tbuckley/cabot-search huggingface dataset:
AB0686 Results of the multinational e-mail survey regarding follow up of patients with l raynaud’s phenomenon.
Authors: I. Foeldvari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Secondary Raynaud phenomenon is an orphan disease in childhood. Currently there are no guidelines how to follow these patients and what is the most sensitive sign to differentiate between primary and secondaryRaynaud's phenomenon. In this survey special issues of this diseases and follow up concepts were surveyed. <h3>Objectives</h3> To learn about the clinical practice regarding diagnosis and follow up concepts fro primary and secondary Raynaud's phenomenon <h3>Methods</h3> Members of the paediatric rheumatology e-mail board and of the juvenile scleroderma working group of the PRES were asked to fill out a survey with 3 items regarding diagnosis and follow up of primary and secondary Raynauds phenomenon. <h3>Results</h3> 28 colleagues responded to the survey with a wide spread geographic distribution. 3 questions were asked and the following responses received. If you see a patients with Raynaud's- phenomenon how often you see them for follow up: 14 of the centres followed the patient every 6 months, 7 every 3 months, 2 centres every two months and other 2 for every 12 months. Which findings do you find helpful to define secondary Raynauds? - you can give several choices: 23 of the centres found a positive nailfold capillaroscopy findings, 12 ANA positivity and 10 antiphospholipid positivity as an important sign for secondary Raynaud's phenomenon. 3 centres considered any sign of rheumatic disease supportive. If you see a patients with secondary Raynaud's phenomenon how often you see them for follow up: 16 of the centres followed the patients every 3 months, 3 of the centres every 6 months, two of the centres every 2 months. 3 of the centres made the follow up dependent in the clinical symptoms. <h3>Conclusions</h3> The range of follow up periods differs widely between the centres. Regarding supportive sign for secondary Raynaud's a positive nailfold capillaroscopy finding appeared to be the most important sign. Prospective collection of clinical data of patients with primary and secondary Raynaud's phenomenon would help us to better understand, the most rational way to follow this patients <h3>Disclosure of Interest</h3> None Declared
Stent migration after stent-in-stent technique using a biodegradable stent
Authors: G. de Roberto, A. de Leone, D. Tamayo, G. Fiori, D. Ravizza, C. Trovato, S. De Lisi, C. Crosta
Journal: Endoscopy (2012)

Self-expanding metal stents (SEMS) seem to be the optimal choice for benign esophageal disorders, especially those not associated with a stricture, such as anastomotic leaks, iatrogenic perforations, and fistulas. On the other hand stent embedding can be an important limitation of SEMS placement, because this precludes safe stent removal [1]. In fact, in the literature there are only a few case series reporting the stent-in-stent technique using SEMS to remove embedded stents (14 – 189 days from the placement of the first stent) [2] [3].
Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages
Authors: Majken Wallerius, Tatjana Wallmann, Margarita Bartish, Jeanette Östling, Artur Mezheyeuski, Nicholas P. Tobin, Emma Nygren, Pradeepa Pangigadde, Paola Pellegrini, Mario Leonardo Squadrito, Fredrik Pontén, Johan Hartman, Jonas Bergh, Angelo De Milito, Michele De Palma, Arne Östman, John Andersson, Charlotte Rolny
Journal: Cancer Research (2016)

Abstract Accumulation of tumor-associated macrophages (TAM) correlates with malignant progression, immune suppression, and poor prognosis. In this study, we defined a critical role for the cell-surface guidance molecule SEMA3A in differential proliferative control of TAMs. Tumor cell–derived SEMA3A restricted the proliferation of protumoral M2 macrophages but increased the proliferation of antitumoral M1, acting through the SEMA3A receptor neuropilin 1. Expansion of M1 macrophages in vivo enhanced the recruitment and activation of natural killer (NK) cells and cytotoxic CD8+ T cells to tumors, inhibiting their growth. In human breast cancer specimens, we found that immunohistochemical levels of SEMA3A correlated with the expression of genes characteristic of M1 macrophages, CD8+ T cells, and NK cells, while inversely correlating with established characters of malignancy. In summary, our results illuminate a mechanism whereby the TAM phenotype is controlled and identify the cell-surface molecule SEMA3A as a candidate for therapeutic targeting. Cancer Res; 76(11); 3166–78. ©2016 AACR.
Abstract 5218: Development of Anti-CD47 therapy for pediatric brain tumors.
Authors: Sharareh Gholamin, Siddhartha S. Mitra, Chase Elliott Richard, Achal Achrol, Doosik Kong, Jun Jae Shin, Michelle Monje-Deisseroth, Yoon-Jae Cho, Irving Weissman, Samuel H. Cheshier
Journal: Cancer Research (2013)

Abstract Introduction: Extensive molecular characterization of Brain tumors done in recent years has proven valuable for tumor classification, risk stratification and outcome prediction for current treatment modalities. However the current standard of care has not improved the prognosis and carries an increased risk of cognitive impairments for children with brain tumors. A characteristic feature of tumor progression and recurrence is its ability to evade the immune system. Our hypothesis is that by modulating the innate immune system we can enhance the ability of macrophages to ‘eat and kill’ brain cancer cells. Recent data suggests that the interaction between the cell surface antigen CD47 and its binding partner SIRPα is a mechanism by which non-solid and solid tumors can evade the innate immune system. To see if anti-CD47 therapy is a potential therapy in malignant pediatric brain tumors we first looked at CD47 expression in freshly isolated patient and postmortem samples from 4 different tumor types; Diffused Intrinsic Pontine Glioma, Medulloblastoma, Ependymoma and ATRTs. We tested the hypothesis that blocking CD47- SIRPα interaction induced phagocytosis in an in-vitro phagocytosis assay. We next established orthotopic xenografts models in immune compromised mice and treated them with anti-CD47 humanized antibody, which is currently being developed for clinical trials in hematopoietic and non-CNS malignancies. Result: CD47 expression was upregulated in all tumor types and was present in &amp;gt;90% of the cells in high grade tumors. Increased CD47 expression was observed in CD15+ and CD133+ putative cancer stem cell population. Blocking the CD47- SIRPα interaction increases tumor phagocytosis by macrophages in-vitro. Systemic treatment with anti-CD47 antibody significantly reduced tumor burden in an orthotopic xenograft setting. Conclusion: Anti-CD47 therapy is a viable and effective treatment modality for pediatric high grade brain tumors. Citation Format: Sharareh Gholamin, Siddhartha S. Mitra, Chase Elliott Richard, Achal Achrol, Doosik Kong, Jun Jae Shin, Michelle Monje-Deisseroth, Yoon-Jae Cho, Irving Weissman, Samuel H. Cheshier. Development of Anti-CD47 therapy for pediatric brain tumors. [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 5218. doi:10.1158/1538-7445.AM2013-5218
SAT0279 Tocilizumab in Refractory Aortitis: Study on 16 Patients and Literature Review
Authors: J. Loricera, R. Blanco, S. Castañeda, A. Humbría, N. Ortego-Centeno, J. Narváez, C. Mata, S. Melchor, E. Aurrecoechea, J. Calvo-Alén, P. Lluch, C. Moll, M. Mínguez, G. Herrero-Beaumont, B. Bravo, E. Rubio, M. Freire, E. Peirό, M.C. González-Vela, J. Rueda-Gotor, T. Pina, V. Calvo-Río, F. Ortiz-Sanjuán, M.A. González-Gay
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Non-infectious aortitis is often refractory to standard immunosuppressive therapy. IL-6 has been implicated in the pathogenesis of aortitis. <h3>Objectives</h3> Our aim was to assess the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. <h3>Methods</h3> We reviewed 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ. <h3>Results</h3> The mean age ± SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (N=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA, and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean ± SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia. <h3>Conclusions</h3> TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs. <h3>Acknowledgements</h3> This study was supported by a grant from "Fondo de Investigaciones Sanitarias" PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from "Instituto de Salud Carlos III" (ISCIII) (Spain). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2984
SAT0420 Ground Reaction Forces in Patients with Knee Osteoarthritis after Intra-Articular Treatments:
Authors: J.L. Garrido-Castro, J. Gil-Cabezas, V. Perez-Guijo, C. Gonzalez-Navas, P. Font-Ugalde, E. Collantes-Estevez
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis of the knee (OA) is the most common disease affecting the musculoskeletal system and one of the most important causes of disability among elderly population. Patients are assessed by questionnaires whose response may be influenced to some subjectivity (WOMAC, VAS, SF36). Gait analysis and ground reaction forces (GRF) produce objective and quantitative results of patient status with well-defined patterns. Vertical force curves are characterized by showing two peaks and a valley, showing a graph like an inverted W. Intra-articular injections of hyaluronic acid for the treatment of knee OA have been shown to reduce pain and improve joint function. In this work we have used GRF as evaluation tool in patients with knee OA before and after applying intra-articular treatments. <h3>Objectives</h3> To analyze ground reaction forces in patients with knee OA before and after intraarticular treatment. <h3>Methods</h3> 26 patients with knee OA (57.68±8.06 years, 1.65±0.88 m, 87.74±13.06 kg) with a high level of affectation (grade II-III according to Kellgren and Lawrence scale) and 6 healthy subjects as control group with similar characteristics (55.33±5.07 years, 1.70±0.77 m,. 88.52±10.15 kg) were analyzed. Intraarticular injections of hyaluronic acid were applied to patients before and after measurements (one and three months). Vertical, mediolateral and anteroposterior GRF were evaluated using a triaxial force plate (Bertec ® FP4060) <h3>Results</h3> GRF in three axis and some temporary values as support time and first peak time in vertical force are showed in table. Significant differences between patients and control group in almost all parameters analyzed were found, showing a biomechanical altered gait. Regarding treatment sensitive measures, we could highlight first time peak in vertical force, force in the valley and difference between peak and valley. Sensitive measures also appear in the other two axis with larger braking and impulse forces. Also a shorter support time appears. <h3>Conclusions</h3> Our study shows that GRF clearly improved approximating to values obtained for control group after intraarticular treatment. The evaluation of GRF in gait could be used as an evaluation tool, not only to demonstrate the biomechanical alteration produced by knee OA, but also as a tool for evaluating the effectiveness of treatment. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3313
Abstract 1529: Knockdown of cathepsin B and uPAR inhibits CD151 and α3β1 integrin-mediated cell adhesion in glioma
Authors: Rama Rao Malla, Sreelatha Gopinath, Kiranmai Alapati, Christopher S. Gondi, Jasti S. Rao
Journal: Cancer Research (2011)

Abstract Glioma is a highly complex brain tumor characterized by deregulation of proteins and genes that play important roles in tumor metastasis. CD151, a member of the tetraspanin family of proteins, tightly associates with integrins and accelerates cell adhesion as a modulator of actin cytoskeletal reorganization. Cathepsin B and uPAR are both overexpressed in gliomas and postulated to play central roles in the mediation of glioma metastasis. In the present study, cathepsin B and uPAR were downregulated in U251 and 4910 glioma cells using siRNA plasmid constructs. We evaluated the involvement of CD151 and its associated signaling molecules in adhesion potential. Immunoblot analysis revealed efficient downregulation of cathepsin B and uPAR after siRNA treatments. In addition, siRNA treatments significantly inhibited glioma cell adhesion to laminin as compared to other extracellular matrix proteins. Brain glioma tissue array analysis revealed the expression of CD151 in several tumor samples when compared with normal brain tissue. Further, treatment of glioma cells with cathepsin B and uPAR siRNA led to the downregulation of CD151 and laminin-binding integrins, α3 and β1. Co-localization and immunoprecipitation experiments revealed that downregulation of cathepsin B and uPAR decreased the interaction of CD151 with uPAR/cathepsin B. Transcriptional suppression of CD151 and α3 and β1 integrins using siRNA significantly decreased glioma cell adhesion to laminin. In addition, downregulation of cathepsin B, uPAR, CD151, α3 and β1 significantly decreased the expression of N-cadherin and β-catenin. Studies on the downstream signaling cascade of uPAR/CD151 have shown that phosphorylation of SRC, FAK and Paxillin were reduced with knockdown of cathepsin B, uPAR and CD151. Treatment with the bicistronic construct reduced CD151, α3β1 integrin, N-cadherin and β-catenin expression levels in pre-established glioma tumors in nude mice as well as in tissue lysates. In conclusion, our results show that downregulation of cathespin B and uPAR alone and in combination inhibit glioma cell adhesion by downregulating CD151 and its associated signaling molecules in vitro and in vivo. This study may be useful in dissecting the pathways involved in tumor cell adhesion and for the identification of novel target proteins for therapeutic intervention of gliomas. 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 1529. doi:10.1158/1538-7445.AM2011-1529
PTH-047 Evaluation Of Patient Satisfaction Following Percutaneous Endoscopic Gastrostomy (peg) Insertion: Day Case Versus In-patient Model In Uhcw Nhs Trust
Authors: LM Ridings, JM Colby, NE Burch
Journal: Gut (2014)

<h3>Introduction</h3> In patients with head and neck (HandN) cancer, standard practice is to insert a prophylactic gastrostomy tube to optimise nutrition and enable nutrition support during treatment. Although traditionally an inpatient procedure, many are now treated as outpatients, allowing a more time and cost effective service. There is very little data however regarding patient satisfaction with this move to a day case model. <h3>Aim</h3> Having recently introduced a new day case PEG service for HandN cancer patients in UHCW NHS Trust, we wanted to evaluate the service and compare patient satisfaction levels in both in-patient and day case cohorts. <h3>Methods</h3> We selected 20 sequential HandN patients who had undergone a day case PEG procedure since the day case service was introduced in March 2013. For comparison, we identified a further 20 sequential HandN patients who had undergone PEG insertion as an in-patient during the previous 12-months (Oct 2012 to Sep 2013). Deceased patients were excluded. A modified GHAA-9 questionnaire was used to assess patient satisfaction with the procedure <sup>[1]</sup>. This questionnaire was sent out retrospectively, and a pre-paid reply envelope was included with the questionnaire. Patients not responding within 1-month were telephoned to ask if they wished to complete the feedback survey. <h3>Results</h3> Day case patients (n = 20) were aged 40–70 yrs (mean 54); 80% male. In-patients (n = 20) were aged 42–81 yrs (mean 60); 59% male. 75% of the day case PEGs were inserted prior to cancer treatment start, versus 45% of in-patient procedures. Those undergoing in-patient insertions utilised 53 bed-days collectively. No patient from either cohort was admitted within 7 or 30 days. There were no major complications in either group. Patient satisfaction questionnaires were returned by 26 (65%): 11 in-patients (55%) and 15 day case (75%). Mean satisfaction score for day case was 36.3 ± 3.8, whereas mean score for in-patients was 32.7 ± 7.8 (max score = 40). Only 1.7% day case patients identified aspects of their PEG procedure that were fair/poor, compared to 7.9% in-patients. In-patients described higher dissatisfaction relating to time from referral to insertion, and delays waiting for insertion once admitted. <h3>Conclusion</h3> Our results suggest greater overall satisfaction in patients undergoing PEG insertion as a day case, with no increase in complications. Moreover the PEG was undertaken in a more timely fashion with the majority (75%) having their PEG inserted prior to treatment start. 53 patient bed days were saved for just 20 procedures which represent a cost saving to the Trust of approximately £13,992<sup>[2]</sup>. <h3>References</h3> 1 Harewood <i>et al.</i><i>Am J Gast</i> 2003;98:1016–1021 2 www.gov.uk/government/uploads/system/uploads/attachment_data/file/213060/2011-12-reference-costs-publication.pdf <h3>Disclosure of Interest</h3> None Declared.
Abstract B10: A novel mechanism of prostate cancer metastasis through the PDGF D/β-PDGFR axis
Authors: Abdo J. Najy, Allen Saliganan, Daniel Bonfil, Hyeong-Reh C. Kim
Journal: Cancer Research (2009)

Abstract Cancer metastasis is a multi-step process permitting malignant cells to invade into a secondary niche. Prostate cancer has a high prevalence of bone metastasis where 90% of diagnosed cases exhibit metastatic bone lesions. Analysis of these metastatic tissues revealed that PDGFRβ (platelet-growth factor receptor β) is upregulated and activated in 80% of the cases. This receptor was thought to be stimulated by its classical ligand PDGF B. However, within bone metastatic prostate cancer, PDGF B is not detected, suggesting another ligand may exist for PDGFR β. Recently, a new PDGF family member, PDGF D, was identified and shown to bind to and activate PDGFR β. Using Oncomine data analysis and immunohistochemical analysis, we demonstrated upregulation of PDGF D in metastatic prostate cancer. To investigate the role of PDGF D in bone metastasis, we established several prostate cancer cell lines engineered to overexpress PDGF D. We observed an increase in prostate carcinoma cell migration as well as adhesion on osteoblast deposited matrix in response to PDGF D upregulation. Cell surface integrins are known to play a crucial role in cell migration and adhesion. Our studies revealed that PDGF D overexpression modulated α1 and α3 expression to mediate the cancer cell malignant phenotype. In the intratibial metastatic mouse model, PDGF D enhanced prostate cancer tumorigenesis and resulted in osteoblastic lesions. Consistent with our in vivo findings, we found that PDGF D supports osteoblast proliferation and differentiation in vitro. Taken together, we propose that PDGF D contributes to prostate cancer bone metastasis through tumor cell surface integrin modulation and stimulation of stromal components within the bone microenvironment. Citation Information: Cancer Res 2009;69(23 Suppl):B10.
PTU-172 Treatment Outcomes For Barrett’s Oesophagus Related Neoplasia Have Improved Over Time With Changes In Endoscopic Practice: Five Year Experience From The First Five Hundred Patients In The United Kingdom Registry
Authors: RJ Haidry, M Banks, A Gupta, M Butt, G Fullarton, H Smart, J Morris, R Willert, R Narayanasamy, M Rodriguez-Justo, M Novelli, L Lovat
Journal: Gut (2014)

<h3>Introduction</h3> Barrett’s oesophagus (BE) is the recognised pre-cursor to oesophageal adenocarcinoma (OAC). Combined endotherapy with endoscopic mucosal resection (EMR) and Radiofrequency ablation (RFA) have emerged as alternatives to surgery for curative treatment of patients with BE related neoplasia over the past 5 years. <h3>Methods</h3> We examine prospective data from United Kingdom (UK) registry of patients undergoing RFA/EMR for early neoplasia arising in BE since the launch of the registry in 2008. Primary outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at 12 months were assessed over two time periods, between 2008–2010 and from 2011–2013. In addition durability of successful treatment, progression to invasive OAC and changes in endoscopic practices were also analysed between the time periods. Before RFA, visible lesions were removed by EMR. Thereafter patients underwent RFA every 3 monthly and biopsies were taken at 12 months. New lesions appearing during RFA treatment were removed by rescue EMR. This treatment algorithm has remained unchanged over past 5 years. <h3>Results</h3> We report on 510 patients who have completed treatment with 12 month histology over past 5 years. CR-D and CR-IM have improved significantly between the former and later time periods from 77% and 56% to 91% and 82% respectively (p &lt; 0.0001). The use of EMR for visible lesions prior to initiating RFA has also increased from 48% to 60% (p = 0.013). Conversely need for rescue EMR has decreased significantly to 3% over the last two and half years compared to 13% during initial time period (p &lt; 0.0001). Progression to invasive OAC is not significantly different (2.8% in 2011–2013 vs. 4% 2008–2010, p = 0.56). <h3>Conclusion</h3> We report one of the largest series of patients undergoing RFA for BE neoplasia. Clinical outcomes have improved significantly over the past 5 years as endoscopists have more experience with improved lesion recognition, and more attention to resection of all visible lesions before RFA. As a result the requirement for rescue EMR during RFA has reduced. Although rate of progression to OAC is lower in the later part of the registry experience, this is not statistically significant and implies that despite advances in endoscopic imaging and technique the rate of progression remains in the region of 2–4% in these high risk patients. <i>All collaborators of the UK RFA registry are acknowledged for their contributions to this work.</i> <h3>Disclosure of Interest</h3> None Declared.