tbuckley/cabot-search huggingface dataset:
Abstract P2-10-25: Prognostic value of relative change in tumor marker CA 27.29 in early stage breast cancer – The SUCCESS trial
Authors: P Hepp, H Tesch, H Forstbauer, M Rezai, T Beck, I Schrader, A Kleine-Tebbe, J Hucke, D Finas, U Soeling, D-M Zahm, E Weiss, MW Beckmann, W Janni, B Rack
Journal: Cancer Research (2012)

Abstract Background: MUC1 based tumor markers like CA27.29 (TM) in breast cancer are routinely used in metastatic disease as early marker for treatment efficacy. However, in early stage disease data is sparse. In this analysis, we looked at the impact of individual change in CA27.29 on prognosis instead of using a threshold. Methods: The SUCCESS Trial compares FEC-docetaxel (Doc) vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment with Zoledronat in 3754 patients (pts) with primary breast cancer (N+ or high risk N0). We measured CA27.29 after surgery but before chemotherapy (CHT) as baseline and compared it to CA27.29 levels 2 years thereafter with the ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). Results: CA27.29 data is available of 2,015 pts. 119 pts (5.9%) had TM over the threshold of 32U/ml before CHT and 56 (2.8%) 2years thereafter. To examine the relative change of tumor marker, pts were divided into 3 groups: increase: change &amp;gt;=5 U/ml; stable: change &amp;lt;±5U/ml; decrease: change &amp;gt; = −5 U/ml. 123 (6.1%) pts had increasing (&amp;gt;=5 U/ml), 1419 (70.4%) had stable, 473 (23.5%) had decreasing TM levels from before CHT to 2 years thereafter. The majority of pts with increasing TM (86 pts; 69.9%) had levels below the usual threshold of 32U/ml at all times. Patients with an increase &amp;gt;=5 U/ml had an 81% increased risk for recurrence (HR = 1.810 [CI: 1.111–2.948]) and reduced overall survival (HR = 1.020 [CI: 1.004–1.037]). In the multivariate analysis taking into account tumor size, nodal status, grading, age, hormonal and HER2/neu receptor status increasing CA27.29 levels were an independent prognostic marker. Conclusions: An increase of the tumor marker CA27.29 2 years after CHT compared to pre-chemotherapy baseline was associated with a worse prognosis. By using this approach, more patients at risk for recurrence were detected than with the standard threshold approach. Therefore, the use of relative change could help to identify more patients at risk for relapse who might benefit from an intensified follow up. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-25.
PTH-071 The Impact of Introducing the 24/7 Emegrency Gastrointestinal Bleed Service on Reducing Hospital Stay and Mortality in a District General Hospital
Authors: Z U Rahman, B Hitchcock, N Mcgrath, S Ahmed, A Dixon
Journal: Gut (2013)

<h3>Introduction</h3> Upper Gastrointestinal (GI) bleed remains the commonest gastrointestinal emergency with a significantly high hospital mortality and prolonged hospital stay[1]. The aim of the study is to audit any difference of the above parameters after the introduction of GI bleed rota in our trust. <h3>Methods</h3> The data was collected from patient records and endoscopy database. Rockall scores were used for risk stratification. Standard statistical methods were used for analysing data. Comparisons were made with the audit results from 2005. <h3>Results</h3> The re audit was conducted as a follow up to the one which was done in 2005, after introducing local upper GI bleed guidelines and 24/7 GI bleed rota. A total of 107 patients (including both in- and outpatients) were referred for upper Gastrointestinal endoscopy with suspected upper GI bleed from 1<sup>st</sup> Jan to 30<sup>th</sup> June 2012. A sample of 39 patients were randomly (every third patient) included in the audit with 19 females and 20 males. The mean age was 69.6yrs (±30yrs). The time interval from presentation to therapeutic endoscopy was 35.35 hours as opposed to 2.82 days according to 2005 audit data. Amongst the endoscopy findings 12.82% (5/39) patients had Gastrooesophageal varices versus no banding in 2005 audit data; there was no significant difference amongst other aetiologies in both audit samples. Thirty day mortality was 7.7%(3/39) as compared to 13.33%(4/30) in 2005.The length of hospital stay was found to be 10.7 days as compared to 12.32days (2005). <h3>Conclusion</h3> The mortality was reduced as the time delay to therapeutic endoscopy reduced. The hospital stay has been shortened by a couple of days in this study sample. The estimated cost of 24/7 GI bleed rota is 15000 pounds per annum which can potentially save significant amount of funding by reducing hospital stay i.e. An investment worth spending on. The incidence of variceal bleeding has increased significantly over the years. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Rockall TA, Logan RFA, Devlin HB,<i> et al.</i> Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJ1995; 311:222–6.
DISECCIÓN ENDOSCÓPICA SUBMUCOSA CON FLUSH-KNIFE EN MODELO PORCINO IN VIVO
Authors: E Albéniz Arbizu, A Pueyo Royo, J Eguaras Ros, A Ciáurriz Munuce, M Fraile González, S Oquiñena Legaz, M Vicuña Arregui, A Guerra Lacunza
Journal: Endoscopy (2010)

Introducción: La resección mucosa endoscópica (RME) y la disección submucosa endoscópica (DSE) son dos técnicas que permiten la extirpación de lesiones neoplásicas intraepiteliales mediante procedimientos no quirúrgicos y aceptablemente poco invasivos.
P2-03-04: Novel Pathways Underlying the Initiation and Transition of DCIS to IDC of HER2−Overexpressing Breast Cancer Model.
Authors: CR Pradeep, W Koestler, M Lauriola, H Nair, R Rao, GB Mills, Y Yarden
Journal: Cancer Research (2011)

Abstract Background: The HER2/Neu -oncogene is amplified in 20–25% percent of human primary breast cancers and this alteration is associated with disease behaviour. The HER2/neu oncogene encodes a receptor-like tyrosine kinase, whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. Whereas signalling pathways emanating from HER2 have been characterized, much less is known about the transcriptionally regulated genes controlled by HER2 that contribute to the initiation of Ductal Carcinoma Insitu (DCIS) and their transition to an invasive ductal carcinoma (IDC). Materials and Methods: Normal and HER2 overexpressing mammary epithelial cells (MCF10A) were grown in extracellular matrix to form 3D structures, When grown in extracellular matrix as 3-dimensional spheroids, control cells developed a hollow lumen, but HER2−overexpressing cells populated the lumen by evading apoptosis. On the next step, uopon the growth factror stimulation HER2−overexpressing cells grown in extracellular matrix, which protruded invasive outgrowths. Highly variable genes were selected from the described phenotypes using RNA isolated from the 3D structures and hybridized to an Affymetrix HuGene 1.0 ST oligonucleotide array. Results: Using microarrays we analysed transcriptional events responsible for the morphological changes and found several novel sets of genes such as integral proteins, transcription factors, matrix proteases, Notch genes and chemokines were highly altered in the HER2 overexpressing group which were not appreciated before. Using gene annotation we defined molecular-pathways responsible for the phenotypical changes. More specifically, our study proposes a two hit model describes the pathways involved in the initiation of the Ductal Carcinoma Insitu and their transition to Invasive Cancer underlying the HER2 transcriptional network. Discussion: According to the proposed model, expansion of ductal hyperplasia is limited by intraluminal apoptosis, unless they overexpress HER2, which drives proliferation and forms DCIS due to HER2 induced Notch pathways genes. Secondly, results obtained with the 3D system and their reflection in clinical outcome, we propose that neither HER2 amplification, nor the presence of GFs, is sufficient for development of IDC, but their co-occurrence can instigate metastasis by the activation of genes of integrin-adhesion signaling. The more virulent scenario combines HER2 amplification with GFs, thereby switching a robust, auto-stimulatory program. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-03-04.
PWE-088 The Impact Of Thiopurine Hypermethylation On Clinical Outcomes In Patients With Ibd
Authors: PA Blaker, S Fong, V Kariyawasam, AM Marinaki, PM Irving, JD Sanderson
Journal: Gut (2014)

<h3>Introduction</h3> 15% of patients with inflammatory bowel disease (IBD) prescribed azathioprine (AZA)/mercaptopurine (MP) demonstrate a skewed drug metabolism with low thioguanine nucleotides (TGN) and unexpectedly high methylmercaptopurine (MeMP) levels. This predicts a lack of treatment efficacy and excess adverse events; however studies on the effect of thiopurine hypermethylation (TH) in adult IBD patients are lacking. Importantly, where identified TH can be circumvented with the use of low dose AZA/MP and allopurinol. The aim of this study is to characterise the impact of TH in IBD patients and determine if thiopurine metabolite profiles at week 4 of treatment can predict its occurrence to allow early combination treatment. <h3>Methods</h3> 273 patients with IBD, who were anti-TNF-α therapy naïve and matched for red blood cell thiopurine-S-methyltransferase activity, were retrospectively identified. Of these 181 patients demonstrated average MeMP:TGN ratios &lt;11 (at least 2 profiles between weeks 12 – 52) and were used as a control group that was compared to 92 patients with average MeMP:TGN ratios ≥11. Clinical outcomes were recorded for the first 12 months of therapy. A failure of AZA/MP as monotherapy was determined by 3 gastroenterologists with expertise in IBD. Thiopurine metabolite profiles were measured in 139 patients at week 4 of therapy and were compared to average metabolite profiles between 12 – 52 weeks of treatment. <h3>Results</h3> The average MeMP:TGN ratios in those with and without TH were 21.0 and 2.52 respectively (p = &lt;0.0001). The normalised dose of thiopurine was higher in patients with TH (1.91 vs. 2.09 mg/ kg; p = &lt; 0.0001). Patients with TH were more likely to fail AZA/MP monotherapy as first line treatment during the first 12 months of therapy, in comparison with patients with normal methylation profiles (p = 0.0088, Gehan-Breslow-Wilcoxon Test). The difference in the number of treatment failures at 12 months was 15.7%. There was no difference in the occurrence of gastrointestinal intolerance, myelotoxicity or pancreatitis between groups, however there was an excess of hepatotoxicity with TH (p = 0.0006; OR = 8.058; 95% CI: 2.188 – 29.670; Fisher’s exact). TH was demonstrated in 83.7% of cases by 12 weeks of therapy. A MeMP : TGN level &gt; 6.17 at week 4 accurately predicted TH (ratio ≥11) after 12 weeks of therapy (AUC = 0.839; p = &lt; 0.0001; sensitivity = 75.4%; specificity = 88.4%). <h3>Conclusion</h3> TH is associated with an excess of thiopurine treatment failures as monotherapy immunosuppression during the first 12 months of treatment. We also confirm its association with hepatotoxicity. A MeMP:TGN &gt;6.17 may be useful in early identification of patients likely to benefit from combination treatment. <h3>Disclosure of Interest</h3> None Declared.
AB0120 Apoptotic Cell-Based Therapy to Treat Collagen-Induced Experimental Arthritis. Rationale for the Use of Apoptotic Cells in the Treatment of Rheumatoid Arthritis
Authors: S. Perruche, A. Clauzon, F. Bonnefoy, E. Toussirot, P. Saas
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Most of the currently available biological agents used in the treatment of rheumatoid arthritis (RA) target a cellular or soluble factor involved in the physiopathology of the disease. Alternatively, cellular therapies are scarce in the therapeutic management of RA. Apoptotic cells display immunologic properties that have been used to resolve inflammation in various experimental models of autoimmune diseases (diabetes, demyelinating diseases) as well as in bone marrow transplantation to favour engraftment and prevent graft versus host disease. Apoptotic cell approach has been successfully assessed to prevent arthritis development in experimental rat model. Here we evaluated a cell-based therapeutic approach based on the immuno-modulatory properties of apoptotic cells to treat RA. <h3>Objectives</h3> to investigate the effects apoptotic cell injection to treat arthritis in a mouse model of collagen-induced arthritis (CIA). <h3>Methods</h3> CIA was induced in susceptible DBA/1 mice using type II bovine collagen immunization. Four to 8 days after arthritis development (d20 post-immunization) mice presenting arthritic symptoms were treated with apoptotic cells (5.10e6 cell/mouse). As control, methotrexate was used (MTX, 15 mg/kg, twice) alone or with apoptotic cells. Regulatory T cells (Treg) were assessed by FACS at time of sacrifice (day 40/45). <h3>Results</h3> Apoptotic cell injection demonstrated a significant decrease of arthritis score (<i>p</i>&gt;0.01; 4 independent experiments), associated with an increased percentage of Treg in the spleen at time of sacrifice (Figure). In addition, MTX was sufficient to decrease arthritis as well and apoptotic cell injection did not influence MTX efficiency and <i>vice-et-versa</i>. Whereas MTX did not affect the percentage of Treg, MTX + apoptotic cell treatment induced a strong increase of Treg in the spleen and draining lymph nodes. <h3>Conclusions</h3> Apoptotic cell injection is an effective treatment to reduce arthritis severity and should be consider in clinic as an alternative method for the treatment of patients with RA. A phase I/II clinical trial using this therapeutic approach is currently planned by our group in patients with RA refractory to biological agents. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2160
Abstract 481: In vivo imaging identifies that myf5+ embryonal rhabdomyosarcoma-propagating cells are dynamically reorganized during tumor growth
Authors: Myron S. Ignatius, Eleanor Chen, Natalie Elpek, Petur Nielsen, Corinne Linardic, Thorsten Mempel, David M. Langenau
Journal: Cancer Research (2011)

Abstract Embryonal rhabdomyosarcoma (ERMS) is a devastating pediatric cancer with specific features of muscle differentiation. Here, we use a transgenic zebrafish model of RAS-induced ERMS and show that myf5+ ERMS cells possess self-renewal potential, confirming that ERMS is a cancer stem cell driven disease. The ERMS-initiating cell is molecularly similar to an activated satellite cell and expresses myf5, m-cadherin, and c-met. To directly visualize tumor-initiating cells in vivo, fluorescent transgenic zebrafish were created that express myf5-GFP, myogenin-h2b-mRFP, and mylz2-lyn-cyan. These transcription factors are expressed during distinct stages of muscle/ERMS development and transgenic reporter lines using these gene promoters allow self-renewing cells to imaged in live animals by confocal microscopy. myf5-GFP+ ERMS-initiating cells from early stage tumors lie in immediate proximity to muscle fibers where normal satellite cells reside. However, as tumors grow, the niche is greatly expanded with the number of myf5-GFP+ cells increasing by 10-fold per fiber. By late stages of tumor growth, myf5-GFP+ ERMS cells are re-localized into a new tumor-specific stem cell niche that is no longer associated with fibers and is separated from more differentiated myogenin+ and myogenein/mylz2 double positive tumor cells. Analysis of human ERMS showed that tumors also contain regional niches of differentiated and undifferentiated cells. Time-lapse imaging of live zebrafish showed that myf5-GFP+ ERMS cells move only locally within the tumor and remain largely confined to stable self-renewing niches. By contrast, myogenin+ cells move dynamically throughout tumors and colonize new areas for tumor growth by both migration through the tissue and entry into the vasculature system. Following colonization by myogenin+ cells, self-renewing myf5+ cells are recruited to new areas of tumor growth. Our findings reconcile the clinical observation that myogenin-positivity in RMS correlates with poor outcome, because it is these cells that intravasate into blood vessels, invade new areas of tumor growth, and recruit slow moving self-renewing cells to newly colonized areas. Taken together, our in vivo imaging studies provide unprecedented access to directly visualize tumor growth in real-time and to define the kinetics of self-renewal and tumor dissemination as has never been assessed in any experimental model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 481. doi:10.1158/1538-7445.AM2011-481
A unified account of abstract structure and conceptual change: Probabilistic models and early learning mechanisms
Authors: Alison Gopnik
Journal: Behavioral and Brain Sciences (2011)

Abstract We need not propose, as Carey does, a radical discontinuity between core cognition, which is responsible for abstract structure, and language and “Quinian bootstrapping,” which are responsible for learning and conceptual change. From a probabilistic models view, conceptual structure and learning reflect the same principles, and they are both in place from the beginning.
Abstract LB-38: Kure It cancer research
Authors: Karen Jones
Journal: Cancer Research (2012)

Abstract Kure It funds researchers conducting innovative projects in the fields of kidney cancer and other underfunded malignancies. Kiure It raised funds in several ways: through annual special events; contributions from family and community foundations; and partnerships with the self storage industry, through which we've created tailored programs and events aimed at raising funding and awareness. Since its inception in 2007, Kure It has raised over one milliion for research. The goal is to raise one million annually going forward. Kure It supports the work of researchers at City of Hope and Cedars-Sinai. 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 LB-38. doi:1538-7445.AM2012-LB-38
Afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following first-line platinum-based chemotherapy: Patient-reported outcome (PRO) data from the LUX-Lung 8 Phase III global trial.
Authors: Shirish M. Gadgeel, Manuel Cobo Dols, Enriqueta Felip, Jean-Charles Soria, Ki Hyeong Lee, Shun Lu, Vassilis Georgoulias, Andrea Fulop, Erdem Goker, Konstantinos N. Syrigos, Alessandro Morabito, Hasan Senol Coskun, Salih Zeki Guclu, Wei Li, Sanjay Popat, Andrea Ardizzoni, Juliane Lungershausen, Bushi Wang, Vikram K. Chand, Glenwood D. Goss
Journal: Journal of Clinical Oncology (2015)

8100 Background: A is an irreversible ErbB family blocker that has shown clinical activity in pts with SCC of the head/neck and lung. The LUX-Lung 8 Phase III global trial compared A and E in pts with SCC of the lung following failure of platinum-based chemotherapy. Between Mar 2012 and Jan 2014, 795 stage IIIB/IV SCC pts were randomized 1:1 to receive A (40 mg/day) or E (150 mg/day) until progression. The primary endpoint of PFS, assessed after 414 events, was significantly higher for A than E (median: 2.4 vs 1.9 months; HR [95% CI]: 0.82 [0.68–1.00]; p = 0.04). PRO analyses of the PFS dataset are presented here. Updated PRO analysis of the OS dataset (to be undertaken after 632 deaths) will be available at the meeting. Methods: PROs were collected every 28 days until progression using the EORTC QLQ-C30/LC13 questionnaires. Percentage of pts improved on therapy, time-to-deterioration (TTD) and changes over time were analyzed for the pre-specified SCC symptoms: cough, dyspnea, and pain. Results: Improvement in global health status (GHS)/QoL was significantly greater with A than E (36.4 vs 27.1% pts; p = 0.026). More pts had an improvement in cough with A vs E (43.6 vs 32.6%; p = 0.010). The proportion of pts with improvements in dyspnea and pain were 49.4 vs 44.8% and 37.5 vs 37.5% with A and E, respectively. There were no significant differences in TTD of symptoms between treatment groups. However, trends favoring A were reported for dyspnea (HR [95% CI]: 0.82 [0.66–1.01]), fatigue (HR [95% CI]: 0.89 [0.73–1.09]), physical (HR [95% CI]: 0.81 [0.64–1.02]), and role (HR [95% CI]: 0.83 [0.67–1.03]) functioning. Changes in mean scores over time significantly favored A vs E for cough (p = 0.007), dyspnea (p = 0.021), and pain (p = 0.024), including chest pain, as well as fatigue (p = 0.006) and role (p = 0.001)/physical (0.024) functioning. Conclusions: Compared to E, A improved SCC symptoms, SCC symptoms over time, and overall GHS/QoL. PRO analyses of LUX-Lung 8 complement the significant improvement observed in PFS with second-line A vs E in pts with SCC of the lung. Clinical trial information: NCT01523587.
When Too Much is Too Little
Authors: R. Sean Morrison, Diane E. Meier, Christine K. Cassel
Journal: New England Journal of Medicine (1996)

A 73-year-old man came to the emergency room because of progressive weakness in his left leg. One year earlier, he had noted a sudden weakness in the left lower leg as he was climbing a flight of stairs. He did not seek medical attention at that time but began to use a cane. Three weeks before his visit to the emergency department, he fell to the floor while attempting to get out of bed. On arising, he had difficulty supporting his weight on his left side. The left-leg weakness subsequently progressed, and he was unable to walk without a . . .