tbuckley/cabot-search huggingface dataset:
Abstract 1535: T Cells engineered to express the IL-13Rα2 specific CAR and a PD-L1 specific switch receptor show increased anti-tumor activity in the Glioblastoma tumor microenvironment
Authors: Abel De Castro, Megan E. Keys, Jonathan Arroyo, Megan E. Prosser
Journal: Cancer Research (2018)

Abstract Glioblastoma multiforme (GBM) is an aggressive brain cancer with poor prognosis with traditional treatments such as chemotherapy and radiotherapy, which often leave lasting and pervasive damage to the individual. GBM cells upregulate the surface protein interleukin 13 receptor subunit alpha-2 (IL13Rα2), which can be targeted as a novel immunotherapeutic marker for the immune response to be initiated. In this study, IL13Rα2 is targeted using a first generation chimeric antigen receptor (CAR) that contains an intracellular zeta chain domain. However, a limitation to this approach is that the tumor microenvironment exhausts the T cells that interact with the tumor through a receptor-mediated response. Programmed Death Ligand 1 (PD-L1) is a molecule that is expressed on cancerous cells that binds to Programmed Death 1 (PD-1) on T cells. When the ligand binds to PD-1 on T cells, there is decreased T cell proliferation, cytokine production, and anti-tumor activity. This problem can be avoided via creation of a switch receptor with a PD-1 extracellular domain fused to transmembrane and intracellular costimulatory CD28, which converts tumor mediated inhibition into stimulation upon ligation of PD-L1. It is hypothesized that the incorporation of additional costimulatory domains will enhance the stimulatory effects of the switch receptor. Engineered T cells expressing varied switch receptors in conjunction with the IL13Rα2-specific CAR have been created and have been assessed in vitro as a basis for glioblastoma treatment. Tests performed include cytokine secretion and T-cell proliferation assays. Results of these preliminary studies suggest that the the inclusion of additional costimulatory domains in the switch receptor design may be advantageous in enhancing anti-tumor responses in the GBM microenvironment. Citation Format: Abel De Castro, Megan E. Keys, Jonathan Arroyo, Megan E. Prosser. T Cells engineered to express the IL-13Rα2 specific CAR and a PD-L1 specific switch receptor show increased anti-tumor activity in the Glioblastoma tumor microenvironment [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 1535.
Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives
Authors: Emmanuel Somm, François R Jornayvaz
Journal: Endocrine Reviews (2018)

Discovered 20 years ago, fibroblast growth factor (FGF)19, and its mouse ortholog FGF15, were the first members of a new subfamily of FGFs able to act as hormones. During fetal life, FGF15/19 is involved in organogenesis, affecting the development of the ear, eye, heart, and brain. At adulthood, FGF15/19 is mainly produced by the ileum, acting on the liver to repress hepatic bile acid synthesis and promote postprandial nutrient partitioning. In rodents, pharmacologic doses of FGF19 induce the same antiobesity and antidiabetic actions as FGF21, with these metabolic effects being partly mediated by the brain. However, activation of hepatocyte proliferation by FGF19 has long been a challenge to its therapeutic use. Recently, genetic reengineering of the molecule has resolved this issue. Despite a global overlap in expression pattern and function, murine FGF15 and human FGF19 exhibit several differences in terms of regulation, molecular structure, signaling, and biological properties. As most of the knowledge originates from the use of FGF19 in murine models, differences between mice and humans in the biology of FGF15/19 have to be considered for a successful translation from bench to bedside. This review summarizes the basic knowledge concerning FGF15/19 in mice and humans, with a special focus on regulation of production, morphogenic properties, hepatocyte growth, bile acid homeostasis, as well as actions on glucose, lipid, and energy homeostasis. Moreover, implications and therapeutic perspectives concerning FGF19 in human diseases (including obesity, type 2 diabetes, hepatic steatosis, biliary disorders, and cancer) are also discussed.
Abstract 4244: Hookah pipe awareness and perceived harmfulness: Prevalence, correlates, and association with smoking cessation outcomes
Authors: Kahee A. Mohammed, Martin W. Schoen, Nosayaba Osazuwa-Peters, Divya S. Subramaniam, Lauren D. Arnold, Leslie Hinyard, Thomas E. Burroughs
Journal: Cancer Research (2018)

Abstract Introduction: Hookah smoking is becoming an increasingly popular choice of tobacco use and is remarkably common among young adults in the United States. This study aimed to evaluate the prevalence and correlates of hookah awareness and perceived harmfulness among US adults and to examine its association with cigarette smoking quit intention and attempt. Methods: Data from the Health Information National Trends Survey 2013 to 2017 were analyzed. The sample included 6,711 adults aged ≥ 18 years. Weighted multivariable logistic regression analyses were performed and adjusted for age, gender, race/ethnicity, education, household income, region, and cigarette smoking status. Results: Overall, 78% of US adults were aware of hookah. Of these, 72% believed hookah pipes were equally harmful as cigarettes, whereas 17.6% believed otherwise. Those who were aware of hookah were less likely to be older (aOR=0.12, 95% CI=0.09 - 0.16), Black (aOR=0.56, 95% CI=0.43 - 0.72) and Hispanic (aOR=0.61, 95% CI=0.48 - 0.79), and lesser-educated (aOR=0.40, 95% CI=0.29 - 0.54) adults. Compared to never smokers, former smokers were 64% (95% CI=1.37 - 1.96) more likely to be aware of hookah. Among those aware of hookah, older (aOR=0.49, 95% CI=0.37 - 0.65), Black (aOR=0.73; 95% CI=0.58 - 0.97), and lesser-educated (aOR=0.69; 95% CI=0.48 - 0.95) were less likely to perceive hookah as less harmful than cigarettes. Those who perceived hookah to be just as harmful as cigarettes were less likely to try to quit cigarette smoking in the past year (aOR=0.49, 95% CI=0.25 - 0.93). Those who perceived hookah to be less harmful than cigarettes were more likely to consider quitting cigarette smoking in the next 6 months (aOR=2.86, 95% CI=1.29 - 6.33). Conclusions: Young, White, and college graduate adults are more likely to believe that hookah smoking is less harmful that cigarettes. These disparities can be used to target behavioral interventions aimed at increasing individuals' perceived risk, knowledge, and perceived harmfulness of hookah smoking. Citation Format: Kahee A. Mohammed, Martin W. Schoen, Nosayaba Osazuwa-Peters, Divya S. Subramaniam, Lauren D. Arnold, Leslie Hinyard, Thomas E. Burroughs. Hookah pipe awareness and perceived harmfulness: Prevalence, correlates, and association with smoking cessation outcomes [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 4244.
Abstract 17521: Roles of Skeletal Muscle in Ventilatory Response to Exercise: Comparison between Myocardial Infarction and Diabetes Mellitus
Authors: Hideki Hayashi, Ryo Tobita, Koji Iwai, Minoru Horie
Journal: Circulation (2016)

Background: Skeletal muscle plays important roles in determining exercise capacity and generating symptoms. This study aims to compare the roles of skeletal muscle in ventilation during incremental...
Abstract 12523: Ventricular Remodeling Post Bariatric Surgery: Sleeve Gastrectomy Vs. Gastric By-pass - A Prospective Study With 3-dimensional Strain
Authors: Thomas E Kaier, Douglas Morgan, Julia Grapsa, David Dawson, Susan B Connolly, Sherif Hakky, Sanjay Purkayastha, Kevin F Fox, Ahmed Ahmed, Jonathan Cousins, Petros Nihoyannopoulos
Journal: Circulation (2013)

Aim: The aim of the study was to examine ventricular remodeling in a group of patients free of cardiac risk factors, before and 6 months post bariatric surgery with the new imaging modality of 3-dimensional strain and compare two surgical techniques: sleeve gastrectomy vs. gastric by-pass. Methods: Fifty-two consecutive patients who were referred to the Bariatric Services of Imperial College NHS Trust were examined with conventional 2D and 3-dimensional strain echocardiography, prior and 6 months after bariatric surgery. They were all free from cardiac disease and risk factors for heart disease such as hypertension, hypercholesterolemia, diabetes and family history of heart disease. Results: The study cohort comprised of 52 bariatric patients with mean age of 44.2 ± 8.7 years and body mass index (BMI) of 42.4 ± 4.6 g/m2. Eighteen patients (34.6%) underwent laparoscopic sleeve gastrectomy and 34 patients laparoscopic gastric by-pass. Twelve patients (23%) were excluded from the 3D strain assessment due to ...
Utility of Absolute and Relative Changes in Cardiac Troponin Concentrations in the Early Diagnosis of Acute Myocardial Infarction
Authors: TobiasReichlin, AffanIrfan, RaphaelTwerenbold, MiriamReiter, WillibaldHochholzer, HannaBurkhalter, StefanoBassetti, StephanSteuer, KatrinWinkler, FedericoPeter, JuliaMeissner, PhilipHaaf, MihaelPotocki, BeatriceDrexler, StefanOsswald, ChristianMueller
Journal: Circulation (2011)

Background—Current guidelines for the diagnosis of acute myocardial infarction (AMI), among other criteria, also require a rise and/or fall in cardiac troponin (cTn) levels. It is unknown whether absolute or relative changes in cTn have higher diagnostic accuracy and should therefore be preferred. Methods and Results—In a prospective, observational, multicenter study, we analyzed the diagnostic accuracy of absolute (Δ) and relative (Δ%) changes in cTn in 836 patients presenting to the emergency department with symptoms suggestive of AMI. Blood samples for the determination of high-sensitive cTn T and cTn I ultra were collected at presentation and after 1 and 2 hours in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing AMI was significantly higher for 2-hour absolute (Δ) versus 2-hour relative (Δ%) cTn changes (area under the receiver operating characteristic curve [95% confidence interval], high-...
Low-power and low-drug-dose photodynamic chemotherapy via the breakdown of tumor-targeted micelles by reactive oxygen species
Authors: Geok Leng Seah, Jeong Heon Yu, Moon Young Yang, Woo Jin Kim, Jin-Ho Kim, Keunchil Park, Jae-Woo Cho, Jee Seon Kim, Yoon Sung Nam
Journal: Journal of Controlled Release (2018)
Ca2+-Calmodulin–Dependent Protein Kinase Phosphorylation of Ryanodine Receptor May Contribute to the β-Adrenergic Regulation of Myocardial Contractility Independently of Increases in Heart Rate
Authors: AliciaMattiazzi, LeticiaVittone, CeciliaMundiña-Weilenmann
Journal: Circulation Research (2008)
Darrel Orlando Ho-Yen
Authors: Colan Maxwell Ho-Yen, Gregory Orlando Ho-Yen
Journal: BMJ (2018)

“Did you see Darrel today? No, but he was definitely in—I heard him!” Darrel Orlando Ho-Yen’s laugh was his trademark and could indeed be heard from quite some distance, usually emanating from the canteen at Raigmore Hospital, where no doubt he was engaged in conversation with intrigued colleagues during a lunch of spam fritters. For Darrel, his laugh was more than an expression of joy, it was a tool, cultivated over a lifetime of many highs and lows and where hard work and a fighting spirit were always in abundance.

Darrel immigrated to London in 1962 from British Guyana and secured a place at Dundee University Medical School …
Omega-3 Fatty Acids Effect on Post-Myocardial Infarction ST2 Levels for Heart Failure and Myocardial Fibrosis
Authors: Bobak Heydari, Shuaib Abdullah, Ravi Shah, Sanjeev A. Francis, Jiazhuo H. Feng, Joseph McConnell, William Harris, Elliott M. Antman, Michael Jerosch-Herold, Raymond Y. Kwong
Journal: Journal of the American College of Cardiology (2018)
Determinants of Surgical Outcome in Patients With Isolated Tricuspid Regurgitation
Authors: Yong-JinKim, Dong-AKwon, Hyung-KwanKim, Jin-ShikPark, SeokyungHahn, Kyung-HwanKim, Ki-BongKim, Dae-WonSohn, HyukAhn, Byung-HeeOh, Young-BaePark
Journal: Circulation (2009)

Background— We sought to identify preoperative predictors of clinical outcomes after surgery in patients with severe tricuspid regurgitation. Methods and Results— We prospectively enrolled 61 consecutive patients (54 women, aged 57±9 years) with isolated severe tricuspid regurgitation undergoing corrective surgery. Twenty-one patients (34%) were in New York Heart Association functional class II, 35 (57%) in class III, and 5 (9%) in class IV. Fifty-seven patients (93%) had previous history of left-sided valve surgery. Preoperative echocardiography revealed pulmonary artery systolic pressure of 41.5±8.7 mm Hg, right ventricular (RV) end-diastolic area of 35.1±9.0 cm2, and RV fractional area change of 41.3±8.4%. The median follow-up duration after surgery was 32 months (range, 12 to 70). Six of the 61 patients died before discharge; thus, operative mortality was 10%. Three of the 55 patients who survived surgery died during follow-up, and 6 patients required readmission because of cardiovascular problems. Th...
Abstract LB-175: The malignancy associated change hypothesis tested through 3D cellular imaging
Authors: Michael Meyer, Laimonas Kelbauskas, Rahul Katdare, Chris Presley, Celeste Hamilton, Daniel Sussman, Tim Bell, Alan Nelson
Journal: Cancer Research (2018)

Abstract Early detection remains by far the most reliable and potent strategy in curing lung cancer. Many current approaches, however, are limited by poor sensitivity or specificity that increase health care costs and potentially risk patient health through unneeded and invasive procedures. The association between cell morphology and cancer has been established in the cytology literature. However, the tumor field effect potentially introduces subtle changes into non-tumor cells that reside in the tumor microenvironment. This phenomenon has given rise to the malignancy associated change (MAC) hypothesis. The Cell-CT™ platform and LuCED® test represent a promising new method for detecting lung cancer with high (92%) sensitivity and (95%) specificity that is based on alterations in cellular morphology. We present a study of 3D morphological alterations in non-tumor cells obtained from sputum of healthy subjects and biopsy confirmed lung cancer patients. Three major cell types were analyzed from 235 patients: bronchial epithelial columnar, squamous intermediate, and mature macrophages (dust cells). We used the Cell-CT platform to measure over 700 different structural biosignatures for each cell. A classifier to test the degree to which the features discriminate between cells from normal or cancer patients was developed and its performance characterized by the area under the ROC curve (aROC) (Table 1). Hierarchical clustering analysis revealed biosignatures of nuclear chromatin organization to be the most differentiating between macrophages from healthy subjects and patients with cancer. Table 1. Classifier development and performance characteristics Cell TypeNumber of cells from cancer patientsNumber of cells from normal patientsSupervised Learning – aROCSquamous Intermediate4,6849530.70Macrophages7,2191,3660.75Columnar cells11,7742,9110.80 Our results confirm the MAC hypothesis based on 3D cellular imaging and suggest that cancer presence in the lung can be detected in patient's sputum based on the morphologic alterations in non-tumor cells. This is important as cancer cells are rare in early stages of cancer, posing challenges in terms of detection sensitivity and specificity. Further work will emphasize boosting of the performance figures above based on the combination of results from the differing methods presented. Citation Format: Michael Meyer, Laimonas Kelbauskas, Rahul Katdare, Chris Presley, Celeste Hamilton, Daniel Sussman, Tim Bell, Alan Nelson. The malignancy associated change hypothesis tested through 3D cellular imaging [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 LB-175.
Interleukin-18/Interleukin-18 Binding Protein Signaling Modulates Atherosclerotic Lesion Development and Stability
Authors: ZiadMallat, AnneCorbaz, AlexandraScoazec, PierreGraber, SamiAlouani, BrunoEsposito, YvesHumbert, YolandeChvatchko, AlainTedgui
Journal: Circulation Research (2001)

Abstract— Interleukin (IL)-18 is the interferon-γ–inducing factor and has other proinflammatory properties. The precise role of IL-18 in immunoinflammatory diseases remains poorly understood. In this study, we show that in vivo electrotransfer of an expression-plasmid DNA encoding for murine IL-18 binding protein (BP) (the endogenous inhibitor of IL-18) prevents fatty streak development in the thoracic aorta of apoE knockout mice and slows progression of advanced atherosclerotic plaques in the aortic sinus. More importantly, transfection with the IL-18BP plasmid induces profound changes in plaque composition (decrease in macrophage, T cell, cell death, and lipid content and increase in smooth muscle cell and collagen content) leading to a stable plaque phenotype. These results identify for the first time a critical role for IL-18/IL-18BP regulation in atherosclerosis and suggest a potential role for IL-18 inhibitors in reduction of plaque development/progression and promotion of plaque stability. The full...
Noel Stephen Cracroft Rice
Authors: Peng Tee Khaw
Journal: BMJ (2018)

Noel Stephen Cracroft Rice was a consultant ophthalmologist who pioneered surgical techniques in corneal and glaucoma surgery, which continue to influence clinical practice today. His parents were a nurse and doctor, and, as a grandson of a vicar, Noel had a strong ethos of duty and doing the right thing. Because of his medical background, he had knowledge of life before the NHS from his parents and was a passionate supporter of the NHS principle. He went up to Clare College in Cambridge where he met his first wife, Brita, and developed a lifelong passion for Scandinavia. He followed in the family tradition of qualifying from Bart’s, where he was house physician to Sir Ronald Bodley-Scott and house surgeon to Alec Badenoch. In 1957 he started his career in ophthalmology under Hyla (Henry) Stallard and continued his training as a surgical flight lieutenant at RAF Halton. After the RAF, he started his training at Moorfields Eye Hospital, where he remained …
Abstract 3435: Differential genomics and transcriptomics between tyrosine kinase inhibitor sensitive versus resistant BCR-ABL dependent chronic myeloid leukemia
Authors: Neetu Singh, Anil Kumar Tripathi, Dinesh Kumar Sahu, Archana Mishra, Margaret Linan, Bianca Argente, Julia Varkey, Rebecca Chowdhry, Avinash Agarwal, Chris Yoo, Ravi Kant, Madan Lal Bhatt
Journal: Cancer Research (2018)

Abstract Previously it has been stated that BCR-ABL1 fusion protein is sufficient to induce CML, but additional genomic changes are required for disease progression. Based on this notion, we profiled control and Tyrosine Kinase Inhibitors (TKI)-treated-CML-samples in different-phases supported by copies of BCR-ABL-transcripts. Molecular-profiling was done through Molecular Inversion Probe (MIP) based array, Human Transcriptomics Array2.0, and Axiom Biobank genotyping-arrays. Transcriptionally, clusters of control, TKI-resistant and -sensitive cases were identified which showed correlation with BCR-ABL transcript-levels with the involvement of 228 pathways. On a comparison between TKI-sensitive versus resistant cases, at the exonic level Cassette Exon splicing event was observed in LAPTM4B (0.46), PIEZO2 (0.32), ANGPT1 (0.29), CFH (0.28), HLTF (0.28), SPTLC3 (0.26); Alternative 3' Acceptor Site splicing (0.22); and Junctional splicing in CD109 and ZNF711. These splicing events led to up-regulation of these transcripts. On further processing through Reactome Pathway, we identified over-expression of Hemostasis pathway in CML-resistant cases with specific involvement of Tie2 and Basigin signalling pathway. Based on CNV profiling, we identified low CNVs in CP-new and CP-UT-TKIs-sensitive cases with undetectable or &amp;lt;10% BCR-ABL copies. While, high CNVs (previously reported gain of 9q34) was observed in BCR-ABL-independent and -dependent TKIs-non-sensitive-CP-UT/AP-UT/B-UT and B-new samples. Further, genotyping CML-CP-UT cases with BCR-ABL 10 to 77.02% copies, we identified and validated rsIDs, rsID239798 and rsID9475077 in linkage with FAM83B which may act as potential therapeutic resistance candidate. BCR-ABL1, additional genetic events, over-expression of Tie-2 and Basigin signalling pathway and rsIDs in linkage with FAM83B in TKI resistant cases can be used for developing a signature profile which may help in monitoring therapy. Citation Format: Neetu Singh, Anil Kumar Tripathi, Dinesh Kumar Sahu, Archana Mishra, Margaret Linan, Bianca Argente, Julia Varkey, Rebecca Chowdhry, Avinash Agarwal, Chris Yoo, Ravi Kant, Madan Lal Bhatt. Differential genomics and transcriptomics between tyrosine kinase inhibitor sensitive versus resistant BCR-ABL dependent chronic myeloid leukemia [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 3435.
Abstract 1813: The role of androgen receptor variant AR-V9 in prostate cancer
Authors: Yeung Ho, Jamie L. Van Etten, Christine Henzler, Yingming Li, Rendong Yang, Elizabeth Tseng, Ting Hon, Tyson Clark, Scott M. Dehm
Journal: Cancer Research (2018)

Abstract The expression of androgen receptor (AR) variants is a frequent, yet poorly-understood mechanism of clinical resistance to AR-targeted therapy for castration-resistant prostate cancer (CRPC). Among the multiple AR variants expressed in CRPC, AR-V7 is considered the most clinically-relevant AR variant due to broad expression in CRPC, correlations of AR-V7 expression with clinical resistance, and growth inhibition when AR-V7 is knocked down in CRPC models. Therefore, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The aim of this study was to understand whether other AR variants are co-expressed with AR-V7 and promote resistance to AR-targeted therapies. To test this, we utilized RNA-seq to characterize AR expression in CRPC models. RNA-seq revealed the frequent coexpression of AR-V9 and AR-V7 in multiple CRPC models and metastases. Furthermore, long-read single-molecule real-time (SMRT) sequencing of AR isoforms revealed that AR-V7 and AR-V9 shared a common 3'terminal cryptic exon. To test this, we knocked down AR-V7 in prostate cancer cell lines and confirmed that AR-V9 mRNA and protein expression were also impacted. In reporter assays with AR-responsive promoters, AR-V9 functioned as a constitutive activator of androgen/AR signaling. Similarly, infection of AR-V9 lentiviral construct in LNCaP cells induced androgen-independent cell proliferation. In conclusion, these data implicate co-expression of AR-V9 with AR-V7 as an important component of constitutive AR signaling and therapeutic resistance in CRPC. Citation Format: Yeung Ho, Jamie L. Van Etten, Christine Henzler, Yingming Li, Rendong Yang, Elizabeth Tseng, Ting Hon, Tyson Clark, Scott M. Dehm. The role of androgen receptor variant AR-V9 in prostate 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 1813.