tbuckley/cabot-search huggingface dataset:
Abstract 14637: Effects of Dietary Patterns in the Severity of Coronary Artery Disease
Authors: George Georgiopoulos, Gerasimos Siasos, Eleni Kokkou, Evangelos Oikonomou, Stathis Dimitropoulos, Christina Chrysohoou, Konstantinos Mourouzis, Maria Anastasiou, Christina Biri, Theodoros Zografos, Alexis Antonopoulos, Aggelos Papanikolou, Dimitris Tousoulis
Journal: Circulation (2015)

Introduction: The impact of diet on atherosclerosis progression is well established. However, the independent predictive value of unhealthy diet in the prognosis and severity of coronary artery disease (CAD) has not been definitely confirmed and clinicians often ignore how to incorporate it in clinical practice. Hypothesis: Dietary patterns may impact CAD severity. Methods: In this cohort study we included 188 consecutive symptomatic stable CAD patients. The diagnosis of CAD was based on coronary angiography and patients were categorized as having severe CAD and non-severe CAD. The diagnosis of severe CAD was based on the presence of either left main coronary artery disease (stenosis≥50%), or three-vessel coronary artery disease, or two-vessel coronary artery disease marked by stenosis of the proximal left anterior descending artery ≥70%. Among several demographics and clinical characteristics all subjects were tested with a validated semi quantitative food frequency questionnaire. Results: Concerning baseline demographic characteristics there was no difference between subjects with severe CAD and non-severe CAD while, the prevalence of severe CAD was higher in current smokers compared to non-smokers. Principal component analysis revealed 8 distinct dietary patterns. The first component-western dietary pattern (increased intake of fat, red meat and carbohydrates and minimal consumption of fruits vegetables and green leafy)- was predictive of severe CAD (AUC:0.73, 95% CIs:0.64-0.83, p&lt;0.001) and more interestingly, can increase the discriminative ability of a multivariate model based on all major risk factors. Conclusion: The unhealthy western type of diet is associated with the severity and extent of coronary artery lesions in patients with stable CAD. These findings highlight the importance of accessing dietary patterns when calculating cardiovascular risk and to take into consideration dietary habits in the management of cardiovascular patients.
Abstract 1820: Overcoming drug resistance in NSCLC with SRC inhibitor
Authors: Soumavo Mukherjee, Dhananjay Suresh, Ajit P. Zambre, Anandhi Upendran, Raghuraman Kannan
Journal: Cancer Research (2018)

Abstract Lung cancer accounts for about 27 percent of all cancer deaths in the United States. Approximately 85 percent of lung cancers are non-small cell type (NSCLC) and, when treated with both chemotherapy and targeted therapies, have a five-year overall survival rate of approximately 16 percent. These statistics clearly emphasize the need for developing treatment methodologies more effective than the current standard of care. Here, we evaluated the efficacy of combined inhibition of SRC and AXL in NSCLC.Dasatinib, a BCR/abl and src family tyrosine kinase inhibitor (TKI) is a drug that has a potential to be used against both EGFR and KRAS mutated lung cancer patients, alone (phase II clinical trial) and in combination with cetuximab (in phase III clinical trial), osimertinib and erlotinib (both in phase II clinical trials) by exploiting its SRC inhibition capabilities. However, NSCLC patients treated with dasatinib often develop resistance and is the major reason for the low median survival in stage IV patients. Recently, AXL pathway has been shown to be upregulated in Dasatinib resistant cells causing activation of EMT, AKT and survival pathways. It has been suggested that auto-phosphorylation of DDR2 and subsequent activation of SHP2/RAS/AKT pathway as a result of AXL upregulation is one of the major reasons for failure to induce apoptosis in cells during dasatinib resistance. Therefore, we examined whether inhibition of AXL resensitized TKI resistant NSCLC to dasatinib. Our results show that AXL knockdown can resensitize cells to dasatinib. IC50 values decreased significantly following AXL inhibition. We have also demonstrated that nanoparticle-mediated AXL knockdown also produces similar resensitization. The details of the study will be presented. Citation Format: Soumavo Mukherjee, Dhananjay Suresh, Ajit P. Zambre, Anandhi Upendran, Raghuraman Kannan. Overcoming drug resistance in NSCLC with SRC inhibitor [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 1820.
Abstract 2454: Identification of a novel lncRNA family that is required for efficient cellular transformation by Bcr-Abl oncogene
Authors: Jilong Chen, Xuefei Wang
Journal: Cancer Research (2018)

Abstract Human genome transcribes abundant long noncoding RNAs (lncRNAs) that are defined as the transcripts longer than 200 nt without protein-coding capacity. Recently, lncRNAs are being continuously recognized as critical regulators for various biological processes. Aberrant expression of lncRNAs has been shown to be a cornerstone in diverse human diseases and cancer development. Chronic myeloid leukemia (CML) is a hematological malignancy associated with a reciprocal translocation between chromosome 9 and 22 that generates the chimeric Bcr-Abl oncogene. About 10% of acute lymphoblastic leukemia (ALL) patients also contain Bcr-Abl oncogene. However, the functional relevance of lncRNAs in Bcr-Abl-mediated leukemia remains obscure. In this study, we perform a comprehensive analysis of lncRNAs in Bcr-Abl-positive K562 cells using a microarray of cDNAs encoding lncRNAs. This analysis revealed 987 upregulated lncRNAs and 1479 downregulated lncRNAs in response to treatment with imatinib, a Bcr-Abl inhibitor. Importantly, we identified a conserved, imatinib-inducible lncRNA (IIR) family, named lncRNA-IIR37. Upregulation of lncRNA-IIR37 has been detected in both human and mouse Abl-transformed cell lines after imatinib treatment. Interestingly, lncRNA-IIR37 levels are significantly lower in leukemic cells derived from Bcr-Abl-positive ALL patients than those in normal control group. Furthermore, altering lncRNA-IIR37 expression remarkably affects survival of Abl-transformed leukemic cells, and tumorigensis induced by leukemic cells in xenograft mouse model. Knockdown of lncRNA-IIR37 in transgenic mice significantly promotes Bcr-Abl-mediated primary bone marrow transformation. These results indicate that lncRNA-IIR37 functions as a suppressor gene in Bcr-Abl-induced tumorigenesis. In addition, we demonstrated that lncRNA-IIR37 directly bound and affected the phosphorylation of STAT5 to regulate leukemic cell survival. Together, our observations suggest that lncRNA-IIR37 is critically involved in Bcr-Abl-mediated leukemogenesis. These results provide novel insights into complicated mechanisms underlying cellular transformation by Bcr-Abl oncogene. Citation Format: Jilong Chen, Xuefei Wang. Identification of a novel lncRNA family that is required for efficient cellular transformation by Bcr-Abl oncogene [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 2454.
Oncostatin M Induces Interleukin-6 and Cyclooxygenase-2 Expression in Human Vascular Smooth Muscle Cells
Authors: CatherineBernard, RégineMerval, MarilyneLebret, PhilippeDelerive, IsabelleDusanter-Fourt, StéphanieLehoux, ChristopheCréminon, BartStaels, JacquesMaclouf, AlainTedgui
Journal: Circulation Research (1999)

Abstract—Oncostatin M (OSM), a cytokine first identified from activated monocytes and T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi’s sarcoma. Little is known about the effects of OSM on normal vascular cells. We thus exposed human aortic smooth muscle cells (hASMCs) to OSM, examined cell proliferation and morphology, and determined interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) expression. OSM had a weak antiproliferative effect. After a 4-day incubation with 100 ng/mL OSM, cell count decreased to 69±3% of control. However, OSM induced striking changes in hASMC morphology, characterized by a polyclonal shape, in contrast to the spindle morphological feature of control hASMCs. OSM stimulated the release of IL-6 by hASMCs in a dose-dependent way; after a 48-hour exposure, values were 8.5±0.7, 29.7±3.5, 50.9±4.4, and 73.8±7.6×103 U/mL (n=6) at OSM concentrations of 0, 1, 10, and 100 ng/mL, respectively. OSM induced marked expression of COX-2 protein and mRNA. Leukem...
Prediction of Intravenous Immunoglobulin Unresponsiveness in Patients With Kawasaki Disease
Authors: TohruKobayashi, YoshinariInoue, KazuoTakeuchi, YasunoriOkada, KazushiTamura, TakeshiTomomasa, TomioKobayashi, AkihiroMorikawa
Journal: Circulation (2006)

Background— In the present study, we developed models to predict unresponsiveness to intravenous immunoglobulin (IVIG) in Kawasaki disease (KD). Methods and Results— We reviewed clinical records of 546 consecutive KD patients (development dataset) and 204 subsequent KD patients (validation dataset). All received IVIG for treatment of KD. IVIG nonresponders were defined by fever persisting beyond 24 hours or recrudescent fever associated with KD symptoms after an afebrile period. A 7-variable logistic model was constructed, including day of illness at initial treatment, age in months, percentage of white blood cells representing neutrophils, platelet count, and serum aspartate aminotransferase, sodium, and C-reactive protein, which generated an area under the receiver-operating-characteristics curve of 0.84 and 0.90 for the development and validation datasets, respectively. Using both datasets, the 7 variables were used to generate a simple scoring model that gave an area under the receiver-operating-chara...
Action of Ryanodine on Mammalian Cardiac Muscle
Authors: Stephenhajdu, Edwardleonard
Journal: Circulation Research (1961)

The relationship between stimulation frequency and twitch tension was determined for isolated strips of rat right ventricle. Prolonged perfusion of the tissue in physiological saline solution results in diminished twitch tension at low rates of stimulation without alteration of contractility at high stimulation frequency. These changes, which develop over a period of several hours of perfusion, can be induced within 15 minutes by the addition of ryanodine. The addition of strophanthidin restores the twitch tension-frequency relationship of the long-perfused rat ventricle to normal. However strophanthidin has no effect on the impaired contractility of ryanodine treated ventricle ; and, conversely, the addition of ryanodine to digitalized ventricle abolishes the action of the glycoside. The effects of ryanodine can be reversed by perfusing the muscle in a solution which is deficient in either sodium or potassium. Because of the opposing actions of ryano-dine and the cardiac glycosides, the effect of ryanodi...
Pulse Oximetry Is Insensitive for Detection of Hepatopulmonary Syndrome in Patients Evaluated for Liver Transplantation
Authors: Kimberly A. Forde, Michael B. Fallon, Michael J. Krowka, Michael Sprys, David S. Goldberg, Karen L. Krok, Mamta Patel, Grace Lin, Jae K. Oh, Carl D. Mottram, Paul D. Scanlon, Steven M. Kawut
Journal: Hepatology (2018)

Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO
Disruption of the IL6/STAT3 signaling pathway and decreased C/EBP and HNF-1 activity in rats with acute liver failure
Authors: Yukio Kamohara, Helene Lilja, Yvette Middleton, Toomas Neuman, Achilles Demetriou, Jacek Rozga
Journal: Hepatology (1998)

Disruption of the IL6/STAT3 signaling pathway and decreased C/EBP and HNF-1 activity in rats with acute liver failure
Direct In Vivo Observation of Subendocardial Arteriolar Response During Reactive Hyperemia
Authors: ToyotakaYada, OsamuHiramatsu, AkihiroKimura, HiroyukiTachibana, YokoChiba, SongfangLu, MasamiGoto, YasuoOgasawara, KatsuhikoTsujioka, FumihikoKajiya
Journal: Circulation Research (1995)

Abstract To study the vasodilatory capacity of subendocardial (ENDO) arterioles, we evaluated the reactive hyperemic responses of ENDO as well as subepicardial (EPI) arterioles in 40 dogs by our needle-probe intravital microscope. We also examined the individual and combined effects of an ATP-sensitive K+ channel blocker (glibenclamide, 200 μg/kg), an inhibitor of nitric oxide synthase (NG-monomethyl-l-arginine [L-NMMA], 2 μmol/min, 20 minutes), and an adenosine-receptor antagonist (8-phenyltheophylline [8PT], 0.75 μmol/min, 15 minutes). The percent increase in end-diastolic diameter of ENDO arterioles was larger (P<.01) than that of EPI arterioles during reactive hyperemia, especially for the arterioles larger than 120 μm (P<.01). The diastolic-to-systolic vascular pulsation amplitude at the peak flow was greater in ENDO than EPI arterioles (25% versus 6%, P<.05). Compared with control conditions, the presence of both glibenclamide and L-NMMA suppressed the vasodilation responses of ENDO arterioles (P<.0...
Direct Cardiac Reprogramming
Authors: TaketaroSadahiro, ShinyaYamanaka, MasakiIeda
Journal: Circulation Research (2015)

The discovery of induced pluripotent stem cells changed the field of regenerative medicine and inspired the technological development of direct reprogramming or the process by which one cell type is directly converted into another without reverting a stem cell state by overexpressing lineage-specific factors. Indeed, direct reprogramming has proven sufficient in yielding a diverse range of cell types from fibroblasts, including neurons, cardiomyocytes, endothelial cells, hematopoietic stem/progenitor cells, and hepatocytes. These studies revealed that somatic cells are more plastic than anticipated, and that transcription factors, microRNAs, epigenetic factors, secreted molecules, as well as the cellular microenvironment are all important for cell fate specification. With respect to the field of cardiology, the cardiac reprogramming presents as a novel method to regenerate damaged myocardium by directly converting endogenous cardiac fibroblasts into induced cardiomyocyte-like cells in situ. The first in v...
Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis
Authors: Maryou B. Lambros, George Seed, Semini Sumanasuriya, Veronica Gil, Mateus Crespo, Mariane Fontes, Rob Chandler, Niven Mehra, Gemma Fowler, Berni Ebbs, Penny Flohr, Susana Miranda, Wei Yuan, Alan Mackay, Ana Ferreira, Rita Pereira, Claudia Bertan, Ines Figueiredo, Ruth Riisnaes, Daniel Nava Rodrigues, Adam Sharp, Jane Goodall, Gunther Boysen, Suzanne Carreira, Diletta Bianchini, Pasquale Rescigno, Zafeiris Zafeiriou, Joanne Hunt, Deirdre Moloney, Lucy Hamilton, Rui P. Neves, Joost Swennenhuis, Kiki Andree, Nikolas H. Stoecklein, Leon W.M.M. Terstappen, Johann S. de Bono
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency. Experimental Design: We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy-number calls, and study disease heterogeneity. Results: Apheresis was well tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5 mL of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5 mL) was 12,546 CTCs. Purified single CTCs could be isolated from apheresis product by FACS sorting; copy-number aberration (CNA) profiles of 185 single CTCs from 14 patients revealed the genomic landscape of lethal prostate cancer and identified complex intrapatient, intercell, genomic heterogeneity missed on bulk biopsy analyses. Conclusions: Apheresis facilitated the capture of large numbers of CTCs noninvasively with minimal morbidity and allowed the deconvolution of intrapatient heterogeneity and clonal evolution. Clin Cancer Res; 24(22); 5635–44. ©2018 AACR.
Abstract 16222: Abnormal Repolarization and Increased Susceptibility to Ventricular Arrhythmias in a Rat Model of Heart Failure With Preserved Ejection Fraction
Authors: Jae Hyung Cho, Rui Zhang, Romain Gallet, Geoffrey de Couto, Eduardo Marbán, Joshua Goldhaber, Eugenio Cingolani
Journal: Circulation (2016)

Introduction: Unlike heart failure (HF) with reduced ejection fraction, where numerous pharmacological and device options are available, no treatments have been proven to be effective in heart fail...
Abstract 3556: Sam68 is required for the growth and survival of non-melanoma skin cancer
Authors: Kai Fu, Fengyi Wan
Journal: Cancer Research (2018)

Abstract Skin cancer is the most commonly diagnosed malignancy in the United States, and the incidence of skin cancer has increased dramatically over the last few decades. Non-melanoma skin cancer (NMSC), which includes squamous cell carcinomas (SCC) and basal cell carcinomas (BCC), is the most common type of skin cancer with substantial associated morbidity and mortality. Whereas targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of non-melanoma skin cancer (NMSC) remains obscure. Here we report that Src-associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2-transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2-transgenic mice. Moreover, Sam68 plays a critical role in DNA damage-induced DNA repair and nuclear factor kappa B (NF-κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC. Citation Format: Kai Fu, Fengyi Wan. Sam68 is required for the growth and survival of non-melanoma skin 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 3556.
Abstract 2217: Concordance of PIK3CA mutations in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer: A systematic literature review
Authors: Alejandra Aguilar, Joni Dean, Elizabeth Anderson, Lea Mollon, Lisa Davis, Terri Warholak, Ayal Aizer, Emma Platt, Aditya Bardiya, Derek Tang
Journal: Cancer Research (2018)

Abstract Introduction: This systematic literature review sought to determine the concordance of PIK3CA mutations in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) patients. Methods: A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts was performed by two independent researchers that included, but was not limited to, keywords: “breast neoplasm,” “PIK3CA protein,” “hormone receptor positive,” and “metastases.” Databases were searched for English-language publications in HR+, HER2- mBC published between January 1993 through August 2017. Studies were included if results reported were specific to patients with HR+, HER2- mBC and reported data comparing PIK3CA mutations from liquid biopsies versus tumor biopsies or primary tumor samples versus metastatic lesion samples. Concordance was assessed between tissue samples (mutations found in primary tumors versus those from metastatic lesions) and between biopsy methods (i.e., tumor biopsy versus liquid biopsy) when the assessment was done at a variety of time points including time of initial diagnosis and time of diagnosis at disease progression. Content analysis was employed to quantify collected data elements. Results: Of 558 studies included for full-text review, four met inclusion criteria (number of patient samples [n]=358). One study (n = 9) found the concordance between the mutation status of primary breast tumors to the mutation status of metastatic lesions to be 100%. Three studies (n = 47; n = 55; n = 247) determined the concordance of PIK3CA mutations between tumor biopsies and liquid biopsies with concordance ranging from 70.4% to 94%. One study found that the concordance of circulating tumor DNA (ctDNA) against tumor biopsy was higher among metastatic lesions only (81.6%) relative to using all tumor samples (either primary or metastatic lesions) (70.4%). Conclusions: Available evidence suggested high level of concordance across sampling methods as well as across time. However, additional evidence is needed to increase study generalizability as well as to assess other possible confounding factors, such as differential timing between tumor and liquid biopsies. Citation Format: Alejandra Aguilar, Joni Dean, Elizabeth Anderson, Lea Mollon, Lisa Davis, Terri Warholak, Ayal Aizer, Emma Platt, Aditya Bardiya, Derek Tang. Concordance of PIK3CA mutations in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer: A systematic literature review [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 2217.
Role of district health management teams in child health strategies
Authors: Tanya Doherty, Nhan Tran, David Sanders, Sarah L Dalglish, David Hipgrave, Kumanan Rasanathan, Thiagarajan Sundararaman, Rajani Ved, Elizabeth Mason
Journal: BMJ (2018)

Well functioning district health systems are essential for planning and implementation of health services, and their efforts are key to improving quality of care and achieving health goals, say <b>Tanya Doherty and colleagues</b>
Reduction of liver fibrosis by rationally designed macromolecular telmisartan prodrugs
Authors: Matthew R. Golder, Jenny Liu, Jannik N. Andersen, Michail V. Shipitsin, Farrukh Vohidov, Hung V.-T. Nguyen, Deborah C. Ehrlich, Sung Jin Huh, Bhavatarini Vangamudi, Kyriakos D. Economides, Allison M. Neenan, James C. Ackley, Joelle Baddour, Sattanathan Paramasivan, Samantha W. Brady, Eric J. Held, Lawrence A. Reiter, Jennifer K. Saucier-Sawyer, Paul W. Kopesky, Donald E. Chickering, Peter Blume-Jensen, Jeremiah A. Johnson
Journal: Nature Biomedical Engineering (2018)
Abstract 18012: Vital Exhaustion is Not Associated With an Increased Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Brittany M Bogle, Nona Sotoodehnia, Anna Kucharska-Newton, Wayne D Rosamond
Journal: Circulation (2016)

Introduction: Vital exhaustion (VE) is a construct characterized by lack of energy, increased fatigue, irritability, and demoralization. Although multiple small studies suggest a positive associati...