and HNSCC cancer cells, and that promoter methylation of its gene frequently occurs during the chronic treatment of anti-EGFR agents. In conclusion, DAPK1 could be a novel target for the improvement of therapeutic benefit of anti-EGFR therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1892. doi:1538-7445.AM2012-1892
P693 NEUROLOGIC DISORDERS DURING HEV INFECTION IN NONIMMUNOCOMPROMISED PATIENTS
Authors: H. Blasco Perrin, P. Cintas, F. Abravanel, R. Gérolami, P. Couzigou, L. d'Alteroche, L. Prudhomme, L. Buscail, C. Bureau, J.P. Vinel, J. Izopet, J.M. Peron
Journal: Journal of Hepatology (2014)
Abstract 4888: Axl receptor signaling in required for stem cell traits and metastasis in breast cancer.
Authors: Crina Tiron, Fanny Pelissier, Katarzyna Wnuk-Lipinska, Ingunn Stefansson, Reeta Virtakoivu, Masaru Miyano, Tone Sandal, David Micklem, James Garbe, Martha Stampfer, Johanna Ivaska, Lars Akslen, Mark LaBarge, James Lorens
Journal: Cancer Research (2013)

Abstract Epithelial-to-mesenchymal transition (EMT) endows carcinoma cells with migratory, survival and stem cell-like attributes that facilitate therapeutic resistance and metastasis. Expression of the Axl receptor tyrosine kinase in aggressive breast cancer correlates with EMT, poor survival and is prevalent in patient metastases. Induction of EMT in immortalized mammary epithelial cells by EMT-transcription factors, TGFbeta or hypoxia upregulates Axl and establishes an autocrine-signaling loop with its ligand, Gas6. Axl receptor signaling is required to maintain EMT-related invasive, drug resistance and cancer stem cell (CSC) traits of malignant breast cancer cells. Targeting Axl signaling with RNAi or pharmacological agents blocks the EMT/CSC gene program and inhibits malignant functions including invasiveness, drug resistance, mammosphere formation, in vivo tumor initiation, and spontaneous metastasis in orthotopic breast cancer models. These results suggest that Axl expression is requisite for the maintenance of EMT and stem cell-like traits during malignant progression. The EMT program is characteristic of normal adult mammary epithelial stem/progenitor cells. Congruently, we show that the Axl receptor expressed on mammary epithelial stem/progenitor cells, and Axl signaling is necessary for mammary epithelial multipotent progenitor activity. Thus Axl receptor signaling represents a novel regulatory pathway linking normal mammary stem/progenitor cells and breast cancer stem cells. Hence, clinical Axl inhibitors represent a novel therapeutic avenue to target EMT/CSC traits of aggressive breast cancer. Citation Format: Crina Tiron, Fanny Pelissier, Katarzyna Wnuk-Lipinska, Ingunn Stefansson, Reeta Virtakoivu, Masaru Miyano, Tone Sandal, David Micklem, James Garbe, Martha Stampfer, Johanna Ivaska, Lars Akslen, Mark LaBarge, James Lorens. Axl receptor signaling in required for stem cell traits and metastasis in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4888. doi:10.1158/1538-7445.AM2013-4888
AB0045 Baff signaling pathway may be involved in the production of matrix metalloproteinase-9 by peripheral monocytes of patients with primary sjögren’s syndrome.
Authors: K. Yoshimoto, M. Tanaka, M. Kojima, H. Ogata, K. Suzuki, H. Kameda, T. Abe, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> B cell activating factor of the TNF family (BAFF) is a type II membrane-bound protein and the extracellular C-terminal fragment is released from the cells as soluble BAFF (sBAFF). BAFF is mainly produced by monocytes and dendritic cells, and regulates proliferation, differentiation, and survival of B cells. In our previous study, we found that the production of IL-6 was significantly enhanced in monocytes of primary Sjögren's syndrome (pSS) upon stimulation with sBAFF. We also found that the expression level of a BAFF receptor (BR3) was significantly elevated in pSS monocytes compared to normal monocytes. These data suggest that the elevated expression of BR3 on monocytes is involved in the abnormal production of IL-6 by pSS monocytes. In this study, we explored other abnormalities of pSS monocytes. We especially focused on matrix metalloproteinases (MMPs), because MMPs were reported to be involved in the pathogenesis of autoimmune diseases. <h3>Objectives</h3> To purpose of this study is to elucidate that elevated expression of BR3 on monocytes is involved in the abnormal production of matrix metalloproteinase-9. <h3>Methods</h3> The expression levels of BR3 and MMPs in monocytes in whole blood samples of pSS patients (n = 19) and age matched normal individuals (n = 14) were analyzed by PCR and FACS. Signal transduction pathways were investigated by exposing sBAFF-stimulated pSS monocytes to several inhibitors against possible downstream targets. <h3>Results</h3> RT-PCR analysis detected the expression of MMP-2 and 9 in peripheral monocytes of both pSS patients and normal individuals. Stimulation of the cells with sBAFF enhanced the expression of the latter. ELISA showed robust enhancement of the production of MMP-9 by pSS monocytes compared to the control. The amount of MMP-9 produced by the cells was positively correlated with the expression level of BR3, suggesting that BAFF-signaling is important for the production of MMP-9 by pSS monocytes. Moreover, the elevated productions of MMP-9 by the cells were significantly suppressed by specific inhibitors against NF-kB and PI3 kinase in a dose dependent manner. <h3>Conclusions</h3> The present study suggests that sBAFF acts through BR3 to activate the expression of MMP-9, and that NF-kB and PI3 kinase are involved in the signal transduction pathway. <h3>References</h3> Yoshimoto K, Tanaka M, Kojima M, Setoyama Y, Kameda H, Suzuki K, Tsuzaka K, Ogawa Y, Tsubota K, Abe T, Takeuchi T. Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjögren's syndrome. Arthritis Res Ther. 2011;13(5):R170. Epub 2011 Oct 21 <h3>Disclosure of Interest</h3> None Declared
Combined use of covered and uncovered self-expandable metal stents in patients with bleeding, obstructing stage IV colorectal cancer
Authors: Antonietta Lamazza, Enrico Fiori, Antonio Sterpetti
Journal: Endoscopy (2014)

Endoscopic placement of self-expandable metal stents (SEMS) represents a valid therapeutic method in selected patients with colorectal obstruction [1] [2] [3] [4] [5]. Here we report on a series of three patients with bleeding, obstructing stage IV colorectal cancer (CRC), who were initially treated with a covered stent, which was later replaced with an uncovered one. Uncovered stents rarely dislodge [5], reducing the possibility of acute colorectal obstruction after patient discharge.
ATRIAL CONDUIT PHASIC FUNCTION SOON AFTER ELECTRICAL CARDIOVERSION OF PERSISTENT ATRIAL FIBRILLATION AS A PREDICTOR OF EARLY ATRIAL FIBRILLATION RECURRENCE
Authors: Anna Degiovanni, Federica De Vecchi, Eleonora Prenna, Enrico Boggio, Paolo Marino
Journal: Journal of the American College of Cardiology (2016)