tbuckley/cabot-search huggingface dataset:
Abstract 2902: Targeting the tight junction protein claudin-1 in colorectal cancer
Authors: Sara Cherradi, Adeline Ayrolles-Torro, Nadia Vezzo-Vié, Eve Combes, Lucile Canterel-Thouennon, Fabien Gava, Valérie Lobjois, Bernard Ducommun, Celine Gongora, Maguy Del Rio
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) is one of the major causes of cancer-related deaths in the Western world. When localized, CRC is often curable by surgery, but the prognosis of patients with metastatic disease remains very poor. The current treatment of metastatic CRC (mCRC) relies on therapy combining chemotherapy and targeted therapies. However, relapses are observed in most cases due to the occurrence of drug resistance. Therefore, more therapeutic options are required particularly by identifying new molecular targets that can be reached by antibodies. We previously showed that Claudin-1 (CLDN1), a major constituent of tight junctions, is overexpressed at the membrane of CRC cells which makes it a good target for antibodies. Besides, CLDN1 is differentially expressed in the new CRC molecular subtypes. We have then developed a monoclonal antibody (mAb) against CLDN1, called 6F6, which targets the extracellular part of CLDN1. Results showed that the 6F6 mAb significantly decreased cell growth, survival, and migration in vitro as well as in vivo. Furthermore, we demonstrated the cytostatic effect of the 6F6 mAb through proliferation assays. We are now deciphering the role of CLDN1 on 3D spheroids, a model that reflects the physiopathology. Using immunofluorescence staining on frozen sections we are exploring the impact of CLDN1 on spheroids proliferation. We are also investigating on the distribution of tight junction proteins implicated on cell proliferation in the presence or absence of CLDN1. CLDN1 is a new promising therapeutic target in CRC, it is now interesting to elucidate its role in colorectal cancer cell proliferation. Keywords: Colorectal, Cancer, Claudin-1, monoclonal antibodies, spheroids, proliferation Citation Format: Sara Cherradi, Adeline Ayrolles-Torro, Nadia Vezzo-Vié, Eve Combes, Lucile Canterel-Thouennon, Fabien Gava, Valérie Lobjois, Bernard Ducommun, Celine Gongora, Maguy Del Rio. Targeting the tight junction protein claudin-1 in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2902.
Quantifying GPIIb/IIIa Receptor Binding Using 2 Monoclonal Antibodies
Authors: MartinQuinn, AdeleDeering, MauraStewart, DermotCox, BrendanFoley, DesmondFitzgerald
Journal: Circulation (1999)

Background—Dosing of glycoprotein (GP) IIb/IIIa receptor antagonists is frequently based on the inhibition of platelet aggregation, which may be influenced by the agonist used or concurrent medications. Here we describe a monoclonal antibody-based technique to quantify total and ligand-occupied GPIIb/IIIa receptors. Methods and Results—In vitro binding of monoclonal antibodies, LYP18 (Mab1) and 4F8 (Mab2), to the GPIIb/IIIa complex, was characterized using purified receptor and to platelets by flow cytometry. Patients undergoing coronary angioplasty received a single 20 mg dose of the oral GPIIb/IIIa antagonist, xemilofiban, or matching placebo, and antibody binding was compared with inhibition of platelet aggregation. Mab1 and Mab2 were bound to purified GPIIb/IIIa and to unoccupied, inactivated receptor on platelets. Mab2 identified the β3 subunit, whereas Mab1 was complex-specific. Neither antibody interfered with the other’s binding, suggesting that they identified distinct sites. Mab1 identified 53 3...
Abstract 16310: A Third Troponin Sample is Neither Cost-Effective Nor Necessary in Patients Suspected of Acute Coronary Syndrome With First Two Negative Troponins
Authors: Reuben Azad, Sara Collins, Marc Cohen
Journal: Circulation (2016)

Introduction: Chest pain patients account for approximately 8% to 10% of the 119 million Emergency department visits yearly in the United States. Troponin is the most sensitive and specific test fo...
Validation of miR-31-3p Expression to Predict Cetuximab Efficacy When Used as First-Line Treatment in <i>RAS</i> Wild-Type Metastatic Colorectal Cancer
Authors: Pierre Laurent-Puig, Marie-Lise Grisoni, Volker Heinemann, François Liebaert, Daniel Neureiter, Andreas Jung, François Montestruc, Yann Gaston-Mathe, Raphaële Thiébaut, Sebastian Stintzing
Journal: Clinical Cancer Research (2018)

MiR-31-3p expression has been shown to be associated with response to anti-EGFR therapy. We investigated the predictive role of this biomarker in the FIRE-3 study population, including its ability to differentiate outcomes between patients receiving anti-EGFR and anti-VEGF therapy.MiR-31-3p expression was measured in primary tumors obtained from 340 patients with RAS WT mCRC enrolled in the FIRE-3 Trial. This included 164 patients randomized to receive FOLFIRI plus cetuximab (FOLFIRI+Cetux) and 176 to FOLFIRI plus bevacizumab (FOLFIRI+Beva). Patients were divided into subgroups defined by low or high miR-31-3p expression using a prespecified cut-off and by treatment arm. Analyses were performed to assess treatment efficacy by subgroup. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and Cox regression models. Investigator-assessed objective response (iOR), early tumor shrinkage at 6 weeks (ETS), and centrally reviewed objective response (cOR) were analyzed using logistic regression models. The predictive value of miR-31-3p expression level was assessed through a treatment interaction test using multivariate models adjusted for potential confounding factors.Low miR-31-3p expressers benefited from cetuximab compared with bevacizumab for PFS [HR, 0.74; 95% confidence interval (CI), 0.55-1.00; P = 0.05], OS (HR, 0.61; 95% CI, 0.41-0.88; P < 0.01), iOR (OR, 4.0; 95% CI, 1.9-8.2; P < 0.01), ETS (OR, 4.0; 95% CI, 2.1-7.7; P < 0.01 and cOR (OR, 4.9; 95% CI, 2.3-10.5; P < 0.01) in multivariate analyses. There was no difference in outcomes for high expressers between treatment arms. MiR-31-3p expression level was predictive of treatment effect for PFS (P = 0.03), OS (P = 0.05), iOR (P = 0.02), ETS (P = 0.04), and cOR (P < 0.01).MiR-31-3p expression level was validated as a predictive biomarker of cetuximab therapy efficacy for patients with RAS WT mCRC.
Acute Kidney Injury Due to Concomitant Vancomycin and Piperacillin-Tazobactam—Reply
Authors: Colin Bergstrom, Srikanth Nagalla, Arjun Gupta
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
AB1452-HPR Which one has a greater effect on function and the psychosocial status in jia?: disease type or the presence of pain
Authors: G Arın, H.E. Sönmez, N.B. Karaca, E. Sağ, A. Özçadırcı, S. Demir, F.B. Oflaz, Y. Bilginer, D. Aydın Haklı, R. Alpar, E. Ünal, S. Özen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is a chronic inflammatory childhood disease with symptoms such as joint inflammation, pain and loss of quality of life.<sup>1</sup> Types of disease and the presence of pain can impact the child psychosocially, as well as affecting functional activity.<sup>2</sup> <h3>Objectives</h3> The aim of this study is to examine the results of functional and psychosocial status according to the disease type and the presence of pain symptoms in children with JIA. <h3>Methods</h3> The study included 71 children diagnosed with JIA who applied to the Hacettepe University İhsan Doğramacı Children's Hospital Rheumatology Department. Following the collection of demographic information, functional status was assessed with the Child Health Assessment Questionnaire (CHAQ) and psychosocial and functional status was assessed with the scale developed in Hacettepe University Faculty of Health Sciences Department of Physiotherapy and Rehabilitation for functional and psychosocial status of children with rheumatism by Edibe Ünal.<sup>3</sup> Children were divided into groups according to disease type as oligoarthritis or polyarthritis and the presence or absence of pain. <h3>Results</h3> Table 1 shows the mean age and numbers of children. There was no difference between the groups according to disease type (p&gt;0,05). On the other hand, comparing scores for the CHAQ total, CHAQ general VAS assessment, functional and psychosocial status according to the presence or absence of pain revealed significant differences (p&lt;0,05). <h3>Conclusions</h3> We conclude that pain has a greater effect on functional, psychosocial and overall disease assessment in children with JIA when compared to the disease type. Thus, it must be taken into consideration that child's ability to cope with pain should be improved. <h3>References</h3> [1] Angelo Ravelli, Alberto Martini. Juvenile idiopathic arthritis.<i>The Lancet</i>2007, 369(9563); 767–778. [2] Laura E Schanberga, John C Lefebvreb, et al. Pain coping and the pain experience in children with juvenile chronic arthritis. Pain1997, 73(2); 181–189. [3] Kısacık Pınar,Ünal Edibe, et al. Juvenil İdiyopatik Artritli Hastalarda Çok Yönlü Bir Değerlendirme Sistemi Oluşturulması Delphi Çalışması. 2016, <i>Annals Of Paediatric Rheumatology</i> <h3>Disclosure of Interest</h3> None declared
Endothelial Nitric Oxide Synthase in Vascular Disease
Authors: UlrichFörstermann, ThomasMünzel
Journal: Circulation (2006)

Nitric oxide (NO·) is an important protective molecule in the vasculature, and endothelial NO· synthase (eNOS) is responsible for most of the vascular NO· produced. A functional eNOS oxidizes its substrate l-arginine to l-citrulline and NO·. This normal function of eNOS requires dimerization of the enzyme, the presence of the substrate l-arginine, and the essential cofactor (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4), one of the most potent naturally occurring reducing agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen species in the vascular wall. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases represent major sources of this reactive oxygen species and have been found upregulated and activated in animal models of hypertension, diabetes, and sedentary lifestyle and in patients with cardiovascular risk factors. Superoxide (O2·−) reacts avidly with vascular NO· to form peroxynitrite (ON...
An<i>ex vivo</i><scp>RNA</scp><i>trans</i>‐splicing strategy to correct human generalized severe epidermolysis bullosa simplex
Authors: P. Peking, J.S. Breitenbach, M. Ablinger, W.H. Muss, F.J. Poetschke, T. Kocher, U. Koller, S. Hainzl, S. Kitzmueller, J.W. Bauer, J. Reichelt, T. Lettner, V. Wally
Journal: British Journal of Dermatology (2018)

Generalized severe epidermolysis bullosa simplex (EBS‐gen sev) is a genetic blistering skin disease in which autosomal dominant mutations in either the keratin KRT5 or KRT14 genes lead to impaired function of the intermediate filament cytoskeleton in the basal epidermis. Here we present an ex vivo RNA trans‐splicing‐based therapeutic approach to correct the phenotype. To correct a mutation within exon 1 of the KRT14 gene, using a 5′‐trans‐splicing approach, where any mutation within the first seven exons could be replaced by a single therapeutic molecule. A therapeutic RNA trans‐splicing molecule containing wild‐type exons 1–7 was stably transduced into an EBS patient‐derived keratinocyte line. Trans‐splicing was confirmed via reverse‐transcriptase polymerase chain reaction, Western blotting and immunofluorescence microscopy. Skin equivalents generated from corrected keratinocytes were grafted onto nude mice and analysed about 8 weeks post‐transplantation for regular epidermal stratification, trans‐splicing‐induced green fluorescent protein expression and blistering. Transplanted skin equivalents generated from trans‐splicing‐corrected patient keratinocytes showed a stable and blister‐free epidermis. KRT14 correction disrupted EBS‐gen sev‐associated proinflammatory signalling, as shown at the mRNA and protein levels. Disruption of the pathogenic feedback loop in addition to overall downregulation of KRT14 expression highlighted the effect of KRT14 correction on the EBS pathomechanism. Our data demonstrate that trans‐splicing‐mediated mRNA therapy is an effective method for the correction of dominantly inherited KRT14 mutations at the transcriptional level. This results in the rescue of the EBS‐gen sev phenotype and stabilization of the epidermis in a xenograft mouse model.
Abstract 11499: Incremental Prognostic Significance of the Elevated Levels of Pentraxin 3 in Patients With Heart Failure With Normal Left Ventricular Ejection Fraction
Authors: Junichi Matsubara, Seigo Sugiyama, Eiichi Akiyama, Hirofumi Kurokawa, Hirofumi Maeda, Koichiro Fujisue, Koichi Sugamura, Eiichiro Yamamoto, Hisao Ogawa
Journal: Circulation (2013)

Backgrounds: Pentraxin 3 (PTX3) is a novel inflammatory maker and produced by various cell types including vasculature and heart. We have shown that PTX3 is significantly elevated in patients with heart failure with normal left ventricular ejection fraction (HFNEF) and it is an independent inflammatory marker correlated with the presence of HFNEF. We investigate whether plasma levels of PTX3 could predict occurrence of future cardiovascular (CV) events in patients with HFNEF. Methods: We conducted a prospective cohort study of 360 HFNEF patients (age 70.5±9.9, male 55.5%) with measuring plasma inflammatory markers (PTX3, high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor-α and interleukin-6) and B-type natriuretic peptide (BNP) and followed CV events, which were a composite of CV death, non-fatal myocardial infarction or ischemic stroke, unstable angina, hospitalization for HF, or coronary revascularization. Results: A total of 106 patients had a CV event. Kaplan-Meier analysis demonstrate...
Elevated Levels of High-Sensitivity C-Reactive Protein and Serum Amyloid-A Late After Kawasaki Disease
Authors: YoshihideMitani, HirofumiSawada, HidetoshiHayakawa, KenzoAoki, HiroyukiOhashi, MasahikoMatsumura, KenjiKuroe, HidetoShimpo, MasatakaNakano, YoshihiroKomada
Journal: Circulation (2005)

Background— Coronary sequelae that persist after Kawasaki disease (KD) have been associated with obstructive changes of the lesions and coronary vascular events in adolescents and young adults. However, little is known about the association between sequelae late after KD and inflammatory markers, which are potential mediators and markers for atherogenesis. Methods and Results— Cross-sectional study was performed to test the hypothesis that coronary sequelae are associated with elevated levels of inflammatory markers in patients late after KD (mean time interval after the onset, 10 years, 10 months). Levels of high-sensitivity C-reactive protein (CRP), serum amyloid-A (SAA), interleukin-6, and soluble intercellular adhesion molecule-1 were measured in the 4 groups (n=80): the referent group (n=15) and KD subgroups with normal coronary arteries from the onset (n=27); with regressed aneurysms (n=18); and with coronary artery lesions, such as persistent aneurysms, stenosis, and occlusion (n=20). CRP levels we...
Abstract 16636: Patient and Hospital-level Predictors of Early Unplanned Pediatric Cardiac Intensive Care Unit Readmissions
Authors: Andrew H Smith, Vijay Anand, Mousumi Banerjee, Katherine E Bates, Marissa A Brunetti, David S Cooper, Jessica Lehrich, Kshitij P Mistry, Sara K Pasquali, Andrew Y Shin, Sarah Tabbutt, Michael G Gaies
Journal: Circulation (2016)

Background: Unplanned readmissions to pediatric cardiac intensive care units (CICU) are associated with higher mortality and greater resource utilization. Patient and hospital factors leading to CICU readmission remain unknown and differences in readmission rates across hospitals have not been reported. Methods: We examined initial CICU encounters in the Pediatric Cardiac Critical Care Consortium (PC4) registry from 10/2013 to 3/2016. The primary outcome was unplanned CICU readmission <48 hours from CICU discharge. Patient, encounter, and hospital factors were compared. Those associated with the outcome (p<0.1) were included in a multivariable logistic regression model with treating hospital as a fixed effect. Patient factors associated with readmission (p<0.05) formed a model to calculate adjusted hospital readmission rates. Results: Of 11,673 included CICU encounters, 62% were surgical (v. medical) and 70% were planned (v. unplanned). There were 175 (1.5%) unplanned CICU readmissions within 48 hours, mo...
Isolation of a Regulatory Region of Activin Receptor-Like Kinase 1 Gene Sufficient for Arterial Endothelium-Specific Expression
Authors: TsugioSeki, Kwon-HoHong, JihyeYun, Seong-JinKim, S. PaulOh
Journal: Circulation Research (2004)

Activin receptor-like kinase 1 (Acvrl1; Alk1) is a type I receptor for transforming growth factor-β (TGF-β). ALK1 plays a pivotal role in vascular development and is involved in the development of hereditary hemorrhagic telangiectasia 2 (HHT2), a dominantly inherited vascular disorder, and pulmonary hypertension. We have previously shown that Alk1 is expressed predominantly in arterial endothelial cells (ECs). Despite recent discoveries of a number of artery-specific genes, the regulatory elements of these genes have not been characterized. To investigate the cis-acting elements essential for the artery-specific Alk1 expression, we have generated a series of transgenic constructs with various lengths and regions of Alk1 genomic fragments connected to a LacZ reporter gene, and analyzed the reporter gene expression in transgenic mice. We found that a 9.2-kb genomic fragment, which includes 2.7-kb promoter region and the entire intron 2, is sufficient to drive arterial endothelium-specific expression. The de...
Abstract 4553: A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint
Authors: Iris Koopmans, Douwe F. Samplonius, Robert J. van Ginkel, Peter J. Wierstra, Sandra Heskamp, Edwin Bremer, Wijnand Helfrich
Journal: Cancer Research (2018)

Abstract PD-L1-blocking antibodies produce significant clinical benefit in selected cancer patients by reactivating functionally-impaired anticancer T cells. However, their efficacy is potentially reduced by ‘on-target/off-tumor' binding to PD-L1 widely expressed on normal cells. This lack of tumor selectivity potentially induces a generalized activation of all antigen-experienced T cells as is evidenced by frequent autoimmune-related adverse events during and after treatment. To address these issues, we constructed a tetravalent bispecific antibody (bsAb), designated PD-L1xEGFR, to direct PD-L1-blockade to EGFR-expressing cancer cells and thus reactivate anticancer T cells more selectively. The IC50 of PD-L1xEGFR for binding to EGFR+ cancer cells was ~140 fold lower compared to an analogous PD-L1-blocking bsAb of irrelevant target antigen specificity (PD-L1xMock). Importantly, treatment with PD-L1xEGFR selectively enhanced activation status, INF-γ production, and activity of anti-CD3xanti-EpCAM-redirected T cells in presence of EGFR+/EpCAM+, but not EGFR-/EpCAM+ carcinoma cells. Similarly, capacity of PD-L1xEGFR to promote proliferation and IFN-γ production by CMVpp65-specific CD8+ effector T cells was enhanced in the presence of EGFR+/CMVpp65+ cancer cells. In contrast, the clinically-used PD-L1-blocking antibody MEDI4736 (durvalumab) promoted T cell activation indiscriminate of EGFR expression on cancer cells. Additionally, in tumor-bearing mice 111In-PD-L1xEGFR showed a significantly higher tumor uptake compared to 111In-PD-L1xMock. In conclusion, PD-L1xEGFR blocks the PD-1/PD-L1 immune checkpoint in an EGFR-directed manner, which promotes a more selective reactivation of anticancer T cells. This novel targeted approach may be useful to enhance efficacy and safety of PD-1/PD-L1 checkpoint blockade in EGFR-overexpressing malignancies. Citation Format: Iris Koopmans, Douwe F. Samplonius, Robert J. van Ginkel, Peter J. Wierstra, Sandra Heskamp, Edwin Bremer, Wijnand Helfrich. A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4553.
Ventricular Afterload and Ventricular Work in Fontan Circulation
Authors: HideakiSenzaki, SatoshiMasutani, JunKobayashi, ToshikiKobayashi, NozomuSasaki, HaruhikoAsano, ShuneiKyo, YujiYokote, AkiraIshizawa
Journal: Circulation (2002)

Background— Recent studies have indicated that there are inherent limitations associated with Fontan physiology. However, there have been no quantitative analyses of the effects of right heart bypass on ventricular afterload, hydraulic power, and resultant overall hemodynamics. Methods and Results— During routine cardiac catheterization, aortic impedance and ventricular hydraulic power were determined, both at rest and under increased ventricular work induced by dobutamine, in 17 patients with Fontan circulation, 15 patients with a single ventricle whose pulmonary circulation was maintained only by Blalock-Taussig shunts, and 13 patients who had normal 2-ventricle circulation. Both vascular resistance (nonpulsatile load on the ventricle) and pulsatile components of ventricular afterload (represented by low-frequency impedance) were significantly higher in the Fontan group than in the other groups (P<0.01), and this was associated with decreased cardiac output in the Fontan patients. In addition, hydraulic...