tbuckley/cabot-search huggingface dataset:
Are Olympic athletes free from cardiovascular diseases? Systematic investigation in 2352 participants from Athens 2004 to Sochi 2014
Authors: Antonio Pelliccia, Paolo Emilio Adami, Filippo Quattrini, Maria Rosaria Squeo, Stefano Caselli, Luisa Verdile, Viviana Maestrini, Fernando Di Paolo, Cataldo Pisicchio, Roberto Ciardo, Antonio Spataro
Journal: British Journal of Sports Medicine (2016)

Olympic athletes represent model of success in our society, by enduring strenuous conditioning programmes and achieving astonishing performances. They also raise scientific and clinical interest, with regard to medical care and prevalence of cardiovascular (CV) abnormalities.Our aim was to assess the prevalence and type of CV abnormalities in this selected athlete's cohort.2352 Olympic athletes, mean age 25±6, 64% men, competing in 31 summer or 15 winter sports, were examined with history, physical examination, 12-lead and exercise ECG and echocardiography. Additional testing (cardiac MRI, CT scan) or electrophysiological assessments were selectively performed when indicated.Prevalence and type of CV findings, abnormalities and diseases found in Olympic athletes over 10 years.A subset of 92 athletes (3.9%) showed abnormal CV findings. Structural abnormalities included inherited cardiomyopathies (n=4), coronary artery disease (n=1), perimyocarditis (n=4), myocardial bridges (n=2), valvular and congenital diseases (n=45) and systemic hypertension (n=10). Primary electrical diseases included atrial fibrillation (n=2), supraventricular reciprocating tachycardia (n=14), complex ventricular tachyarrhythmias (non-sustained ventricular tachycardia, n=7; bidirectional ventricular tachycardia, n=1) or major conduction disorders (Wolff-Parkinson-White (WPW), n=1; Long QT syndrome (LQTS), n=2).Our study revealed an unexpected prevalence of CV abnormalities among Olympic athletes, including a small, but not negligible proportion of pathological conditions at risk. This observation suggests that Olympic athletes, despite the absence of symptoms or astonishing performances, are not immune from CV disorders and might be exposed to unforeseen high-risk during sport activity.
Abstract 4056: Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses
Authors: Hiroaki IKUSHIMA, Tadatsugu TANIGUCHI
Journal: Cancer Research (2015)

Abstract The eradication of cancer cells requires communication between cells which constitute the complex immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate arm of the immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. In addition, although signal-transducing pattern recognition receptors are known to play important roles in innate immune responses against invading pathogens through recognition of pathogen-associated molecular patterns (PAMPs), it is still enigmatic whether and how these receptors contribute to anti-tumor immune responses. In this study, we show that the innate immune pattern recognition receptor Dectin-1 expressed on dendritic cells (DCs) and macrophages is critical to NK-mediated killing of tumor cells. We also show that tumor cell-mediated Dectin-1 signaling is instigated by the receptor recognition of N-glycan structures on tumor cells, which we term tumor-associated molecular patterns (TAMPs). As such, the TAMP-Dectin-1 signaling causes activation of the Interferon Regulatory Factor 5 (IRF5) transcription factor and subsequent induction of genes required for the full-blown killing activity of NK cells. The importance of these events is underscored by the observation of massive tumor metastasis in mice genetically deficient in either Dectin-1 or IRF5. Thus, these results reveal a hitherto unrecognized facet of pattern recognition receptors in the orchestration of anti-tumor innate immune responses; recognition of TAMPs. This study is the first demonstration that an innate immune pattern recognition receptor potentiates anti-tumor immune responses, offering new insight into anti-tumor activity of the innate immune system with implications for anti-tumor immunotherapy. Citation Format: Hiroaki IKUSHIMA, Tadatsugu TANIGUCHI. Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4056. doi:10.1158/1538-7445.AM2015-4056
Patients with Non-Hodgkin’s Lymphoma Receiving Myelosuppressive Chemotherapy with First and Subsequent Cycle Pegfilgrastim Support Experience Low Rates of Neutropenic Complications: Preliminary Results of FIRST, a Prospective Community-Based Study.
Authors: Howard Ozer, Stephen J. Noga, Vicki A. Morrison, Beiying Ding, Roger Dansey
Journal: Blood (2005)
Abstract 2382: Exploring the relationship between reelin signaling and breast cancer metastasis
Authors: Elvira Khialeeva, Joan Chou, Ellen M. Carpenter
Journal: Cancer Research (2015)

Abstract We have investigated the role of reelin signaling in the progression of metastatic breast cancer. Reelin signaling serves to position neurons in the developing central nervous system, but functions of this signaling pathway in other tissues have not been studied until recently. Our laboratory discovered that the reelin pathway is an important regulator of mammary gland development. We showed that reelin and Dab1, the intracellular adaptor protein for reelin, are required for timely development and proper morphology of the mammary gland. We also found that normal mammary epithelial cells (MECs) can respond to exogenous reelin by slowing their migration rate. Since aberration of developmental pathways is often implicated in breast cancer progression, we studied the possible roles of the reelin pathway in this process. We found that reelin signaling pathway components are differentially expressed across a variety of human breast cancer cell lines. We also showed that mouse mammary carcinoma 4T1 cells do not respond to reelin by slowing their migration, likely through downregulation of Dab1 mRNA. Orthotopic injections of 4T1 cells into Balb/C mice are used to model stage IV triple negative breast cancer, and resulted in aggressive tumors that produced numerous metastases in the lungs by 4 weeks post-injection. In order to find whether reelin signaling functions in the tumor microenvironment, we injected 4T1 cells into mice that lack reelin or Dab1 (reeler and Dab1 mutant mice). We found that 4T1 tumor growth was delayed in reeler mutants, and we are currently in the process of assessing the metastatic burden in these mice. We did not see differences in tumor growth or metastatic lung colonization in Dab1 mutant mice. These results indicate that the reelin signaling pathway may promote tumor growth via Dab1-independent, non-canonical signaling events. Citation Format: Elvira Khialeeva, Joan Chou, Ellen M. Carpenter. Exploring the relationship between reelin signaling and breast cancer metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2382. doi:10.1158/1538-7445.AM2015-2382
18F-FDG and 68Ga-DOTATATE PET/CT in von Hippel-Lindau Disease–Associated Retinal Hemangioblastoma
Authors: Georgios Z. Papadakis, Corina Millo, Inderbir S. Jassel, Ulas Bagci, Samira M. Sadowski, Apostolos H. Karantanas, Nicholas J. Patronas
Journal: Clinical Nuclear Medicine (2016)

Retinal hemangioblastomas are highly vascular benign tumors that can be encountered either sporadically or within the von Hippel-Lindau (VHL) syndrome. We report a case of a VHL patient with retinal hemangioblastoma who underwent PET/CT scans using 18F-FDG and 68Ga-DOTATATE. The tumor showed low-level 18F-FDG and increased 68Ga-DOTATATE activity, suggesting cell-surface overexpression of somatostatin receptors. The presented case indicates the clinical applications of somatostatin receptor imaging with 68Ga-DOTA–conjugated peptides in detection and follow-up of VHL manifestations, screening of asymptomatic gene carriers, and in diagnosis of sporadic retinal hemangioblastomas, which may have similar features on MRI with other retinal tumors.
134. Generation of Light-Emitting Somatic-Transgenic Mice for Disease Modelling of Hypoxic Ischaemic Encephalopathy
Authors: Rajvinder Karda, Juliette M.K.M. Delhove, Suzanne M.K. Buckley, Ahad A. Rahim, Eridan Rocha-Ferreira, Dany P.B. Perocheau, Joanne Ng, Tristan R. Mckay, Henrik H. Hagberg, Simon N. Waddington, Mark R. Johnson
Journal: Molecular Therapy (2015)

Hypoxic Ischemic Encephalopathy (HIE), occurs in 2-3 per 1000 live births. 25% of surviving affected newborns will suffer from severe life-long neurological disability. HIE is associated with reactive astrogliosis and inflammation. During this process the activity of STAT3 and NFkB transcription factors is increased, and glial fibrillary acidic protein (GFAP) expression is upregulated in astrocytes. Light producing transgenic mice, where luciferase expression is controlled by a surrogate promoter or by a minimal promoter downstream of tandem, synthetic, transcription factor binding elements, are used to provide an in vivo readout of disease processes. In this study, we aimed to deliver STAT3 and NFkB activated or GFAP promoter driven luciferase reporter constructs to brains of neonatal mice as a form of assessing the amount of astrogliosis and inflammation in a mouse model of HIE. A rodent GFAP promoter, and STAT3 and NFkB response elements were each cloned into a lentivirus vector upstream of the genes encoding a codon-optimised firefly luciferase and green fluorescent protein. Lentivirus vector pseudotyped with either gp64 or VSV-g viral envelope glycoproteins were injected intra-cranially into CD1 outbred neonatal (P0) mice, and luciferase expression was monitored continually by whole body bioluminescence imaging of conscious mice. Vector containing NFkB response element was also injected into P0 mice, which underwent HIE surgery at P7. The two pseudotypes gp64 and VSV-g exhibited different cellular tropisms within the central nervous system; VSV-g predominately targeting neuronal cells whereas gp64 transducing cells of fibrillary astrocytic morphology. Long-term expression of luciferase was observed. Following induction of HIE, the most severely affected mice lost weight. We observed a significant correlation between the luciferase expression 24 hours after surgery and weight 7 days after surgery (P = 0.0007) in mice which had received the gp64 pseudotyped NFkB biosensor; the most severely affected HIE mice had the lowest luciferase expression and weight. However, the HIE mice which had received the VSV-g pseudotyped NFkB biosensor failed to show this correlation between the luciferase expression and weight (P=0.479). This indicates that NFkB-controlled luciferase expression in astrocytes is predictive of brain injury. We are now investigating the mechanism of this predictive relationship.
National Institutes of Health Consensus Development Conference Panel statement: Management of hepatitis C
Journal: Hepatology (1997)

The objective of this article is to provide health care providers, patients, and the general public with a responsible assessment of current available methods to diagnose, treat, and manage hepatitis C. A non-Federal, non-advocate, 12-member panel representing the fields of general internal medicine, hepatology, gastroenterology, infectious diseases, medical ethics, transfusion medicine, epidemiology, biostatistics, and the public participated. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1,600. The literature was searched through Medline, and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after conference. Hepatitis C is a common infection with variable course that can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The course of illness may be adversely affected by various factors, especially alcohol consumption. Therefore, more than one drink per day is strongly discouraged in patients with hepatitis C, and abstinence from alcohol is recommended. Initial therapy with interferon alfa (or equivalent) should be 3 million units three times per week for 12 months. Patients not responding to therapy after 3 months should not receive further treatment with interferon alone, but should be considered for combination therapy of interferon and ribavirin or for enrollment in investigational studies. Individuals infected with the hepatitis C virus (HCV) should not donate blood, organs, tissues, or semen. Safe sexual practices, including the use of latex condoms, is strongly encouraged for individuals with multiple sexual partners. Expansion of needle exchange programs should be considered in an effort to reduce the rate of transmission of hepatitis C among injection drug users.
156. Cationic Lipopolymers for BCR-ABL siRNA Delivery and Growth Arrest in Chronic Myeloid Leukemia Tumors
Authors: Juliana Valencia-Serna, K.C.B. Remant, Xiaohong Yang, Hamid M. Aliabadi, Manoj B. Parmar, Xiaoyan Jiang, Hasan Uludag
Journal: Molecular Therapy (2015)

Chronic Myeloid Leukemia (CML) is a disease initiated by hematopoietic stem cells after chromosomal translocation, which results in a BCR-ABL fusion oncogene. This fusion causes permanent activation of ABL tyrosine kinase that leads to myeloid cell expansion and accumulation of immature blast in bone marrow and bloodstream [1]. The shortcomings of current leukemia treatments i.e., acquired drug resistance and drug insensitivity, call for development of new treatments [2]. To this end, we have designed a carrier system using cationic lipo-polymers and evaluated the potential of siRNA therapy in vitro and in vivo using this polymer system. Cationic lipo-polymers were prepared by grafting aliphatic lipids (palmitic acid, PA, α-linoleic acid, αLA and carboxyl end-capped αLA) onto 1.2 kDa polyethyleneimine (PEI) via N-acylation [3]. The carboxyl-end capped αLA (tαLA) was prepared by coupling αLA with mercaptopropionic acid through thio-ester linkage. Structural functionalities of tαLA and modified PEIs were analyzed through 1H-NMR spectroscopy and TNBS assay. GFP-expressing CML cells (GFP-K562 cells) were used as cell model and siRNA specific to BCR-ABL as therapeutic model. To create polymer/siRNA complexes that are more conducive for dissociation, polyanionic additive (hyaluronic acid, HA) was incorporated along with siRNA to PEI- tαLA complexes. GFP silencing efficacy of PEI in GFP-K562 cells was significantly increased (~ 60%) by hydrophobic modification and it was higher/or comparable to commercial agents, e.g. Lipofectamine™ 2000, Turbofect™ and PEI25. Addition of HA into complexes further increased the GFP silencing efficacy (~ 80%). A significant cell growth arrest was observed in day-6 and day-9 in GFP-K562 cells compared to control groups after the treatment with PEI1.2-αLA/BCR-ABL complexes. To evaluate the in vivo therapeutic efficacy, five-week old female nu-nu mice (Taconic Farms) were employed as animal models. Subcutaneous treatment (vicinity of the tumor) with PEI1.2-αLA/BCR-ABL was substantially effective in reducing tumor volumes starting from day 3 (Figure 1). ddPCR supports this silencing effect by revealing a reduction in BCR-ABL mRNA expression. Similar results were found when tumors were injected with siRNA intra-peritoneally. These preliminary results demonstrate the use of hydrophobically modified small molecular weight PEIs as effective carriers for siRNA delivery and therefore their potential for therapeutic use in the treatment of CML.
KIT Mutations Define Characteristic Gene Expression Signatures in Core Binding Factor Leukemias.
Authors: Sonja C. Schmid-Fetzer, Juan Du, Stephan Kurz, Claudia Scholl, Sandrine Sander, Andrea Corbacioglu, Annika C. Russ, Stefan Frohling, Richard Schlenk, John R. Pollack, Konstanze Dohner, Hartmut Dohner, Lars Bullinger
Journal: Blood (2007)
Abstract 470: Nicotine reduces survival via augmentation of paracrine HGF-MET signaling in the pancreatic cancer microenvironment
Authors: Daniel Delitto, Dongyu Zhang, Song Han, Brian S. Black, Andrea E. Knowlton, Adrian C. Vlada, George A. Sarosi, Kevin E. Behrns, Ryan M. Thomas, Xiaomin Lu, Chen Liu, Thomas J. George, Steven J. Hughes, Shannon M. Wallet, Jose G. Trevino
Journal: Cancer Research (2015)

Abstract Smoking is an established risk factor for the development of pancreatic adenocarcinoma (PC). However, the relationship between smoking and PC tumor biology is incompletely defined. We report reduced overall survival (OS) in PC patients who continued smoking after surgical resection with curative intention (HR 1.93; P = .040). We further demonstrate augmented paracrine signaling via the hepatocyte growth factor (HGF)/c-Met pathway as a result of nicotine exposure in the PC microenvironment. Specifically, HGF, secreted by patient-derived PC tumor associated stroma (TAS), activates the c-Met receptor in PC cells. This paracrine activation subsequently leads to downstream induction of inhibitor of differentiation-1 (Id1) in PC cells, previously established as a mediator of chemoresistance. Further delineation of the signaling pathway demonstrates HGF-induced Id1 expression is abrogated by silencing of c-Met or pharmacologic inhibition. In patient-derived PC xenografts, nicotine treatment augmented tumor growth and metastasis; tumor lysates from nicotine-treated mice demonstrated elevated HGF expression and phospho-Met levels. Additionally, patients with high intratumoral phospho-Met levels exhibited reduced overall survival compared to those with low phospho-Met levels (Median OS 6.1 vs. 15.2 months, respectively; P = .028). Taken together, our data reveal that nicotine promotes the progression of PC via a microenvironment-dependent, paracrine signaling mechanism. Citation Format: Daniel Delitto, Dongyu Zhang, Song Han, Brian S. Black, Andrea E. Knowlton, Adrian C. Vlada, George A. Sarosi, Kevin E. Behrns, Ryan M. Thomas, Xiaomin Lu, Chen Liu, Thomas J. George, Steven J. Hughes, Shannon M. Wallet, Jose G. Trevino. Nicotine reduces survival via augmentation of paracrine HGF-MET signaling in the pancreatic cancer microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 470. doi:10.1158/1538-7445.AM2015-470
Prognostic Role of Host Immune Gene Polymorphisms for Patients with Diffuse Large B-Cell Lymphoma Treated with Rituximab and Chemotherapy. A Study Based on 554 Patients Included in the GELA (Groupe d'Etude des Lymphomes de l'Adulte) Prospective Multicentric Program LNH2003,
Authors: Herve Ghesquieres, Fabrice Jardin, Sophie Pallardy, Aurélie Verney, Anne Laure Borrel, Nicolas Ketterer, Christian Recher, Richard Delarue, Andre Bosly, Bertrand Coiffier, Rene-Olivier Casasnovas, Olivier Fitoussi, Frederic Peyrade, Vincent Ribrag, Diana Zelenika, Herve Tilly, Corinne Haioun, Gilles Andre Salles
Journal: Blood (2011)
Allele Matching At HLA-C or DRB1 Is Associated with Improved Survival After Reduced Intensity Double Umbilical Cord Blood Transplantation
Authors: Alfred L. Garfall, Haesook T Kim, Corey Cutler, Vincent T Ho, John Koreth, Philippe Armand, Yi-Bin A. Chen, Steven L. McAfee, Bimalangshu R. Dey, Deborah Liney, Edwin Alyea, Robert J. Soiffer, Thomas R. Spitzer, Joseph H. Antin, Karen K. Ballen
Journal: Blood (2012)
Abstract 620: Monitoring leptomeningeal metastasis treatment response using tumor cell free DNA from cerebral spinal fluid
Authors: Melanie Hayden Gephart
Journal: Cancer Research (2015)

Abstract Background: Cerebral Spinal Fluid (CSF) from brain tumor patients contains tumor cell free DNA (cfDNA), which may provide a non-invasive and routinely accessible method to obtain tumor genomic information. This “liquid biopsy” method would prove considerably less morbid compared to an open removal of tumor tissue from the brain. The opportunities of cfDNA in CSF have not been systematically studied in CSF, particularly in relation to how metastatic brain tumor cfDNA may respond to intrathecal therapy. Methods: A patient who presented with elevated intracranial pressure from metastatic melanoma to the leptomeninges underwent serial therapuetic lumbar punctures, approximately every two weeks over a period of three months. CSF was obtained through an informed consent, IRB approved protocol. The primary melanoma tumor was known to have a BRAF mutation 1799T&amp;gt;A (V600E). cfDNA was isolated from the CSF, and sequenced to confirm the presence of this same tumor-specific BRAF mutation. Droplet Digital PCR (ddPCR) quantified the mutant DNA amount and fraction in CSF. These results were compared to the clinical cytology results from the same sample. Results: Six time points were collected in 61 days. Tumor cfDNA was detectable in the first five time points. Mutant DNA fraction decreased from 53% to almost zero. The total amount of mutant DNA decreased from 220 copies per ml of CSF to 4 copies per ml of CSF. This result was concordant with the patient's clinical response to therapy. Conclusion: Tumor cfDNA was found in CSF from a cancer patient with leptomeningeal metastases. Both the mutant fraction and total copies of mutant DNA corresponded with the patient's response to systemic therapy. This non-invasive method may provide a powerful tool for identifying and monitoring the genetic fingerprint of brain metastases. Citation Format: Melanie Hayden Gephart. Monitoring leptomeningeal metastasis treatment response using tumor cell free DNA from cerebral spinal fluid. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 620. doi:10.1158/1538-7445.AM2015-620
Metformin Induces p53-Dependent Mitochondrial Stress in Therapy-Sensitive and -Resistant Lymphoma Pre-Clinical Model and Primary Patients Sample with B-Cell Non-Hodgkin Lymphoma (NHL)
Authors: Juan J Gu, Qunling Zhang, Cory Mavis, Myron S. Czuczman, Francisco J. Hernandez-Ilizaliturri
Journal: Blood (2015)
TP53 Mutation Is Rare In Primary Myelofibrosis
Authors: Wesley O. Greaves, Shalini Verma, Tigist Bisrat, Hamed Rahimi, Abhaya Paladugu, Carlos E. Bueso-Ramos, Keyur P. Patel, Rajyalakshmi Luthra, Hui Yao, Srdan Verstovsek
Journal: Blood (2011)