tbuckley/cabot-search huggingface dataset:
Abstract P3-08-07: HER2 positive breast carcinomas: trend in evolution between 1998 and 2008 and relationship with clinico-pathological characteristics in a population based study.
Authors: F Beltjens, A Bertaut, S Pigeonnat, N Pouget, S Guiu, M-L Poillot, C Charon-Barra, B Coudert, S Dabakuyo, P Fumoleau, P Arveux, L Arnould
Journal: Cancer Research (2012)

Abstract Background: Determination of HER2 status in invasive breast carcinomas is now mandatory for the optimal treatment of the patient. A vast majority of initial published studies described positivity in about 20 to 25 % of breast carcinomas, but the proportion of HER2 positive gene expression in women with breast cancer varies in the literature from 9 to 74%. The population of the tumor analyzed (for example histologic types, stage, age), the type of the assays used and the lack of uniformity or quality controls in detection assays may partly explain these differences. Our study describes the evolution of HER2 positive invasive breast cancer proportions during a period of 10 years and identifies clinical and pathological characteristics of these positive tumors. Methods: Based on the regional, population-based breast cancer registry, we identify 2396 patients diagnosed with invasive breast cancer in the Côte-d'Or department and treated in a single institution between 1998 and 2008. The HER2 status was determined by immunohistochemistry and by fluorescence in situ hybridization by a single team that performed regular internal quality controls and participated to multiannual external international quality control programs. Results: During the 1998–2008 period, 12.8% of invasive breast cancers were identified as HER2 positive, with no trend to annual variations (p = 0.27). During the same period, despite an increase of 45% of the annual diagnosed cancers in the institution, the clinical and pathological characteristics such as age, tumor size, grade, hormonal receptors expression remain stable. We only noticed a slight but significant increase of lobular carcinomas (p = 0.036). In multivariate analysis, HER2 positivity was as expected associated with: hormonal receptor negative status (OR = 1.7 [IC95%: 1.2–2.4], p = 0.0035), metastatic presentation at diagnosis (OR = 2 [IC95%: 1.2–3.4], p = 0.0092), ductal subtype (OR = 1.9 [IC95%: 1.1–3.1], p = 0.0178) and high SRB grade (OR = 2.8 [IC95%: 1.7–4.5] for SBR II, OR = 5.4 [IC95%: 3.2–9.1] for SBR III, p = 0.0035). Conversely, patients older than 75 years presented mostly HER2 negative tumors (OR = 0.5 [IC95%: 0.3–0.8], p &amp;lt; 0.0001). Conclusions: This population based study on HER2 breast cancer status emphasizes that in a population with stable clinical and tumoral characteristics, when standardized and controlled assays are used, the proportion of HER positive tumors remains stable over a large period and is lower than usually reported (12.8%). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-07.
Resolution of Hepatopulmonary Syndrome After Methadone Withdrawal as Demonstrated by Right to Left Shunt Study
Authors: Bjoern Kitzing, Paul J Torzillo, Kevin C Allman
Journal: Clinical Nuclear Medicine (2011)

We present the right to left shunt study findings of a 50-year-old male patient with hepatitis C cirrhosis, who complained of worsening dyspnea on exertion. Follow-up images showed resolution of hepatopulmonary syndrome following methadone withdrawal although there had been no improvement in his liver disease. This was unusual and may have been due to the effect of opiate receptors on nitric oxide signaling in the pulmonary vasculature.
P1028 NON-INVASIVE SCORE SYSTEM FOR FIBROSIS (NISF) IN CHRONIC LIVER DISEASE: A NEW MODEL COMBINING BIOCHEMICAL, ELASTOGRAPHIC AND ULTRASOUND DATA
Authors: S. Gaia, D. Campion, M. Spandre, A. Cantamessa, F. Brunello, A. Evangelista, L. Cosso, P. Carucci, E. Rolle, G. Ciccone, E. Bugianesi, S. Carenzi, M. Rizzetto
Journal: Journal of Hepatology (2014)
P10 Randomised Placebo Controlled Trial to Evaluate Chronic Dosing Effects of Propranolol in Steroid Treated Persistent Asthmatics
Authors: PM Short, PA Williamson, WJ Anderson, BJ Lipworth
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Beta-blockers are associated with acute bronchospasm in asthmatics. However preliminary unblinded studies have shown potential therapeutic benefits with chronic beta-blockade on airway hyper-responsiveness (AHR) in steroid naïveasthmatics. We examined the effects on AHR of propranolol versus placebo in steroid treated persistent asthmatics. <h3>Methods</h3> A double-blind randomised placebo controlled crossover trial of propranolol in mild-to-moderate asthmatics receiving inhaled corticosteroids (ICS) was performed (NCT01074853). Participants underwent a six to eight week dose titration of propranolol or placebo as tolerated to a maximum of 80mg per day. Tiotropium was given concurrently for the first four to six weeks of each treatment period. Primary outcome was methacholine challenge (without tiotropium). Secondary outcomes included histamine challenge (with and without tiotropium), pulmonary function, heart rate, blood pressure, mini-asthma quality of life questionnaire (mini-AQLQ) and asthma control questionnaire (ACQ). <h3>Results</h3> 18 patients completed: mean (SEM); age 36 (4), FEV1% 93 (2), ICS ug/day 440 (66). No significant difference was observed in methacholine or histamine challenge following exposure to propranolol versus placebo. For methacholine challenge (without tiotropium) the doubling dilution difference (DDD) was 0·04 (95%CI –0·56 – 0·63), p=0·89. For histamine challenge without tiotropium the DDD was 0·42 (95%CI –0·09 – 0·93), p=0·10; and with tiotropium was DDD 0·26 (95%CI –0·36 – 0·87), p=0·39. Salbutamol induced chronotropic response was significantly blunted following propranolol versus placebo: mean difference 25bpm (95%CI 14 – 37), p&lt;0·001. No difference was found for ACQ, mean difference 0·18 (95%CI –0·23 – 0·58), p= 0.79 or mini-AQLQ, mean difference 0.14 (95%CI –0·19 – 0·46), p=0·84. <h3>Conclusions</h3> This is the first placebo controlled study to assess the effects of chronic non selective beta-blockade in steroid treated persistent asthmatics, showing no significant effect of propranolol compared to placebo on AHR to either methacholine or histamine and no change in ACQ or AQLQ.
Abstract 2937: The LKB1-STRADα axis regulates vimentin to control cancer cell metastasis
Authors: Erik Kline, Katherine Hales, Adam I. Marcus
Journal: Cancer Research (2011)

Abstract Lung cancer remains the most lethal form of cancer, and non-small cell lung cancer (NSCLC) patients have a 5-year survival rate of only 15-25%. Metastasis is the major cause of death in nearly all cancer cases. Therefore, determining which genes are altered during cancer invasion and the functional consequences of their alteration will broaden our understanding of metastatic disease and unveil novel targets for anti-metastatic therapies. The pleiotropic tumor suppressor LKB1 is mutated in ∼30% of NSCLC cases and is the third most frequently mutated gene in lung adenocarcinoma. Originally recognized as a regulator of the energy stress pathway and cell cycle signaling, we and others have identified LKB1 and its activating co-factor STRADα as regulators of the lung cancer cell polarity program through the small Rho GTPase cdc42 and its downstream binding partner p21-activated kinase (PAK). We expand these studies and investigate the LKB1-STRADα pathway during the transition from cell polarity to cell motility. We show that when a cancer cell becomes motile, STRADα re-localizes to associate with vimentin intermediate filaments in a motility-dependent manner. Vimentin is specifically overexpressed in invasive human tumors, which also correlates with metastatic disease, poor prognosis, and reduced patient survival. To dissect the mechanistic basis of this observation, we tested the hypothesis that STRADα regulates vimentin function to oversee cancer cell motility. STRADα loss results in aberrant lamellipodia formation, uncoordinated movement, and vimentin bundling. Conversely, STRADα overexpression disassembles the vimentin network with no apparent effect on cell survival. A phospho-proteomic screen in isogenic NSCLC cell lines showed that out of 580 possible proteins the cdc42 GEF, VAV2, demonstrated the greatest loss in phosphorylation upon vimentin depletion. Western blot analysis confirmed that vimentin-depletion decreased phosphorylation of VAV2 at residue Y-142. Dual overexpression of LKB1 and STRADα enhances VAV2 phosphorylation in vimentin-positive cells but not in vimentin-depleted cells. These findings suggest a cell polarity-motility program whereby LKB1-STRADα initiates cell polarity through cdc42-PAK, then STRADα re-localizes to the vimentin cytoskeleton to oversee vimentin dynamics. LKB1-STRADα also regulates VAV2 phosphorylation through vimentin signaling. These results link the LKB1-STRADα tumor suppressor pathway to the lung cancer cell polarity and motility programs, and explain how defects in the LKB1-STRADα alter lung cancer invasion. 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 2937. doi:10.1158/1538-7445.AM2011-2937
SP0018 Development of eular recommendations for non-pharmacological management of hip and knee osteoarthritis
Authors: L. Fernandes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Current recommendations on the management of hip and knee osteoarthritis put much emphasis on non-pharmacological management. They are, however, not sufficiently specific about the content, timing, intensity, frequency, duration and mode of delivery. <h3>Objectives</h3> The aim of this project is to develop evidence and expert opinion-based EULAR recommendations for non-pharmacological management of osteoarthritis of the hip and knee and propose a future research agenda. <h3>Methods</h3> A Steering Group consisting of 22 participants was established in February 2011. The group consists of the convenor and co-applicants, experts (rheumatology health professionals, rheumatologists, orthopaedic surgeons, general practitioners and people with hip and/or knee osteoarthritis), a clinical epidemiologist and a person in charge of the literature search. A preliminary literature search of practice guidelines and overviews of reviews was performed to obtain an overview of current recommendations and addressed treatment modalities. The results from the preliminary literature search and potential topics for propositions were discussed at the first Steering Group meeting in June 2011, where 17 of the participants were present. A Delphi procedure was held by e-mail between July and October 2011. All participants contributed actively in all Delphi rounds. A specific literature search for each proposition is currently in progress in electronic databases (Medline, Embase, AMED, PsychINFO, CINAHL, PEDro, Cochrane Database of Systematic Reviews, DARE, Cochrane Central Register of Controlled Trials). Retrieved studies on effectiveness of relevant interventions will be methodologically evaluated and the level of evidence on interventions will be graded using EULAR 1 to 4 grades. During the second Steering Group meeting in May 2012, evidence will be reviewed and expert opinion will be documented where evidence is insufficient or absent. Recommendations will then be finalized with the strength of each recommendation graded from A to D. <h3>Results</h3> Eleven propositions were agreed after five Delphi rounds. The full set of recommendations, evidence level and strength of recommendation for each of the proposition, and a proposed research agenda for identified evidence gaps will be presented at the EULAR Congress in June 2012. <h3>Conclusions</h3> This project will yield a set of recommendations for the non-pharmacological management of hip and knee osteoarthritis, based on evidence and expert opinion, and employing a systematic literature search and Delphi techniques. In addition, the project will identify areas of interest where research is lacking, resulting in a research agenda. The results of this project will contribute to the quality of care for people with hip and knee osteoarthritis across Europe. <h3>Disclosure of Interest</h3> None Declared
Abstract 4015: Amplification of GEP at chromosome 17q21 and its overexpression in human liver cancer.
Authors: Man Kuen Yung, Chi Wai Yip, Phyllis Fung Yi Cheung, Siu Tim Cheung
Journal: Cancer Research (2013)

Abstract Amplification of GEP at chromosome 17q21 and its overexpression in human liver cancer Hermann M.K. Yung, Wallace C.W. Yip, Phyllis F.Y. Cheung and Siu Tim Cheung Department of Surgery, The University of Hong Kong. Introduction: Hepatocellular carcinoma (HCC) is the 3rd most lethal cancer worldwide. Curative treatments, such as surgical resection, are limited to only a small group of patients. Granulin-epithelin precursor (GEP), which is a secretory growth factor, has been shown to enhance the growth, invasion, metastasis and chemo-resistance of HCC. GEP was found to overexpress in tumors compared to the non-tumor counterpart, and the overexpression correlates to poor prognosis in HCC patients. Antibody targeting GEP inhibited tumor growth in vivo. However, the overexpression mechanisms in HCC are not clear. Hypothesis: Gene amplification may be one of the mechanisms for GEP overexpression as its locus, 17q21, is frequently amplified. Method: Quantitative Microsatellite Analysis (QuMA) was used to determine the copy number alteration of the GEP gene locus. In this method, quantitative PCR was used to quantify the GEP and microsatellite loci. The genomic stable microsatellite loci were used as reference. Copy number variations were determined by normalization of HCC data to the copy numbers of blood samples from healthy donors, which were defined as diploid 2N. GEP mRNA level was quantified by real-time RT-PCR. Correlations between GEP copy number and its mRNA expression level were analyzed. Results: GEP DNA copy numbers were quantified in a panel of clinical HCC (n=60). Amplification of GEP locus was observed in 30% (20/60) HCC, and the amplification frequency was comparable to published reports on chromosome 17q. Overall, GEP copy number correlated to the mRNA overexpression levels (n=60, r=0.267, P=0.039). For HCC with GEP gene locus amplification (n=20), tight correlation with GEP expression levels were observed (r=0.646, P=0.002). Summary: We showed that GEP gene was frequently amplified in HCC, and this amplification correlates to the expression level of GEP. Fluorescent in situ hybridization (FISH) will be performed to further investigate the amplification status. Citation Format: Man Kuen Yung, Chi Wai Yip, Phyllis Fung Yi Cheung, Siu Tim Cheung. Amplification of GEP at chromosome 17q21 and its overexpression in human liver cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4015. doi:10.1158/1538-7445.AM2013-4015
Abstract P5-04-03: Antibodies in Single Chain Format Against HER2/neu Antigen: Promising Agents for Breast Cancer Immunotherapy
Authors: M Asgharpour, F Nejatollahi, M. Jaberipour
Journal: Cancer Research (2010)

Abstract Introduction: HER2/neu gene is overexpressed in 25-30% of breast cancers and is associated with increased metastatic potential and poor prognosis. Blocking the HER2/neu signaling has been the focus of most therapeutic approaches. Although monoclonal antibodies have shown some success in the inhibition of tumor growth, the HAMA reaction has limited the use of these agents. Human recombinant antibodies offer a potential alternative and provide valuable clinical agents for cancer immunotherapy. Our aim was to produce a source of specific single chain antibodies (scFv) against HER2/neu and assess their effects on cancer cell line. Materials and Methods: A phage antibody display library of single chain Fv (scFv) was panned against three HER2/neu epitopes and differentiated by BstN1 fingerprinting. The selected clones were screened for the ability to bind the HER2/neu positive cell line (SKBR-3) by flowcytometry. The cell line was treated with 3 specific scFvs and the expression of HER2/neu transcript was measured by real time PCR. The effects of the selected scFv antibodies on the cell line were evaluated by MTT assay. Results: one specific clone was isolated against each epitope. Flowcytometry assay showed that the clones bound to HER2/neu expressing cell line with intensity range 75-80%. Real time PCR results revealed that scFv-II, -III and combination of all the three scFvs downregulated HER2/neu gene expression (Fig 1). All the single chain types alone and in combination significantly inhibited the proliferation of the SKBR-3 cells in the MTT proliferation assay (Fig 2). Conclusion: Herceptin (Trastuzumab) is a humanized antibody against HER2/neu which is approved by the FDA for treatment of HER2/neu positive breast cancers. Researches have shown multiple life-threatening side effects of Herceptin on the patients and also the overall objective response rate to herceptin is only 15-20%. Therefore there is a need for development of an alternative. The human origin, small size (20-30kDa), rapid blood clearance and good tumor penetration of human scFvs offer potential advantages for the use of these agents in cancer immunotherapy. Our results suggest that the highly specific anti-HER2/neu human scFvs that inhibit the proliferation of the breast cancer cell line could contribute in breast cancer immunotargeting approaches. In vivo assessment of the antibodies is under investigation to show the therapeutic effects of the selected scFvs. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-04-03.
Abstract 1456: Cerebrospinal fluid vascular endothelial growth factor in patients with brain metastases from breast cancer
Authors: Susan S. Song, Chris Malchow, Edwin Lok, Kenneth Swanson, Eric T. Wong
Journal: Cancer Research (2010)

Abstract There is a rising incidence of brain metastases from breast cancer. Having an improved means of detecting and monitoring such brain metastases would be valuable. Using samples stored in our Cerebrospinal Fluid (CSF) Bank, we identified 176 samples from 71 patients with brain metastases from breast cancer. The CSF VEGF levels were measured using enzyme-linked immunosorbent assay and normalized to phosphate buffered saline. The highest CSF VEGF ratios from individual patients were correlated with patient survival. The median CSF VEGF ratio was 1.043, with a range of 0.575 to 22.060. At the time of analysis, 51 patients were deceased while 30 were alive, with a median survival of 4 months. The median survival of patients with CSF VEGF ratio ≤ 1.000 was 7 months (range 1 to 31 months) versus 2.5 months (range 0.5 to 60 months) for those with CSF VEGF &amp;gt; 1.000. Furthermore, increasing CSF VEGF levels also appear to correlate with increasing number of brain metastases detected on magnetic resonance imaging. We conclude that VEGF is a potential biomarker in the CSF for brain metastases from breast cancer. 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 1456.
THU0213 Synovial Fluid VEGF and Serum Leptin Could Reflect Progression of Knee Osteoarthritis According to Ultrasonographic Studies
Authors: H.R. Kim, S.-H. Lee, H.-Y. Kim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> VEGF contributes in the pathogenesis of osteoarthritis and it could be a potential therapeutic target of osteoarthritis <h3>Objectives</h3> This study aimed to determine synovial fluid biomarkers which could reflect the progression of osteoarthritis and accord with radiological and ultrasonographic studies. <h3>Methods</h3> Thirty four patients with knee osteoarthritis who were detected joint effusion by clinical examination. Both knee joints were examined using plain radiograph and ultrasonography. The questionnaires were done including visual analog scale (VAS), Western Ontario McMaster Universities Osteoarthritis Index and Health Assessment Quesionnaire (HAQ). Synovial fluid (SF) and serum levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-13, leptin, resistin, and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immonosorbent assay. <h3>Results</h3> Among 34 patients, 14 patients were categorized as KL grade 2, 16 as KL grade 3, and 4 as KL grade 4. SF VEGF level was positively correlated with KL grades and it was higher in patients with KL grade 4 than those with KL grade 2. SF VEGF correlated with ultrasonographic findings such as the length of medial osteophytes and lateral osteophytes. The amount of effusion was positively correlated with SF resistin and negatively correlated with leptin. Serum leptin level had positive correlation with HAQ and the length of medial osteophytes. MMP-13 or COMP levels were not correlated with radiographic or ultrasonographic findings. There was no difference in synovial fluid and serum levels of VEGF between osteoarthritis and rheumatoid arthritis patients. <h3>Conclusions</h3> Synovial fluid VEGF and serum leptin could be biomarkers for advanced knee osteoarthritis and it accords with radiographic and ultrasonographic findings. <h3>References</h3> Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM et al: Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 2000; 133:635-646. Golightly YM, Marshall SW, Kraus VB, Renner JB, Villaveces A, Casteel C et al: Biomarkers of incident radiographic knee osteoarthritis: do they vary by chronic knee symptoms? Arthritis Rheum 2011; 63:2276-2283. Lingaraj K, Poh CK, Wang W: Vascular endothelial growth factor (VEGF) is expressed during articular cartilage growth and re-expressed in osteoarthritis. Ann Acad Med Singapore 2010; 39:399-403. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1242