tbuckley/cabot-search huggingface dataset:
Abstract SY08-01: AMPK and mTOR in nutrient signaling, metabolism, and autophagy regulation.
Authors: Joungmok Kim, Ryan Russell, Haxin Yuan, Kun-Liang Guan
Journal: Cancer Research (2013)

Abstract Autophagy is a stress response protecting cells from unfavorable conditions, such as nutrient starvation. The cellular energy sensor AMPK and key growth controller mTOR, both are regulated by nutrient status, play major roles in autophagy regulation. The class III phosphatidylinositol-3 kinase, Vps34, forms multiple complexes and regulates both intracellular vesicle trafficking and autophagy induction. We show that AMPK plays a key role in regulating different Vps34 complexes. AMPK inhibits the non-autophagy Vps34 complex by phosphorylating Vps34 and suppresses overall PI(3)P production and protects cells from starvation. In parallel, AMPK activates the pro-autophagy Vps34 complex by phosphorylating Beclin1 to induce autophagy. Atg14L, an autophagy essential gene present only in the pro-autophagy Vps34 complex, inhibits Vps34 phosphorylation but increases Beclin1 phosphorylation by AMPK. As such, Atg14L dictates the differential regulation (either inhibition or activation) of different Vps34 complexes in response to glucose starvation. In addition, the Vps34 complex is regulated by mTOR, which is inhibited by nutrient starvation. mTOR phosphorylates Beclin to inhibit the autophagy specific Vps34 complex. Our study reveals an intricate molecular regulation of Vps34 complexes by AMPK and mTOR in nutrient stress response and autophagy. Citation Format: Joungmok Kim, Ryan Russell, Haxin Yuan, Kun-Liang Guan. AMPK and mTOR in nutrient signaling, metabolism, and autophagy regulation. [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 SY08-01. doi:10.1158/1538-7445.AM2013-SY08-01
Abstract 1888: HPV viral load and alcohol synergize to increase the risk of cervical intraepithelial neoplasia (CIN)1 in HPV positive women: Korean HPV Cohort Study
Authors: Mi Kyung Kim, Sang Hoon Lee, Kyung-Jin Min, Jae Kwan Lee
Journal: Cancer Research (2011)

Abstract Purpose: To investigate the associations between alcohol and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer in women with high risk HPV-positive in the Korean HPV cohort study (KHPV). Subjects and Methods: The KHPV recruited 1,243 women, aged 18-65 from March 2006 up to December 2009, including HPV-positive women with normal cytology (n=147), CIN1 (n=164), CIN2/3 (n=161) and cervical cancer (n=202). Detailed information on consumption of alcoholic beverages at baseline and on other lifestyle factors during lifetime was collected from questionnaires. Multinomial logistic analysis estimated the multivariate-adjusted odds ratio. Results: Drinkers had an increased risk of CIN1 (OR = 2.16; 95% CI: 1.26 – 3.72) compared to nondrinkers, after adjusting for potential confounders. The amount of alcohol consumption (p for trend = 0.027), and the frequency of alcohol consumption (p for trend = 0.037) were significantly associated with the risk of CIN1. In addition, alcohol drinking had significant effects on the risk of CIN1 in the analyses adjusted for multivariables (OR=19.1, 95% CI=6.60-55.3, interaction p &amp;lt;0.001). The relative excess risk due to interaction was 15.7, and the attributable proportion due to the interaction and synergy index were 0.71, and 3.89, respectively. No associations were found between alcohol drinking and CIN2/3 and cervical cancer. Conclusion: Our data showed HPV and alcohol synergize to increase the risk of CIN1 among high-risk HPV-positive women. 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 1888. doi:10.1158/1538-7445.AM2011-1888
759 IMPACT OF ENTECAVIR VERSUS LAMIVUDINE ON HEPATIC COVALENTLY CLOSED-CIRCULAR DNA AND TOTAL HEPATIC HBVDNA IN NUCLEOSIDE-NAÏVE HBeAg POSITIVE CHRONIC HEPATITIS B PATIENTS
Authors: S. Bowden, S. Locarnini, T.-T. Chang, Y.-C. Chao, K.-H. Han, R.G. Gish, R. de Man, C. Llamoso, H. Tang
Journal: Journal of Hepatology (2013)
Abstract LB-126: A pooled shRNA screen for erlotinib sensitizers in Kras-mutant non-small cell lung cancer
Authors: Shaun Cordes, Nick Dompe, James Lee, Li Li, Celina Rivers, Zhijun Tang, Wilman Luk, Greg Bennett, David Shames, Zora Modrusan, David P. Davis
Journal: Cancer Research (2010)

Abstract Erlotinib is a small-molecule inhibitor of the epithelial growth factor receptor (EGFR) that provides a survival benefit in patients with chemoresistant non-small cell lung cancer (NSCLC). In the second and third line setting, patients whose tumors harbor activating mutations in Kras showed less benefit than patients with tumors harboring wild type Kras. To identify genes whose inhibition sensitizes Kras-mutant NSCLC cells to erlotinib, we performed a whole-genome pooled-shRNA screen and identified 337 shRNAs that were selectively depleted in erlotinib-treated cells. We subsequently validated 148 of the top 200 hits in an siRNA-based viability assay and selected 37 hits for further analysis. We are currently characterizing these hits in a panel of ∼10 additional NSCLC lines to identify targets with broad cell line activity that synergize with erlotinib to induce apoptosis. Our current understanding of the relationships between our top hits and erlotinib sensitivity will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-126.
COMMON OR RARE GENETIC VARIATION IN THE CHEMOKINE RECEPTORS CCR2, CCR5, AND CX3CR1 DOES NOT RELATE TO CORONARY HEART DISEASE OR MYOCARDIAL INFARCTION IN HUMANS
Authors: Jessica R. Golbus, Nathan Stitziel, Nilesh Samani, Jeanette Erdmann, Heribert Schunkert, Panos Deloukas, Danish Saleheen, Martin Farrall, Ruth McPherson, Hugh Watkins, Sekar Kathiresan, Muredach Reilly
Journal: Journal of the American College of Cardiology (2016)
Radio-Guided Surgery and Postoperative PET/CT Scan of a Surgical Specimen of an Intraosseous Meningioma in a Patient With Neuroendocrine Tumor of the Pancreas
Authors: Marius Meiser, Thomas Winkens, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2015)

A 63-year-old man with a previously resected neuroendocrine tumor of the pancreas underwent 68Ga DOTATOC PET/CT, which showed intense 68Ga DOTATOC uptake in the left calvarium. Radio-guided surgery and subsequent histology revealed an intraosseous meningioma. Complete removal was proven by a PET/CT scan of the surgical specimen.
PMO-033 Glucose and lipid regulation is modulated by vascular adhesion protein-1 (VAP1) in non-alcoholic fatty liver disease (NAFLD)
Authors: S Karim, E Liaskou, F Ling, K MacAulay, S Jalkanen, D H Adams, P F Lalor
Journal: Gut (2012)

<h3>Introduction</h3> NAFLD is characterised by steatosis, chronic inflammation and fibrosis. The underlying mechanisms include insulin resistance, increased free fatty acid flux from de-novo lipogenesis and decreased lipid oxidation. Vascular Adhesion Protein—1 (VAP -1), is an adhesion molecule with semicarbazide- sensitive amine oxidase activity (SSAO), which is also expressed as a soluble protein in serum (sVAP-1) and elevated in inflammatory liver diseases such as NAFLD. VAP-1 has been shown to modulate glucose and lipid uptake in muscle and adipose tissue and thus we investigated whether it may contribute to glucose and lipid homeostasis in human liver tissue. <h3>Methods</h3> We have used precision cut liver slices (PCLS) from normal and diseased human liver specimens and cultured human sinusoidal endothelium (HSEC) and hepatocyte cells in combination with VAP-1 substrates (200 μM methylamine or benzylamine) and inhibitors (400 μM bromoethylamine) to perform standard ex vivo radiolabelled glucose uptake and fatty acid uptake assays using oil red O quantification following exposure of cells to Oleic and Palmitic acid (PA). Immunohistochemical staining and qPCR were performed using standard techniques and for confirmatory experiments HSEC were transfected with enzymatically active/inactive VAP1. <h3>Results</h3> QPCR confirmed upregulation of VAP-1 mRNA (DDCT=1.144 p=0.03) in NASH vs normal liver and also changes in FABP1, -4, -5, FATP3, -4 (p≤0.05 for all) and GLUT-1, 2, 3, 5, 8, 9 and 12 in NAFLD compared to normal individuals. Results were confirmed using immunohistochemical staining. Exposure of human PCLS to sVAP-1 and methylamine typically resulted in a 38%–54% increase in PA uptake (p≤0.01 for all) and a 20% increase in hepatocyte glucose uptake in vitro which could be inhibited using bromoethylamine. Transduction of HSEC with enzymatically active VAP-1 also increased glucose uptake which was prevented in the absence of enzyme activity. Interestingly methylamine treatment of human liver resulted in decreased expression of mRNA for glucose transporters and an increase in some lipid transporters including FABP6, FATP and LRP8, and H<sub>2</sub>O<sub>2</sub> produced by SSAO activity increase lipid uptake by hepatic cells. <h3>Conclusion</h3> In conclusion, we demonstrate for the first time global alterations in cellular expression of glucose and lipid transporter proteins in human NAFLD. We confirm that VAP-1 is elevated in disease and that SSAO activity of VAP-1 results in enhanced hepatic lipid and glucose uptake and changes in transporter expression. Thus we propose that bioactive metabolites of SSAO activity contribute to the metabolic derangement evident in fatty liver disease. <h3>Competing interests</h3> None declared.
Groin Hernias in Adults
Authors: Robert J. Fitzgibbons, R. Armour Forse
Journal: New England Journal of Medicine (2015)

Watchful waiting is safe for men with asymptomatic inguinal hernias, but data from randomized trials suggest that most men will ultimately undergo surgery, primarily because of pain. Watchful waiting is not recommended in women, given their higher prevalence of femoral hernias.
Abrupt Relapse of <i>ALK</i>-Positive Lymphoma after Discontinuation of Crizotinib
Authors: Carlo Gambacorti-Passerini, Lara Mussolin, Laurence Brugieres
Journal: New England Journal of Medicine (2016)

ALK-directed therapy is effective in ALK-positive lymphomas, but the appropriate duration of therapy is unclear. In two patients in whom crizotinib was discontinued, recurrence was rapid (within days). Further ALK-directed therapy induced responses.
Protective effect of<i>Lactobacillus rhamnosus</i>231 against N-Methyl-N′-nitro-N-nitrosoguanidine in animal model
Authors: Viral Gosai, Padma ambalam, Maya Raman, C.R. Kothari, R.K. Kothari, B.R.M. Vyas, Navin R. Sheth
Journal: Gut Microbes (2011)

The protective effect of Lactobacillus rhamnosus 231 (Lr 231) against potent carcinogen N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) in the rat model is studied. Daily feeding with Lr 231 improved the body weight of male Wistar rats compared with control groups. Fecal azoreductase (p < 0.001) and nitroreductase (p < 0.01) enzyme activity decreased significantly in Lr 231 group in comparison with control groups that received only phosphate buffer or MNNG. Oral administration of MNNG led to a significant increase in Glutathione transferase (GST) while Glutathione reductase (GSH) showed decreased activity. Conversely, feeding Lr 231 showed significantly increased GSH and decreased GST activity in comparison to the MNNG group, emphasizing the protection provided by Lr 231 against MNNG. Histopathological analysis of liver, spleen and colon showed decreased signs of inflammation in the Lr 231 group. The present study highlights that inclusion of active Lr 231 in regular diets could be used to prevent MNNG induced colon carcinoma.
MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis
Authors: Takashi Yokoyama, Mayuka Nakatake, Takeshi Kuwata, Arnaud Couzinet, Ryo Goitsuka, Shuichi Tsutsumi, Hiroyuki Aburatani, Peter J.M. Valk, Ruud Delwel, Takuro Nakamura
Journal: Journal of Clinical Investigation (2016)

The TALE-class homeoprotein MEIS1 specifically collaborates with HOXA9 to drive myeloid leukemogenesis. Although MEIS1 alone has only a moderate effect on cell proliferation in vitro, it is essential for the development of HOXA9-induced leukemia in vivo. Here, using murine models of leukemogenesis, we have shown that MEIS1 promotes leukemic cell homing and engraftment in bone marrow and enhances cell-cell interactions and cytokine-mediated cell migration. We analyzed global DNA binding of MEIS1 in leukemic cells as well as gene expression alterations in MEIS1-deficent cells and identified synaptotagmin-like 1 (Sytl1, also known as Slp1) as the MEIS1 target gene that cooperates with Hoxa9 in leukemogenesis. Replacement of SYTL1 in MEIS1-deficent cells restored both cell migration and engraftment. Further analysis revealed that SYTL1 promotes cell migration via activation of the CXCL12/CXCR4 axis, as SYTL1 determines intracellular trafficking of CXCR4. Together, our results reveal that MEIS1, through induction of SYTL1, promotes leukemogenesis and supports leukemic cell homing and engraftment, facilitating interactions between leukemic cells and bone marrow stroma.
Efficacy of palliative chemotherapy for metastatic breast cancer according to HER2-status and basal cytokeratin expression.
Authors: S Kahlert, P Mainka, E Knall, K Bauer, D Mayr
Journal: Cancer Research (2009)

Abstract Abstract #6123 Introduction: The majority of patients (pts.) with metastatic breast cancer (MBC) will receive cytotoxic therapy (CT) at one time. Predictive factors for the choice of the optimal regimen are not available with the exception of the Her2-status. Triple-negative tumors, especially basal-like tumors are associated with impaired prognosis and sensitivity to CT in several studies without the option of endocrine or anti-her2 targeted treatment. Usually identification of these cases is done by gene expression assays. We tried to identify effective CT regimens in a retrospective trial for this subgroup.&amp;#x2028; Methods: We reviewed all patient files of women receiving at least one line of palliative CT in our institution from 1991 to 2005 and searched the archive of the institute of pathology for evaluable paraffin embedded tissue. In available material estrogen receptor (ER), progesterone receptor (PgR), Her2 Status and basal cytokeratins CK 5/6 and CK14 were determined by IHC and/or FISH (Her2). A tumor was defined as basal-like, if CK5/6 or CK14 were expressed in more than 10% off all tumor cells. The tumors were divided into four subgroups: ER/PgR positive and HER2 negative (ER/PgR+), Her2 positive (HER+), triple negative and no expression of CK5/6 or CK 14 (non-basal) and triple negative basal-like tumors (basal).&amp;#x2028; Results: We identified 240 pts. receiving 455 lines of palliative CT (240 1st line, 114 2nd line, 53 3rd line and 48 4th – 7th line). Regimens contained anthracyclines (44%), taxanes (27%), vinca alkaloids (15%), capecitabine (8%), platinum salts (4%) and trastuzumab (15%). 43% of the regimens were combination therapies.&amp;#x2028; The subgroups were ER/PgR+ (46%), HER+ (28%), non-basal (10%) and basal (16%). Survival of basal tumors was significantly shorter (10.7 months (mo.)) than the other groups (non-basal 23.7, HER+ 22.0 and ER/PgR+ 28.1 mo., p=0.001). Mean time to treatment failure (TTF) in the four groups was 2.1 (basal), 4.0 (non-basal), 5.5 (HER+) and 5.7 mo. (ER/PgR+).&amp;#x2028; Although anthracycline based therapies showed longer TTF in all four groups, the difference reached significance only in ER/PgR+ pts. (5.0 vs. 7.2 mo., p=0.004). Taxanes showed significantly lower TTF in ER/PgR+ pts. (6.3 vs. 4.3 mo., p=0.03). Use of combination therapy showed significant benefit for ER/PgR+ pts. (6.0 vs. 9.4 mo., p=0.008 (1st line only)).&amp;#x2028; Capecitabine, vinca alkaloids and platinum salts were used too seldom to draw conclusions.&amp;#x2028; Conclusions: Use of IHC for CK5/6 and CK14 helped to identify a subgroup of pts. with adverse prognosis of MBC compared to the other groups. This finding is consistent for all types of CT. We were not able to detect regimens of superior efficacy for this subgroup. The availability of IHC can ease additional studies in larger cohorts. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6123.
S68 The National Early Warning Score (NEWS) &amp; iatrogenic harm - could the NEWS for COPD patients be improved?
Authors: L Hodgson, S Bax, M Montefort, J Zahra, R Venn, H Ranu, J Congleton
Journal: Thorax (2013)

<h3></h3> The National Early Warning Score (NEWS) system is in use throughout NHS Acute Trusts. It reliably picks up the small proportion of patients at high risk of death during their admission. However, during Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), where target saturations are 88–92% in selected patients, a high proportion of patients have NEWS 'alerts' when their oxygen levels are within the target range set by their clinician. This results in referral for urgent review by medical staff and/or an inappropriate increase of inspired oxygen which could exacerbate hypercapnic respiratory failure. We therefore propose a simple modification to the NEWS system in patients at risk of hypercapnic respiratory failure. Three points are added for target saturations of 85% or less and two points are added for target saturations of 86–87%. For target saturations of 88–92%, no additional points will be added. This modification would be at the senior clinicians' discretion. We reviewed the observations of 1119 patients admitted with a primary diagnosis of AECOPD and compared them to 15,953 patients aged over 50 admitted to one of two acute medical units. Admission saturations were reviewed and compared with in-patient mortality. Use of the current NEWS system resulted in 40% of patients with AECOPD scoring 2–3 points on their saturation alone despite most being in the saturation range recommended by the BTS<sup>1</sup>. In addition, their risk of mortality was significantly lower than patients without COPD in the same saturation range (See table 1). Our proposed modified NEWS system results in an improved ability to identify the patients at higher risk of mortality, thereby resulting in more efficient utilisation of medical resources and the reduction of inappropriate use of oxygen and risk of hypercapnic respiratory failure. We have shown that the current NEWS system leads to a significant number of patients with AECOPD alerting when they have nationally recommended target oxygen saturations. A simple adjustment of the alerting threshold in this cohort could improve the system. This could also be applicable to other respiratory patients with or at risk of hypercapnic respiratory failure. 1. BTS guideline for emergency oxygen use.
Consequences of heat shock protein 72 (Hsp72) expression and activity on stress-induced apoptosis in CD30+ NPM–ALK+ anaplastic large-cell lymphomas
Authors: P Bonvini, E Zorzi, L Mussolin, M Pillon, C Romualdi, M Peron, E S G d'Amore, L Lamant, A Rosolen
Journal: Leukemia (2012)
DEACTIVATION OF VENTRICULAR ASSIST DEVICES: WHO AND WHEN RESULTS OF AN ACC MEMBERSHIP SURVEY
Authors: Elizabeth D. Blume, Kimberlee Gauvreau, Stephanie Cooper, Paul Hauptman, Sarah Goodlin, Scott Hummel, Richard Josephson, Caroline Doherty, Jorge Brenes Salazar, Mathew Maurer, Abby Cestoni, Kelly Ann Light-McGroary, Craig Alpert, James Kirkpatrick
Journal: Journal of the American College of Cardiology (2016)
FRI0136 Current profile of comorbidities in patients with rheumatoid arthritis (RA) in comparison to community controls:
Authors: T. Sokka, H. Kautiainen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Several clinical cohorts and databases over the past decades indicate that RA is associated with a high number of comorbidities. Along with tight control of RA inflammatory activity, the role of those comorbidities may diminish that are associated with inflammatory activity. <h3>Objectives</h3> To study the profile of comorbidities in patients with RA and community controls. <h3>Methods</h3> All RA patients from a hospital district of 275,000 people are included in a RA database. For each RA patient, three age, sex and habitat matched control subjects were randomly sampled from the population register. Patients and control subjects were mailed an extended health assessment questionnaire which also included a list of comorbidities with a request to indicate with "x" diseases that apply. <h3>Results</h3> The response rate was 70% including 1635 RA patients (with median disease duration of 11 years) and 4264 controls; 73% were female, the mean age was 65 years in both groups. Prevalence of cardiovascular diseases and traditional CV risk factors were similar between groups or lower in RA. Prevalence of lung diseases, fibromyalgia (FM), osteoporosis (OP), and cataracts was higher in RA patients, whereas prevalence of cancer, chronic back pain, and musculoskeletal trauma was higher in population. <h3>Discussion</h3> Results indicate higher prevalence for lung comorbidity, OP, and cataracts in RA, related to RA and/or its treatments. More frequent diagnostic tests may influence prevalence of OP and FM. RA may protect from life style that is associated with chronic back pain and musculoskeletal trauma. Prevalence of CV disease and its risk factors was similar between the groups or lower in RA, indicating favorable changes compared to historical data. <h3>Disclosure of Interest</h3> None Declared
UNFRACTIONATED HEPARIN VERSUS LOW-MOLECULAR-WEIGHT HEPARIN ANTICOAGULANT BRIDGING IN LEFT-SIDED MECHANICAL HEART VALVE PATIENTS: THE HI-LOW STUDY
Authors: Einar Hart, Timion A. Meijs, Jan Westerink, Thomas C. Dessing, Rosemarijn Jansen, Berto Bouma, Robert Riezebos, Wilco Tanis, Wim Jan van Boven, Vikash Hindori, Nynke Wiersma, Steven Chamuleau
Journal: Journal of the American College of Cardiology (2016)
SP0018 The Practical Case: Is it Really Easy to Distinguish Gout from CPPD by Ultrasound? Live Case with Patient
Authors: C. Dejaco
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Musculoskeletal ultrasound may be useful to discriminate between similar arthritic entities. In case of suspected crystalline arthropathy, sonography may identify calcium pyrophosphate deposition (CPPD) or monosodium urate (MSU) crystals with a high sensitivity and specificity. At large joints CPPD crystals typically appear as thin hyperechoic bands and/or hyperechoic sparkling spots within hyaline cartilage whereas MSU depositions are observed as hyperechoic enhancements (homogeneous thickening or focal deposition) of the superficial margin of articular cartilage causing the "double contour" sign. At wrists or knees, CPPD deposits may also appear as hyperechoic rounded areas within the fibrocartilage. In small joints, CPPD crystals may imitate a double contour sign; however, at dynamic investigation deposits are displaceable whereas MSU crystals "stick" at the hyaline cartilage. An intratendinous tophus usually causes disarrangement of fibrillar echotexture and cloudy hyperechogenic bands which may generate an acoustic shadow. CPPD calcifications of tendons are typically linear and may be extensive. In summary, characteristic ultrasound findings at joints, fibrocartilage and tendons may help to distinguish between gout and pseudogout in patients with suspected crystalline arthropathy. <h3>Disclosure of Interest</h3> None Declared
THE NEUTROPHIL TO LYMPHOCYTE RATIO IS AN INDEPENDENT PREDICTOR OF SHORT- AND LONG-TERM MORTALITY IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Gaetano M. De Ferrari, Stefano Cornara, Alberto Somaschini, Andrea Baldo, Claudia Pavesi, Gabriele Crimi, Silvia Pica, Marco Ferlini, Rita Camporotondo, Massimiliano Gnecchi
Journal: Journal of the American College of Cardiology (2014)