tbuckley/cabot-search huggingface dataset:
ESTUDIO RETROSPECTIVO DE LAS ULTRASONOGRAFÍAS ENDOANALES EN TRES DIMENSIONES (3D) REALIZADAS EN EL HOSPITAL UNIVERSITARIO “12 DE OCTUBRE” DE MADRID
Authors: M Algara San Nicolas, M Pérez Carreras, J Díaz Tasende, P Delgado, P Pelaez, J Pascual, P Martinez Montiel, B Casis, S Rodriguez, G Castellano Tortajada
Journal: Endoscopy (2013)

Introducción: La ultrasonografía endoanal (USEA) es una técnica sencilla y de gran utilidad en el diagnóstico y manejo terapéutico de las enfermedades anorrectales, mejorando su resolución espacial con el uso de la sonda en 3D. Objetivo: Estudiar la utilidad de la USEA con la sonda rígida 3D desde su implantación en nuestro hospital. Material y Método: Estudio retrospectivo de las USEA-3D realizadas en nuestro centro desde noviembre-2008 hasta junio-2013. Analizamos las características demográficas de los pacientes, indicaciones y diagnósticos. Resultados: Se realizaron 755 USEA (exploraciones/año: 116/2009; 146/2010; 183/2011; 195/2012; 114/junio-2013); 58% mujeres/42% varones; edad 47 ± 14 años. Motivos de solicitud: sepsis perianal (fístula y/o absceso) (49%; 367/755); incontinencia (32%; 241/755); proctalgia (6%; 42/755); neoplasia anal (1%; 7/755); otros (12%; 92/755). Procedencia de peticiones: Ap. Digestivo (57%), Cirugía General (39%). Diagnósticos: sepsis perianal (41%); normalidad (25%); defectos esfinterianos (13%); cicatriz obstétrica (9%); otros (12%). La incontinencia se asoció a USEA normal en el 44% de casos; Características de las fístulas: transesfinterianas (44%; 140/316); interesfinterianas (32%; 101/316); extraesfinterianas (10%; 32/316); supraesfinterianas (6%; 19/316); otras (8%; 24/316); complejas 59% (186/316); asociadas a Crohn (22%; 71/316). Se inyectó H2O2 en 259/316 (82%), identificándose el orificio fistuloso interno (OFI) en 77% (199/259); Localización de abscesos: peri/postanal 66% (93/141), isquiorrectal 24% (34/141), otras 10% (14/141). Conclusiones: 1. En nuestro hospital, el numero de solicitudes de USEA ha aumentado progresivamente (fundamentalmente desde gastroenterología y cirugía general); 2. La principal indicación de USEA en nuestra serie ha sido la sepsis perianal; 3. Cerca de la mitad de los pacientes con incontinencia fecal no presentaron alteraciones en la USEA; 4. La fístula perianal fue el diagnóstico más frecuente en nuestro centro; 5. La inyección de H2O2 permitió localizar el OFI en el 77% de los casos; 6. El 66% de abscesos se localizaron en el espacio peri/postanal.
Abstract A10: Increased mesenchymal progenitor cells in RB1−/− bone
Authors: Elizabeth Kong, Gabriel Gutierrez, David Thomas, Philip Hinds
Journal: Cancer Research (2009)

Abstract The retinoblastoma pathway is deregulated in 90% of human cancers owing to the mutation of one or more pathway members. Yet, the molecular pathogenesis of tumors with a loss of the retinoblastoma gene, RB1, (retinoblastoma and osteosarcoma) are poorly understood. To understand the role of pRb in tumor formation we have focused on a tissue in which malignancies commonly have RB1 deletions, bone. Human osteosarcoma cells, in general, exhibit no signs of terminal differentiation, and are defined by the ability to form bone. We hypothesize that osteosarcoma is caused by molecular/genetic disruptions of the osteogenic differentiation pathway. Homozygous null RB1 mice die during early embryonic day, E11.5-13.5, before any significant skeletal development or mineralization occurs. Therefore, we utilized the cre/lox system to create a bone targeted RB1 knockout animal. RB1−/− mice display defects in bone formation. Furthermore, isolation and characterization of primary calvarial cells (dorsal skull cells) from these animals show that pRb abates progression of pre-osteoblasts to mature osteoblasts. As osteoblasts are known progeny of primitive mesenchymal stem cells (MSC), we next asked if diminished differentiation resulted in an increase in MSCs. MSCs are pluripotent cells that can differentiate into a variety of cell types. I have shown in the absence of RB1, calvarial cells can differentiate into multiple lineages including bone and fat, where as cells fromWT littermates are restricted to the osteoblast lineage. Colony formation assays, a functional in vitro assay, suggest RB1−/− cells have increased progenitor cell number, and through sphere formation assays we have shown an increased self-renewal capacity. There is also a significantly larger population of Sca-1 (a stem cell marker) positive cells in RB1−/− cultures compared toWT littermates. In addition, utilization of microarray technology suggests a unique RB1 dependent gene expression pattern in osteogenesis. This is consistent with our previous work showing the necessity of the pRb/Runx2 (a master regulator in bone development) interaction to turn on osteocalcin transcription, a late marker in differentiation. We have begun to identify a possible mechanism for pRb regulation early in osteogenesis through the Hedgehog signaling pathway that explains the increased pluripotency of mesenchymal cells in the absence of RB1. Therefore, we have identified an increased number of bone progenitor cells that are pluripotent from RB1−/− mice, and a possible mechanism for pRb regulation early in osteogenesis and malignant tumor formation. Citation Information: Cancer Res 2009;69(23 Suppl):A10.
Abstract 3754: Characterization of NMS-P285, a new highly selective and potent BRAF inhibitor
Authors: Maurizio Pulici, Nadia Amboldi, Wilma Pastori, Chiara Marchionni, Gabriella Traquandi, Sabrina Cribioli, Rosita Lupi, Michele Modugno, Elena Casale, Alessandra Scolaro, Eduard Felder, Daniele Donati, Antonella Isacchi, Enrico Pesenti, Arturo Galvani, Marina Ciomei
Journal: Cancer Research (2012)

Abstract Aberrant activation of the MAPK-mediated pathway components, RAF-MEK-ERK, is frequently found in human cancers and clearly contributes to oncogenesis. In particular, one of the three isoforms of RAF, BRAF, presents activating somatic mutations in 60% of melanomas, 50% of thyroid cancers, 10% of colon and 20% ovarian carcinomas. The most common BRAF mutation, substitution of glutamic acid for valine at position 600 within the activation segment of the kinase domain, accounts for 90% of mutated BRAF cases, and results in elevated kinase activity with consequent enhanced promotion of cell survival and proliferation. BRAF selective inhibitors as vemurafenib and dabrafenib have recently shown excellent results in patients with advanced melanoma expressing BRAF V600E mutant form. Here we describe the in vitro and in vivo properties of a novel potent and selective BRAF inhibitor belonging to the arylthiazole class of compounds. This, NMS-P285, is a potent inhibitor of both wild-type and mutated BRAF, with no cross-reactivity in a panel of 61 kinases. This compound occupies the ATP-binding pocket of the activated form of the enzyme (DFG motif in), partly filling the kinase back pocket, (i.e. type I ½ inhibitors). NMS-P285 has an antiproliferative activity in the low nanomolar range only against cell lines bearing BRAF V600E or V600D mutations. Its mechanism of action is confirmed: a strong inhibition of MAPK pathway was observed in BRAF mutated cells whereas in non-BRAF mutated cells MEK activation was not observed. NMS-P285 possesses a favourable in vitro ADME profile and a very good preliminary PK in mouse. When orally administered to mice with BRAF mutated human xenograft tumors, NMS-P285 resulted more potent than both vemurafenib and dabrafenib demonstrating high antitumor activity with strong and persistent tumor regression observed in all mice. Mechanism of action was demonstrated also ex vivo in A375 bearing mice: MAPK pathway resulted to be completely inhibited up to 6 hours after a single treatment at 30 mg/kg. In conclusion, NMS-P285 is a candidate suitable for preclinical development. 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 3754. doi:1538-7445.AM2012-3754
An Unusual Case of Positive Somatostatin Receptor Scintigraphy in Squamous Cell Carcinoma of Head and Neck
Authors: John T. Doan, Charles D. Arnold
Journal: Clinical Nuclear Medicine (2011)

We report an unusual case of positive somatostatin receptor scintigraphy in a patient with squamous cell carcinoma of the head and neck. A 49-year-old man presented with a left neck mass. Whole-body In-111 pentetreotide images along with SPECT/CT revealed uptake over the left neck mass consistent with a somatostatin receptor-avid tumor. At surgery, the mass was removed along with an unsuspected lesion at the tongue base. Pathology revealed invasive squamous cell carcinoma in both. This is the first described case of squamous cell carcinoma of the neck demonstrating somatostatin receptor avidity.
Comparaison de l'échografie de contraste et de la tomodensitométrie multicoupes dans le bilan préopératoire des lésions secondaires hépatiques
Authors: R Vialle, J Roumy, C Silvain, JP Richer, JP Tasu
Journal: Endoscopy (2011)

Introduction: Comparer les sensibilités de l'échografie de contraste et de l'imagerie tomodensitométrique multicoupes dans le cadre du bilan préopératoire des lésions secondaires hépatiques.
938 NATURAL HISTORY OF SCLEROSING CHOLANGITIS IN CRITICALLY ILL PATIENTS (SC-CIP): PREDICTORS AND OUTCOME
Authors: G. Kirchner, E. Klingsiek, J. Hartl, J. Langgartner, I. Zuber-Jerger, M. Scherer, B. Salzberger, H.-J. Schlitt, M. Müller, C. Gelbmann
Journal: Journal of Hepatology (2013)
GLOBAL INTRACORONARY INFUSION OF ALLOGENEIC CARDIOSPHERE-DERIVED CELLS IMMEDIATELY AFTER CORONARY REPERFUSION IMPROVES EJECTION FRACTION AND REMOTE ZONE FUNCTION INDEPENDENT OF CHANGES IN INFARCT VOLUME
Authors: Brian Raymond Weil, Gen Suzuki, Umesh C. Sharma, James A. Fallavollita, John Canty
Journal: Journal of the American College of Cardiology (2015)
AB0116 HIF-2alpha dependent rankl induction and osteoclastogenesis is augmented by inflammatory cytokines
Authors: S. Revu, X. Zheng, V. Sunkari, A. Krishnamurthy, I. Botusan, S.-B. Catrina, A. Catrina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and consecutive local hypoxia, leading to cartilage and bone destruction. Hypoxia promotes osteoclasts formation in vitro but its role in mediating bone destruction in the presence of chronic inflammation has not previously been investigated <h3>Objectives</h3> We aimed to investigate the effect of hypoxia on the RANKL/OPG system and bone destruction in the presence of pro inflammatory stimuli. <h3>Methods</h3> We investigated the in vitro effect of hypoxia on RANKL/OPG expression in osteoblast-like (Saos2) cells. Cells were cultured in normoxic (21% pO<sub>2</sub>) or hypoxic (0.5% pO<sub>2</sub>) conditions with or without TNFα. Expression of RANKL and OPG mRNA was detected by rtPCR. Cellular and soluble forms of RANKL and OPG proteins were determined by Western blot and ELISA respectively. Functional contributions of the hypoxia inducible factor (HIF)-1 and 2 alpha were investigated by selective siRNA transfection. To confirm the direct interaction between HIF and RANKL promoter we performed Chromatin Immunoprecipitationc (ChIP) assays for both HIF1 and HIF-2. Hypoxia direct effect on osteoclastogenesis was also evaluated on a dentine pit formation assay using peripheral blood mononuclear cells from RA patients. Statistical analysis was performed using one-way ANOVA. <h3>Results</h3> Hypoxia exposure changes the bone metabolism balance by induction of cellular RANKL mRNA and protein expression and reduction of the soluble OPG protein levels. Concomitant exposure to TNFα has an additive effect inducing a further increase of the RANKL/OPG ratio. Small interfering RNA against HIF 2alpha but not HIF 1alpha was able to abolish hypoxia effect on cellular RANKL expression. ChIP assay confirmed a direct interaction between HIF-2 alpha and at least one hypoxia responsive element (HRE) in the RANKL promoter. Furthermore hypoxia-mimicking using prolyl hydroxylases inhibitors and TNF have an additive effect in promoting RANKL-independent osteoclastogenesis <h3>Conclusions</h3> TNF and hypoxia are additive in promoting HIF2alpha dependent RANKL induction but also RANKL-independent osteoclastogenesis. Our findings propose hypoxia as an important player in the bone metabolism imbalance observed in the setting of chronic joint inflammation. <h3>Disclosure of Interest</h3> None Declared
SAT0289 Impact of Psoriatic Arthritis (PSA) On Health Care Utilization (HCU) and Quality of Life (Qol)
Authors: M. Khraishi, R. Aslanov, S. Khraishi, H. Zurel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PSA) is a chronic condition that affects up to 1% of the general population and is associated with progressive joint damage, disability, and serious co-morbidities. <h3>Objectives</h3> To assess and compare utilization of healthcare services by patients with Early (EPsA) and Established (EstPsA) PsA To assess patients' Quality of Life over 12 months <h3>Methods</h3> 151 patients with PsA were recruited from a rheumatology clinic and followed prospectively for a 12-month period. Fifty eight patients had EPsA and 93 had EstPsA (defined as &lt;2 and ≥2 years from onset of arthritis symptoms, respectively). The HCU was examined using "Health Care Utilization Resource Use" form. The QoL was evaluated using EUROQOL-5D and SF36 tools. The association of disease severity with patients' utilization of health care services and their QoL were also analyzed and compared between two cohorts. <h3>Results</h3> At baseline, patients with EPsA utilized more health care services for arthritis and co-morbidities (e.g. CHD, Diabetes and Infections) than those with EstPsA: "ER" (0.12 vs. 0.09), "Doctor's Office Visit" (0.91 vs. 0.72), "Specialist Visit" (0.86 vs.0.73), "Psychologist/Counsellor"(0.07vs.0.05) and "Physiotherapy/Rehabilitation" (0.26 vs. 0.19). Patients with EstPsA used more "Walk in Clinic" (0.12 vs. 0.09) and "Hospital Admittance" (0.05 vs. 0.02) services. DAS28 was strongly associated with HCU in both cohorts (EPsA: OR=1.3, p=0.049, 95%CI 1.0-1.7; EstPsA: OR=1.6, p=0.001, 95%CI 1.2-2.1). DAS28 and HAQ significantly correlated with QoL in both cohorts: EPsA: r=-0.28, p=0.002 and r=-0.41, p&lt;0.001, respectively; EstPsA: r=-0.35, p&lt;0.001 and r=-0.43, p&lt;0.001, respectively. By 12 months, EPsA patients non-significantly improved their Physical Health, while EstPsA patients showed significant improvement in both Physical (48.3 vs. 56.4, p=0.021) and Mental (61.1 vs. 68.2, p=0.026) components of SF36. EQ-5D Visual Analog Scale also showed significant improvement for EstPsA patients. <h3>Conclusions</h3> PsA causes considerable disability and affects the QoL of patients even at early stages of the disease. Traditionally, it was felt that longer disease duration leads to greater health care utilization. However, our findings showed that patients with EPsA seem to utilize more health care services. Early initiation of treatment with DMARDs may reduce the burden of PsA on the health care system and improve patients' well-being and quality of life. <h3>Disclosure of Interest</h3> M. Khraishi Grant/research support from: Dr. Khraishi received non restricted research grants from Hoffman-La Roche Canada, Amgen and Pfizer Canada, and Abbott Canada, R. Aslanov: None Declared, S. Khraishi: None Declared, H. Zurel: None Declared
Abstract PR12: Early TCRα expression during T cell development for the generation of enhanced-affinity TCRs for TCR gene therapy.
Authors: Thomas M. Schmitt, Philip D. Greenberg, David H. Aggen, David Kranz, Sebastian Ochsenreither
Journal: Cancer Research (2013)

Abstract Thymic selection eliminates T cells expressing TCRs with a high affinity for self-antigen. However, many of the most promising tumor antigens for T cell-based cancer immunotherapies are unmodified self-antigens. Therefore, tumor-specific T cells often have a low avidity for tumor antigens, thus limiting the efficacy of this approach. TCR gene therapy using TCR genes that have been modified for increased affinity can overcome this limitation. The generation of enhanced affinity TCRs generally involves saturation mutagenesis targeting the complementarity determining regions of the TCR genes to be modified. However, this approach requires considerable trial and error, and is still not always successful at generating a higher affinity TCR without promiscuous off-target activity. We have developed a system for selecting high affinity tumor antigen-specific TCRs from a population of T cells selected by agonist signaling during T cell development in vitro. The αβ/γδ lineage choice is in part dictated by the strength of TCR/pre-TCR signaling during early T cell development, such that the pre-TCR provides a weak signal that drives αβ T cell development while the mature γδ TCR provides a stronger signal that drives γδ T cell development. In TCR transgenic mice, early expression of the transgenic TCRα chain prior to β-selection can also provide a stronger γδ-like signal through the mature αβ TCR, leading to the development of lineage redirected TCRαβ+ CD4/CD8 double negative (DN) γδ wanna-be” cells. The development of these DN TCRαβ+ cells is enhanced in the presence of cognate antigen or TCR crosslinking; suggesting that early expression of an antigen-specific TCRα chain before β-selection could promote the generation of DN TCRαβ+ cells in the presence of antigen, through a process in which the introduced TCRα chain pairs with an endogenous TCRβ chain to produce an αβ TCR with high affinity for the target antigen. To test this hypothesis, the TCRα chain from a tumor antigen-specific TCR was transduced into hematopoietic progenitor cells and a library of TCRβ chains was isolated from the lineage redirected DN TCRαβ+ T cells that developed. Several TCRβchains of varying CDR3 lengths were isolated that confer enhanced affinity for the target antigen when paired with the introduced TCRα chain. This abstract is also presented as Poster A13. Citation Format: Thomas M. Schmitt, Philip D. Greenberg, David H. Aggen, David Kranz, Sebastian Ochsenreither. Early TCRα expression during T cell development for the generation of enhanced-affinity TCRs for TCR gene therapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr PR12.
Abstract PD10-05: Do the Results of Metastatic Breast Tumour Biopsies Affect Patient Survival Outcomes? Results from a Large Prospective Trial
Authors: E Amir, N Miller, W Geddie, H Maung, OC Freedman, M Oldfield, J Napolskikh, F Kassam, C Simmons, M. Clemons
Journal: Cancer Research (2010)

Abstract Background: Differences in receptor status between primary and metastatic breast cancer are well recognized. We have previous demonstrated substantial receptor discordance rates resulting in a change in management in 14% of patients. However, while retrospective studies suggest that discordance can be associated with a worse patient prognosis, there are currently no prospective data assessing the impact of such discordance on survival outcomes. Methods: A single-center prospective biopsy study was performed. Patients with either recurrent or progressive disease underwent biopsy of their metastases. Subsequent treatment choices were modified according to the results and patients were followed up for progression or death. To account for the differing times at which patients entered the study, progression-free survival (PFS) was calculated as the duration between biopsy and either progression or death. Overall survival (OS) was defined as the duration from diagnosis of metastatic disease to death. A Cox propotional hazards model accounting for duration of metastatic disease and visceral versus non-visceral metastatic disease was utilized. Results: 121 biopsies were completed and 38% of cases showed discordance between the primary and the recurrence. Survival data were available from 96 patients. After a median follow-up of 11 months, 76 patients (79%) had progressed and 38 (40%) had died. There was no difference in median PFS between concordant and discordance cases (5.9 vs. 6.5 months, HR 0.89, p=0.61). There was a non-significant trend towards worse OS in discordant cases (50.6 vs. 57.8 months, HR 0.77, p=0.47). When compared with the primary tumour a gain of HER2 was associated with a poor survival, while loss of HER2 was associated with improved outcome. Metastatic biopsies showed a trend towards better prediction of response to endocrine therapy with tumors losing progesterone receptor expression between primary and metastatic disease having worse DFS on endocrine therapy. Conclusion: We have previously shown that performing metastatic biopsies is associated with a substantial rate of receptor discordance between primary and metastatic disease. The current analysis demonstrates that this discordance is associated with a trend towards worse OS, but not PFS. Knowledge of the receptor status of metastatic disease allows better prognostication between HER2-postive and HER2-negative disease and also allows for improved prediction of response to endocrine therapy. Metastatic biopsies should therefore be considered in patients with recurrent breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-05.
Improvement of Factor X Deficiency during Pregnancy
Authors: Jerome I. Brody, Stuart C. Finch
Journal: New England Journal of Medicine (1960)

THE primary purpose of this report is to describe the salutary effect of pregnancy on the coagulation defect due to factor X (Prower-Stuart factor) deficiency in a recently diagnosed case of this syndrome. Also of importance is the fact that the patient was known all her life to have had a bleeding tendency that was, on separate occasions, diagnosed as idiopathic thrombocytopenic purpura and congenital hypoprothrombinemia.Case ReportA 27-year-old married woman was admitted to the Grace-New Haven Community Hospital on February 4, 1959, because of severe hematuria and epistaxis of 48 hours' duration. At the age of 5 years . . .
[Low-Level Radiation Harmed Humans near Three Mile Island]: Response
Authors: Steve Wing, David Richardson, Donna Armstrong
Journal: Environmental Health Perspectives (1997)

ResponseMangano correctly notes that the doseresponse relationships in our analyses of cancer incidence in relation to the Three Mile Island (TMI) accident (1) are supralinear.The goodness of fit statistics would have been larger (and corresponding p-values smaller) had