tbuckley/cabot-search huggingface dataset:
AB0534 Does the Presence of ANCA in Patients with Lupus Nephritis (LN) Help to Distinguish A Subset?
Authors: M. Neves, R.V.P. Irlapati, D.A. Isenberg
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Antineutrophil cytoplasm antibodies (ANCA) are known to occur in some patients with systemic lupus erythematosus (SLE), with a prevalence of 15 to 20% [1]. The perinuclear pattern (pANCA) predominates in this setting. Among SLE patients, ANCA positivity is more frequent in those with LN. ANCA positivity in LN patients was also associated with increased disease activity assessed by the SLE disease activity index (SLEDAI) [2]. <h3>Objectives</h3> The aim of our study was to characterize a population of patients with LN that showed ANCA positivity and determine if they had any other distinguishing features. <h3>Methods</h3> Patients with LN and an ANCA test result, both by immunofluorescence and enzyme-linked immunosorbent assay (ELISA), were retrospectively assessed. The parameters analyzed were age of onset of SLE and nephritis, gender, ethnicity, clinical manifestations, anti-dsDNA antibodies, antibodies to extractable nuclear antigens (ENA), and kidney histological classification (WHO). <h3>Results</h3> Eight out of 67 patients with LN who had been tested (approximately 12%) had positive ANCA (pANCA 6 and cANCA 2). All were female. The mean age at SLE diagnosis was 27±17.7 years and the mean age at renal disease onset was 31.2±16.5 years. The clinical manifestations were as follows: arthralgia (n=7), skin rash (n=6), Raynaud syndrome (n=5), serositis (n=2), neurolupus (n=2), myositis (n=1). The incidence of Raynaud9s in the ANCA positive LN cases was significantly higher than in the patients without ANCA (p=0.0211). Six patients had positive anti-dsDNA antibodies and 5 patients had positive antibodies to ENA. The kidney biopsies showed WHO class II in 2, class III in 1, class IV in 3 and class V in 2 patients. Overall, these figures were not distinguishable from the 195 patients in total with renal SLE that we have followed in the long term. <h3>Conclusions</h3> We could not distinguish a clinical phenotype for our LN patients who were ANCA positive, although interestingly we noted a high prevalence of Raynaud9s syndrome. Whether or not ANCA positivity can predict digital vasculitis in LN patients will need further studies. <h3>References</h3> Sen D, Isenberg DA. Antineutrophil cytoplasmic autoantibodies in systemic lupus erythematosus. Lupus. 2003; 12: 651-658. Pradhan VD, Badakere SS, Bichile LS, Almeida AF. Anti-neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. J Assoc Physicians India. 2004; 52: 533-537. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1606
Abstract P4-08-02: A Comparison between AQUA Quantitative Fluorescent Immunohistochemistry and Conventional Immunohistochemistry for Hormone Receptors
Authors: JMS Bartlett, M Gustavson, D Stocken, D Rimm, J Christiansen, CJH van de Velde, A Hasenburg, D Kieback, H Putter, C Brookes, C Markopoulos, L Dirix, T Robson, C Seynaeve, M Dolled-Filhart, C Jones, L Graves, J McGuire, D. Rea
Journal: Cancer Research (2010)

Abstract Background: We have previous data showing that quantitation of hormone receptors can be highly informative in determining risk of early relapse in ER positive early breast cancer treated with tamoxifen or exemestane. Both quantitative immunohistochemistry (QIHC) and flouresecent immunohistochemistry (F-IHC as measured by AQUA technology) are highly prognostic over a wide expression range. We have explored the results of both assays to determine if current assays provide maximum information using current approaches. Patients &amp; Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. Quantitative AQUA and IHC analysis (using image quantitation) of ER and PgR was performed centrally (Edinburgh &amp; HistoRx). Results from both assays were compared and their prognostic impact on DFS at 2.75 years examined. Results: Both AQUA and QIHC demonstrated linear relationships between intensity of staining for either ER or PgR and DFS at 2.75 years. For both PgR and ER AQUA provided significantly greater prognostic information that QIHC. However AQUA staining explained only 29% and 68% of the variability in ER and PgR QIHC results by logistic regression. Using both AQUA and QIHC data in a forward stepwise selection survival model demonstrated that AQUA and QIHC provided similar prognostic information over 70% and 50% of the range for ER and PgR respectively. High ER QIHC and low ER AQUA scores, and low PgR IHC and high PgR AQUA scores provided prognostic information unique to either platform. Conclusion: Both QIHC and AQUA analysis of HR expression provides significant and highly important information on DFS risk in early breast cancer. It appears that these two platforms provide overlapping prognostic information and that the range of ER and PgR expression which impacts patient outcome is wider than measured by either system alone. Further investigation of the clinical significance of this broader range of hormone receptor expression in treatment decisions is warranted. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-02.
Abstract LB-267: GRB7: A novel target in basal breast cancer
Authors: Orsi Giricz, Stephanie C. Pero, David N. Krag, Joseph A. Sparano, Paraic A. Kenny
Journal: Cancer Research (2010)

Abstract Basal breast cancers lack expression of estrogen and progesterone receptors and HER2, rendering them non-responsive to the most commonly used targeted therapies in breast cancer. These tumors are typically more aggressive, more locally invasive and more likely to metastasize to the brain than other breast cancer subtypes and, consequently, have a poor prognosis. GRB7 is a cytoplasmic adaptor protein that interacts with receptor tyrosine kinases, relaying information to their downstream signaling cascades. It also plays a role in integrin signaling and cell migration by binding focal adhesion kinase (FAK) and ephrin receptors. It is a part of the HER2 amplicon and is frequently overexpressed in HER2-amplified breast tumors. Breast tumors in which HER2 and GRB7 are both co-amplified and co-overexpressed have a poor prognosis. We and others have recently determined that high levels of GRB7 are associated with recurrence in women with triple-negative breast cancer treated with anthracyclines (Sparano et al. J Clin Oncol 27(15s) 500). In this study, we have tested the hypothesis that triple-negative breast cancer cell lines are dependent on GRB7 for proliferation, migration and invasion. We have utilized a highly specific cell-penetrating peptide inhibitor of GRB7 (G7-18NATE) and tested its effects on a panel of 5 basal breast cancer cell lines in a series of culture assays: monolayer wound healing assays (motility on 2D substrates), transwell invasion assays (in vitro invasiveness) and 3D Matrigel cultures (morphogenesis in 3D environment). In all cases evaluated, the Grb7 inhibitory peptide impaired the proliferation, migration and invasion of these cell lines, even though these cells express low levels of GRB7 compared to HER2-amplified cell lines. These data implicate GRB7 as a key mediator of several important phenotypes of basal breast cancer cells and suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important targets for the development of specific therapies for this disease. This work was supported in part by Susan G. Komen for the Cure (KG091136). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-267.
Abstract 2085: Mir-30 acts as an anti-metastatic microRNA and is downregulated in non-small cell lung cancer (NSCLC)
Authors: Kumarswamy Regalla, Giridhar Mudduluru, Paolo Ceppi, Miroslaw Kozlowski, Jacek Nikliński, Heike Allgayer
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNAs) are small (around 22 nt) endogenous non-coding RNAs which regulate gene expression by base-pairing to the 3′-UTR of the target mRNA, causing translational repression or mRNA degradation. Recently, miRNAs have been shown to regulate cancer metastasis by virtue of their ability to co-ordinately repress multiple target genes. Epithelial-mesenchymal transition (EMT), which is characterized by repression of E-cadherin expression, and increased cell mobility, plays a very important role in cancer metastasis and fibrosis development. Recent evidence suggests that microRNA-30 (miR-30) acts as an antifibrotic agent and reduces tumor weight in animal models. In the present study, we have identified that the miR-30 family of miRNAs may function as anti-metastatic miRNAs by inhibiting EMT. We have studied the expression of miR-30 in various NSCLC cell lines and found that miR-30 expression is inversely proportional to the invasive capabilities of the cells. Correspondingly, all ‘mir-30 high’ cells are E-cadherin (epithelial marker) positive and N-cadherin (mesenchymal marker) negative, and vice-versa. ‘miR-30 low’ cell lines displayed several fold higher migratory and invasive abilities when compared with ‘miR-30 high’ cell lines. Similarly, in a chicken embryonic metastasis assay, we found that the number of metastasizing cells to lungs and livers of developing chicken was significantly reduced when miR-30 was over-expressed in ‘miR-30 low’ cells compared with mock-transfected cells. Over-expression of miR-30 also inhibited TGF-beta induced EMT in ‘miR-30 low’ cells, confirming the role of miR-30 in EMT inhibition. Search for miR-30 targets, that can modulate E-cadherin expression, using web based target analysis tools, have identified that Snail, which induces EMT primarily via transcriptional repression of E-cadherin, is a putative target of miR-30. Luciferase and Western blotting experiments have confirmed that miR-30 targets Snail. Finally, we have screened the expression of miR-30 in 47 consecutive NSCLC patients and found that miR-30 is down-regulated in tumours of about 80% of patients compared with their corresponding normal tissue. Collectively, these observations suggest that members of miR-30 are down regulated in non-small cell lung cancer, and inhibit EMT by targeting Snail. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2085.
Endoscopic hemostasis with multiple hemoclips and an endoloop for uncontrolled peptic ulcer bleeding
Authors: D. Kim, C.-I. Kwon, J. Chung, K. Ko, M. Kim, S. Hong, P. Park
Journal: Endoscopy (2011)

A method using a combination of multiple hemoclips and an endoloop was introduced for treating peptic ulcer bleeding and the large mucosal defects after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) [1] [2] [3] [4]. We report the combined use of multiple hemoclips and an endoloop in patients with uncontrolled peptic ulcer bleeding. The endoscopic examination and therapy were performed using a one-channel endoscope. In contrast to a two-channel endoscope, a one-channel endoscope permits separating one catheter containing a clip from the other catheter containing an endoloop, and it also provides a wide range of therapeutic actions during combination therapy. The combination therapy was conducted using the step-by-step method ([Figs. 1] and [2]).
THU0403 Sinonasal sarcoidosis: Review of clinical and imaging features: 7 year experience:
Authors: R. Joshi, J. Zenga, A. Getz, N. Debnath
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sarcoidosis is a chronic granulomatous disease that affects multiple organ systems including the upper respiratory tract. Sinonasal involvement is rare. <h3>Objectives</h3> Objective is to describe clinical characteristics of patients with sinonasal sarcoidosis and determine whether these patients exhibit characteristic sinus computed tomography (CT) findings based on Lund-Mackay scores (LM). <h3>Methods</h3> A retrospective review performed on 39 patients presenting to a tertiary academic medical center with a biopsy-proven diagnosis sarcoidosis and paranasal sinus CT imaging from 2004-2011. <b>Results:</b> One patient is on Rituximab salvage therapy, after failing all other steroid sparing agents. Main side effects include iatrogenic Cushing’s, opportunistic infections (OIs) and osteopenia. OIs include nontuberculous mycobacterial infection, cryptococcal osteomyelitis and Aspergillus niger infection. Incidentally 4 unusual cancers were noted: lacrimal gland sarcoma, inferior turbinate carcinoma-in-situ, myeloma and metastatic ovarian carcinoma. <h3>Conclusions</h3> Lund-Mackay score is an assessment tool to facilitate treatment decisions in chronic rhinosinusitis. Mean “normal” LM score in patients who undergo head imaging for non-rhinologic reasons is 4. Sinonasal sarcoid involvement has been estimated between 0.7 to 6% in various studies, but true incidence remains unclear due to nonspecific symptoms and lack of physician awareness. Mean LM score in sinonasal sarcoid may not elevated. However, the presence of nodular mucosal thickening of the nasal cavity, septum and sinuses may suggest sinonasal involvement of this chronic granulomatous disease in patients with symptoms of sinusitis. Single center experience of first line steroid sparing agent is Methotrexate, although individual patient co-morbidities drive this decision. Although uncommon, coexistent sinonasal sarcoidosis should be considered during the evaluation of sarcoid patients. <h3>References</h3> Reed J, DeShazo R, Houle T et al. Clinical features of Sarcoid Rhinosinusitis. The American Journal of Medicine, 2010, 123: 856-862. Hopkins C, Browne J, Slack R et al. The Lund-Mackay staging system for chronic rhinosinusitis: How is it used and what does it predict? Otolaryngology- Head and Neck Surgery, 2007, 137: 555-561. <h3>Disclosure of Interest</h3> R. Joshi: None Declared, J. Zenga: None Declared, A. Getz: None Declared, N. Debnath Consultant for: Entellus Medical, Speakers Bureau: Alcon
Abstract 2800: BAY 94-9392 – A new derivative of L-glutamate for tumor specific PET imaging
Authors: Norman Koglin, Andre Mueller, Matthias Friebe, Mathias Berndt, Heribert Schmitt-Willich, Volker Gekeler, Ludger M. Dinkelborg
Journal: Cancer Research (2011)

Abstract There is a high demand for a tumor specific imaging, staging and therapy monitoring by PET. Currently, FDG (2-[F-18]fluoro-2-deoxyglucose) is the commonly used agent for tumor detection and staging. However, this method cannot differentiate between tumor and inflammatory lesions. In addition, FDG does not accumulate in tumors with low glycolytic activities, such as prostate cancer. It is not optimal for specific detection of brain tumors and metastases due to a high background signal resulting from healthy brain metabolism. The amino acids L-glutamine and L-glutamate as well as their corresponding transporters play a key role in the adapted intermediary metabolism of tumors. We synthesized and evaluated a new PET imaging agent BAY 94-9392, a derivative of L-glutamate. This agent was successfully used for tumor detection with high sensitivity and specificity as demonstrated in various preclinical models. Methods: The radiosynthesis of (4S)-4-(3-[F-18]fluoropropyl)-L-glutamate (BAY 94-9392) was established on a commercial synthesis module. BAY 94-9392 was investigated in a variety of tumor cell lines as well as tumor models for uptake, biodistribution, mode of action, and its potential to differentiate between tumor versus inflammation. Results: BAY 94-9392 is specifically transported by the cystine/glutamate exchanger (xCT, SLC7A11) and it is not metabolized. Compared to FDG, the agent displayed a high accumulation rate in a panel of tumor cells. PET imaging with excellent tumor visualization and high tumor to background ratios was achieved in a variety of preclinical tumor models. BAY 94-9392 did not accumulate in inflammatory lesions, whereas FDG shows a strong uptake in this turpentine oil induced and histopathologically confirmed rat model. Conclusions: BAY 94-9392 is a new, promising tumor specific PET tracer. Both preclinical and clinical studies are in progress for further characterization. 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 2800. doi:10.1158/1538-7445.AM2011-2800
Abstract 4208: Constitutive activation of Wnt/beta-catenin signaling induces uterine developmental defects
Authors: Yongyi Wang, Ron Smits, Patrick Franken, Yundan Jia, J. Anton Grootegoed, Curt W. Burger, Riccardo Fodde, Leen J. Blok
Journal: Cancer Research (2010)

Abstract Background: Wnt/beta-catenin signaling plays a regulatory role in uterine development and function. To study this role of Wnt/beta-catenin signaling during embryogenesis in more detail, we employed an AmhR2 promoter-driven C-recombinase (Jamin et al., 2002) to conditionally inactivate the Apc gene in mesenchymal cells surrounding the müllerian duct. As a consequence of Apc inactivation, defects in the destruction complex are expected to result in the intracellular accumulation of beta-catenin and the subsequent constitutive activation of canonical Wnt signaling. Methods: [Apc15Lox/15lox;AmhR2-Cre] conditional Apc knockout mice were generated. Cre expression and AmhR2 promotor activity was verified by staining for beta-galactosidase activity in [AmhR2-LacZ] and [AmhR2-Cre;ROSA26-LacZlox] reporter mice. Furthermore, recombination of the Apc gene was verified for different laser micro-dissected regions of the uterus, from 8-week-old mice, by PCR. Uterine defects were examined by immunohistochemical staining for various uterine markers. Results: It was observed that the Cre-mediated Apc gene deletion mainly took place in the myometrial layers of the uterus. Recombination in the stroma and epithelium of the lumen and glands was low. Microscopically, the affected mice showed a significant reduction in the number of glands and a somewhat disorganized stroma. The main defects, however, were observed in the myometrial layer of the uterus, where clear disorganization of muscle fibres and in 50% of cases visible loss of musculature was apparent. As a consequence of these defects, the mice displayed reduced litter sizes and some mice were incapable of normal delivery. Conclusion: AmhR2-Cre driven embryonic knock-down of Apc results in a defect of the myometrial layer of the uterus. Effects on the endometrium were observed to be less profound. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4208.
Single-scope endoscopic ultrasound-guided rendezvous-assisted biliary stent insertion
Authors: L. Fujii, C. Gostout, M. Levy
Journal: Endoscopy (2012)

Endoscopic retrograde cholangiography (ERC) is the most common method employed for drainage of malignant biliary obstructions. When ERC fails, bypass, either percutaneously or surgically, is available; more recently, endoscopic ultrasound-guided biliary drainage (EUS-BD) has been described [1] [2] [3]. Most endoscopists perform EUS-BD using a rendezvous approach in which the bile duct is accessed using an echoendoscope and a guide wire is inserted in an antegrade direction through the obstruction and into the duodenum. The echoendoscope is then withdrawn and the guide wire is left in place. A side-viewing or forward-viewing endoscope must then be passed so that the guide wire can be grasped and retrograde stent insertion performed. Alternatively, the echoendoscope may be used both to access the bile duct and to insert a biliary stent via an antegrade approach. However, the angle of access may prohibit antegrade stent insertion and necessitate a rendezvous procedure. We describe a variant of the rendezvous approach in which the entire procedure was performed using only the echoendoscope after efforts at antegrade stent insertion had initially failed.
FEASIBILITY AND DIAGNOSTIC POTENTIAL OF REGADENOSON STRESS 2D-SPECKLE TRACKING ECHOCARDIOGRAPHY FOR DETECTION OF INDUCIBLE ISCHEMIA: INITIAL RESULTS OF THE SINGLE CENTER, PROSPECTIVE, RANDOMIZED, COMPARATIVE, SAME-SETTING STUDY OF REGADENOSON STRESS SPECT VERSUS 2D SPECKLE TRACKING ECHO (LEXI-ECHO TRIAL)
Authors: Aiden Abidov, Ahmed Pasha, Arun Kannan, Nisreen Yaghmour, Evbu Enakpene, Vincent Sorrell
Journal: Journal of the American College of Cardiology (2015)
Ovarian cancer linked to p53 gene
Authors: S. Mayor
Journal: BMJ (1997)

Researchers have found evidence suggesting that over half of all ovarian cancers may be linked to mutations in a critical regulatory gene that is strongly linked to ovulation.

A team from Duke University Medical Center in the United States tested for the presence of mutations in the regulatory gene–p53–in samples of ovarian tumours from 197 patients. All of these women were asked about their age …