tbuckley/cabot-search huggingface dataset:
Abstract 4101: Fibroblast growth factor receptor (FGFR) 2 IIIc, is a novel molecular target for suppressing pancreatic cancer cell growth and migration
Authors: Toshiyuki Ishiwata, Yoko Matsuda, Kiyoko Kawahara, Tetsushi Yamamoto, Kiyoshi Teduka, Eiji Uchida, Murray Korc, Zenya Naito
Journal: Cancer Research (2010)

Abstract Background: Fibroblast growth factor receptor (FGFR) isoforms IIIb and IIIc arise as a consequence of alternative splicing of the carboxy-half of the third immunoglobulin (Ig)-like domain, with IIIb isoforms being mainly expressed in epithelial cells and IIIc isoforms expressed mainly in mesenchymal cells. In pancreatic ductal adenocarcinoma (PDAC), the FGFR1 IIIb isoform mediates inhibition of cancer cell proliferation, migration, and invasion, while FGFR1 IIIc mediates cancer cell proliferation. We have previously reported that the FGFR2 IIIb isoform, also known as keratinocyte growth factor receptor/KGFR, is expressed in PDAC, and its expression correlates with VEGF-A expression and venous invasion. Furthermore, there was a significant correlation between co-expression of FGFR2 IIIb and KGF, and a poor therapeutic response. Single nucleotide polymorphisms (SNPs) of the FGFR2 gene are associated with breast and endometrial cancers, and missense mutations or copy number gains of the FGFR2 gene occur in breast and gastric cancers. A class switch of FGFR2IIIb to FGFR2IIIc is reportedly associated with a more-malignant phenotype in prostate and bladder cancers. Accordingly, in the present study we examined the role of FGFR2 IIIc in PDAC. Methods: FGFR2 IIIc expression levels were examined in six pancreatic cancer cell lines using real-time PCR and western blot analyses. Immunohistochemical analysis using anti-FGFR2 IIIc antibodies was performed on 51 pancreatic cancer patients, and FGFR2 IIIc mRNA expression was confirmed by in situ hybridization analysis. FGFR2 IIIc stably transfected KLM-1 cells were prepared and the growth rates in vitro and in vivo were compared with mock cells. The effects of specific anti- FGFR2 IIIc antibodies on the growth and migration of PANC-1 cells were also examined. Results: FGFR2 IIIc was localized in cancer cells in 37 of 51 PDAC samples (73%), and the expression correlated with retroperitoneal invasion. FGFR2 IIIc expression was detected in all six pancreatic cancer cell lines, and the expression level was high in PANC-1 cells and low in KLM-1 cells. The growth rates of FGFR2 IIIc stably transfected KLM-1 cells were higher than those of mock cells in vitro and in the subcutaneous tissue of nude mice, whereas anti-FGFR2 IIIc antibodies inhibited the growth and migration of PANC-1 cells. Conclusion: These findings indicate that FGFR2 IIIc is commonly overexpressed in PDACs, where it promotes cancer cell growth and migration. Thus, FGFR2 IIIc may serve as a novel therapeutic target in PDAC. 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 4101.
Abstract 3167: Deciphering the genomic heterogeneity in malignant melanoma by genomic profiling of clonal tumor populations.
Authors: Thomas Lorber, Tanja Dietsche, Joël Gsponer, Alexander Rufle, Michael Barret, Lukas Sommer, Katharina Glatz, Christian Ruiz, Lukas Bubendorf
Journal: Cancer Research (2013)

Abstract 1) Background Melanoma is a heterogeneous disease and even though consistent genetic patterns among different subtypes have been revealed, clinical trials have failed to significantly improve survival. However, most of the genomic studies do not take into consideration the underlying genomic heterogeneity. In this study, we used genomic profiling of sorted clonal tumor populations in order to investigate the genomic heterogeneity and the clonal evolution in malignant melanoma. 2) Methods Multiple biopsies from melanoma patients were subjected to flow-sorting based on DNA content. The tumor specific marker SOX10 was used as an additional parameter to exclude contribution of normal tissue. Resulting clonal tumor populations were genomically characterized by usage of high resolution aCGH. A TMA was constructed for validation of the findings. 3) Results DNA content based flow sorting of small human melanoma biopsies was successfully implemented and revealed the co-existence of distinct clonal populations (diploid as well as aneuploid) within these samples. The use of the additional marker SOX10 allowed us to uncover and sort pure diploid tumor populations from diploid fractions admixed with normal cells. These findings were confirmed by aCGH. 4) Conclusions Human malignant melanoma is composed of different clonal populations with population-specific genomic aberrations. The use of SOX10 allowed unraveling of pure tumor populations within the diploid peaks, which would have been obscured by the use of DNA content alone. Further genomic analyses of these sorted clonal tumor populations are fundamental for the understanding of the genomic heterogeneity and its potential impact on metastasis and therapy response in malignant melanoma. Citation Format: Thomas Lorber, Tanja Dietsche, Joël Gsponer, Alexander Rufle, Michael Barret, Lukas Sommer, Katharina Glatz, Christian Ruiz, Lukas Bubendorf. Deciphering the genomic heterogeneity in malignant melanoma by genomic profiling of clonal tumor populations. [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 3167. doi:10.1158/1538-7445.AM2013-3167
WHICH REPERFUSION THERAPY IS BETTER IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION WITHIN 3 HOURS OF THE ONSET OF SYMPTOMS? FROM KOREA ACUTE MYOCARDIAL INFARCTION REGISTRY (KAMIR)
Authors: Sang Yeub Lee, Min Kim, Ju-Hee Lee, Sang Min Kim, Jang-Whan Bae, Kyung-Kuk Hwang, Dong-Woon Kim, Myeong-Chan Cho
Journal: Journal of the American College of Cardiology (2014)
A2.30 Common variants on XQ28 conferring risk for rheumatoid arthritis in Tunisian and French populations
Authors: O Khalifa, N Balandraud, N Lambert, M Martin, A Senechal, D Genevieve, C Picard, G Lefranc, B M'madi, E Pardoux, T Mahjoub, F Apparailly
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by a chronic destructive inflammation in synovial joints that is about three times more common in women than in men. Investigations into RA genetics have identified several susceptibility loci. Among these, multiple single-nucleotide polymorphisms (SNPs) at an X chromosome locus harbouring IRAK1 and TMEM187 have previously been shown to be associated with susceptibility to RA in Greek, Chinese, and Korean populations. The present study aimed at investigating the association between critical polymorphisms in Xq28, from rs1059702 (C/T) and rs1059703 (C/T) in IRAK1 through rs13397 (A/G) in TMEM187 with risk for RA in two novel populations: Tunisian and French. In addition, the present study aimed at comparing the differences in genotypic distribution in both populations. <h3>Material and methods</h3> A case–control study of 493 RA patients and 507 healthy controls age and sex matched was conducted in both Tunisian and French. All RA patients were ACPA positive. DNA was isolated from total blood using standard phenol chloroform method. All subjects were genotyped for the three polymorphisms using a direct sequencing with the BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems). The genotype distribution, haplotype analysis, and the linkage disequilibrium (LD) were analysed using the Bayesian method, and PLINK 1.07 and Haploview 4.2 softwares, respectively. <h3>Results</h3> The three polymorphisms respected Hardy-Weinberg equilibrium, both in Tunisian and French populations. The associations between both IRAK1 rs1059703 and TMEM187 rs13397 polymorphisms and RA susceptibility were found (p &lt; 0.001 and p = 0.004, respectively) in women, but not in men. The genotype CC of rs1059703 represented a protective factor for RA (OR = 0.29, 95% CI = 0.17–0.50). Linkage disequilibrium between the 3 SNPs was weak (D = 8–16). There were 5 haplotypes with a frequency higher than 5%, constructed from the Xq28 polymorphisms. Haplotype GTC was associated with decreased risk for RA (p = 0.00075), whereas the haplotype ACC was significantly associated with increased risk for RA (p &lt; 0.001). Correlation analyses with clinical and biological parameters are in progress. <h3>Conclusion</h3> Our case-control study replicated for the first time the association of the Xq28 chromosomal region with RA risk in Tunisian and French populations, and suggested that RA susceptibility is associated with rs1059703 polymorphism in IRAK1 and rs13397 polymorphism in TMEM187 only for female patients. These data further support the involvement of X chromosome in RA susceptibility.
AB0490 Inequities in access to biologic dmards for patients with rheumatoid arthritis across 46 european countries:
Authors: P. Putrik, S. Ramiro, M. Pavlova, T. Kvien, T. Uhlig, A. Boonen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the treatment of patients with RA, EULAR recommends to initiate biologic DMARDs after failing synthetic DMARDs. However, biologics are costly, and it is not known to what extent limited access to these drugs can hamper implementation of the EULAR recommendations. A poor ability to adhere to these recommendations might contribute to health disparities previously seen in RA patients across countries [1]. <h3>Objectives</h3> To explore access to biologics across Europe along the three dimensions of access: availability, affordability and acceptability. <h3>Methods</h3> Number of reimbursed drugs, prices of biologics, and data on cultural acceptability of biologics were collected by questionnaire sent to one representative rheumatologist in 48 countries of the European Region. To ensure comparability, national prices were converted into international dollars ($) to adjust for the countries’ purchasing power parity (PPP). Data on socio-economic welfare (gross domestic product (GDP), health expenditure, median income and minimum wage) were retrieved from web-based sources. Data on RA health status (DAS28, HAQ, TJC, SJC, ESR) were retrieved from the literature (QUEST RA) [1]. Indicators of access in each axis were correlated with indicators of welfare and RA health status using Spearman correlations. <h3>Results</h3> In total, 46 countries (response rate 96%) provided data. With respect to <i>availability</i>, in 10 countries no biologics were reimbursed, while 5 or more were reimbursed in 26 countries. With respect to <i>affordability</i>, annual average prices per patient of all available biologics varied from €10,189 (Belarus) to €128;28,108 (Ukraine), corresponding to a price ratio of 2.8. However, after adjusting the prices for PPPs, prices ranged from int.$14,446 to int.$92,074 (price ratio 6.4). Cultural <i>acceptability</i> ranged from 0 to 10 (10 poorest acceptability). Number of reimbursed drugs showed moderate to very strong positive correlation with the economic welfare and inverse correlation with the RA health status. While national prices seemed to be slightly lower in low income countries, after adjusting to PPP prices were strongly inversely correlated with economic welfare and positively with RA health. The sum-score of the acceptability was negatively associated with the economic indicators, and positively with the RA health status (table). <h3>Conclusions</h3> European countries with lower socio-economic status seem to have less access to biologics in terms of lower availability, affordability and acceptability (more barriers), while health of RA patients is worse. This implies inequity in access for innovative care disfavoring patients in poorer societies. <h3>References</h3> Sokka T et al. Ann Rheum Dis 2009;68,1666-72. <h3>Disclosure of Interest</h3> None Declared
Abstract 5098: Participation of Crk-associated substrate (CAS) in human pancreatic cancer cell migration, invasion and metastatic processes
Authors: Hirotaka Okamoto, Hideki Fujii
Journal: Cancer Research (2015)

Abstract Introduction; Crk-associated substrate (CAS, p130Cas) is a major tyrosine phosphorylated protein in cells transformed by v-crk and v-src oncogenes. In non-transformed cells, CAS localizes to focal adhesions and undergoes tyrosine phosphorylation in response to integrin-mediated signaling. In the current study, we evaluate the role of CAS in cell migration, invasion and metastatic processes in human pancreatic cancer cells. Materials and Methods; We investigated that CAS tyrosine kinase activity and tumor cell migration, invasion to endothelial cell monolayer in human pancreatic cancer cell lines, in vitro. CAS tyrosine phosphorylation were measured by immunoblotting and immunoprecipitation using anti-CAS monoclonal antibody and anti-phosphotyrosine antibody. Tumor cell migration was measured with Matrigel-coated modified-Boyden's chamber assay. Tumor cell invasion to endothelial cell monolayer was assayed with a co-culture invasion bioassay. Results; Tyrosine phosphorylation of CAS in human pancreatic cancer cells were induced during tumor cell migration and invasion. Phosphorylated tyrosine level of CAS was coincident with invasion capability in human pancreatic cancer cell lines, PSN-1, MiaPacaII, Panc1, despite of similar protein expression level. Protein tyrosine kinase inhibitor, Herbimycin A, had an inhibitory effect on migration and invasion as well as CAS tyrosine phosphorylation in tumor cells. Conclusion; These results indicated that CAS tyrosine phosphorylation in pancreatic tumor cells was correlated with invasive capability, suggesting a pivotal role of CAS in migration, invasion and metastatic processes. Citation Format: Hirotaka Okamoto, Hideki Fujii. Participation of Crk-associated substrate (CAS) in human pancreatic cancer cell migration, invasion and metastatic processes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5098. doi:10.1158/1538-7445.AM2015-5098
IMPACT AND UTILITY OF POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF INFLAMMATORY ACTIVITY IN TAKAYASU's ARTERITIS
Authors: Luis Alfonso Marroquin Donday, Erick Alexanderson Rosas, Maria E. Soto-Lopez, Jose E. Telich-Tarriba, Alejandro Ricalde Alcocer, Aloha Meave, Hugo G. Rodriguez-Zanella, Fernando Inarra-Talboy, Antonio Jordan-Rios
Journal: Journal of the American College of Cardiology (2016)
Nasal Carriage as a Source of<i>Staphylococcus aureus</i>Bacteremia
Authors: Christof von Eiff, Karsten Becker, Konstanze Machka, Holger Stammer, Georg Peters
Journal: New England Journal of Medicine (2001)

The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patient's own flora.
VASCULAR INFLAMMATION IN THE AORTA IS RELATED TO CORONARY PLAQUE BURDEN IN PSORIASIS
Authors: Taufiq Salahuddin, Balaji Natarajan, Mariana Selwaness, Ahmed Sadek, Martin Playford, Julia Doveikis, Navya Nanda, David Bluemke, Nehal Mehta
Journal: Journal of the American College of Cardiology (2015)
PWE-015 Pudendal Nerve Stimulation for Faecal Incontinence
Authors: G Thomas, A George, T Dudding, R J Nicholls, C Vaizey
Journal: Gut (2013)

<h3>Introduction</h3> Sacral nerve stimulation (SNS) is an established treatment for faecal incontinence (FI). However, only 50–60% of patients will have a good response to SNS. Further treatment is difficult for those who do not respond to SNS. Pudendal nerve stimulation (PNS) was first reported for FI in 2005. Since then only one small study has further reported its use for FI. We aimed to assess PNS for FI in those who have failed to improve with SNS. <h3>Methods</h3> Recruited patients underwent test PNS. Those who experienced a ≥ 50% reduction in frequency of FI episodes underwent permanent PNS. The primary outcome measure was the change in frequency of FI episodes. Further outcome measures were further bowel diary data, St Marks FI Score, Rockwood FI QOL Score, SF-36 QOL Score and anorectal physiological changes. <h3>Results</h3> Ten patients underwent test PNS. Five experienced a ≥ 50% improvement in frequency of FI episodes, and underwent permanent stimulation. One withdrew from the study at six months. At median follow up of 24 (3–36) months, the median frequency of FI improved from 5 (18.25) to 2.5 (3) per week; p = 0.043. Three maintained a ≥ 50% improvement in soiling. There was a significant improvement in the St Marks FI score, 19 (6) to 16 (4.5); p = 0.042. There were no significant changes in the ability to defer defecation or in quality of life measures. <h3>Conclusion</h3> PNS may be an effective treatment for FI for those who have failed to improve with SNS <h3>Disclosure of Interest</h3> None Declared.
Comparison Between Cortical Distribution of I-123 Iomazenil and Tc-99m HMPAO in Patients With Alzheimer's Disease Using SPECT
Authors: ANDREA VARRONE, ANDREA SORICELLI, ALFREDO POSTIGLIONE, MARCO SALVATORE
Journal: Clinical Nuclear Medicine (1999)

Purpose: To compare brain perfusion and synaptic density in Alzheimer's disease assessed using I-123 iomazenil SPECT with brain perfusion assessed using Tc-99m HMPAO SPECT. Materials and Methods: Early and delayed I-123 iomazenil SPECT images acquired 20 and 180 minutes after injection were compared with Tc-99m HMPAO SPECT studies acquired 15 to 20 minutes after injection in five patients with Alzheimer's disease. Results: Visual analysis of I-123 iomazenil images showed more severe (n = 4) and extensive (n = 3) defects than did Tc-99m HMPAO. Semiquantitative analysis was performed by normalizing the uptake of Tc-99m HMPAO and I-123 iomazenil in individual brain regions in the cerebellum and expressing these values as a ratio of the occipital regions. The analysis of brain regional ratios in Tc-99m HMPAO studies showed a low but significant correlation with ratios of delayed (r = 0.325, P < 0.05) images in the I-123 iomazenil studies. Furthermore, when compared with Tc-99m HMPAO, early (P < 0.01) and delayed mean ratios (P < 0.05) were significantly less in the frontal regions; early mean ratios were significantly less in the temporal regions (P < 0.05), and delayed (P < 0.05) mean ratios were significantly less in the parietal regions. Conclusions: Tc-99m HMPAO images were better correlated with I-123 iomazenil images, indicating cortical synaptic density (delayed images). I-123 iomazenil SPECT in patients with Alzheimer's disease provided more sensitive information than Tc-99m HMPAO, allowing evaluation of brain perfusion and synaptic density.
P664The anti-cancer drug Artemisinin protects against myocardial ischaemia-reperfusion injury via the recruitment of PI3K-AKT-p70S6k cell survival pathway.
Authors: M Babba, O Janneh, HL Maddock, A Hussain
Journal: Cardiovascular Research (2014)

Introduction: Recent studies have emphasised an important role for Artemisinin as an effective and potent anticancer cancer drug, with significantly less adverse effects in comparison to traditional chemotherapeutic agents. Most of the widely used cancer treatments are limited in use due to their dose dependent cardiotoxicity. Artemisinin has been found to be cardioprotective against myocardial ischaemia-reperfusion (IR) injury and and the aim of this study was to determine whether this protection involves recruitment of the PI3K-AKT-p70S6k-BAD cell survival pathway.
CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas
Authors: Mélanie Juilland, Montserrat Gonzalez, Tabea Erdmann, Yara Banz, Zala Jevnikar, Stephan Hailfinger, Alexandar Tzankov, Michael Grau, Georg Lenz, Urban Novak, Margot Thome
Journal: Blood (2016)
Abstract 5070: Identification of DKK2 as a candidate gene that facilitates tumor reoccurrence upon MYC inactivation
Authors: Stacey J. Adam, Liwen Xu, Asa Karlsson, Dean W. Felsher
Journal: Cancer Research (2010)

Abstract The MYC oncogene is prevalently activated in human hematopoietic cancers, especially T-cell acute lymphoblastic leukemia (T-ALL) and Burkitt's lymphoma. Utilizing the Tet-system to generate a conditional model of MYC-induced T-ALL, our laboratory has demonstrated that MYC inactivation induces sustained tumor regression. However, after prolonged MYC inactivation some tumors eventually escape MYC dependence and reoccur. Our results support the hypothesis that tumors escape complete dependence on MYC by acquiring additional genetic or epigenetic changes, leading to altered gene function that may substitute totally or partially for MYC. Specifically, using Spectral Karyotypic Analysis (SKY) and array Comparative Genomic Hybridization (aCGH) we have obtained evidence that the Wnt/ β-catenin related gene, DKK2, may play a role in the mechanism by which tumors escape dependence upon MYC. We demonstrate DKK2 facilitates the ability of MYC-driven lymphomas to reoccur even in the presence of sustained oncogene inactivation. We have evidence that cellular context may play a pivotal role in DKK2's ability to aid tumor reoccurrence. Our data also suggest a mechanism by which DKK2 functions, alone or in conjunction with other Wnt/β-catenin pathway members, to maintain tumorigenesis or facilitate tumor reoccurrence in murine and human MYC-driven tumors in the presence of sustained MYC inactivation. Discovering that DKK2 overexpression may aid in lymphoma reoccurrence is a highly novel finding as DKK2 has never been implicated as an oncogene in lymphoma. Results presented here provide critical new insights into the mechanism by which MYC-driven cancers may obtain chemotherapeutic resistance and reoccur even in the presence of sustained drug therapy. 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 5070.
Folic Acid Therapy and Spinal-Cord Degeneration in Pernicious Anemia
Authors: John N. Baldwin, Donald J. Dalessio
Journal: New England Journal of Medicine (1961)

SINCE the classic description of the features of pernicious anemia by Addison in 1855, considerable progress has been made in diagnosis and therapy. The Schilling test has made accurate diagnosis possible, and the availability of vitamin B12 for parenteral use has rendered treatment easy and convenient. Nonetheless, a significant number of cases have been reported in the medical literature in which treatment with folic acid, either intentionally or inadvertently, has so altered the natural history of the disease as to obscure the diagnosis, at least as it is made on a clinical basis. Yet folic acid remains an ingredient . . .