tbuckley/cabot-search huggingface dataset:
Abstract 1689: Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis for 7-carboxymethylguanine and 7-carboxyethylguanine in human liver DNA
Authors: Mingyao Wang, Guang Cheng, Li Chen, Peter W. Villalta, Stephen S. Hecht
Journal: Cancer Research (2010)

Abstract The carcinogenic nitrosamines N-nitrososarcosine (NSAR) and 3-(methylnitrosamino)propionic acid (MNPA) have been detected in the diet, tobacco products, and human urine. Metabolic activation of NSAR by methyl hydroxylation would produce a DNA carboxymethylating agent while similar metabolism of MNPA would produce a carboxyethylating agent, each of which would be expected to react at the 7 position of guanine to give 7-carboxymethylguanine (7-CMG) and 7-carboxyethylguanine (7-CEG), respectively. Furthermore, acrylic acid, a major industrial product, environmental contaminant and likely endogenous metabolite, and β-propiolactone, are also known to react with DNA to give 7-CEG. We developed a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS-SRM) method to quantify these adducts in human liver DNA. [15N5]7-CMG and [15N5]7-CEG were synthesized and used as internal standards. After addition of the internal standards, the DNA was hydrolyzed enzymatically and the hydrolysate was partially purified by solid-phase extraction. The fraction containing 7-CMG and 7-CEG was treated with acetyl chloride in methanol to convert them to the corresponding methyl esters. After re-purification by solid-phase extraction, the appropriate fraction was analyzed by LC-ESI-MS/MS-SRM for the transitions m/z 224[M + H]+ → m/z 164[(M + H) - C2H4O2]+ for 7-CMG and m/z 238[M + H]+ → m/z 152 [BH]+ for 7-CEG. Human liver DNA samples had clear peaks co-eluting with [15N5]7-CEG, but no peaks were observed at the retention time of 7-CMG. The on column detection limits were approximately 10 and 5 fmol, respectively, for the methyl esters of 7-CMG and 7-CEG. The detection limit for the methyl ester of 7-CEG in DNA (starting with 1 mg) was approximately 8 fmol. Known addition studies using 7-CEG and calf thymus DNA demonstrated that the method was accurate and precise. Artifactual formation of 7-CEG during DNA isolation and enzyme hydrolysis was excluded. The method was applied for the analysis of 27 human liver samples. 7-CEG, but not 7-CMG, was detected in each sample, mean ± S.D, 408 ± 375 fmol/µmol guanine (82 adducts per 109 nucleotides), range 17 − 1491 fmol/µmol guanine. This is the first report demonstrating the presence of 7-CEG in DNA from humans. While MNPA, β-propiolactone and acrylic acid are possible sources of this DNA adduct, we consider acrylic acid to be the most likely because of its ubiquitous occurrence and probable endogenous formation from the lipid peroxidation product acrolein. 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 1689.
SAT0461 Infliximab Treatment in Children: Frequency of Infusion Reactions and Role of Desensitization
Authors: F. A. Aeschlimann, K. D. Hofer, E. Cannizzaro, S. Schroeder, R. Lauener, R. K. Saurenmann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Infliximab (IFL) is a monoclonal tumour necrosis factor alpha inhibiting antibody which is frequently used to treat children with refractory arthritis and uveitis. The most frequent and limiting adverse events are anaphylactic infusion reactions caused by anti-drug antibodies. <h3>Objectives</h3> The objective of our study was to describe the frequency and the long-term course of anaphylactic reactions in a cohort of patients treated with IFL. <h3>Methods</h3> After a search of the rheumatology database the charts of all patients treated with IFL were retrospectively reviewed for IFL infusion reactions. Factors such as IFL dosage, infusion interval, co-medication and the time until the first occurrence of an infusion reaction were collected, as well as the treatment and course since the first infusion reaction until the last follow up visit. <h3>Results</h3> A total of 2098 IFL infusions were given to 78 patients (22 male, 56 female) between Oct 2000 and Dec 2011. Indication for IFL use was refractory JIA in 46 pat (59%), uveitis in 15 pat (19%) and both arthritis and uveitis in 13 pat (17%), while 4 pat (5%) had other systemic inflammatory diseases. The mean IFL treatment duration was 3.7 years. All patients received co-medication with methotrexate or leflunomide. Allergic infusion reactions (respiratory or gastrointestinal symptoms, rash, malaise or low blood pressure)occurred in 35 infusions (1.7% of all infusions) of 11 patients (14%). Allergic reactions occurred after a mean treatment time of 340 (range 41-780) days. In 6/11 patients the allergic reaction was preceded by arthritis flare. Four patients chose to stop treatment immediately because of the allergic reaction. For the other 7 patients we didn’t discontinue IFL treatment after allergic reaction, but used high dose antihistamine premedication and in 5/7 pat methylprednisolon premedication for the following infusions. Additionally we reduced the IFL infusion interval in 4/7 pat and increased the IFL dose in 2/7 pat. 2 pat pursued the treatment with the same IFL interval and dose. With this regimen 5 patients (71%) were able to continue IFL treatment for a mean of 2.8 years while 2 patients discontinued because of repeated allergic reactions. <h3>Conclusions</h3> Allergic infusion reactions occurred in 14% of our patients. Treatment with antihistamine drugs, methylprednisolon and increased/more frequent IFL administration allowed &gt;70% of our patients to continue IFL treatment despite allergic reactions. We hypothesize that the continued IFL administration led to desensitization. <h3>Disclosure of Interest</h3> None Declared
Abstract 3970: DRAK2 inhibits the TGF-B signaling pathwsy through interaction with TGF-B receptors
Authors: Kyung-Min Yang, Seong-Jin Kim
Journal: Cancer Research (2010)

Abstract Transforming growth factor β (TGF-β) controls a diverse set of cellular responses, including proliferation, differentiation, migration, apoptosis and immune modulation. In recent years, research has begun to unravel the mechanisms that tune the TGF-β signaling pathway. These mechanisms include interactions and modifications that regulate the stability of TGF-β's signaling machinery, receptors and Smads. In addition, they are known to be of major importance for maintaining proper physiological TGF-β signaling. In this study, we have identified a novel TGF-β receptor binding protein called DRAK2 (DAP kinase-related apoptosis-inducing kinase 2). Here, we show that DRAK2 inhibits TGF-β-induced Smad2/3 phosphorylation. To identify the interaction between TGF-β receptors and DRAK2, we performed immunoprecipitation, immunofluorescence staining and in situ proximity ligation assay. DRAK2 specifically bound to the TGF-β receptors. Although ectopic expression of DRAK2 did not inhibit the interaction between TGF-β receptor type I and type II, transient transfection of DRAK2 reduced TGF-β-dependent reporter activity. In stable cell lines that overexpress DRAK2, DRAK2 suppressed the phosphorylation of Smad2 and Smad3 and activity of Smad2-specific (ARE) and Smad3-specific (CAGA) reporters. Furthermore, the expression of DRAK2 attenuated TGF-β-induced translocation of Smad2 and Smad3 from the cytoplasm to nucleus. Conversely, the knockdown of DRAK2 enhanced the TGF-β signaling pathway including TGF-β-dependent promoter activity and phosphorylation of Smad2 and Smad3. Thus, these results suggest that DRAK2 may be a negative regulator in the TGF-β signaling pathway. 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 3970.
AB0089 Tofacitinib Mediates Synovial Angiogenesis in Psoriatic Arthritis
Authors: W. Gao, J. McCormick, M. Connolly, D.J. Veale, U. Fearon
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Psoriatic Arthritis (PsA) is a common, chronic immune-mediated inflammatory disease, characterised by synovitis, progressive destruction of articular cartilage/bone, and is associated with psoriasis. Janus Kinase and Signal Transducer and Activator of Transcription (JAK/STAT), a critical signalling pathway involved in inflammatory mechanisms, has been implicated in the pathogenesis of PsA. <h3>Objectives</h3> To examine the effect of Tofacitinib (A novel JAK inhibitor CP-690,550) on pro-inflammatory pathways in PsA. <h3>Methods</h3> Primary PsA synovial fibroblasts (PsASFC) and whole tissue PsA synovial explant cultures were established from PsA biopsies obtained at arthroscopy. Phospho-STAT3 and 1 (p-STAT3 and p-STAT1) expression were quantified by western blot in PsA synovial explants and PsASFC following culture in the presence of Tofacitinib (0.5μM and 1μM). The effect of Tofacitinib on PsASFC migration, invasion, matrigel network formation and MMP2/9 were quantified by wound repair assays, transwell invasion chambers and zymography. Cytokine expression of IL-6, IL-8 and IL-10 in <i>ex-vivo</i> synovial explants were assessed by ELISA. <h3>Results</h3> Tofacitinib significantly decreased p-STAT3 and p-STAT1 expression in PsASFC and PsA synovial tissue explant cultures <i>ex vivo</i>. Tofacitinib significantly decreased spontaneous secretion of IL-6 (p&lt;0.05), IL-8 (p&lt;0.05) and induced IL-10 (p&lt;0.05) expression in PsA explant cultures. Functionally, PsASFC invasion, matrigel network/tube formation, migration, and pro-MMP-2/-9 activities, were inhibited in the presence of Tofacitinib (p&lt;0.05) <h3>Conclusions</h3> This study demonstrates that Tofacitinib inhibits pro-inflammatory pathways in PsA, suggesting that JAK-STAT inhibition may be a potential therapeutic agent for the treatment of PsA. <h3>Disclosure of Interest</h3> W. Gao: None declared, J. McCormick: None declared, M. Connolly: None declared, D. Veale Grant/research support: Abbvie, MSD, Pfizer, Roche, Consultant for: Pfizer, Roche, Speakers bureau: Abbott, MSD, Pfizer, Roche, U. Fearon: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4256
SP0101 Raising Awareness - the Perspective of the Bone and Joint Decade
Authors: A. Woolf
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Over 1.7 billion people worldwide are affected by musculoskeletal conditions which have the fourth greatest impact on the overall health of the global population, considering both death and disability. This burden is at enormous cost to individuals and society and has increased by 45% over the last 20 years. Decision makers, non-expert clinicians and the public worldwide lack awareness of the scale of the problem and do not understand what can potentially be achieved given higher priority and policies. There are effective interventions that will reduce this burden but they are not implemented with equity across and between countries. Health priorities focus on conditions with high mortality but fail to focus on those which affect a large sector of society and have a negative economic impact through health and social care costs and also on productive work. This is at a time of extended longevity and the need to be productive into older age. The challenges apply in all countries, in all continents. The musculoskeletal community is aware of these issues and the need to influence decision makers. A challenge we have is that there are a wide range of conditions that affect musculoskeletal health and these are managed by a wide range of professionals who do not always work together. The Bone and Joint Decade has created an international alliance that brings together organisations for all such professionals as well as scientific and patient organisations. It considers all conditions that affect musculoskeletal health and works on initiatives to provide the evidence to make the optimisation of musculoskeletal health a public health priority. The Bone and Joint Decade has organised the Global Alliance for Musculoskeletal Health to call for explicit plans by governments, health policy makers at the regional level and the WHO to deal with the large and growing burden of musculoskeletal conditions and injuries on individuals and society through: 1) promotion of a lifestyle that will optimise musculoskeletal health at all ages; 2) Implementation of effective measures to prevent musculoskeletal disorders and injuries; 3) identification and treatment of those who are at highest risk; 4) access to timely, safe, appropriate treatment to control symptoms, and diseases where possible, to prevent unnecessary disability; 5) access to appropriate rehabilitation and self-management programmes to reduce any disability, 6) enabling people to participate in the labour market; 7) research to advance knowledge and care. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6171
Abstract 3946: Genome-wide characterization of hypoxic breast cancer transcriptome
Authors: Hani Choudhry, Spyros Oikonomopoulos, Adrian Harris, Ioannis Ragoussis
Journal: Cancer Research (2012)

Abstract Hypoxia is a common feature of most solid tumors and is associated with poor prognosis in breast cancer. In the current study, we investigated the hypoxia transcription landscape of an ER positive breast cancer cell line [MCF7] using high throughput strand-specific total RNA sequencing (tssRNA-seq). MCF7 cells were grown under hypoxia and normoxia (24 hours, 1% O2), and we found about 7.3% of annotated genome got significantly differential expressed in hypoxic stress, which includes 79% (1293) up regulated and 21% (344) down regulated transcripts (P value of &amp;lt;0.01, fold &amp;gt;1.5). Analysis revealed deregulation of a range of non coding transcripts including piwiRNA (0.36%), miRNA (0.098%), sn/snoRNA (0.028%), tRNA (4.5%), lncRNA (6.5%) under hypoxia (P value of &amp;lt;0.01, fold &amp;gt;1.5). Many non-poly A transcripts and natural anti-sense transcripts (n=71) were detected and differently expressed in hypoxia. We characterized two significant up regulated natural anti-sense transcripts in hypoxia and found that these transcripts are long (&amp;gt;200bp), lack of protein coding frames, localized in nucleus and found highly expressed (range fold &amp;gt;5-15) in different hypoxic breast cancer cell lines. To define which hypoxic altered transcripts are dependent on, hypoxia-inducible factor (HIF), we suppressed HIF-alpha subunits in hypoxic MFC-7 cells using short interfering RNA and subjected them to mRNA-seq. Results revealed that HIF-1, HIF-2 and combined HIF-1/2 knockdown resulted in significant down-regulation of 179, 84 and 149 transcripts, respectively, which were up regulated in hypoxic MCF-7 cells. Despite detection of previously reported HIF dependent transcripts, we detected a substantial number of HIF dependent transcripts (n=64) that were not reported before as hypoxia regulated genes. To our understanding, this is first study to show hypoxia dependent natural anti-sense transcripts and genome-wide HIF dependent transcripts analysis at single base pair resolution in hypoxic tumors. These finding will open new avenues in our efforts to understand the hypoxia induced transcriptional response. 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 3946. doi:1538-7445.AM2012-3946
RESULTADOS DE LA RESECCION ENDOSCOPICA DE POLIPOS PLANOS GRANDES DEL COLON (&gt; 2 cm)
Authors: J De La Peña García, P Iruzubieta Coz, D Hernández Amunarriz, Á Terán Lantarón, PL Fernández Gil, B Castro Senosiain, J Cabezas Delgado, MT Arias Loste, S Menendez Secades
Journal: Endoscopy (2013)

Introducción: La resección de pólipos planos del colon es técnicamente difícil, siendo límite cuando superan los dos cm. Objetivo: Analizar las características técnicas de la resección endoscópica y su resultado en una serie consecutiva de pólipos planos de colon mayores de 2 cm. Material y Método: Busqueda de pólipos planos mayores de 2 cm resecados endoscópicamente. Registro de numero de sesiones realizadas, complicaciones, resección en fragmentos, resección completa y necesidad de cirugía de rescate. Tecnicas endoscópicas: mucosectomia (MUC), elevación (E) y resección con asa (A); Mucosectomia avanzada (MA), (E)+incisión circunferencial (IC)+(A); mucosectomia avanzada+disección (MAD), disecando partes del pólipo con disectotomos (D) y Disección endoscópica submucosa: E+IC+ D sin uso de asa. Resultados: Entre Abril de 2007 y Marzo 2013 hemos resecado 40 polipos planos con un tamaño medio de 2,5 cm (2 – 5 cm), 19 en colon izquierdo, 21 en derecho. El seguimiento medio ha sido de 6 meses (desde 1 a 72), 24 pacientes presentaban antec personales relevantes (ASA III). En 14 casos se realizó DES y en el resto Mucosectomia de diferente complejidad. La resección fue en un fragmento en 7 casos y en multiples en el resto. En 18 casos se resecó un ca in situ. Hubo 4 perforaciones (dos precisaron tto quirúrgico) y 2 hemorragias que precisaron tto endoscópico. Se resecó todo el pólipo en 31 casos (77,5%) con necesidad de nuevas sesiones o terapias en 12 de ellos y la reseccion fue incompleta en 9 casos (3 por carcinoma avanzado) de los cuales 5 se resolvieron con cirugía. Hubo cinco muertes en esta serie debido a causas distintas a la patología del colon. Conclusiones: La resección de pólipos planos grandes planos es una técnica endoscópica segura aunque laboriosa. Es necesario entrenar las técnicas avanzadas de resección y mucosectomia.
Brief Intensive Chemotherapy for Metastatic Non-Small-Cell Lung Cancer: A Phase II Study of the Weekly CODE Regimen
Authors: N. Murray, D. Osoba, A. Shah, R. Page, H. Karsai, C. Little
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Brief Intensive Chemotherapy for Metastatic Non-Small-Cell Lung Cancer: A Phase II Study of the Weekly CODE Regimen Get access Nevin Murray, Nevin Murray * Division of Medical Oncology, British Columbia Cancer Agency, Vancouver and Victoria, BC, Canada and Department of Medicine, University of British ColumbiaVancouver * Correspondence to: Nevin Murray, MD, British Columbia Cancer Agency, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar David Osoba, David Osoba Division of Medical Oncology, British Columbia Cancer Agency, Vancouver and Victoria, BC, Canada and Department of Medicine, University of British ColumbiaVancouver Search for other works by this author on: Oxford Academic PubMed Google Scholar Amil Shah, Amil Shah Division of Medical Oncology, British Columbia Cancer Agency, Vancouver and Victoria, BC, Canada and Department of Medicine, University of British ColumbiaVancouver Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth Page, Ruth Page Division of Medical Oncology, British Columbia Cancer Agency, Vancouver and Victoria, BC, Canada and Department of Medicine, University of British ColumbiaVancouver Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen Karsai, Helen Karsai Division of Medical Oncology, British Columbia Cancer Agency, Vancouver and Victoria, BC, Canada and Department of Medicine, University of British ColumbiaVancouver Search for other works by this author on: Oxford Academic PubMed Google Scholar Cameron Little Cameron Little Division of Medical Oncology, British Columbia Cancer Agency, Vancouver and Victoria, BC, Canada and Department of Medicine, University of British ColumbiaVancouver Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 3, 6 February 1991, Pages 190–194, https://doi.org/10.1093/jnci/83.3.190 Published: 06 February 1991 Article history Received: 30 August 1990 Revision received: 16 November 1990 Accepted: 19 November 1990 Published: 06 February 1991
The Usefulness of Tc-99m Sestamibi Scintimammography in the Diagnosis of Squamous Cell Carcinoma of the Breast
Authors: H Ohta, T Saito, S Yamamoto, M Ukikusa, H Awane, M Shintaku
Journal: Clinical Nuclear Medicine (1998)

Primary squamous cell carcinoma of the breast is very rare, and diagnosis of a benign lesion often is made by mammography or ultrasonography in these cases. The authors present a case of squamous cell breast carcinoma in which Tc-99m sestamibi scintimammography was very useful in the evaluation of the disease.
What are CX<sub>3</sub>CR1<sup>+</sup>mononuclear cells in the intestinal mucosa?
Authors: Jan Hendrik Niess
Journal: Gut Microbes (2010)

Intestinal dendritic cells (DC) and macrophages play a key role for the maintenance of intestinal integrity by initiating innate and adaptive immune responses. Although DC and macrophages have been viewed as distinct lineages, the reliability of surface markers for the definition of DC and macrophages has recently been questioned. Here, I will discuss the ontogeny and function of CX3CR1+ mononuclear cells in the small and large intestine.
Abstract 3136: c-Kit / CD117 is a predictive prognostic marker for patients with basal-like breast cancer
Authors: Shinichiro Kashiwagi, Masakazu Yashiro, Tsutomu Takashima, Naoki Aomatsu, Hidemi Kawajiri, Hiroaki Tanaka, Naoyoshi Onoda, Bunzo Nakata, Tetsuro Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2011)

Abstract Purpose: The mortality of breast carcinoma is decreasing because of recent developments in diagnostic techniques and therapies; however, the mortality of the basal-like breast cancer (BLBC) remains poor. BLBC a poorly characterized subtype of tumor with no validated clinical assay to identify them. In breast cancer, although there were some reports of survival analysis regarding c-Kit expression, the significance of c-Kit expression is controversial. In addition, little is known about the c-Kit expression levels of BLBC. The aim of this study is to clarify the correlation between c-Kit and BLBC. Experimental Design: A total of 667 patients who had undergone resection of a primary breast cancer at our institute were enrolled. ER, PR, HER2, EGFR, CK5/6 and c-Kit expression were assessed by immunohistochemistry. We examined the association between BLBC and other clinicopathologic variables, and evaluated the significance of c-Kit expression. Results: Of informative 667 breast cancer cases, basal-like phonotype was 149 (78.4%) of 190 cases of triple-negative phenotype. c-Kit expression was found in 111 patients (16.6%), and it was significantly many results in BLBC (42/149, 28.2%) (p&amp;lt;0.001). The c-Kit positive patients experienced significantly poorer outcomes in terms of overall survival (p&amp;lt;0.001). In 149 patients with BLBC, a statistically significant difference was observed between c-Kit positive and negative in regard to the degree of high age (p=0.037), lymph node metastasis (p=0.008) and lymphatic invasion (p=0.017). In BLBC, cases with c-Kit expression showed a poor overall survival time (p&amp;lt;0.001), and disease-free interval period (p&amp;lt;0.001), and it was an independent indicator of a poor prognosis by multivariate analyses (p=0.024, OR=2.291). Conclusions: c-Kit is one of predictive prognostic marker and molecular targets in BLBC. 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 3136. doi:10.1158/1538-7445.AM2011-3136
VALIDITY OF REAL-TIME SINGLE-BEAT VERSUS MULTI-BEAT FULL-VOLUME CAPTURE THREE-DIMENSIONAL ECHOCARDIOGRAPHY FOR QUANTIFICATION OF RIGHT VENTRICULAR VOLUME: VALIDATED BY CARDIAC MRI
Authors: Eiichi Hyodo, Takafumi Nagaura, Kohei Moribayashi, Koichi Tamita, Atsushi Yamamuro, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2015)