tbuckley/cabot-search huggingface dataset:
LA COLANGIOPANCREATOGRAFÍA ENDOSONOGRÁFICA (CPES) COMO PRIMERA OPCIÓN DE DRENAJE DUCTAL TRAS EL FRACASO DE LA CPRE
Authors: N Alcaide Suárez, C De la Serna Higuera, P Díez Redondo, L Sancho del Val, MT Herranz, P Gil Simón, S Gómez de la Cuesta, M Pérez-Miranda
Journal: Endoscopy (2010)

Introducción y objetivos: Cada vez se recurre más a la CPES tras fallar la CPRE, aunque la ratio CPES:CTP (colangio transhepática percutánea) es 1:2 para drenaje biliar y su uso en wirsung es aún menor. Evaluamos técnica, seguridad y eficacia de la CPES como primera opción tras CPRE.
Abstract 2727: Predicting lung cancer risk based on a novel proteomic signature of bronchial lesions
Authors: S.M. Jamshedur Rahman, Adriana L. Gonzalez, Erin H. Seeley, Lisa J. Zimmerman, Xueqiong J. Zhang, Ming Li, Takefumi Kikuchi, Pierre Chaurand, M. Lisa Manier, Sandy Olson, Ronak Shah, Aloson Miller, Joe B. Putnam, York E. Miller, Wilbur A. Franklin, David P. Carbone, Yu Shyr, Richard A. Caprioli, Pierre P. Massion
Journal: Cancer Research (2010)

Abstract A biomarker signature to identify individuals at-risk for lung cancer would be of great clinical value. We hypothesized that the bronchial epithelium expresses a subset of proteins that once increased confer an elevated risk for lung cancer. We have therefore developed a proteomic approach to assess the risk for lung cancer. From our previous studies, we selected 11 matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) features to distinguish normal bronchial epithelium and low grade preinvasive lesions from high grade preinvasive lesions and invasive lung tumors. We tested this signature in an independent validation set consisting of bronchial specimens from 60 patients. The prediction accuracy was 78% with 73% sensitivity and 81% specificity. There was a 19-fold increased risk of having lung cancer for individuals with a signature intensity above the third quartile (95% CI, 5.65-64.81). We identified 10 of the 11 features corresponding to 7 proteins, thymosin ß4, ubiquitin, acyl-coA binding protein, cystatin A, S100A11, cytochrome c and macrophage migration inhibitory factor. The identity of these proteins was validated by immunohistochemistry, Western blotting and MALDI imaging mass spectrometry (IMS). MALDI IMS localized the candidate biomarker proteins specifically to high grade preinvasive lesions and invasive tumors. This novel proteomic signature may facilitate the selection and monitoring of high risk individuals for lung cancer early detection and chemoprevention strategies. 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 2727.
CT DERIVED ATHEROSCLEROTIC PLAQUE BURDEN AND MORPHOLOGY ARE ASSOCIATED WITH IMPAIRED MYOCARDIAL BLOOD FLOW USING [15O]H2O PET INDEPENDENT OF LUMINAL OBSTRUCTION
Authors: Roel Driessen, Wijnand Stuijfzand, Ibrahim Danad, Pieter Raijmakers, James Min, Jonathon Leipsic, Marc Huisman, Adriaan Lammertsma, Albert van Rossum, Niels Van Royen, Paul Knaapen
Journal: Journal of the American College of Cardiology (2016)
Abstract 4782: Two-dimensional gel analysis of protein expression profile in patients with invasive squamous cell carcinoma of the uterine cervix for identification of differentially expressed proteins in relation to response to radiation therapy
Authors: Radhika Srinivasan, Swati Sood, Sujata Ghosh, Firuza Patel
Journal: Cancer Research (2012)

Abstract Background: Cancer of uterine cervix is the second most common cancer and an important cause of cancer related mortality among women worldwide. These patients are treated by chemoradiation, response to which is a major factor affecting their outcome. Objective: To identify differentially expressed proteins in the tissue biopsies of patients with invasive cervical cancer by two-dimensional gel electrophoresis [2-DE] and correlate it with their clinical outcome. Methods: After an informed consent, 10 patients of invasive squamous cervical cancer, stage IIB, between 40-50 years treated with chemoradiation as per standard protocol were recruited. Based on the 24 month-outcome, there were two groups (N=5): i) Evidence of disease (ED) and ii) No evidence of disease (NED). Pooled protein from the tissue biopsies were subjected to 2-DE using pH 3-10 IPG strips of 7cm length, silver stained and expression profile compared using Image Master 7.0 software (GE Healthsciences). The differentially expressed protein spots were identified and isoelectric point (pI) &amp; Molecular Weight (MW) was determined from the plot of relative electrophoretic mobility (Rf) values of the marker against their respective molecular weight and the plot of pI marker against their respective distance from the anode respectively. The TagIdent software was used for their identification. Results: Out of a total of 327 spots identified, 89 spots showed differential expression, of which 40 were highly significant (ANOVA p &amp;lt;0.03) between ED vs NED groups. Conclusion: 2-DE has provided preliminaryinformation regarding differentially expressed proteins which may help identify biomarkers for prediction of outcome in patients with invasive cervical cancer which needs further confirmation. Differentially expressed proteins in NED vs ED groups in invasive cervical cancer 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 4782. doi:1538-7445.AM2012-4782
TCTAP A-103 A Two-year Experience of an Early Invasive Protocol for Suspected Acute Mesenteric Ischemia: A Single Center Pilot Study: A Two-Year Experience of an Early Invasive Protocol for Suspected Acute Mesenteric Ischemia: A Single Center Pilot Study
Authors: Mu-Yang Hsieh, Chih-Cheng Wu
Journal: Journal of the American College of Cardiology (2015)
P2-18-06: Conventional Trastuzumab Is an Antagonist of Natural Killer Cells: Making the Case for Fucose-Depleted Trastuzumab.
Authors: JJ Listinsky, GP Siegal, CM Listinsky
Journal: Cancer Research (2011)

Abstract The discovery of the HER2 receptor and later the development of trastuzumab (an anti-HER2 antibody) were major advances leading toward the treatment of a significant proportion of human breast cancers. Trastuzumab (Herceptin®) is a humanized monoclonal IgG1 whose discrete antitumor effects are exerted through the 2 main components of the antibody. Trastuzumab's FAB portion binds to the HER2 extracellular domain, interrupting HER2 signaling. The FC portion then engages the activating receptor (FcγRIIIa) on an effector cell, usually a natural killer (NK) cell and instigates a lytic attack via antibody-dependent cellular cytotoxicity (ADCC). The value of trastuzumab in breast cancer therapy is well established, but, there are limitations to the drug's effectiveness. These include: (1) unresponsive tumors with low or equivocal HER2 expression; (2) de novo (primary) resistance to therapy in over 50% of patients with HER2−positive tumors; (3) frequent emergence of secondary resistance often after short exposure periods; (4) competition of plasma IgG proteins with antibodies for binding to the activating FC receptors on NK cells; and (5) the high cost of trastuzumab treatment, raising concerns for the economic sustainability of this form of therapy. Trastuzumab and other therapeutic antibodies share a structural feature that is critical to their effectiveness: a specific oligosaccharide which is covalently linked to the FC region at asparagine 297 (Asn297) in each of the 2 heavy chains. This oligosaccharide, a mannosyl-chitobiose core, is “core-fucosylated” with a single α-L-fucose (fucose) sugar attached via an α(1,6) linkage. In 2002, Shields et al. developed a novel form of trastuzumab which lacked core fucose in the Fc region [J Biol Chem 2002; 277: 26733–40]. When compared to conventional trastuzumab, the fucose-depleted trastuzumab was 43-fold more potent in provoking ADCC against HER2−expressing human breast cancer cells in vitro. Subsequent studies with several monoclonal antibodies have elucidated the role of core fucose in inhibiting ADCC, by reducing the affinity of trastuzumab's Fc portion for the activating FC receptors located on effector cells. The superior ADCC effect of fucose-depleted trastuzumab has now been demonstrated in vivo [Junttila TT et al., Cancer Res 2010; 70: 4481–4489]. We review both in vitro and in vivo evidence from multiple laboratories (working with trastuzumab, rituximab and other therapeutic antibodies) to argue that fucose-depleted trastuzumab offers several potential advantages over conventional trastuzumab. Such advantages in clinical use, we postulate, include (1) treatment of patients with trastuzumab-resistant tumors, (2) treatment of patients with equivocal or low expression of HER2, and (3) decreased cost of treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-06.
Inheritable and Congenital Hyperbilirubinemia
Authors: Louis M. Sherwood, Edith E. Parris, Irwin M. Arias
Journal: New England Journal of Medicine (1971)

BILIRUBIN is an orange organic anion and a catabolic product of heme degradation that does neither any good nor any harm except to a few unfortunate newborn infants whose nervous systems seem to be uniquely susceptible to neuronal damage by bile pigment. Abnormalities affecting the formation, distribution and removal of bile pigment in man are manifested by a yellow color of the skin and scleras that has attracted the interest of physicians and patients since antiquity. Inheritable abnormalities in any one of these areas usually result in hyperbilirubinemia, which is an easily recognized phenotypic manifestation. As a result, it is . . .
Abstract 4621: EMP2 regulates the tumor microenvironment and is a novel therapeutic target for triple negative breast cancer
Authors: Lee Goodglick, Maoyong Fu, Jonathan Braun, Madhuri Wadehra
Journal: Cancer Research (2012)

Abstract Breast cancer remains the most common malignancy in women, with the aggressive triple negative subtype accounting for nearly half of all breast cancer deaths. In this abstract, we describe a novel tetraspan protein, epithelial membrane protein-2 (EMP2) that is highly expressed in the majority of breast cancer tumors examined compared to healthy mammary epithelium. In particular, high levels of EMP2 were observed in over 70% of triple negative breast cancer cases examined. In tumor cells, EMP2 altered the integrin expression profile as well as promoted endothelial cell migration and tube formation through upregulation of VEGF. We produced a fully human intact IgG1 to test their effect on EMP2 expressing breast cancer cell lines. In vitro treatment with anti-EMP2 IgG1 decreased Src and FAK activation and resulted in cell death. Moreover, cultured supernatant from treated cells reduced endothelial cell migration and capillary-like tube formation. To determine the in vivo efficacy of EMP2 treatment, we first characterized potential toxicity from systemic administration. Anti-EMP2 IgG1 produced no observable toxicity (weight, CBC counts, tissue pathology) when administered at 10mg/kg over 7 weeks. Using similar conditions in preclinical xenograft and syngeneic mouse models, anti-EMP2 IgG1 decreased tumor growth with induction of necrosis. This effect was specific as no difference in tumor size was observed in EMP2 negative (Ramos) cell tumors. As in vitro and in vivo cytotoxicity was observed in both triple negative cell lines as well as cells expressing estrogen and progesterone receptors and/or Her-2/neu, these results present compelling evidence that EMP2 is a novel therapeutic target in triple negative breast cancers as well as other variants. 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 4621. doi:1538-7445.AM2012-4621
Mitochondrial DNA Deletions in Progressive External Ophthalmoplegia and Kearns-Sayre Syndrome
Authors: Carlos T. Moraes, Salvatore DiMauro, Massimo Zeviani, Anne Lombes, Sara Shanske, Armand F. Miranda, Hirofumi Nakase, Eduardo Bonilla, Lineu C. Werneck, Serenella Servidei, Ikuya Nonaka, Yasutoshi Koga, Alfred J. Spiro, A. Keith W. Brownell, Beny Schmidt, Donald L. Schotland, Mary Zupanc, Darryl C. DeVivo, Eric A. Schon, Lewis P. Rowland
Journal: New England Journal of Medicine (1989)

We investigated the correlations of deletions of mitochondrial DNA in skeletal muscle with clinical manifestations of mitochondrial myopathies, a group of disorders defined either by biochemical abnormalities of mitochondria or by morphologic changes causing a ragged red appearance of the muscle fibers histochemically. We performed genomic Southern blot analysis of muscle mitochondrial DNA from 123 patients with different mitochondrial myopathies or encephalomyopathies. Deletions were found in the mitochondrial DNA of 32 patients, all of whom had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns—Sayre syndrome, a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebellar ataxia. The deletions ranged in size from 1.3 to 7.6 kilobases and were mapped to different sites in the mitochondrial DNA, but an identical 4.9-kilobase deletion was found in the same location in 11 patients. Biochemical analysis showed decreased activities of NADH dehydrogenase, rotenone-sensitive NADH–cytochrome c reductase, succinate–cytochrome c reductase, and cytochrome c oxidase, four enzymes of the mitochondrial respiratory chain containing subunits encoded by mitochondrial DNA. We conclude that deletions of muscle mitochondrial DNA are associated with ophthalmoplegia and may result in impaired mitochondrial function. However, the precise relation between clinical and biochemical phenotypes and deletions remains to be defined. (N Engl J Med 1989; 320:1293–9.)
PWE-291 MAPK signalling regulates the development of a cholangiocellular phenotype from HCC in post-TACE liver transplants
Authors: V Iansante, Y Zen, A Barbarulo, C Starling, S Chokshi, N Heaton, R Williams, C Bubici, A Quaglia, S Papa
Journal: Gut (2012)

<h3>Introduction</h3> During normal liver wound-healing, tissue injury causes inflammation and cell death, which in turn orchestrates compensatory cell proliferation and regeneration.<sup>1</sup> If resolution of the injury cannot be obtained the resulting unchecked healing process can lead to cancer. Similar injury-induced repair mechanisms occur in response to chemotherapeutic treatments.<sup>1</sup> We recently found that the use of pre-transplantation TACE for HCC promotes the development of a mixed cholangiocellular phenotype that is associated with the expression of CD133, a marker of hepatic progenitor cells (HPC). This phenomenon is associated with higher post-transplantation tumour recurrence.<sup>2</sup> The molecular bases for the development of the cholangiocellular phenotype have not been investigated before. In this study we identified key oncogenic effectors involved with a <i>“switch”</i> from HCC to cholangiocellular phenotype resulting from liver injury induced by TACE treatment. <h3>Methods</h3> Ten cases of post-TACE (doxorubicin/lipiodol) treated HCC examined after transplantation at King9s College Hospital were selected for the study. HCC patients not treated by TACE before transplantation were used as control group. Formalin-fixed section from main tumour mass embedded in paraffin blocks were used to perform immunohistochemistry in order to delineate which component of the MAPK signalling pathway is associated with the hepatocholangiocellular phenotype and expression of HPC markers (CD133 and CK19). <h3>Results</h3> Among the post-TACE liver explants, approximately 50% of the neoplastic cells resembling bile ductules (cholangiocellular differentiation) showed nuclear expression of a specific phospho-activated component of the MAPK cascade. Furthermore, half of the cells positive for activated-MAPK showed proliferative activity, as determined by Ki67 staining. Expression of activated-MAPK was not detected in the non-TACE treated group of liver transplant. <h3>Conclusion</h3> The development of the mixed hepato-cholangiocellular phenotype in HCC patients after TACE-inflicted liver injury relates to activation of a specific MAPK signalling pathway that promotes proliferation of HPC. Attenuation of this signalling pathway could be used to prevent the “<i>uncontrolled”</i> proliferation and differentiation of progenitor cells before liver transplantation in HCC patients, and thus improving the tumour recurrence rate. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Papa S</b>, <i>et al. Biol Chem</i> 2009;<b>390</b>:965–76. 2. <b>Zen C</b>, <i>et al. Liver Transpl</i> 2011;<b>17</b>:943–54.
Abstract C32: Proteome analysis of pancreatic cancer tissue for identification of novel biomarkers
Authors: Ganepola Ganepola, Paritosh Suman, Cohava Gelber
Journal: Cancer Research (2009)

Abstract Pancreatic cancer is the 4th largest cancer in US with mortality rate almost equal to incidence. The tumor usually presents at a late stage ruling out any curative surgery. Focus of pancreatic cancer research currently is mainly on early diagnosis and development of novel cancer therapeutics. Identifying sensitive, specific and reliable surrogate markers by genomic and proteomic methods1 in cancer tissue, blood or other bodily secretions can prove promising to reach this goal. We are applying standard proteomic techniques like gel electrophoresis and MS (mass spectrometry) with a goal to identify potential biomarkers and new drug targets for the design and development of effective therapeutics in serum and pancreatic tissue samples. Pancreatic cytosolic and membrane proteins were extracted from the 4 pairs of cancerous and adjacent normal tissue. Cytosolic protein fractions were run on PF-2D, traditional 1D and 2D SDS-PAGE. LC/MS/MS was used to identify differently expressed banding patterns. Multiple proteins were found to be either up (24) or downregulated (11). Compared to cytosolic proteins membrane proteins are priced for its accessibility on tumor tissue making these ideal for diagnosis and therapeutics. Isolating only plasma membrane proteins is very challenging due to low extraction efficiency, extremely low abundancy and poor solubility. Total cellular membrane protein was extracted and analyzed by SDS-PAGE and LC/MS/MS, and significant banding pattern differences were observed with 35 upregulated and 14 downregulated proteins with annexin 1, annexin A2 and annexin 5, tumor rejection antigen 1, prolyl 4-hydroxylase, calreticulin precursor, heat shock 70kDa protein 5, chaperonin and alpha 2 actin being the most significantly overexpressed. Findings were confirmed by probing western blots with anti-annexin 1 and 2 antibodies. Our findings suggest these differently expressed proteins can be explored as potential biomarkers after further validation. In contrast, analysis of serum samples by same techniques was futile due to exceedingly low abundance of protein and peptide fraction containing potential biomarkers due to masking by albumin and globulins as well as enzymatic degradation. At present we are continuing the validation of our preliminary findings on larger sample size by using differential protein profiling technologies, immunohistochemistry and quantitative proteomics. Also we are planning to use affinity bait molecule with nanoparticles2 which can help overcome the limitations faced with serum samples in identification of de novo biomarkers. Citation Information: Cancer Res 2009;69(23 Suppl):C32.
Qualitative judgments, quantitative judgments, and norm-sensitivity
Authors: Paul Egré
Journal: Behavioral and Brain Sciences (2010)

Abstract Moral considerations and our normative expectations influence not only our judgments about intentional action or causation but also our judgments about exact probabilities and quantities. Whereas those cases support the competence theory proposed by Knobe in his paper, they remain compatible with a modular conception of the interaction between moral and nonmoral cognitive faculties in each of those domains.
AB0449 Baseline Procalcitonin (PCT) Level as A Predictive Marker for Clinical Remission (DAS28-ESR, CDAI) at 52 Weeks in Biologic NaÏVe Rheumatoid Arthritis (RA) Patients Treated by TOCILIZUMAB (TCZ); A Single Center Retrospective Study
Authors: S. Tsuji, A. Yura, M. Katayama, A. Watanabe, S. Teshigawara, M. Yoshimura, E.K. Tanaka, Y. Harada, K. Kagawa, Y. Katada, M. Matsushita, S. Ohshima, J. Hashimoto, Y. Saeki
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The goal in treating RA has changed from clinical remission to structural remission with the increased use of biological agents (Bio) which target the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. PCT, a useful marker of infection, has been shown to increase in mRNA expression in peripheral blood mononuclear cells by stimulated by pro-inflammatory cytokine, IL-6 or TNF-α. <h3>Objectives</h3> This study investigates whether the levels of following parameters (PCT, modified HAQ (mHAQ), MMP-3, RF, ESR, CRP and ACPA) at baseline (BL) of TCZ treatment can be used to predict clinical remission (DAS28-ESR, CDAI) at 52 weeks after the start of TCZ treatment. <h3>Methods</h3> Bio naïve RA patients who can be observed at Week 52 were analyzed in this study. PCT (n=34), mHAQ (n=48), matrix metalloproteinase (MMP)-3 (n=54), RF (n=54), ESR (n=53), CRP (n=56) and ACPA (n=52) were assessed at BL. The patients were divided into 2 groups, based on DAS28-ESR remission (DAS28-ESR&lt;2.6) at Week 52. For each variable where there was a significant difference between the remission and non-remission groups, receiver operating characteristic (ROC) analysis was performed and cut-off values (COV) were found. For each of those variables, 2 groups were formed by dividing the Bio naïve RA at the COV: the under COV (U) group and over COV (O) group, and the Week 52 clinical remission (DAS28-ESR, CDAI) rate in each group were analyzed. <h3>Results</h3> The variables with a significant difference between the remission and non-remission groups were PCT (p=0.001), mHAQ (p=0.014), RF (p=0.003), ESR (p=0.001) and CRP (p=0.041). The COVs were 0.027 ng/ml for PCT, 100U/ml for RF, 0.38 for mHAQ, 18 mm/hr for ESR, 1.96 mg/dl for CRP. For each variable, the DAS28-ESR remission rate in U group (PCT: 100%, mHAQ: 70.8%, RF: 77.8%, ESR: 87.5% and CRP: 64.3%) was significantly higher than in O group. Additionally, the CDAI remission rate in U group (PCT: 50.0% (p=0.040) and RF: 32.1% (p=0.026)) was significantly higher than in O group, but not others. For PCT at BL, DAS28-ESR or CDAI were no different between the U group and O group and no correlation with DAS28-ESR or CDAI were observed. BL DAS28-ESR was significantly lower in U groups for all other variables. Furthermore, BL PCT had correlation with DAS28-ESR and CDAI at Week 52. <h3>Conclusions</h3> BL PCT level is a useful predictive marker for clinical remission (DAS28-ESR, CDAI) at week 52 in Bio naïve RA treated by TCZ. Moreover, unlike other variables, it is not affected by the BL disease activity level. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2437