tbuckley/cabot-search huggingface dataset:
Abstract B27: Osimertinib (AZD9291) is sensitive and bound with affinity to <i>EGFR</i> exon 20 insertion mutant models
Authors: Yusoo Lee, Tae Min Kim, Dong-Wan Kim, Yong-Oon Ahn, Soyeon Kim, Bhumsuk Keam, Miso Kim, Dae Seog Heo
Journal: Clinical Cancer Research (2018)

Abstract Background: Although EGFR exon 20 insertion mutation is the third most common among EGFR-mutant NSCLC, this mutation has not been well studied and the first-generation EGFR TKIs are ineffective. In addition, the efficacy of the third-generation EGFR TKIs is controversial. Methods: Various EGFR exon 20 insertion mutation models were developed using Ba/F3 system as follows: C-helix (n=1, A763_Y764insFQEA) and loop following C-helix (n=7). In addition, SNU-3173 cell line was derived from NSCLC patient with EGFR exon 20 insertion mutation. Cell viability assays were performed using EGFR TKIs (gefitinib, erlotinib, dacomitinib, afatinib, rociletinib, olmutinib, nazartinib, and osimertinib). Immunoblotting was performed to evaluate the downstream signals of EGFR pathway. Additionally, the docking homology models of EGFR exon 20 insertion mutations with osimertinib were developed with SWISS-Model and SwissDock for estimation of the structural appropriateness. Results: Cell viability assay showed that EGFR exon 20 insertion mutants are resistant to the first-generation EGFR TKIs, except for A763_Y764insFQEA mutant Ba/F3 cells. IC50 values of second-generation EGFR TKIs are five- to hundreds-folds lower than gefitinib and erlotinib. Dacomitinib and afatinib have good efficacy for the most of them, and regulated down signaling pathways. The third-generation TKIs showed moderate efficacy against EGFR exon 20 insertion mutants. Overall, osimertinib has the most successful inhibition of EGFR exon 20 insertion mutants (IC50 values for C-helix and loop following C-helix mutants for afatinib, &amp;lt;0.1nM and 16.7-352.5nM; rociletinib 1022.1nM and 288.0-3034.6nM; olmutinib, 351.8nM and 30.4-626.7nM; osimertinib 131.6nM and 14.7-65.7nM; and nazartinib, 351.8nM and 36.3-509.9nM, respectively). Ribbon diagram with in silico homology docking simulations showed how exon 20 insertion mutations change the structures of kinase domain and the suitable binding values with various EGFR exon 20 insertion mutant subtypes with osimertinib. Conclusions: Osimertinib showed an outstanding effectiveness against various EGFR exon 20 insertion mutations. In addition, docking simulation of in silico homology models corresponded with the in vitro results. Consequently, osimertinib is effective against EGFR exon 20 insertion mutant models. Citation Format: Yusoo Lee, Tae Min Kim, Dong-Wan Kim, Yong-Oon Ahn, Soyeon Kim, Bhumsuk Keam, Miso Kim, Dae Seog Heo. Osimertinib (AZD9291) is sensitive and bound with affinity to EGFR exon 20 insertion mutant models [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B27.
Prognostic Implication of the United States Food and Drug Administration-defined BCG-unresponsive Disease
Authors: Roger Li, William B. Tabayoyong, Charles C. Guo, Graciela M. Nogueras González, Neema Navai, H. Barton Grossman, Colin P. Dinney, Ashish M. Kamat
Journal: European Urology (2018)
The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity
Authors: Jorge Domínguez-Andrés, Boris Novakovic, Yang Li, Brendon P. Scicluna, Mark S. Gresnigt, Rob J.W. Arts, Marije Oosting, Simone J.C.F.M. Moorlag, Laszlo A. Groh, Jelle Zwaag, Rebecca M. Koch, Rob ter Horst, Leo A.B. Joosten, Cisca Wijmenga, Alessandro Michelucci, Tom van der Poll, Matthijs Kox, Peter Pickkers, Vinod Kumar, Henk Stunnenberg, Mihai G. Netea
Journal: Cell Metabolism (2018)
Abstract 14643: Absence of Hspb1 Increases Endothelium-dependent Protease Activated Receptor 2-mediated Vasorelaxation in a Female but Not Male Arteries
Authors: Vivek K Pulakazhi Venu, Mahmoud Saifeddine, Mahmoud El-Daly, Darrell Belke, Morley D Hollenberg, Edward R O’Brien
Journal: Circulation (2016)

Introduction: Previously, we and others demonstrated that Heat Shock Protein 27 (HSP27; gene: Hspb1) plays an important endothelial cell (EC) role in the synthesis and secretion of VEGF, as well as EC migration and re-endothelialization. As well we noted an important role of estrogens and ovarian function in modulating HSP27 expression. In this study we sought to examine the potential role of HSP27 in vaso-reactivity and blood pressure regulation - specifically looking for differences in male (M) vs. female (F) mice. Methods/Results: Ex-vivo Study of Aorta: Isolated aortic rings from Hspb1-/-, Hspb1 over-expressing (Hspb1o/e) and wildtype (WT) mice were contracted with phenylephrine (PE) and EC-dependent relaxation responses to Acetylcholine (Ach) and a potent G-protein coupled proteinase-activated receptor-2 (PAR2) agonist, 2-furoyl-LIGRLO-NH2 (2-fLI) were measured in the absence and presence of L-NAME to block NO synthesis. In Hspb1-/- mice NO-independent relaxation was greater in F compared to M mice (...
Specific Association of <i><scp>HLA</scp>–<scp>DRB</scp>1*03</i> With Anti–Carbamylated Protein Antibodies in Patients With Rheumatoid Arthritis
Authors: Cristina Regueiro, Luis Rodríguez‐Rodríguez, Ana Triguero‐Martinez, Laura Nuño, Angel L. Castaño‐Nuñez, Alejandro Villalva, Eva Pérez‐Pampín, Yolanda Lopez‐Golan, Lydia Abasolo, Ana M. Ortiz, Eva Herranz, Dora Pascual‐Salcedo, Ana Martínez‐Feito, María Dolores Boveda, Juan J. Gomez‐Reino, Javier Martín, María Francisca Gonzalez‐Escribano, Benjamín Fernández‐Gutiérrez, Alejandro Balsa, Isodoro González‐Álvaro, Antonio González
Journal: Arthritis & Rheumatology (2018)

Recognition of a new type of rheumatoid arthritis (RA)-specific autoantibody, the anti-carbamylated protein antibodies (anti-CarP), has provided an opportunity to improve the management and understanding of RA. The current study was undertaken to assess the relationship between anti-CarP antibodies and HLA-DRB1 alleles in RA.Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme-linked immunosorbent assay. HLA-DRB1 alleles were determined using either hybridization techniques or imputation from HLA-dense genotypes. Results of these analyses were combined in a meta-analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA-DRB1 alleles were compared between the antibody-positive RA subgroups and the double-negative subgroup of RA patients stratified by anti-citrullinated protein antibody (ACPA)/anti-CarP antibody status, and also between the 4 RA patient strata and healthy controls.Meta-analysis was conducted with 3,709 RA patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA-DRB1*03 carriers in the ACPA-/anti-CarP+ subgroup as compared to ACPA-/anti-CarP- RA patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA-DRB1*03 with ACPA-/anti-CarP+ RA was independent of the presence of the shared allele (SE) and any other confounders analyzed. No other allele was specifically associated with the ACPA-/anti-CarP+ RA patient subgroup. In contrast, frequency of the SE was significantly increased in the ACPA+/anti-CarP- and ACPA+/anti-CarP+ RA patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA-DRB1*03) were associated with protection from ACPA+ RA.These findings indicate a specific association of HLA-DRB1*03 with ACPA-/anti-CarP+ RA, suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA alleles to RA susceptibility.
The post-2009 influenza pandemic era: time to revisit antibody immunodominance
Authors: Kristien Van Reeth
Journal: Journal of Clinical Investigation (2018)

The current inactivated influenza vaccines rely on the induction of neutralizing antibodies against the head domain of the viral hemagglutinin (HA). The HA head contains five immunodominant antigenic sites, all of which are subject to antigenic drift, thereby limiting vaccine efficacy. Bypassing the immune system's tendency to focus on the most variable regions of the HA may be a step toward more broadly protective influenza vaccines. However, this requires a better understanding of the biological meaning of immunodominance, and of the hierarchy between different antigenic sites. In this issue of the JCI, Liu et al. determined the immunodominance of the five antigenic sites of the HA head in experimentally infected mice, guinea pigs, and ferrets. All three species exhibited different preferences for the five sites of the 2009 pandemic H1N1 strain. Moreover, human subjects exhibited yet a different pattern of immunodominance following immunization with the standard inactivated influenza vaccine. Together, these results have important implications for influenza vaccine design and interpretation of animal models.
Abstract 20677: Critical Protective Role of Myocardial Extracellular Superoxide Dismutase (SOD3) in Pressure Overload-Induced Cardiac Oxidative Stress and Hypertrophy
Authors: Chongxu Zhang, Mei Zheng, Sudhahar Varadarajan, Young-Eun Cho, Xingshan Zhao, Masuko Ushio-Fukai, Rongxue Wu, Tohru Fukai, Lei Xiao, Qiong Zhao
Journal: Circulation (2016)

We recently reported that a transgenic (TG) mouse model with cardiac-specific overexpression of a dominant-negative (DN) mutant (V204A) of NADPH oxidase (NOX) subunit p67phox attenuated transverse ...
Abstract 16541: Do Coding Schemas Used to Identify Bleeding-Related Hospitalizations in Claims Analyses of Nonvalvular Atrial Fibrillation Patients Agree?
Authors: Craig I Coleman, Tatsiana Vaitsiakhovich, Elaine Nguyen, Erin R Weeda, Nitesh A Sood, Thomas J Bunz, Bernhard Schaefer, Anna-Katharina Meinecke, Daniel Eriksson
Journal: Circulation (2017)

Introduction: Schemas to identify bleeding-related hospitalizations in claims data differ in both the billing codes used and coding positions allowed. Objective: To assess agreement among commonly used bleeding-related hospitalization coding schemas for claims analyses of nonvalvular atrial fibrillation (NVAF) patients. Methods: Within MarketScan claims data, we identified adults with NVAF newly started on an oral anticoagulant (OAC) from 1/2012-6/2015. Billing code schemas developed by Cunningham et al., Yao et al. and the US Food and Drug Administration (FDA) Mini-Sentinel program were used to identify bleeding-related hospitalizations as a surrogate for major bleeding. Bleeds were subcategorized as intracranial hemorrhage (ICH), gastrointestinal (GI) or other. Schema agreement was assessed by comparing incidence, rates of events/100 person years (PYs) and Cohen’s κ statistic. Results: We identified 151,738 new users of OACs with NVAF (median; 25%, 75% range CHA2DS2-VASc score=3 (2, 4) and HASBLED score...
Cognitive decline as a result of impaired sleep and glucose levels during chemotherapy treatment in breast cancer patients.
Authors: Liliana Moyers-Ruiz, Tamas Hickish, Andrew Mayers, Simon Thompson
Journal: Journal of Clinical Oncology (2013)

e20713 Background: Sleep efficiency might be altered during chemotherapy treatment. Cognitive decline has been associated with sleep disruption, impaired glucose levels, and chemotherapy treatment. We hypothesize that the biological factors considered in this study are playing an important role. Anecdotical reports have shown discrepancy with neuropsychological batteries results, therefore a qualitative interview and memory self-reports will be conducted for the cancer group. Methods: A sample of 32 Breast cancer patients and 29 healthy controls has been recruited in the Dorset area in the UK. The chemotherapy group will be tested three times within de course of their treatment (baseline, mid-treatment, after treatment). The radiotherapy participants will be tested three times within a period of four months, and the healthy control group two times within a four-month period. A subset of chemotherapy participants will be tested six months after chemotherapy. A neuropsychological battery is being used to assess cognitive function, and sleep efficiency is analysed using a sleep monitor and validated self-reports; Furthermore, glucose levels will be analysed for the chemotherapy group, and an online semi-qualitative interview will be conducted for cancer patients for a thematic analysis, along with a Prospective Memory questionnaire. Results: Preliminary data shows that sleep efficiency is disturbed during the course of chemotherapy, although not statistically significant, there is a trend in decreased sleep efficiency percentage when we compared baseline and mid-chemotherapy assessment The strongest tendency is observed on the PSQI self-report, showing an increase in Global PSQI score . Glucose levels show an increase during mid-treatment, although preliminary analyses show no significant effect. Memory data is still under scrutiny and more data will be reported at the poster presentation, along with assessments for times three and four. Conclusions: The inclusion of a semi-qualitative study will add a very important information to this study when test results are compered with anecdotical and self-reports.
Global Orbital Infarction Syndrome After a Carotid Artery Dissection
Authors: Davinia Larrosa Campo, David Fuentes Castañón, Sergio Calleja Puerta
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Tretinoin in New Lotion Formula
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Point‐of‐care screening for sickle cell disease in low‐resource settings: A multi‐center evaluation of HemoTypeSC, a novel rapid test
Authors: Cindy Steele, Annette Sinski, Jacqueline Asibey, Marie‐Dominique Hardy‐Dessources, Gisèle Elana, Colleen Brennan, Isaac Odame, Carolyn Hoppe, Mark Geisberg, Erik Serrao, Charles T. Quinn
Journal: American Journal of Hematology (2018)

Abstract Sickle cell disease (SCD) is a common, life‐threatening genetic disorder that is best managed when diagnosed early by newborn screening. However, SCD is most prevalent in low‐resource regions of the world where newborn screening is rare and diagnosis at the point‐of‐care is challenging. In many such regions, the majority of affected children die, undiagnosed, before the age of 5 years. A rapid and affordable point‐of‐care test for SCD is needed. The diagnostic accuracy of HemoTypeSC, a point‐of‐care immunoassay, for SCD was evaluated in individuals who had SCD, hemoglobin C disease, the related carrier (trait) states, or a normal hemoglobin phenotype. Children and adults participated in low‐, medium‐ and high‐resource environments (Ghana [ n = 383], Martinique [ n = 46], and USA [ n = 158]). Paired blood specimens were obtained for HemoTypeSC and a reference diagnostic assay. HemoTypeSC testing was performed at the site of blood collection, and the reference test was performed in a laboratory at each site. In 587 participants, across all study sites, HemoTypeSC had an overall sensitivity of 99.5% and specificity of 99.9% across all hemoglobin phenotypes. The test had 100% sensitivity and specificity for sickle cell anemia. Sensitivity and specificity for detection of normal and trait states were &gt;99%. HemoTypeSC is an inexpensive (&lt;$2 per test), accurate, and rapid point‐of‐care test that can be used in resource‐limited regions with a high prevalence of SCD to provide timely diagnosis and support newborn screening programs.
Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy
Authors: Carmela Passaro, Quazim Alayo, Isabel DeLaura, John McNulty, Korneel Grauwet, Hirotaka Ito, Vivek Bhaskaran, Marco Mineo, Sean E. Lawler, Khalid Shah, Maria C. Speranza, William Goins, Eric McLaughlin, Soledad Fernandez, David A. Reardon, Gordon J. Freeman, E. Antonio Chiocca, Hiroshi Nakashima
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM. Experimental Design: NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1. Results: NG34scFvPD-1–infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response. Conclusions: NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.
68Ga-PSMA-11 PET/CT in Newly Diagnosed Prostate Adenocarcinoma
Authors: Nurhan Ergül, Burçak Yilmaz Güneş, Uğur Yücetaş, Mahmut Gökhan Toktaş, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2018)

Introduction Prostate-specific membrane antigen (PSMA) ligand PET/CT is an emerging modality to detect the metastatic disease, especially in intermediate- and high-risk prostate cancer (PCa). In this study, we analyzed the contribution of 68 Ga-PSMA-11 PET/CT in staging and therapy management of newly diagnosed PCa. Materials and Methods A total of 78 patients with biopsy-proven PCa who were referred for 68 Ga-PSMA-11 PET/CT for primary staging were retrospectively analyzed. The patients were divided into risk groups according to the D'Amico risk stratification criteria. All of the patients had undergone pelvic MRI, and 65 patients had bone scintigraphy also. The findings of 68 Ga-PSMA-11 PET/CT were compared with these conventional imaging (CI) methods for staging of the disease. The relations between SUV max of the primary tumors and Gleason scores (GSs), prostate-specific antigen (PSA) levels, and metastatic extent of the disease were analyzed. Results Of 78 patients, 5 patients were in low-risk group, 18 patients were in intermediate-risk group, and 55 patients were in high-risk group. Metastatic disease was found in 40 (51.2%) of 78 patients in 68 Ga-PSMA-11 PET/CT. Ten patients had regional lymph node metastases, and 30 patients had distant metastases. 68 Ga-PSMA-11 PET/CT changed the staging in 44 (56.4%) of 78 patients compared with CI. There was significant difference between the SUV max of the tumors with GSs of 6 and 7 compared with GSs of 8, 9, and 10 ( P = 0.003). The SUV max were significantly different between the patients with no metastasis (n = 38) and patients with regional lymph node metastases or distant metastases (n = 40; 16.1 ± 10.9, 28.7 ± 25.8, P = 0.003, respectively). There was significant difference between the SUV max of patients with PSA level less than 10 ng/mL compared with patients with PSA level of 10 or greater and less than 20 ng/mL and PSA 20 ng/mL or greater ( P = 0.009). A weak correlation between PSA and primary tumor SUV max was also found ( r = 0.21). Conclusions 68 Ga-PSMA-11 PET/CT is an important imaging modality for primary evaluation of newly diagnosed PCa changing the disease stage substantially. Also the SUV max of the primary tumor has a relation with GS, metastatic extent of disease, and PSA levels defining the prognosis.
Abstract 14946: Ubiquinol Improves Endothelial Function in Patients With Heart Failure With Reduced Ejection Fraction: A Single Center, Randomized Double-Blind Placebo-Controlled Cross-Over Study
Authors: Chika Kawashima, Yasushi Matsuzawa, Eiichi Akiyama, Ryosuke Sato, Masaaki Konishi, Hiroyuki Suzuki, Yuichiro Kimura, Toshiaki Ebina, Masami Kosuge, Kiyoshi Hibi, Noriaki Iwahashi, Nobuhiko Maejima, Kazuo Kimura
Journal: Circulation (2016)

Introduction: Despite the current evidence based therapies, the outcomes of heart failure with reduced ejection fraction (HFrEF) patients remain poor. Endothelial dysfunction is reportedly associat...