tbuckley/cabot-search huggingface dataset:
Abstract B29: Inactivation of suppressor of fused alone is not sufficient to cause medulloblastoma
Authors: Thevagi Satkunendran, Ryan J. Ward, Peter B. Dirks, Chi-chung Hui
Journal: Cancer Research (2009)

Abstract Hedgehog (Hh) signaling is essential for embryonic development and adult homeostasis. Aberrant pathway activity can result in various developmental disorders and tumors. The Hh receptor Patched (PTCH1) is a negative regulator of the pathway and acts as a tumor suppressor. We and others have shown that suppressor of fused (SU(FU)) and KIF7 are two major negative regulators of the pathway downstream of PTCH1. Medulloblastoma (MB), the most common and aggressive pediatric brain tumor arising in the cerebellum, involves deregulation of Hh signaling. Similar to those observed in patients with PTCH1 mutations, Ptc1+/− mice spontaneously develop MB. In Ptc1+/− mice, the incidence of MB increases upon exposure to DNA damaging agents or a compounded loss of other tumor suppressor genes, such as p53. SU(FU) mutations have been found in MB, suggesting that SU(FU) is also a tumor suppressor in the cerebellum. However, we found that Su(fu)+/− mice do not develop any spontaneous MB, and that upon neonatal exposure to X-ray irradiation as well as a chemical carcinogen, these mice do not form any tumors. To examine the potential tumor suppressor function of Su(fu) in the brain, we performed conditional deletion of Su(fu) in neural progenitors. In mice, deletion of Su(fu) in neural progenitors using the Nestin-Cre line resulted in a disorganized cerebellum and motor defects. Unexpectedly, unlike Nestin-Cre;Ptc1f/- mice which developed MB, MB formation was not observed in Nestin-Cre;Su(fu)f/- mice. In contrast, similar to those reported previously, 100% of Su(fu)+/−;p53−/− mice developed MB between 2.5–4 months of age. Molecular analysis of primary tumor cell lines from these MBs revealed a loss of the wild type Su(fu) allele in the tumors. Together, these observations indicate that loss of Su(fu) alone is not sufficient for transformation into MB and suggest that other molecules, such as Kif7, may possess compensatory functions in the suppression of the tumor phenotype. Currently, we are examining the effects of Kif7 inactivation alone and in conjunction with Su(fu) inactivation on MB formation. Citation Information: Cancer Res 2009;69(23 Suppl):B29.
RESECCIÓN MUCOSA ENDOSCÓPICA DE LESIONES COLÓNICAS DE GRAN TAMAÑO O COMPLEJAS. EVALUACIÓN PROSPECTIVA DE LOS PRIMEROS 100 CASOS
Authors: P Huelin Alvarez, C Guarner Argente, A Gonzalez Blanco, M Concepcion Martin, E Alvarado Tapias, M Blasi Puig, C Gomez Oliva, S Sainz Saez De La Torre, C Guarner Aguilar
Journal: Endoscopy (2013)

Introducción: La resección mucosa endoscópica (RME) permite el tratamiento de lesiones planas o grandes que previamente se derivaban a cirugía. Objetivo: Evaluar la seguridad y eficacia de la implantación de la RME en un hospital de tercer nivel. Material y Método: Evaluación prospectiva de las 100 primeras RME colónicas realizadas en nuestro centro en lesiones grandes o complejas. Resultados: En 2 años se realizaron 100 RME en pacientes con edad media de 70 ± 10 años, (64% varones). El 91% eran ASA I-II. La medida media de los pólipos fue de 29 ± 16 mm, con RIC 20 – 32 y máximo de 120 mm. Su localización fue preferentemente en colon derecho/ciego (37%), colon transverso (25%), colon izquierdo (14%), recto (11%). Según la clasificación de Paris la mayoría de lesiones fueron tipo IIa y Is (45y 38%). Diez pacientes se remitieron a cirugía sin intento de resección o tras mínimo intento por signos de irresecabilidad. Se realizó resección en bloque en el 33% y fragmentada en el 67%. En un 32% se completó con gas Argón. Siete pacientes presentaron hemorragia controlada durante el procedimiento. Se registraron 12 complicaciones en 10 pacientes. Dos durante el procedimiento: 1 perforación tratada de manera conservadora y 1 crisis hipertensiva. Se observaron 6 hemorragias tardías, 3 síndromes postpolipectomía y una fiebre autolimitada. Se ha realizado endoscopia de seguimiento en 41 pacientes hasta el momento, observando persistencia/recidiva en 10 (24%). Ocho tratadas endoscopicamente y 2 derivadas a cirugía. El éxito terapéutico fue del 95% en los pacientes con seguimiento a los que se completó la resección inicial. Conclusiones: La RME de lesiones colónicas grandes o complejas se puede implantar de forma segura y eficaz. Una minoría de pacientes presenta lesiones no resecables o que precisan cirugía durante su seguimiento. En un porcentaje no despreciable persiste lesión en el seguimiento.
DIRECT CAROTID WALL SHEAR STRESS IN ACUTE CORONARY SYNDROME PATIENTS DECREASED AFTER ONE MONTH MEDICAL MANAGEMENT
Authors: Sang-Rok Lee, Lae-Young Jung, Soo Kyoung Song, Ji-Young Yoon, Yi-Shik Kim, Sun Hwa Lee, Kyoung-Suk Rhee, Jei-Keon Chae, Won-Ho Kim, Jae-Ki Ko
Journal: Journal of the American College of Cardiology (2015)
Abstract 5077: Signaling through the cytoplasmic tail of MUC1 directly activates transcription of the metastasis promoting growth factor CTGF in pancreatic adenocarcinoma
Authors: Michelle Behrens, Paul Grandgenett, Jennifer Bailey, Pankaj Singh, Chun-Hui Yi, Michael Hollingsworth
Journal: Cancer Research (2010)

Abstract Transmembrane mucin MUC1 is highly expressed in pancreatic adenocarcinoma and contributes to tumor growth, invasion, and metastasis. Differential phosphorylation of the cytoplasmic tail of MUC1 (MUC1.CT) by growth factor receptor tyrosine kinases is associated with morphogenetic signal transduction, as it enables interactions with signal transducers and leads to nuclear accumulation of MUC1.CT. MUC1.CT contains no known DNA binding motif but localizes to promoters of genes implicated in tumorigenesis in complex with transcription factors, modulating their regulatory activity. Using microarray analysis, we identified genes differentially transcribed in S2013 pancreatic adenocarcinoma cells stably overexpressing MUC1. These data were correlated with transcriptional targets of MUC1.CT identified on a genome-wide scale in pancreatic adenocarcinoma cells using a combination of chromatin immunoprecipitation and promoter array methodologies (ChIP-on-chip). We further investigated the transcriptional regulation of one novel target, connective tissue growth factor (CTGF/CCN2), by MUC1.CT. CTGF is highly expressed in pancreatic cancer and is a known mediator of tumor growth, angiogenesis, and metastasis. Overexpression of MUC1 significantly increased CTGF expression in pancreatic tumor cells in response to EGF, PDGF-BB, or HGF stimulation. The MUC1.CT becomes phosphorylated by EGFR, PDGFR-beta, and c-Met and overexpression of MUC1 constructs harboring mutations within the target phosphorylation motifs for these receptor tyrosine kinases reduced CTGF expression. We determined that MUC1.CT directly regulated the CTGF gene transcription through co-occupancy with transcription factors at several regions within and surrounding the CTGF promoter. MUC1 overexpression promoted localization of mutant p53 (R273H) and beta-catenin to the CTGF promoter, while decreasing occupancy by a repressor of CTGF transcription, c-Jun. We propose that MUC1, when overexpressed in pancreatic adenocarcinoma, enables expression of CTGF in response to growth factor stimulations by promoting mutant p53 and beta-catenin transcriptional activity and alleviating CTGF transcriptional repression by c-Jun. Taken together, these results reveal a novel signaling pathway that selectively induces CTGF expression in MUC1-overexpressing pancreatic tumor cells. 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 5077.
Abstract 1395: CD16+ dendritic cells (DC) promote squamous carcinoma cell (SCC) survival, and SCC affect DC phenotype and migration
Authors: Zoya B. Kurago, Lalitha Ramanathapuram
Journal: Cancer Research (2011)

Abstract In the inflammatory mucosal microenvironment of head and neck squamous cell carcinoma (HNSCC), dendritic cells (DC) are prominent; they express CD16, and are usually in direct contact with tumor cells. Mucosal and inflammation-associated DC develop from monocytes, and monocyte-derived DC are used in HNSCC immunotherapy. However, beyond apoptotic tumor cell uptake and presentation of tumor antigens by DC, HNSCC cell interactions with DC are poorly understood. Using co-cultures of monocyte-derived DC and established HNSCC cell lines we found that carcinoma cells induced significant increases in CD16 expression on DC while promoting a CD1a+CD86dim immature phenotype, similar to that observed in HNSCC specimens. Moreover, HNSCC cells strongly affected DC migration, both steady-state and CCL21-induced. The effects of carcinoma cells on migration were donor-dependent, and CCL21-induced migration directly correlated with HNSCC-mediated effects on CCR7 and CD38 expression on DC. Most remarkably, the numbers of live detached HNSCC cells were orders of magnitude higher in DC-HNSCC co-cultures than in parallel HNSCC cell cultures without DC. This study provides a novel insight into the outcomes of DC-HNSCC interactions relevant to the tumor microenvironment. 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 1395. doi:10.1158/1538-7445.AM2011-1395
SP0073 A New Paradigm to Managing the Impact of Inflammatory Foot and Ankle Disease
Authors: J. Woodburn
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Foot and ankle involvement is common in inflammatory joint disease. Recent evidence has identified persistent foot disease, pain and walking disability in patients in disease remission state. We propose a new paradigm of allied health professions led (podiatry) management strategies which align to the treat-to-target principles. These exploit extended scope practice primarily directed towards diagnostic ultrasound, targeted treatment to residual inflammatory lesions, and mechanical-based therapies including custom foot orthoses for joint protection and functional optimisation. Therefore delegates on attending this lecture will be able to: - Appreciate the role of inflammatory and mechanical factors in foot and ankle on disease impact (impairments and associated disability), - Understand more fully extended podiatry assessment and management strategies based on the treat-to-target principle, - Describe structured patient management targeting residual inflammatory lesions and mechanical deficits in the foot and ankle. <h3>Disclosure of Interest</h3> None Declared
Soft-Tissue Involvement by Adenocarcinoma Imaged During Bone Scintigraphy
Authors: Z Bordy, E Pasztarak, G Bánsági, E Sik
Journal: Clinical Nuclear Medicine (1997)

A large and well-delineated photopenic area in extraskeletal tissue seen on Tc-99m MDP three-phase bone imaging. This scintigraphic lesion of the left thigh proved to be a metastasis of lung adenocarcinoma.
Evidence that the adenosine triphosphate‐binding cassette G5/G8‐independent pathway plays a determinant role in cholesterol gallstone formation in mice
Authors: Helen H. Wang, Xiaodan Li, Shailendra B. Patel, David Q.‐H. Wang
Journal: Hepatology (2016)

The adenosine triphosphate‐binding cassette (ABC) sterol transporter, Abcg5/g8 , is Lith9 in mice, and two gallstone‐associated variants in ABCG5/G8 have been identified in humans. Although ABCG5/G8 plays a critical role in determining hepatic sterol secretion, cholesterol is still secreted to bile in sitosterolemic patients with a defect in either ABCG5 or ABCG8 and in either Abcg5/g8 double‐ or single‐knockout mice. We hypothesize that in the defect of ABCG5/G8, an ABCG5/G8‐independent pathway is essential for regulating hepatic secretion of biliary sterols, which is independent of the lithogenic mechanism of the ABCG5/G8 pathway. To elucidate the effect of the ABCG5/G8‐independent pathway on cholelithogenesis, we investigated the biliary and gallstone characteristics in male wild‐type (WT), ABCG5(‐/‐)/G8(‐/‐), and ABCG8 (‐/‐) mice fed a lithogenic diet or varying amounts of cholesterol, treated with a liver X receptor (LXR) agonist, or injected intravenously with [ 3 H]sitostanol‐ and [ 14 C]cholesterol‐labeled high‐density lipoprotein (HDL). We found that ABCG5(‐/‐)/G8(‐/‐) and ABCG8 (‐/‐) mice displayed the same biliary and gallstone phenotypes. Although both groups of knockout mice showed a significant reduction in hepatic cholesterol output compared to WT mice, they still formed gallstones. The LXR agonist significantly increased biliary cholesterol secretion and gallstones in WT, but not ABCG5(‐/‐)/G8(‐/‐) or ABCG8 (‐/‐), mice. The 6‐hour recovery of [ 14 C]cholesterol in hepatic bile was significantly lower in both groups of knockout mice than in WT mice and [ 3 H]sitostanol was detected in WT, but not ABCG5(‐/‐)/G8(‐/‐) or ABCG8 (‐/‐), mice. Conclusions: The ABCG5/G8‐independent pathway plays an important role in regulating biliary cholesterol secretion, the transport of HDL‐derived cholesterol from plasma to bile, and gallstone formation, which works independently of the ABCG5/G8 pathway. Further studies are needed to observe whether this pathway is also operational in humans. (H epatology 2016;64:853‐864)
Two cases of human cutaneous anthrax in Bosnia and Herzegovina, September 2014
Authors: J Arapović, S Skočibušić, B Jelavić, H B Ivanković, M Jurić, D Mamić, S Grgić, J Lesko, M Leventić, I Soldo, J Ravlija, J Nikolić
Journal: Eurosurveillance (2015)

Two cases of human cutaneous anthrax were reported in September 2014 in south-western Bosnia and Herzegovina. The two men were involved in slaughtering a cow and handled its Bacillus anthracis-infected meat. Anthrax has been sporadically observed in livestock in Bosnia and Herzegovina, but no confirmed human cases had been reported in the country in the last two decades. Clinicians in the country should be aware that anthrax may occur in humans, arising from exposure to infected animals.
Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis
Authors: Stefano Crippa, Claudio Bassi, Roberto Salvia, Giuseppe Malleo, Giovanni Marchegiani, Vinciane Rebours, Philippe Levy, Stefano Partelli, Shadeah L Suleiman, Peter A Banks, Nazir Ahmed, Suresh T Chari, Carlos Fernández-del Castillo, Massimo Falconi
Journal: Gut (2016)

Objective To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians’ recommendation, patient personal choice or comorbidities precluding surgery. Methods In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific survival (DSS) were obtained. Results Of 281 patients identified, 159 (57%) had BD-IPMNs and 122 (43%) had MD-IPMNs; 50 (18%) had high-risk stigmata and 231 (82%) had worrisome features. Median follow-up was 51 months. The 5-year OS and DSS for the entire cohort were 81% and 89.9%. An invasive pancreatic malignancy developed in 34 patients (12%); 31 had invasive IPMNs (11%) and 3 had IPMN-distinct pancreatic ductal adenocarcinoma (1%). Independent predictors of poor DSS in the entire cohort were age &gt;70 years, atypical/malignant cyst fluid cytology, jaundice and MD &gt;15 mm. Compared with MD-IPMNs, BD-IPMNs had significantly better 5-year OS (86% vs 74.1%, p=0.002) and DSS (97% vs 81.2%, p&lt;0.0001). Patients with worrisome features had better 5-year DSS compared with those with high-risk stigmata (96.2% vs 60.2%, p&lt;0.0001). Conclusions In elderly patients with IPMNs that have worrisome features, the 5-year DSS is 96%, suggesting that conservative management is appropriate. By contrast, presence of high-risk stigmata is associated with a 40% risk of IPMN-related death, reinforcing that surgical resection should be offered to fit patients.
AB0206 Results of a smoking-cessation program for patients with arthritis in a rheumatology department.
Authors: A. Naranjo, A. Bilbao, C. Erausquin, S. Ojeda, F. M. Francisco, J. C. Quevedo, I. Rúa Figueroa, R. López, C. García de Llanos, C. Rodríguez-Lozano
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Autoimmune rheumatic diseases are associated with increased cardiovascular mortality compared to the general population <h3>Objectives</h3> To evaluate the impact of an intervention carried out by the rheumatologist and nurse in smoker patients. <h3>Methods</h3> We selected consecutive active smokers attended at the rheumatology clinics with rheumatoid arthritis, spondyloarthritis or connective diseases. The intervention consisted of two phases: 1) A baseline visit which included the rheumatologist advice on the benefits of quitting smoking, oral and written in a specific information form for rheumatic patients. Patients completed a questionnaire that included smoking-dependence tests and previous quit attempts. 2) A telephone follow-up visit at the 3rd month done by the rheumatology nurse, which included oral reinforcement, the offer of an additional visit and the possibility of pharmacological treatment to help quitting. The primary outcome variable was the percentage of smokers with total abstinence in the last 7-days of a phone interview at 3, 6 and 12 months. The secondary endpoint was a reduction in cigarette consumption by at least 50%. <h3>Results</h3> 945 patients participated in the study, 233 (24.7%) were former smokers and 185 (19.5%) were current smokers. In the last five years, 55 patients quit smoking, sothe annual withdrawal rate was 4.6%. The smoking cessation rate in 152 participants was 11.8% at 3 months, 14.4% at 6 months and 15.7% at 12 months (Table). The OR at 12 months compared with the previous smoking cessation rate was 3.8 (CI 95%: 1.8-8.1). 29 patients (19%) reduced ≥ 50% of the cigarette consumption at 12 months. In a linear regression analysis in which the dependent variable was smoking cessation at 12 months, a score of less dependence (p=0.03) and previous quit attempts (p=0.04) were significantly associated with definitive smoking cessation. <h3>Conclusions</h3> An educational program for smoker patients, which includes oral and written advice by the rheumatologist and the nurse, makes that one out of six patients cease to smoke at 12 months. As far as we know, this is the first interventional study in smokers with arthritis. It has the advantage of a simple design that can be easily integrated into routine daily practice. <h3>Disclosure of Interest</h3> None Declared
Case 36-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Martin A. Samuels, Suzanne de la Monte
Journal: New England Journal of Medicine (1994)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 36-1994 — A 49-Year-Old Man with Hypopituitarism, Multifocal Neurologic Defects, and an Intracranial Mass
Single-Gene Mutations Resulting in Reproductive Dysfunction in Women
Authors: Eli Y. Adashi, Jon D. Hennebold
Journal: New England Journal of Medicine (1999)

Fertility in women is regulated by a series of highly coordinated and synchronized interactions in the hypothalamic–pituitary–ovarian axis (Figure 1A). The central regulator of the axis is the group of neurons that secrete gonadotropin-releasing hormone (GnRH).1 Their cell bodies reside in the arcuate nucleus, and their exons terminate in the median eminence near the hypothalamic–pituitary portal vasculature. These neurons are unique in that they have an intrinsic firing frequency such that GnRH is secreted in pulses at 60-to-90-minute intervals into the portal vasculature to be conveyed to the anterior pituitary gland. There GnRH binds to specific cell-surface receptors on the . . .
SAT0252 HLA-B27 Homozygosity has No Influence on Radiographic Damage in Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data
Authors: T.-J. Kim, I.-H. Sung, K.-S. Na, S. Lee, K. B. Joo, T.-H. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is no consensus as to whether HLA-B27 homozygosity influences the clinical features of ankylosing spondylitis (AS). We already reported that HLA-B27 homozygosity has no influence on clinical and functional disability in AS. However, we did not assess spinal bony progression at that time, further radiographic study was needed to evaluate the influence of HLA-B27 on bony ankylosis. <h3>Objectives</h3> To evaluate the influence of homozygosity for HLA-B27 on the radiographic damage in AS <h3>Methods</h3> A total of 368 AS patients with positive HLA-B27 status from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were recruited for this study. HLA-B27 positive patients out of all AS patients were assessed for whether they had homozygosity or heterozygosity for HLA-B27. First, all data were stratified in relation to the carrier state of positive HLA-B27 for cross-sectional survey. Then we compared the radiographic damage score between groups. Second, we evaluated collected clinical and radiographic parameters at two different time points. Then we compared radiographic progression between groups. To use the mSASSS, cervical and lumbar spinal radiographs were examined by two experienced bone and joint radiologists (S. Lee, K.B. Joo). <h3>Results</h3> The agreement between the two readers regarding mSASSS was very good: ICC coefficient 0.70 (95% CI 0.60–0.81). The mean age (SD) of the AS patients was 37.0 (9.2) years, and the mean disease duration (SD) was 15.6 (9.1) years. Of these patients, 34.5% (127 patients) had HLA-B27 homozygosity. The mean mSASSS unit (SEM) was not significantly different between groups (homozygosity 28.57±4.12 vs heterozygosity 23.34±3.44, P = 0.344) on cross-sectional survey. When it comes to radiographic progression between groups over 5 years, there was no significant difference in spite of adjusting for confounding variable (homozygosity 4.98±0.98 vs heterozygosity 4.21±0.82, P = 0.562). <h3>Conclusions</h3> The carrier state of positive HLA-B27 plays no role in determining the radiographic progression in AS. <h3>Disclosure of Interest</h3> None Declared