tbuckley/cabot-search huggingface dataset:
Abstract P3-05-04: Intra-tumor heterogeneity as a predictor of therapy response in HER2 positive breast cancer
Authors: IH Rye, Å Helland, A Sætersdal, B Naume, V Almendro, K Polyak, A-L Børessen-Dale, HG Russnes
Journal: Cancer Research (2012)

Abstract Background: Breast cancer is known to be a heterogeneous disease both at the clinical and molecular level. In addition, heterogeneity can also exist within a given tumor, and subpopulations can have distinct phenotypic and genomic features. Little is known about the relationship between intra-tumor heterogeneity and prediction of response to treatment. This study aimed at using a combination of immunofluorescence and fluorescence in situ (FISH) technique (“double immunoFISH”) to identify intra-tumor heterogeneity in tumors from neo-adjuvant treated patients prior to and after therapy, searching for features predicting the response to neo adjuvant treatment. Material and methods: Twentytwo patients diagnosed with HER2 positive, neo-adjuvant treated breast cancer ((3–4 FEC100 followed by 4 docetaxel plus trastuzumab, 3qw) were selected. Half of the patients had complete response and the others had partial response. By double immunoFISH both phenotypic (ER and HER2 protein) and genomic changes (copy number of HER2 gene and centromere 17) were assessed in the same cells simultaneously on biopsies before and after treatment. The samples were photographed in a Zeiss Axio Imager M1 with 5 fluorescence channels and analyzed with axiovision software. The intensity and localization of HER2 and ER immunofluorescence were semi-quantitatively estimated while the HER2 and centromere 17 FISH signals were counted in 100 cells. Results: The patients with partial response displayed a high grade of cell-to-cell diversity regarding HER2 copy number, nuclear shape and size and the expression of the membrane protein HER2. This was in contrast to the results from the complete responders who showed a reduced diversity and were more frequently ER negative. In the patients with partial response, a higher diversity was seen after treatment. Conclusion: The genomic variability prior to therapy was higher in the partial-responders vs. the complete responders, and the remaining tumor was even more heterogeneous after treatment than prior to treatment. Double immunoFISH is a valuable tool for visualization of both phenotypic and genomic alterations in the same cell in FFPE sections. The cohort will be expanded to explore the diversity further, and the results will be presented. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-04.
Case 35-2014
Authors: Sarah E. Wakeman, Brian B. Ghoshhajra, David M. Dudzinski, Timothy Wilens, Peter L. Slavin
Journal: New England Journal of Medicine (2014)

A 31-year-old woman with substance-use disorder was admitted to this hospital because of fevers and chest pain. CT of the chest revealed multiple thick-walled nodular opacities throughout both lungs. Diagnostic tests were performed, and management decisions were made.
Infusional 5-fluorouracil-based combination chemotherapy as first-line treatment for recurrent ampulla of vater cancer.
Authors: P. Lin, C. Hsu, Y. Tien, S. H. Kuo, C. H. Lin, Y. Lin
Journal: Journal of Clinical Oncology (2010)

e14673 Background: Ampulla of vater cancer (AVC) is a rare malignancy. Limited data are available regarding the efficacy of systemic chemotherapy in patients with recurrent or metastatic AVC. Infusional 5-fluorouracil (5-FU) and its combination have been commonly used as first-line therapy for patients with advanced GI tract cancers. The study sought to evaluate the efficacy of infusional 5-FU-based combination chemotherapy in patient with advanced AVC. Methods: A retrospective analysis of patients diagnosed at a single institute between 1999 and 2009 was performed. To be enrolled, patients needed to meet the following criteria: adenocarcinoma of ampulla of Vater diagnosed by surgical pathology, local recurrence or metastasis after curative resection, and receiving first- line combination chemotherapy based on weekly 24-h infusion of 5-FU and leucovorin (LV) or biweekly 48-h infusion of 5-FU and LV. Results: Twenty patients (M:F = 11:9), with a median age of 63 years, were enrolled. The median time to tumor recurrence was 12 months. Seven patients had local recurrence at prior operation field; 13 developed metastatic diseases involving liver, lung, peritoneum, distal lymph node, and bone in 3, 3, 3, 3, and 2 patients, respectively. The chemotherapy regimen was infusional 5-FU in combination with cisplatin, oxaliplatin, gemcitabine, and others in 6, 4, 6, and 4 patients, respectively. Among 18 patients eligible for response evaluation, there were 2 PR (1 treated with cisplatin plus 5-FU, 1 treated with oxaliplatin plus 5-FU), 7 SD, and 9 PD. The median PFS and OS were 3 months (range, 0.5 ∼ 11) and 10 months (range, 0.5 ∼ 20), respectively. Conclusions: Infusional 5-FU based combination chemotherapy showed only modest activity in recurrent/metastatic AVC. However, our data suggest that infusional 5-FU in combination with a platinum deserves further study in advanced AVC. No significant financial relationships to disclose.
Applications of predictive control in neuroscience
Authors: Bruce Bridgeman
Journal: Behavioral and Brain Sciences (2013)

Abstract The sensory cortex has been interpreted as coding information rather than stimulus properties since Sokolov in 1960 showed increased response to an unexpected stimulus decrement. The motor cortex is also organized around expectation, coding the goal of an act rather than a set of muscle movements. Expectation drives not only immediate responses but also the very structure of the cortex, as demonstrated by development of receptive fields that mirror the structure of the visual world.
The Washington University Sentence Completion Test compared with other measures of adult ego development
Authors: G E Vaillant, L McCullough
Journal: American Journal of Psychiatry (1987)

One hundred seven men who had been studied prospectively from age 18 to age 63 completed the Washington University Sentence Completion Test at age 55 +/- 2 years. Ego level as assessed by the Sentence Completion Test correlated significantly with psychosocial maturity, with number of psychiatric visits, and, perhaps, with creativity. Ego level as assessed by the Sentence Completion Test did not correlate with mental health, psychopathology, or maturity of defenses. The authors discuss possible reasons for these findings.
AB0249 Serum Visfatin Determination in Rheumatoid Arthritis
Authors: J.V. Polyakova, E.S. Simakova, B.V. Zavodovsky, L.E. Seewordova, I.A. Zborovskaya
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There are now some data about role of adipose tissue in the pathogenesis of chronic inflammatory processes. Adipokines can influence on inflammation in rheumatoid arthritis (RA) and other rheumatic diseases. The literature contains some data on relieving of collagen-induced arthritis in mouse model with pharmacological visfatin inhibition injection. We suppose that visfatin is involved in the processes of degradation of cartilage and development of inflammation in joint disease by stimulating of interleukin-6 and 8, tumor necrosis factor, metalloproteinase-1 and 3 production. <h3>Objectives</h3> The aim of this study was to investigate clinical and pathogenic significance of visfatin determination in sera of RA patients. <h3>Methods</h3> We observed 170 people: 120 patients with diagnosed RA and 50 healthy controls (HC). Serum visfatin levels were measured by ELISA- test (RaiBiotech, cat No. EIA-VIS-1). <h3>Results</h3> We revealed that visfatin level in HC was 2,30+1,72 ng/ml, (mean and standard error accordingly), in RA patients - 6,27+0,59 ng/ml (p&lt;0,001). We noted increased visfatin level in 46 RA patients (38,3%). We divided 120 RA patients into 2 subgroups – 1st (n=46) with high visfatin level in sera, and 2nd (n=74) - with normal visfatin concentration. We revealed that patients in 1st group had a higher level of activity index DAS28 (II-III degree of activity), high levels of autoantibodies to cyclic citrullinated peptide, higher levels of C-reactive protein and erythrocyte sedimentation rate. <h3>Conclusions</h3> The present study shows visfatin may have important significance in RA pathogenesis. RA patients with high visfatin level in sera have more aggressive form of disease. In this study serum visfatin strongly correlated with systemic inflammation markers and functional impairment in RA. Thus serum visfatin could be used as marker of RA activity and progression. We suppose visfatins inhibition may be used as a new pharmacological target in RA treatment. <h3>References</h3> Busso N., Karababa M., Nobile M. et al. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS ONE 2008; 3: e2267. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2011
Surgeon General's Report Focuses on Dietary Fat
Authors: E. Carbone
Journal: JNCI Journal of the National Cancer Institute (1988)

Surgeon General's Report Focuses on Dietary Fat Get access Elena Carbone Elena Carbone Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 13, 7 September 1988, Pages 993–994, https://doi.org/10.1093/jnci/80.13.993 Published: 07 September 1988
von Willebrand factor is dimerized by protein disulfide isomerase
Authors: Svenja Lippok, Katra Kolšek, Achim Löf, Dennis Eggert, Willem Vanderlinden, Jochen P. Müller, Gesa König, Tobias Obser, Karoline Röhrs, Sonja Schneppenheim, Ulrich Budde, Carsten Baldauf, Camilo Aponte-Santamaría, Frauke Gräter, Reinhard Schneppenheim, Joachim O. Rädler, Maria A. Brehm
Journal: Blood (2015)
Prognostic and predictive value of enzymes of the sphingolipid metabolism in breast cancer.
Authors: E Ruckhäberle, A Rody, R Gaetje, K Engels, U Holtrich, T Karn, M Kaufmann
Journal: Cancer Research (2009)

Abstract Abstract #6014 Backround:&amp;#x2028; Sphingolipids do not only have structural roles for the cell membrane, but also act as effector molecules and second messengers in signal transduction with links to cancer initiation, progression and treatment response. Knowledge of sphingolipid's impact on breast cancer and its prognosis is limited to in vitro data. Clinical data is rare but needed.&amp;#x2028; Material and Methods: We analyzed gene expression of 43 proteins from the sphingolipid pathways in different subtypes of breast cancer using microarray data of 1269 tumor samples (test set n=171; validation sets n=1098). Kaplan Meier analysis of disease free survival was performed to examine the prognostic value of different markers. In addition immunohistochemistry was done to determine whether the genes of the sphingolipid rheostat are expressed in cancer or stroma cells of the tumor.&amp;#x2028; Results: Significant relationships of several genes of the sphingolipid metabolism with clinical parameters were obtained. Sphingosine kinase 1 (SPHK1), ceramide galactosyltransferase (UGT8), and Ganglioside GD3-Synthase (ST8SIA1) displayed higher expression among ER negative tumors. In contrast, glucosylceramidesynthase (GCS), dihydroceramidesynthases (LASS4, LASS 6) and acid ceramidase (ASAH1) were higher expressed in ER positive samples. Survival analysis revealed a significant worse outcome of patients with high SPHK1 expression. LASS 6 and GCS gene expression had no prognostic impact when the estrogen receptor status was taken into account in multivariate analyses. Immunohistochemistry identified the carcinoma cells as the major source of SPHK1 expression in the tumor.&amp;#x2028; Conclusions: These studies of a large cohort of clinical breast cancer samples reveal that sphingolipids do play a role in breast cancer. Enzymes of the sphingolipid metabolism have impact on the prognosis of breast cancer patients and targeting the sphingolipid rheostat can open new treatment options. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6014.
Treatment of Advanced Wegener's Granulomatosis with Azathioprine and Duazomycin a
Authors: Stephen R. Kaplan, John P. Hayslett, Paul Calabresi
Journal: New England Journal of Medicine (1968)

Azathioprine (Imuran) was used in combination with duazomycin A, a glutamine antagonist, for treatment of two patients with advanced Wegener's granulomatosis with renal involvement. Prolonged survival, remission of systemic signs and symptoms, roentogenologic improvement of pulmonary lesions, reduction in proteinuria and arrest of progression of renal insufficiency were observed, despite persistent histologic lesions in repeat kidney biopsies. Immunologic tests for humoral antibodies and delayed-type hypersensitivity indicated effective suppression of these immune responses to a new antigen but no alteration in pre-existing immunity. These results and absence of toxic complications encourage further studies of this rational combination of chemotherapeutic agents to assess the extent of their effectiveness in immunologic disorders.
AB0462 The performance of new EULAR/ACR RA remission criteria in patients treated with biologic agents: Real-life experience
Authors: E.G. Favalli, M. Biggioggero, A. Marchesoni, P.L. Meroni
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> new EULAR/ACR rheumatoid arthritis (RA) criteria for the definition of clinical remission have recently been proposed and their effectiveness is still on debate. <h3>Objectives</h3> to examine the performance of new EULAR/ACR RA remission criteria and the different progression of disability in patients with remission defined by Disease Activity Score (DAS)28-CRP or Simplified Disease Activity Index (SDAI), in a population of patients treated with anti-TNF agents in a set of clinical practice. <h3>Methods</h3> our database includes 345 RA patients treated with TNF blockers between October 1999 and October 2011. The analysis was limited to those patients that had at least a 12-months follow-up and was performed retrospectively. DAS28-CRP, SDAI, and Health Assessment Questionnaire Disability Index (HAQ-DI) were collected at baseline and 12 months. The proportion of patients achieving SDAI clinical remission (&lt;3.3) was compared with the one defined by DAS28-CRP(&lt;2.6) using the chi-square test. One year HAQ-DI mean values in the two remission subgroups were compared using the Mann-Whitney test. <h3>Results</h3> Out of 345 patients, 323 (177 infliximab, 56 etanercept, and 90 adalimumab) met the inclusion criteria of this study. The mean age was 54.7 years and the mean RA duration was 13.9 years. At 12 months, SDAI clinical remission was achieved by 11% and DAS28-CRP clinical remission by 25% of patients (p&lt;0.0001). All 35 SDAI-remission patients were found in the DAS28-CRP group. In contrast, out of 82 DAS28-CRP-remission patients, 47 were not found in the SDAI-remission group. Twelve months mean HAQ-DI value was significantly lower in the SDAI-remission patients compared to the DAS28-CRP-remission group (0.171 vs 0.441, respectively; p=0.015). <h3>Conclusions</h3> In a set of clinical practice, our data confirm that remission defined by SDAI is more stringent than the one defined by DAS28-CRP. Furthermore, the use of SDAI remission criteria as treatment target can be useful to better prevent disability in RA patients. <h3>References</h3> Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials. Arthritis Rheum 2011; 63 (3): 573-586. Gülfe A, Aletaha D, Saxne T, et al. Disease activity level, remission and response in established rheumatoid arthritis: performance of various criteria sets in an observational cohort, treated with anti-TNF agents. BMC Muscoloskelet Dis 2009; 10: 41. <h3>Disclosure of Interest</h3> None Declared
548 UNEXPECTED INCREASE OF HEPATITIS B SURFACE ANTIGEN (HBSAG) CONCENTRATIONS DURING TREATMENT WITH NUCLEOS(T)IDE ANALOGUES 12-24 MONTHS BEFORE VIROLOGICAL BREAKTHROUGH AND RESISTANCE
Authors: S.B. Wiegand, J. Jaroszewicz, B. Zacher, K. Wursthorn, K. Deterding, M.P. Manns, H. Wedemeyer, M. Cornberg
Journal: Journal of Hepatology (2012)
Abstract 5197: Identification of prognostic cancer stem cell marker profiles in aggressive metastatic colorectal cancer
Authors: Crystal Hessman, Eric Anderson, Melissa Wong
Journal: Cancer Research (2011)

Abstract Background: Despite recent advances in screening and treatment, metastatic colorectal cancer (CRC) remains a leading cause of cancer-related death in the United States. A subset of patients with metastatic disease to the liver may achieve long-term survival with metastasectomy. However, the majority of patients with liver metastases have a median survival of approximately 2 years despite treatment. Several studies have proposed that cancer stem cells (CSC) may be linked to metastasis, treatment resistance and recurrence, but to date, no one has examined whether the expression of CSC markers can be prognostic indicators of recurrence and overall survival in metastatic CRC. Methods: Formalin-fixed, paraffin-embedded metastatic CRC tissue samples were obtained from patients treated with metastasectomy of liver disease. Using standard immunohistochemical techniques, tissue samples were stained with antibodies to previously characterized CSC markers CD166, CD133, CD44 and CD26. Cellular expression patterns for solitary and multiple CSC markers were analyzed using an automated open source image quantification program (CellProfiler 2.0). Expression profiles were then correlated to patient outcomes (disease recurrence and overall survival). Results: Variable expression of CSC markers was seen between long- and short-term survival as well as rate of recurrence. Patients with an increased overall survival showed a higher level of CD44 expression. Co-expression of CD44 and CD166 correlated to increased disease-free survival. Conclusion: In this study, we identify a subset of CSC markers that correlates to disease behavior and tumor biology in metastatic CRC. Further delineation of CSC profiles may give valuable clues to therapeutic resistance as well as offer new therapeutic targets in the treatment of this disease. 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 5197. doi:10.1158/1538-7445.AM2011-5197
O140 INTEGRATIVE MICRORNA PROFILING IDENTIFIES MIR-21 AND MIR-155 AS POTENTIAL REGULATORS IN ALCOHOLIC HEPATITIS
Authors: D. Biaya, S. Affò, D. Rodrigo-Torres, O. Morales-Ibanez, J. Altamirano, M. Coll, M. Vila, J.J. Lozano, V. Arroyo, J. Caballería, R. Bataller, P. Ginés, P. Sancho-Bru
Journal: Journal of Hepatology (2014)
OP0177 A High Frequency of N-Glycans in the Acpa-Igg Variable Domain Modulates Reactivity to Citrullinated Antigens
Authors: H.U. Scherer, Y. Rombouts, A. Willemze, J. van Beers, J. Shi, P. Kerkman, G. Janssen, P. van Veelen, A. Zaldumbide, R. Hoeben, G. Pruijn, A. Deelder, G.-J. Wolbink, T. Rispens, T.W. Huizinga, M. Wuhrer, L. Trouw, R. Toes
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Antibodies against citrullinated proteins antigens (ACPA) are the most relevant prognostic and diagnostic biomarker for rheumatoid arthritis (RA). ACPA positive patients are characterized by progressive disease, a high rate of joint destruction, and a low chance to achieve remission. Despite these strong and well-defined associations with clinical phenotype, however, molecular mechanisms underlying the citrulline-specific immune response are incompletely understood. Of note, this immune response is highly polyclonal with considerable cross-reactivity, develops and matures prior to disease onset, and is of remarkably low avidity. These features indicate that the underlying B cell response is different from "conventional" antibody responses, but also different from other autoantibody responses such as the high affinity double-stranded DNA antibody response in SLE. <h3>Objectives</h3> To study molecular characteristics of ACPA in order to obtain insight into the properties of the underlying B cell response. <h3>Methods</h3> Serum of ACPA positive RA patients was fractionated by size exclusion chromatography and analysed for the presence of ACPA-IgG by ELISA. In addition, ACPA-IgG and non-citrulline-specific IgG were affinity purified from serum and synovial fluid and analysed by gel electrophoresis. Electrophoresis bands were excised, enzymatically digested and subsequently analysed by HPLC and mass-spectrometry. Recombinant monoclonal ACPA were used to study binding affinity for multiple antigens by surface plasmon resonance. <h3>Results</h3> In almost all donors studied (23 out of 24), ACPA-IgG molecules were found to have a higher molecular weight than non auto-reactive IgG. Structural analysis pinpointed this observation to a high frequency of N-glycans in the ACPA variable regions, which was found on up to 90% of all ACPA. These Fab-glycans were linked to N-glycosylation sites generated by somatic hypermutation, were absent from other disease-specific autoantibodies, were characterized by a high degree of sialylation, and clearly differentiated ACPA from "conventional" IgG molecules. Moreover, ACPA Fab glycans modulated reactivity to citrullinated antigens. <h3>Conclusions</h3> These data describe a unique and completely novel feature of the citrulline-specific immune response in RA, with important implications for ACPA pathogenicity and disease prognostication. The high frequency of variable domain Fab glycans points to specific developmental abnormalities of the underlying B cell response. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4717
Indications et résultats de l'application endoscopique du macroclip OTSC: Etude rétrospective chez 84 patients
Authors: E Wedi, A Sportes, J Huppertz, M Delvaux, J Hochberger
Journal: Endoscopy (2014)

Le macro clip OTSC (OVESCO, Allemagne) est un nouvel outil endoscopique qui permet la suture endoscopique de lésions hémorragiques, perforations de la paroi digestive et orifices fistuleux. Cette technique a été utilisée avec succès dans la prise en charge des hémorragies digestives sévères, des perforations, fistules et lors de procédures expérimentales de type NOTES. Le but de notre étude était d'analyser rétrospectivement les résultats de cette technique chez des patients non sélectionnés afin d'en préciser les indications et résultats cliniques.
SP0025 Recent Developments in Imaging the Cartilage
Authors: D. Loeuille
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Osteoarthritis (OA) is an articular disease that reflects a complex interplay of biochemical, biomechanical, metabolic and genetic factors, which are often triggered by injury, and mediated by inflammation, catabolic cytokines and enzymes. Articular cartilage is a non calcified tissue well identified on MRI, helpful to define normal cartilage and to quantify cartilage abnormalities according to semi-quantitative scoring methods. We presented articular lesions related to cartilage loss in knees and hips. We discussed the interest of conventional MRI and non-invasive quantitative magnetic resonance imaging (qMRI) (volumetric and cartilage thickness measurement, T2 mapping, dGEMRIC, <i>T</i>1<i>r</i> mapping) techniques to assess biochemical and mechanical cartilage abnormalities and to establish their association with morphological cartilage lesions and/or to predict them. We concluded by other promising imaging technics able to be used in the future to depict cartilage abnormalities. <h3>Disclosure of Interest</h3> None Declared