tbuckley/cabot-search huggingface dataset:
AB0506 Longitudinal change of the titer of anti-mda5 antibody and association with prognosis in dermatomyositis with interstitial pneumonia
Authors: R. Nakashima, R. Fujiwara, Y. Hosono, Y. Imura, N. Yukawa, H. Yoshifuji, K. Ohmura, T. Fujii, T. Mimori
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-MDA5 antibody is one of dermatomyositis-specific autoantibodies and its characteristic clinical meanings have been reported. It associates with clinically amyopathic dermatomyositis (CADM), hyperferritinemia, acute or subacute interstitial pneumonia (A/SIP) and poor prognosis especially in Asian patients. Recently, an ELISA system which can detect anti-MDA5 antibody was established and some reported that its titer seems to be associated with disease activity. However, it has not been yet clear how anti-MDA5 titer changes during long term or whether it associates with other clinical markers. <h3>Objectives</h3> We followed anti-MDA5 titer closely and longitudinal clinical course. <h3>Methods</h3> We prepared recombinant His-MDA5 protein (520a.a. of c-terminus) expressed in <i>Eschericha coli</i>. After confirming antigenic activity of the recombinant protein using immunoblotting, we made an ELISA system. Efficiency was confirmed using the sera from 31 Japanese DM patients (23 anti-MDA5-positive and 8 anti-MDA5 negative patients) and 25 healthy controls. The presence of Anti-MDA5 was confirmed by immunoprecipitation using <sup>35</sup>S-methionine-labeled HeLa cells. Sera from 14 anti-MDA5-positive patients were collected during disease course (range: 3-133 weeks). The titer at 0, 4, 8, 12 weeks of the disease course were compared. The association between the titer and several serum markers (ferritin, KL-6, IL-6 and M-CSF) were assessed. <h3>Results</h3> The cut-off point was defined at 56.7 U on the basis of mean+4SD of healthy controls and both sensitivity and specificity of the ELISA were 100%. In anti-MDA5-positive patients, the antibody titer tended to be higher in the deceased (n=7) than in the alive (n=11) but there was no statistical significance (p=0.057). In the alive patients, the anti-MDA5 titer gradually decreased especially 8 weeks after the desease onset. After 11 weeks, the antibody titer decreased under the cut-off point in some patients and after 52 weeks, the titer went down to the mean level of the healthy control in 4 of 5 patients. There was no association between anti-MDA5 titer and serum ferritin or IL-6 levels before treatment but anti-MDA5 titer was correlated with serum ferritin in 3 of 6 patients at longitudinal study in each disease course. In one patient, KL-6 was also associated with the antibody titer. IL-6 and M-CSF were not associated with the titer during the disease course. <h3>Conclusions</h3> The ELISA system for anti-MDA5 antibody is useful not only in diagnosis of DM but also in estimating prognosis and following disease activity during longitudinal time course in each patients. <h3>References</h3> Sato S, et al. Mod Rheumatol 2012 May 29 [ahead of print] Gono T, et al. Rheumatology (Oxford). 2012 Sep;51(9):1563-70. <h3>Disclosure of Interest</h3> None Declared
Abstract 286: Expression and role of fibroblast growth factor receptor2 IIIc in human uterine cervical intraepithelial neoplasia (CIN) and invasive cervical cancer
Authors: Rieko Kawase, Toshiyuki Ishiwata, Yoko Matsuda, Munehiko Onda, Kiyoshi Teduka, Kiyoko Kawahara, Toshiyuki Takeshita, Zenya Naito
Journal: Cancer Research (2010)

Abstract Fibroblast growth factor receptors (FGFR) FGFR1 through FGFR3 possess IIIb and IIIc isoforms as the result of alternative splicing of the immunoglobulin-like domain. The IIIb isoforms are mainly expressed in normal epithelial cells, and IIIc isoforms are expressed in mesenchymal cells. Single nucleotide polymorphisms (SNPs) of the FGFR2 gene are associated with endometrial cancer, and missense mutations or copy number gains of the FGFR2 gene occur in breast cancer. In uterine cervical cancer, FGFR2 IIIb, also known as keratinocyte growth factor receptor (KGFR), was reported to be highly expressed in squamous cell carcinoma (SCC), which accounts for 90% of all cervical cancer patients. However, there has been no report on the expression and roles of FGFR2 IIIc in cervical cancer. In the present study, we determined the expression and roles of FGFR2 IIIc in CIN and cervical SCC. In noncancerous cervical tissues, FGFR2 IIIc immunoreactivity was either not present or very faintly localized in squamous epithelial cells. In CINs 1 and 2, FGFR2 IIIc was localized at the basal to lower two-thirds of squamous epithelium, whereas FGFR2 IIIc was strongly expressed in most of the squamous epithelium, except for the superficial layer in CIN 3. FGFR2 IIIc protein was detected in keratinizing and non-keratinizing types of SCC in all cervical cancer patients examined (8 and 21 cases, respectively). In situ hybridization (ISH) analysis using an FGFR2 IIIc-specific antisense RNA probe showed that the expression patterns of FGFR2 IIIc mRNA are similar to those of FGFR2 IIIc protein in noncancerous and CIN tissues. In addition, FGFR2 IIIc mRNA was strongly expressed in the invasive fronts of cancer cell nests in cancer tissues. Moreover, full-length FGFR2 IIIc cDNA, subcloned to pIRES2-EGFP vector, was stably transfected into CaSki cells, which are derived from a well-differentiated type of SCC. The growth rates of the FGFR2 IIIc-transfected CaSki cells were higher than those of mock cells in vitro. Cell migration assays did not show any differences between FGFR2 IIIc-transfected CaSki cells and mock cells. To assess the effect of FGFR2 IIIc expression on tumorigenicity, the CaSki cells were injected into nude mice. The FGFR2 IIIc-transfected CaSki cells tended to form larger subcutaneous tumors than mock cells in nude mice. These findings suggest that FGFR2 IIIc plays important roles in the carcinogenesis and proliferation of cervical cancer cells. FGFR2 IIIc is considered to be a novel therapeutic target for inhibiting the growth of CIN and cervical 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 286.
Increased 18F-FDG Uptake of Widespread Endometriosis Mimicking Ovarian Malignancy
Authors: Jingjie Ge, Chuantao Zuo, Yihui Guan, Xuyin Zhang
Journal: Clinical Nuclear Medicine (2014)

Endometriosis is a benign disease characterized by the implantation of functional endometrial tissue in ectopic locations. We present a case of a 42-year-old woman with widespread endometriosis that mimicked ovarian malignancy on FDG PET/CT. Increased FDG uptake was observed not only in the right ovary, but also in the liver capsule, perihepatic nodules, greater omentum, and the mesentery. This case indicates that widespread endometriosis may be a cause of multiple FDG uptakes in women of reproductive age and should always be kept in mind in the differential diagnoses of suspicious malignancy.
AB0573 Demographic and Clinical Features of Behcet's Disease (BD) in Two Cohort Patients from North Caucasus
Authors: F. Izmailova, Z. Alekberova, D. Ishchenko, L. Denisov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Behcet9s disease (BD) is chronic disorders characterized by multisystem manifestation. Several studies showed regional differences in BD presentation. The data about BD on Caucasus through passed Silk Road is not enough. <h3>Objectives</h3> The aim of our study is to compare BD in two ethnic cohorts from North Caucasus. <h3>Methods</h3> A total of 111 consecutive BD patients (82 male and 29 female) seen in the Research Institute of Rheumatology RAMS (Moscow). All of them fulfilled the classification criteria ISGBD [1]. <h3>Results</h3> The patients were divided into two groups: I – 85 patients from Dagestan, II – 26 patients from Chechnya. The frequency of mostclinical manifestations of BD (%) was similar in comparable groups. Percentage of oral aphthae, genital ulcer, skin and eye disease – 96, 79, 75, 53 in I group and 100, 85, 81, 50 – in II group. Number of patients with HLA B51 positivity and familyaggregation observed more offen in Chechenian cogort (81% and 27% vs 69% and 20%) The frequency of ocular vascular disease and among the inhabitants of Dagestan appeared to be significantly higher among men. When comparing manifestations of BD in men and women of the Chechen population, significant differences were obtained only for cutaneous manifestations (p&lt;0,04). <h3>Conclusions</h3> Our results demonstrate no difference between most manifestations of BD in two ethnic populations. In both groups of patients there was male predominance. <h3>References</h3> International Study group for Behcet9s disease: Criteria for Behcet9s Lancet, 1990, 335, 1078-1080 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2448
Abstract LB-300: The role of WNT7B in prostate cancer bone metastasis
Authors: Dali Zheng, Tianhua Zhou, Keith F. Decker, Kaidi Wang, Li Jia
Journal: Cancer Research (2012)

Abstract Prostate cancer is the most common cancer for men in the US. It is well known that the androgen receptor (AR), a master transcription factor in prostate, plays a critical role in all stages of prostate cancer. There has been a dedicated interest in identification of downstream AR target genes responsible for prostate cancer growth and progression. Using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq), we identified WNT7B as a direct AR target gene in both androgen-dependent LNCaP and androgen-independent C4-2B cells. Knockdown of WNT7B by RNA interference inhibits the growth of LNCaP and C42B cells, accompanied by a corresponding increase in apoptosis as determined by Caspase-3 and -7 activities. Overexpression of WNT7B promotes the growth of C4-2B cells in the absence of androgen. One of the major challenges in prostate cancer research is the propensity for bone metastasis, which displays characteristic osteoblastic lesions. Since WNT7B plays an important role in bone formation, we asked whether prostate cancer-produced WNT7B induces osteoblast differentiation using an in vitro model of the murine osteoblast precursor ST2 cell line. We found that in a co-culture system, overexpression of WNT7B in LNCaP and C42B cells induces osteoblastic differentiation of ST2 cells, as indicated by increased alkaline phosphatase production, bone sialoprotein (an early marker for osteoblast differentiation) expression, and mineralization. On the other hand, knockdown of WNT7B in prostate cancer cells inhibits the differentiation of ST2 cells. These results indicate that WNT7B can stimulate the growth of prostate cancer cells as an autocrine agent and induce osteoblastic differentiation in bone metastases as a paracrine agent. WNT7B may be a potential therapeutic target for prostate cancer bone metastasis. 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 LB-300. doi:1538-7445.AM2012-LB-300
Abstract 2939: Chk1 inhibition and Wee1 inhibition combine synergistically to inhibit cellular proliferation
Authors: Kurtis D. Davies, Francis Sullivan, Ira von Carlowitz, Yvan Le Huerou, Eli Wallace, Richard D. Woessner, Stefan Gross
Journal: Cancer Research (2011)

Abstract Inhibition of the checkpoint kinase Chk1, both as a monotherapy and in combination with DNA damaging cytotoxics, is a promising therapeutic strategy for human cancer. However, much remains to be learned in regard to the patient populations that will respond best to a Chk1 inhibitor and the optimal therapeutics to combine with a Chk1 inhibitor. In an effort to discover sensitizing mutations and novel combination strategies for Chk1 inhibition, we performed a synthetic lethality siRNA screen with the selective Chk1 inhibitor Chk1-A. This screen employed a custom made library of siRNAs against 197 genes (3 siRNAs per gene), most of which are involved in cell-cycle control or DNA damage repair. One of the most prominent and consistent hits across runs of the screen performed in PC3, LNCaP, and A549 cell lines was Wee1 kinase. MK-1775 is a small molecule inhibitor of Wee1 that is currently in early stage clinical trials. In confirmation of the results obtained from the siRNA screen, we found that Chk1-A and MK-1775 synergistically inhibited proliferation in multiple cell types. The combination of the two molecules resulted in up to a 5-fold enhancement of anti-proliferative activity compared to what would be expected from pure additivity. This anti-proliferative synergy correlated with a synergistic induction of apoptosis. We explored the mechanism of the impressive synergy by examining the cellular and biochemical effects of the Chk1-A and MK-1775 combination. We found that co-treatment with the two inhibitors resulted in dramatic decreases in inhibitory phosphorylation of cyclin-dependent kinases 1 and 2, increases in DNA damage, and the collapse of DNA replication. In conclusion, the combination of a Chk1 inhibitor and a Wee1 inhibitor may be an effective treatment strategy for cancer. 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 2939. doi:10.1158/1538-7445.AM2011-2939
New Scrutiny of Outpatient Therapy With I-131
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2011)

Recently, there has been a Congressional examination of the safety to the public when outpatients are treated with I-131. The regulations regarding this procedure are being scrutinized to make sure that public safety is being protected. An evaluation of the data indicates that when Nuclear Regulatory Commission regulations are properly followed, the use of I-131 therapy is safe for the community. Furthermore, doing these procedures as an outpatient saves money and is more convenient for the patient. However, physicians also recognize that a small minority of patients who need I-131 treatment should be treated in the hospital.
858 COULD PEG-INTERFERON AND RIBAVIRIN BE EFFECTIVE AND SAFE IN THALASSEMIC PATIENTS WITH CHRONIC HEPATITIS C?
Authors: S. Madonia, R. Barone, G. Restivo Pantalone, E. Sinagra, G. Perricone, M.C. Renda, A. Piazza, A. Maggio, M. Cottone
Journal: Journal of Hepatology (2013)
Marketing of e-cigarettes should follow the rules laid down for tobacco advertising
Authors: P. M. English
Journal: BMJ (2014)

We studied the risk of hypersensitivity pneumonitis and other interstitial lung diseases (ILDs) among pigeon breeders. This is a retrospective follow-up study from 1980 to 2013 of 6920 pigeon breeders identified in the records of the Danish Racing Pigeon Association. They were compared with 276 800 individually matched referents randomly drawn from the Danish population. Hospital based diagnoses of hypersensitivity pneumonitis and other ILDs were identified in the National Patient Registry 1977–2013. Stratified Cox regression analyses estimated the hazard ratios (HR) of hypersensitivity pneumonitis and other ILDs adjusted for occupation, residence and redeemed prescription of medication with ILDs as a possible side-effect. Subjects were censored at death, emigration or a diagnosis of connective tissue disease. The overall incidence rate of ILD was 77.4 per 100 000 person-years among the pigeon breeders and 50.0 among the referents. This difference corresponded to an adjusted HR of 1.56 (95% CI 1.26–1.94). The adjusted HRs of hypersensitivity pneumonitis and other ILDs for pigeon breeders were 14.36 (95% CI 8.10–25.44) and 1.33 (95% CI 1.05–1.69), respectively. This study shows an increased risk of ILD among pigeon breeders compared with the referent population. Protective measures are recommended even though ILD leading to hospital contact remains rare among pigeon breeders.
Abstract 5098: Novel characteristic proteins of large cell neuroendocrine carcinoma of lung
Authors: Masaharu Nomura, Tetsuya Fukuda, Takeshi Kawamura, Hiromasa Tojo, Sayaka Mikami, Makoto Kihara, Yasuhiko Bando, Tatsuo Ohira, Masahiro Tsuboi, Harubumi Kato, Adi F. Gazdar, Gyorgy Marko Varga, Toshihide Nishimura, Norihiko Ikeda
Journal: Cancer Research (2011)

Abstract Large cell neuroendocrine carcinoma (LCNEC) is a subtype of large cell carcinoma (LCC), which has a neuroendocrine feature like small cell lung carcinoma (SCLC). We applied a novel emerging proteomic method using tissues to identify characteristic proteins of LCNEC. Proteins from cancer cells, which collected from formalin fixed paraffin-embedded (FFPE) tissues by laser microdissection were extracted and subjected to liquid chromatography / mass spectrometry. Proteins identified by database search were semi-quantified and subjected further to statistical evaluation. We identified three characteristic proteins of LCNEC, aldehyde dehydrogenase 1 family, member A1 (AL1A1), aldo-keto reductase family 1, member C1 (AK1C1) and C3 (AK1C3) that have been considered as some of cancer stem cell markers. Immunohistochemical verification showed those proteins correlated well with the frequency of immunopositive cells with AL1A1 the greatest. These results suggest that candidate biomarkers of LCNEC are related to cancer stem cells, consistent with its undifferentiated and aggressive nature. 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 5098. doi:10.1158/1538-7445.AM2011-5098
CONTEMPORARY SINGLE-STAGE TETRALOGY OF FALLOT REPAIR: EXCELLENT SURVIVAL BUT PHYSICAL OR NEURODEVELOPMENTAL COMPROMISE IN ONE FIFTH
Authors: Eric Pham-Hung, An Duong, Alexandra Page, Michael Gritti, Sara Hussain, Travis Wilder, Mike Seed, Steven Miller, Glen Van Arsdell, Edward Hickey
Journal: Journal of the American College of Cardiology (2015)
O3.05 * CHEMOTHERAPY INDUCED PERIPHERAL NEUROTOXICITY (CIPN): THE IMPACT OF SENSORY ATAXIA ON PATIENT REPORTED ASSESSMENT OF MOTOR IMPAIRMENT
Authors: P. Alberti, C.-P. Group
Journal: Neuro-Oncology (2014)

INTRODUCTION: we present a secondary analysis of the data set obtained in the previously published CI-PeriNomS study, aimed at standardizing outcome measures in Chemotherapy Induced Peripheral Neurotoxicity (CIPN). In this analysis we focus on sensory ataxia in order to assess if its occurrence, even in absence of a relevant motor impairment, can be reported by patients with descriptions which might be misleading for the treating physician (e.g. complaining of difficulty in manipulation). METHODS: subjects affected with stable CIPN were enrolled in the CI-PeriNomS study and were neurologically assessed with different outcome measure tools while at the same time they filled several Patient Reported Outcome Measures (PROs). For the purpose of the present analysis, neuropathy evaluation was scored using the clinical version of the Total Neuropathy Score (TNSc®) using the items addressing motor symptoms and impairment in vibration sensibility and strength. Appropriated questions were selected for comparison with PROs among the original data set of questions used to create the Rasch built specific questionnaire, with a focus on those referring to manipulation and gait unbalance/postural instability. Correlations among variables were obtained through Spearman correlation. RESULTS: two hundred eighty one patients were available for the analysis; 77% of them had no motor impairment both in hands and feet at the TNSc® strength assessment. Nevertheless, 52% of subjects reported difficulty in manipulating objects and 53% difficulty in controlling distal parts of lower limbs. Conversely, vibration threshold was impaired in 70% in lower limbs and in 47% in upper limbs. Significant correlation was found between vibration threshold impairment in upper limbs and level of discomfort reported when asking patients about object manipulation, in particular when asking on “buttoning a shirt” (p < 0.001) and “zipping/unzipping trousers” (p < 0.001). DISCUSSION AND CONCLUSION: sensory ataxia is an important issue in CIPN population and it should be properly assessed and estimated, while frequently it can be misdiagnosed as motor impairment if a careful neurological examination is not performed. Vibration threshold might be a useful to suggest sensory ataxia presence due to reduced sensory perception. Recognition of sensory ataxia is a key issue since this condition can benefit from physical therapy.
A2.27 Affinity measurements of anti-citrullinated protein/peptide antibodies in sera of rheumatoid arthritis patients by applying biosensor analysis
Authors: E Szarka, K Huber, A Magyar, A Iliás, P Aradi, T Gáti, B Rojkovich, G Nagy, F Hudecz, G Sármay
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Anti-citrullinated peptide/protein antibodies (ACPA) have diagnostic significance and a pathological role in rheumatoid arthritis (RA). Multiple specificities of ACPA have been described, targeting various proteins such as filaggrin, fibrin, vimentin, collagen, enolase and some citrullinated peptides of Epstein-Barr virus nuclear antigen (EBNA) as well. Specificities as well as affinities of ACPA may influence its ability to trigger inflammatory cytokine production, modifying local and systemic inflammation in patients. Therefore we compared binding affinities of serum samples from 60 RA patients to citrullinated 19mer filaggrin peptide. <h3>Materials and methods</h3> The peptide specific IgG was affinity purified from sera of RA patients on insolubilized citrullinated peptides derived from filaggrin, fibrin, collagen, and vimentin. Peptide specific IgG concentrations in sera were calculated by ELISA, using a calibration curve prepared from the affinity purified IgG. Binding affinities of IgG and serum samples were tested on citrullinated peptide covalently coupled to the surface of ProteOn XPR36 GLH sensor chip. The 1:1 binding model was employed to calculate the apparent affinity constant, K<sub>D</sub>. <h3>Results</h3> 26 of the 60 serum samples have shown measurable binding affinity to citrullinated filaggrin peptide with K<sub>D </sub>values between 10<sup>–5</sup>–10<sup>–7</sup>M. In general, individual sera showing multiple specificities to citrullinated peptides in ELISA possess a higher K<sub>D</sub> to filaggrin peptide. An inverse correlation was observed between disease severity (DAS28 index) and binding affinities. Surprisingly, high degree of cross-reactivity was detected between affinity purified IgGs specific for citrullinated filaggrin, fibrin, vimentin and collagen. <h3>Conclusions</h3> Biosensor analysis has shown that ACPA are very heterogeneous regarding both specificities and affinities, furthermore, the affinity purified IgGs from individual ACPA are highly cross-reactive. Support: National Research, Development and Innovation Office (OTKA104846) and ELTE KMOP-4.2.1/B-10–2011–0002