tbuckley/cabot-search huggingface dataset:
Abstract 56: Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis through upregulated TAGLN expression
Authors: Bingya Liu, Beiqin Yu, Jianfang Li, Liping Su
Journal: Cancer Research (2012)

Abstract Fibroblasts play a significant role in tumorigenesis, tumor progression and metastasis, but their detailed molecular characteristics and clinical significance are unclear. TAGLN is an actin-binding protein played an important role in tumorigenesis. Here, we aimed to the interaction between cancer cells and their microenvironments to study how the fibroblasts isolated from human gastric carcinomas facilitate tumorigenesis through TAGLN. Gene expression profiling and real-time PCR and Western blot in gastric carcinoma samples indicated that TAGLN expression was up-regulated in gastric carcinoma. However, further investigation by IHC shown that TAGLN was expressed in tumor stoma, not in tumor cells. TAGLN expression was promoted mutually by fibroblasts and MKN-45 co-culture. Decreased expression of TAGLN suggested that carcinoma-associated fibroblasts (CAF) can enhance tumor metastasis through upregulated TAGLN by MMP-2 and the FAK pathway. 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 56. doi:1538-7445.AM2012-56
A10.13 IGG FC galactosylation changes and predicts response to methotrexate in early rheumatoid arthritis
Authors: AH Hensvold, SL Lundström, D Rutishauser, L Klareskog, RA Zubarev, AJ Ytterberg, AI Catrina
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Responses to methotrexate (MTX) treatment for Rheumatoid arthritis (RA) vary across patients, creating the need to find factors that can predict patient response. One potential factor is the ratio between agalactosylated <i>versus</i> galactosylated Fc-glycans. This ratio is known to change according to inflammation- and immune-regulatory disease activities. <h3>Material and methods</h3> Using a shotgun proteomics approach, we screened for isotype-specific Fc-glycopeptides directly in serum from 12 healthy individuals and from 59 early RA patients prior to and following three months of MTX treatment. Treatment response was defined according to the European League against rheumatism (EULAR) after three months of treatment. Uni- and multivariate-statistics were employed to interrogate the acquired Fc-glycan data and clinical information. <h3>Results</h3> An increase in galactosylated glycans was observed following three months of MTX treatment in patients with moderate and good responses to treatment. Furthermore, MTX non-responders had a significantly lower abundance of galactosylated glycans in blood samples that were collected before treatment compared to the baseline levels of individuals with moderate and good responses to treatment. By using the log<sub>10</sub>-ratio between the major agalactosylated and mono- and di-galactosylated Fc-glycans of IgG<sub>1</sub>, non-responding patients were distinguished from responding patients with 70% sensitivity and 69% specificity. In rheumatoid factor and/or anti-citrullinated peptide-antibody positive patients (n = 44) this sensitivity was increased to 80%. <h3>Conclusions</h3> Herein we show that the IgG-Fc-galactosylation status has predictive value for MTX response in early RA, and that it has potential as a predictive factor for use within the clinics.
RNA-Seq-Derived Whole Genome Transcriptomic Profiling Following Challenge to Mt. Cedar in a Pollen Challenge Chamber Uncover Novel Insights Into Allergic Rhinoconjunctivitis Pathogenesis
Authors: Nathan Harper, John Castiblanco, Cynthia Rather, Charles Andrews, Daniel Ramirez, Robert L. Jacobs, Weijing He, Sunil Ahuja
Journal: Journal of Allergy and Clinical Immunology (2013)
Communicating the Rhythm
Authors: Anna E. Bortnick, Fermin Garcia, Daniel M. Kolansky
Journal: New England Journal of Medicine (2010)

To the Editor: Accurate hand-off communication among health care providers has been a focus of quality improvement and hospital accreditation.1 Although much emphasis has been placed on in-hospital transfers of care, there is a growing focus on communication between emergency medical services and emergency department physicians.2,3 In Pennsylvania, state law mandates that required information collected in the field be filed as a patient care report that is incorporated into the chart,4 but rhythm strips from the field are neither mandated nor routinely included, since older models of automatic external defibrillators (AEDs) do not save or print out data. When . . .
Lobular Breast Carcinoma
Authors: Anna Margherita Maffione, Laura Camilla Lisato, Annalisa Rasi, Maria Cristina Marzola, Patrick M. Colletti, Domenico Rubello
Journal: Clinical Nuclear Medicine (2014)

A patient with diffuse osteosclerotic bone metastases from invasive lobular breast carcinoma is presented with both F-FDG PET/CT and bone scans negative for hypermetabolic lesions. Skeletal metastases were documented by CT and bone marrow biopsy, and high increased CA 15-3 level was recorded. This case report points to the potential risk of false-negative FDG PET and bone scans examination in lobular carcinoma type.
Abstract 4010: New <i>AXIN2</i> germline variant in a Spanish family with an attenuated form of FAP without oligondontia or ectodermal dysplasia signs
Authors: Barbara Rivera, Jose Perea, Eloy Sanchez, Manuel Villapun, Eva Sanchez-Tome, Fatima Mercadillo, Mercedes Robledo, Javier Benitez, Miguel Urioste
Journal: Cancer Research (2012)

Abstract Familial Adenomatous Polyposis (FAP) is a colorectal cancer syndrome caused mainly by mutations in the APC gene (50-80% of the cases), and some mutations in MUTYH, usually in recessive and milder cases. Additionally, the genetic cause of 20% of classic forms and 50% of attenuated forms of the disease remain unclear. AXIN2 is a partner of the APC protein in the b-catenin destruction complex. Mutations in AXIN2 have been described in patients with oligodontia and other ectodermal dysplasia features in association with colorectal neoplasia or adenomatous polyps. We studied the AXIN2 gene in a series of APC/MUTYH mutation negative families and identified a novel variant, c.1387C&amp;gt;T;p.R463P, as the possible genetic cause of an attenuated FAP phenotype (AFAP). The autosomal dominant AFAP phenotype was not associated with any extracholonic manifestations or ectodermal dysplasia features. However, hyperplastic polyps were observed in some AXIN2-variant carriers. Thus, from a clinical point of view this family displayed some features that differ from previously described families with AXIN2 mutations. The variant c.1387C&amp;gt;T;p.R463P is located in the b-catenin binding domain, an area highly conserved throughout evolution. The variant segregates with the affected family members and was not present in 800 healthy Spanish controls. We were able to confirm loss of heterozygosity in 3 out of 5 polyps from the proband and his affected sister. AXIN2 and b-catenin expression patterns were tested by inmunofluorescence staining: both proteins are overexpressed in adenomatous polyps compared with normal colorectal ephitelium from the proband. Moreover, no colocalization of the two proteins could be observed by confocal microscopy. These results support a possible pathogenic role for this AXIN2 variant in our family and highlight the implication of AXIN2 in some cases of FAP syndrome. We argue comprehensives and functional studies will be necessary to clarify the role of AXIN2 in familial colorectal cancer predisposition. 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 4010. doi:1538-7445.AM2012-4010
Deletion of STAT5 prevents HER2/Neu/ErbB2-induced mammary tumor development.
Authors: D Yamaji, GW Robinson, WJ Muller, L Hennighausen
Journal: Cancer Research (2009)

Abstract Abstract #3045 HER2 (ErbB2/Neu in rodents) is overexpressed in a number of breast cancers and it activates several intracellular signaling pathways by recruiting adaptor proteins. Among them, Shc or Gab2 signaling mediates ErbB2/Neu-induced mammary tumor progression. HER2 activates the transcription factors STAT5A/B but their contribution to the etiology of breast cancer remains to be elucidated. STAT5 mediates signals from a wide variety of cytokine receptors, including the EGFR and ErbB4. Further, constitutive activation of STAT5 has been observed in human breast cancer, leukemia and many solid tumors. To address whether STAT5 mediates HER2/ErbB2/Neu-induced breast cancer progression, both Stat5 genes were deleted specifically in ErbB2/Neu oncogene (known as HER2 in human)-expressing mammary epithelial cells in mice. Briefly, transgenic mice carrying floxed Stat5 alleles (Stat5fl/fl mice) were mated with transgenic MMTV/NIC mice expressing both activated Neu/ErbB2 and Cre recombinase from the same bicistronic transcript due to the presence of an internal ribosome entry site (IRES) between the two cDNA sequences (NIC) under the control of mouse mammary tumor virus (MMTV) long terminal repeat. Whole mount staining of mammary tissue of MMTV/NIC mice demonstrated that mammary glands of control virgin NIC mice (MMTV/NIC;Stat5+/+) exhibited hyperplastic lesions at 5 months of age, while no lesions were detected in NIC mice that lacked STAT5 (MMTV/NIC;Stat5fl/fl). Histological analysis revealed the absence of hyperplastic or neoplastic lesions in MMTV/NIC;Stat5fl/fl mammary glands. These results indicate that inactivation of Stat5 results in the absence of hyperplasias in spite of overexpression of ErbB2/Neu in mammary epithelium and suggest that activation of STAT5 contributes to the development of HER2-induced breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3045.
PWE-062 Can magnetic neural stimulation improve anorectal sensitivity in IBS?
Authors: T Algladi, M L Harris, P Whorwell, B Issa, P Paine, S Hamdy
Journal: Gut (2012)

Introduction Visceral pain is a major clinical problem being a primary feature of irritable bowel syndrome (IBS). Treatments for this condition are limited, but there is increasing evidence that neural stimulation may be able to alter pain thresholds in the somatic literature. By contrast, little is known about the role of neurostimulation applied to visceral pain and its ability to alter sensitivity. The aim of this study was to ascertain whether repetitive magnetic stimulation (MS) applied to the lumbosacrum and motor cortex can alter anorectal sensitivity in IBS patients. Methods Participants: 10 IBS patients (9 females, age range 22 and 54 years). All IBS patients fulfilled Rome III criteria for IBS. Anorectal electrical sensory measurements were performed via a stimulating catheter positioned in the rectum, 10 cm from the anal verge andan anal plug. Sensory and pain thresholds in the rectum and anal sphincter were determined using trains of electrical stimuli, repeated three times. Anorectal sensory and pain thresholds were performed at baseline before intervention and then immediately, 30 and 60 min after each intervention. Interventions comprised 3 neurostimulation paradigms delivered in random order over separate days: repetitive 1 Hz lumbosacral magnetic stimulation (rLSMS), repetitive 10 Hz cortical transcranial magnetic stimulation (rTMS) and sham in the form of tilted coil. Results Data (mean±SEM) were analysed by two way ANOVA (see [Abstract PWE-062 tables 1][1] and [2][2]) showed a significant increase in sensory (ST) and pain (PT) thresholds immediately, at 30 and 60 min in the rectum following both 1 Hz rLSMS (ST (p=0.015, 0.048 and 0.022, respectively), PT (p=0.014, 0.004 and 0.012, respectively)) and 10 Hz rTMS (ST (p=0.046, 0.041 and 0.017, respectively), PT (p=0.005, 0.02 and 0.007, respectively)). In addition, only 10 Hz rTMS increased anal sphincter pain thresholds immediately, at 30 and 60 min after the intervention (PT (p=0.032, 0.004 and 0.001, respectively)). Sham stimulation had no effect on any of the anorectal sensory parameters. View this table: Abstract PWE-062 Table 1 View this table: Abstract PWE-062 Table 2 Conclusion The application of repetitive magnetic stimulation to lumbosacral area and motor cortex is able to modulate human visceral sensitivity in IBS patients and holds promise as a future therapeutic intervention. Competing interests None declared. [1]: #T1 [2]: #T2
THU0084 Low Cardio-Respiratory Fitness is Associated to Increased Arterial Stiffness in Patients with Ankylosing Spondylitis:
Authors: I.J. Berg, A.G. Semb, S. Halvorsen, C. Fongen, D. van der Heijde, T.K. Kvien, H. Dagfinrud, S.A. Provan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Physical activity is a cornerstone in treatment of ankylosing spondylitis (AS). We have previously shown that AS patients have lower cardio-respiratory fitness (CRF) than population controls. CRF is inversely associated with cardiovascular (CV) mortality and morbidity in the general population. Patients with AS have increased risk of cardiovascular disease (CVD), but the etiology is not clear. Lower CRF may be associated with increased risk of CV in AS. Arterial stiffness is a marker of CVD, and associations between CRF and arterial stiffness has not been explored previously in patients with AS. <h3>Objectives</h3> To evaluate associations between CRF and arterial stiffness. <h3>Methods</h3> This is a cross-sectional study on AS patients (mNY criteria). Information on demographics and medication was assessed from questionnaires. Arterial stiffness, measured as Pulse Wave Velocity (PWV) and Augmentation Index (AIx,) was recorded using the Sphygmocor apparatus (AtCor). CRF was assessed as peak oxygen uptake (VO<sub>2</sub>peak) by a maximal walking treadmill test (modified Balke protocol). Statistics were performed using SPSS version 21. Univariate associations between lnPWV/AIx (dependent variable) and VO<sub>2</sub>peak as well as possible confounders/factors, were analyzed in separate linear regression models adjusted for age and gender. Variables with a p-value of less than 0.25 were included in a backwards multivariate linear regression models. <h3>Results</h3> The 113 AS patients had the following characteristics: Mean (SD) age 48.4 (11.3) years, 72 (64%) males, 18 (16%) smokers, mean (SD) BMI 25.6 (3.5) (kg/m<sup>2</sup>), 73 (65%) used NSAIDs, 24 (21%) used TNF-inhibitors, 14 (12%) used statins, 28 (25%) used antihypertensive medication and median (IQR) CRP (mg/l) 3 (2-10). In regression models VO<sub>2</sub>peak was significantly inversely associated with lnPWV independent of other factors (table). Similar results were found for AIx: (beta(95%CI)) -0.33 (-0.55- -0.10), p=0.01. <h3>Conclusions</h3> CRF measured by VO<sub>2</sub>peak was inversely associated with arterial stiffness indicating that reduced CRF can be related to increased risk for CVD in AS patients. Studies on the effect of increasing CRF on risk of CVD in AS patients are warranted. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2753
Clinical Practice Guidelines for Pediatric Complicated Appendicitis
Authors: Diana Lee Farmer
Journal: JAMA Surgery (2016)

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Abstract 1910: Acquired resistance to HER2 targeted therapy: A common mechanism
Authors: Jessica Christenson, Susan E. Kane
Journal: Cancer Research (2012)

Abstract There are currently two FDA approved targeted therapies being utilized in the clinic to treat Her2+ breast cancer, trastuzumab and lapatinib. Acquired resistance has become a major concern and several mechanisms for resistance have been proposed. The upregulation of a truncated transcriptional variant of Darpp-32, known as t-Darpp, is a characteristic shared by several independently developed trastuzumab-resistant cell lines. Moreover, exogenous t-Darpp overexpression is sufficient for conferring trastuzumab resistance. No consistent mechanism, however, has been identified for lapatinib resistant cells. By inhibiting signaling through Her2+ pathways such as PI3K/Akt and Erk, lapatinib induces a strong apoptotic response by down-regulating survivin and inducing BIM. Darpp-32 and t-Darpp both have been linked to apoptosis, with t-Darpp identified as having anti-apoptotic properties through its regulation of Bcl-2. The purpose of the current study was to determine if t-Darpp or other dysregulated apoptosis proteins play a role in lapatinib resistance. Lapatinib-resistant SKBR3 cells (Her2+, ER-) were selected by continuous exposure to increasing concentrations of lapatinib (0.3-2.0µM) over the course of one year. Using Sulforhodamine B and colony forming assays, we found that individual clones and pools of SK/LapR cells were, on average, 50-fold resistant to lapatinib, relative to parental SKBR3 cells. This resistance phenotype was stable even after cells were maintained for 1 month outside of drug. As observed in trastuzumab resistance and similar to previous reports of lapatinib-resistant cells, we found that SK/LapR cells had sustained PI3K/Akt signaling in the presence of lapatinib, whereas parental cells did not. Additionally, survivin inactivation and BIM induction by lapatinib seemed to be partially impaired in SK/LapR cells. Finally, SK/LapR cells appeared to down-regulate Darpp-32 and up-regulate t-Darpp, similar to what we have reported in BT474 cells selected for resistance to trastuzumab. Although t-Darpp overexpression is sufficient to confer resistance to trastuzumab, this does not appear to be the case for lapatinib resistance – SK.tDp cells transfected with a t-Darpp cDNA are not resistant to lapatinib. Experiments are currently underway to determine if the t-Darpp overexpression that we observe in SK/LapR cells is required for lapatinib resistance. Identifying a shared mechanism of resistance to lapatinib and trastuzumab would provide a novel therapeutic target that could be widely used among Her2+ breast cancer patients to ameliorate acquired drug resistance. 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 1910. doi:1538-7445.AM2012-1910
1322 RELATION BETWEEN THE ADIPOCYTE HYPERTROPHY DEGREE AND ADIPOSE TISSUE MACROPHAGE INFILTRATION WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) PROGRESSION IN MORBID OBESITY
Authors: A. Carazo Gallego, L. Sanjuan, M. Caba-Molina, T. Caballero, J.A. Muñoz-Gámez, A. Gila, J. González-Rubio, A. Membrives, M. Ana, R. Quiles, J. López-Viota, M. De la Mata, E. Ruiz- Escolano, A. Ruiz-Extremera, J. Salmerón
Journal: Journal of Hepatology (2013)
SAT0148 Cardiovascular Risk Estimation in Rheumatoid Arthritis: What is Missing in Traditional Risk Estimators?: Table 1.
Authors: G. Ozen, M. Sunbul, P. Atagunduz, H. Direskeneli, K. Tigen, N. Inanc
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cardiovascular (CV) disease is one of the major causes of mortality in RA. Although the CV risk in RA is well-recognized, detection of high risk patients and prevention of CV disease are still major challenges. <h3>Objectives</h3> To determine which CV risk estimation index is better in RA patients and to determine the factors that may improve CV risk estimation in RA. <h3>Methods</h3> One-hundred and six consecutive RA patients without history of CV disease or diabetes mellitus were assessed. Systematic Coronary Risk Evaluation (SCORE) and 2013 American College of Cardiology/American Heart Association (ACC/AHA) 10-year atherosclerotic CV disease risk (ASCVD) indices and their modified versions (mSCORE and mASCVD risk) according to EULAR recommendations were calculated. All patients were evaluated with carotid ultrasonography (US). Carotid intima-media thickness (cIMT) &gt;0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). <h3>Results</h3> The study cohort consisted of 106 RA patients (F/M=93/13, mean age 51.7±11.3) with a mean disease duration of 9.9±6.2 years. RF and anti-CCP positivity were 78.3% and 61.3%, respectively. The EULAR multiplier factor was used in 41 (38.6%) patients. The mean mSCORE was 1.70±2.95% and mASCVD risk was 4.4.1±5.83%. The mSCORE defined 6 (5.7%) patients and mASCVD defined 28 (26.4%) patients as having high/very high CV risk (mSCORE≥5%, mASCVD≥7.5%). Concerning US results, 28 (26.4%) patients had either cIMT&gt;0.90 mm or carotid plaques. The mASCVD risk better identified US+ patients, that of the US+ patients 16 (57.1%) were in mASCVD high/very high risk group whereas only 4 (14.3%) of the US+ patients were in high/very high risk group according to mSCORE (<i>P</i>&lt;0.0001). However mASCVD risk still has failed to identify 42.9% of US+ patients. When traditional risk factors and disease characteristics of US+ and US – patients were compared, it was found that US+ patients were older at diagnosis, had higher triglyceride levels and erythrocyte sedimentation rates. Furthermore current methotrexate use was lower in US+ patients along with similar rates of biologic treatment and other traditional risk factors (Table 1). <h3>Conclusions</h3> EULAR recommendation for CV risk assessment, SCORE, seems inadequate even after modification according to RA characteristics. On the other hand ACC/AHA 10-year ASCVD risk index is better in estimating CV risk in RA patients. However, still additional modificiations, like age at disease onset, methotrexate usage, ESR are required to fully identify high-risk RA patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3063