tbuckley/cabot-search huggingface dataset:
Abstract #869: Potentiation of the response to ionizing radiation in breast tumor cells by the vitamin D3 analog, EB 1089
Authors: Molly Hilliker, David Gewirtz
Journal: Cancer Research (2009)

While chemotherapy and radiation treatment may be initially effective at suppressing breast cancer growth, disease recurrence and tumor metastasis remain as primary causes of disease morbidity and mortality. Recurrent and metastatic breast tumors also tend to be significantly less responsive to therapy than the primary disease. Our goal has been to developed approaches to enhance the response to radiation (and chemotherapy) and prevent tumor cell regrowth. Pretreatment with 1-25 dihydroxy vitamin D 3  or an analog, EB1089, enhances the response to both doxorubicin and fractionated radiation (FIR) in p53 wild type breast cancer cell lines. A 72-hour exposure of MCF-7 cells to 100nM of EB1089 prior to 5x2Gy FIR results in an 80% reduction in viable cell number over 96 hours post-irradiation as well as suppression of clonogenic survival. Apoptosis, mitotic catastrophe and senescence are all evident, but autophagy appears to play the central role in the radiosensitization by EB1089 and in prevention of the proliferative recovery that is observed with irradiation alone (where the cells tend to undergo accelerated senescence prior to recovery). Since promotion of autophagy can be cytoprotective as well as cytotoxic, cells exposed to FIR alone, EB 1089 alone, EB1089 + FIR or tamoxifen were incubated with chloroquine, an inhibitor of the autophagic pathway. Chloroquine had no effect on sensitivity to FIR or EB 1089 alone, which induce minimal autophagy; chloroquine enhanced sensitivity to tamoxifen, consistent with a cytoprotective effect of autophagy on the response to tamoxifen. Chloroquine did not interfere with the radiation sensitization induced by EB 1089; however, the cells appeared to shift to an apoptotic mode of cell death. These observations suggest that 1-25 dihydroxy vitamin D 3  and its analogs may commit the breast tumor cells to one or more modes of cell death upon subsequent stress such as irradiation or exposure to drugs that induce DNA damage. Studies are in progress utilizing other pharmacologic inhibitors of autophagy (3-methyl adenine and bafilomycin) as well as genetic knockdown of the expression of autophagy related genes such as ATG5 and Beclin-1 to confirm that interference with autophagy drives the cells towards alternative modes of cell death. Additional studies in progress are designed to evaluate the effects of EB1089 treatment on radiation sensitivity in breast tumor cells that are resistant to both chemotherapeutic drugs and irradiation, focusing on breast tumor cells that overexpress Her-2/neu (MCF7/HER2), as well as p53 mutant BT474 and SKBR3 cells with endogenous overexpression of Her-2. We are further evaluating whether the sensitization to doxorubicin observed in previous studies with EB 1089 and 1-25 dihydroxy vitamin D 3  also occurs through the promotion of autophagy.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 869.
Pharmacists as Integral Members of the Cardiovascular Team
Authors: Dave L. Dixon, Teresa M. Salgado, Antonio Abbate
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
抗原特異的免疫の抗原と活性化の細胞質送達のための生物活性多糖類に基づくpH感受性重合体【Powered by NICT】
Authors: Yuba Eiji, Yamaguchi Ayaka, Yoshizaki Yuta, Harada Atsushi, Kono Kenji
Journal: Biomaterials (2017)
Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE
Authors: Brian M. Alexander, Sujuan Ba, Mitchel S. Berger, Donald A. Berry, Webster K. Cavenee, Susan M. Chang, Timothy F. Cloughesy, Tao Jiang, Mustafa Khasraw, Wenbin Li, Robert Mittman, George H. Poste, Patrick Y. Wen, W.K. Alfred Yung, Anna D. Barker
Journal: Clinical Cancer Research (2017)

Glioblastoma (GBM) is a deadly disease with few effective therapies. Although much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is composed of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage to support registration. Therapeutic arms with biomarkers may be added to the trial over time, while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice. Clin Cancer Res; 24(4); 737-43. ©2017 AACR.
Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study
Authors: Patrick Musicha, Jennifer E Cornick, Naor Bar-Zeev, Neil French, Clemens Masesa, Brigitte Denis, Neil Kennedy, Jane Mallewa, Melita A Gordon, Chisomo L Msefula, Robert S Heyderman, Dean B Everett, Nicholas A Feasey
Journal: The Lancet Infectious Diseases (2017)

Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance.In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time.Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016.The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting.Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).
Preclinical Characterization of Combinability and Potential Synergy of Anti-CD20/CD3 T-Cell Dependent Bispecific Antibody with Chemotherapy and PD-1/PD-L1 Blockade
Authors: Liping Laura Sun, Peiyin Wang, Robyn Clark, Maria Hristopoulos, Diego Ellerman, Mary Mathieu, Yu-Waye Chu, Hong Wang, Klara Totpal, Allen J. Ebens, Andrew G. Polson, Stephen Gould
Journal: Blood (2016)
コンピュータ断層撮影および光音響イメージングのための造影剤としての調整可能な,生分解性金ナノ粒子【Powered by NICT】
Authors: Cheheltani Rabee, M Ezzibdeh Rami, Chhour Peter, Pulaparthi Kumidini, Kim Johoon, Jurcova Martina, C Hsu Jessica, Blundell Cassidy, I Litt Harold, A Ferrari Victor, R Allcock Harry, M Sehgal Chandra, P Cormode David
Journal: Biomaterials (2016)
<i>Notes from the Field</i>: Death of a Farm Worker After Exposure to Manure Gas in an Open Air Environment — Wisconsin, August 2016
Authors: John M. Shutske, Rebecca A. Larson, Daniel M. Schaefer, Liz Y. Binversie, Scott Rifleman, Cheryl Skjolaas
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Excellent Clinical Outcome for Relapsed and Refractory Lymphoma Patients with Haplo-Cord Allogeneic Stem Cell Transplantation
Authors: Jingmei Hsu, Andrew Artz, Sebastian A. Mayer, Michael R. Bishop, Adrienne A. Phillips, Sonali M. Smith, Usama Gergis, Justin Kline, Tsiporah B. Shore, Koen van Besien
Journal: Blood (2016)
Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy
Authors: Thomas Borchert, Daniela Hübscher, Celina I. Guessoum, Tuan-Dinh D. Lam, Jelena R. Ghadri, Isabel N. Schellinger, Malte Tiburcy, Norman Y. Liaw, Yun Li, Jan Haas, Samuel Sossalla, Mia A. Huber, Lukas Cyganek, Claudius Jacobshagen, Ralf Dressel, Uwe Raaz, Viacheslav O. Nikolaev, Kaomei Guan, Holger Thiele, Benjamin Meder, Bernd Wollnik, Wolfram-Hubertus Zimmermann, Thomas F. Lüscher, Gerd Hasenfuss, Christian Templin, Katrin Streckfuss-Bömeke
Journal: Journal of the American College of Cardiology (2017)

Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype. (International Takotsubo Registry [InterTAK Registry] [InterTAK]; NCT01947621)
Abstract 15966: Frontal QRS-T Angle: Normal Range for Latinos and Association of an Abnormal Angle With Comorbidities
Authors: Milena S Marcolino, Edson A Carvalho, Thales M Santos, Daniel M Palhares, Antonio L Ribeiro
Journal: Circulation (2016)

Introduction: Frontal QRS-T angle has been shown to be a predictor of all-cause mortality in patients with cardiac disease and even among the general population. There is heterogeneity in the defin...
Abstract 297: Effects of p53 Stabilization During Heart Failure Progression on Telomere Repeat Binding Factor 2 and Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α in the SHHF Rat
Authors: Christopher B Nelson, Adam J Chicco, Susan M Bailey
Journal: Circulation Research (2012)

The tumor suppressor protein p53 is a cellular stress sensor and transcription factor classically accepted to target the transcription of genes that induce senescence and apoptosis. Diverse stressors including genomic or telomeric DNA damage, telomere uncapping, hypoxia, oxidative stress, and mechanical stress increase stable cellular p53. In models of heart failure and in human failing hearts, p53 is increased. High p53 has also been suggested to be necessary for the transition from hypertrophy to heart failure. In recent years it has become clear that senescence and apoptosis may not be the only significant deleterious effects of increased cellular p53. It has been suggested that p53 can decrease mitobiogenesis and cellular ATP production by direct repression of PGC1-a expression. Additionally, P53 has been shown to stimulate the expression of Siah1, an E3 ubiquitin ligase that mediates degradation of the telomere binding protein TRF2. TRF2 loss is a form of telomere uncapping that, in cell culture models, causes a subsequent DNA damage response including further p53 stabilization. The relative importance of these p53 linked pathways has yet to be explored in the progression of hypertensive heart failure. Spontaneously Hypertensive Heart Failure rats (SHHF) rats were sacked at four stages during heart failure progression and LV removed for western blot analysis. Compared to young (2-4 month) rats, 14-15 month rats showed significantly increased p53 levels (2.3 fold), normal TRF2 levels, and slightly decreased PGC1-a (.98 fold). Old SHHFs (20-22mo) had p53, TRF2, and PGC1-a levels similar to 14-15 month rats (2.1, 1.09, and.83 fold, respectively). Rats with end stage heart failure showed a significant 4.5 fold increase in p53 expression, with a corresponding decrease in TRF2 (.74 fold, p=.087), and increase in PGC1-a (1.3 fold, nonsignificant). These data are in agreement with previous suggestions that increased p53 is most important during the transition from hypertrophy to heart failure, and suggest that levels of p53 encountered in the SHHF model have little effect on PGC1-a and mitobiogenesis, but may mediate an increase in telomere uncapping during heart failure.
Abstract 12260: Sex Differences in Cardiac Troponin I and the Risk of Death or Major Cardiovascular Events in Primary Prevention
Authors: Brendan M Everett, Robert J Glynn, Tanja Zeller, Stefan Blankenberg, Paul Ridker
Journal: Circulation (2015)

Introduction: Circulating cardiac troponin I concentrations are higher in men than in women, but the biological causes and clinical implications of this observation are poorly understood. Methods and Results: We measured cardiac troponin I with a novel high-sensitivity assay (hsTnI) in 4696 women and 8260 men enrolled in the JUPITER trial who had LDL-C &lt; 130 mg/dL and hsCRP ≥ 2.0 mg/L and no diabetes or clinical evidence of vascular disease. Median (IQR) hsTnI was higher in men [3.6 ng/L (2.7-5.3)] than in women [3.1 ng/L (2.3-4.5); P&lt;0.0001]. A higher proportion of men (3.7%) than women (2.9%) were above the proposed upper reference limit of 24 ng/L (P=0.008). In linear regression models, sex remained a significant predictor of natural log normalized hsTnI after adjusting for a wide array of confounders, including age, race, height, weight, lipids, fasting glucose, blood pressure, and renal function. Across quintiles of hsTnI measured at baseline, the unadjusted incidence rate of the composite outcome of myocardial infarction, stroke, hospitalization for unstable angina, revascularization, or death increased across hsTnI categories but appeared similar in women and men (Figure 1). In adjusted Cox models stratified by sex, the increase in the relative risk of the composite endpoint across quintiles of hsTnT appeared similar in men and women (Figure 2; P-interaction=0.45). Conclusions: In a contemporary primary prevention population, women have lower baseline cardiac troponin I concentrations but similar increases in the rates of vascular events and death across troponin I categories.
Comprehensive Echocardiographic and Cardiac Magnetic Resonance Evaluation Differentiates Among Heart Failure With Preserved Ejection Fraction Patients, Hypertensive Patients, and Healthy Control Subjects
Authors: Ify R. Mordi, Satnam Singh, Amelia Rudd, Janaki Srinivasan, Michael Frenneaux, Nikolaos Tzemos, Dana K. Dawson
Journal: JACC. Cardiovascular imaging (2017)
ホスホロチオエート最適化された2′‐O‐メチルRNA分子ビーコンを用いた生細胞におけるRNA転写物の単一分子の検出と追跡【Powered by NICT】
Authors: Zhao Dan, Yang Yantao, Qu Na, Chen Mingming, Ma Zhao, J Krueger Christopher, A Behlke Mark, K Chen Antony
Journal: Biomaterials (2016)
Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial
Authors: Karsten Geletneky, Jacek Hajda, Assia L. Angelova, Barbara Leuchs, David Capper, Andreas J. Bartsch, Jan-Oliver Neumann, Tilman Schöning, Johannes Hüsing, Birgit Beelte, Irina Kiprianova, Mandy Roscher, Rauf Bhat, Andreas von Deimling, Wolfgang Brück, Alexandra Just, Veronika Frehtman, Stephanie Löbhard, Elena Terletskaia-Ladwig, Jeremy Fry, Karin Jochims, Volker Daniel, Ottheinz Krebs, Michael Dahm, Bernard Huber, Andreas Unterberg, Jean Rommelaere
Journal: Molecular Therapy (2017)
PTU-037 Cryoballoon therapy is effective in the treatment of patients with refractory oesophageal neoplasia after unsuccessful first line endoscopic eradication therapy
Authors: D Alzoubaidi, C Magee, D Graham, L Lovat, R Haidry
Journal: Gut (2017)

Introduction  Endoscopic eradication therapy EET with endoscopic mucosal resection EMR for visible lesions followed by Radiofrequency ablation RFA for flat Barrett’s oesophagus BE is the gold standard treatment for patients with BE related neoplasia. EMR and ESD are effective in the eradication of early squamous cell neoplasia ESCN. The efficacy of EET is favourable with reported eradication rates of dysplasia CR-D and intestinal metaplasia CR-IM in BE of over 90% and 80% respectively. In a minority of patients EET is unsuccessful and alternative therapies are desirable. Cryoablation with the Cryoballoon device (C2 therapeutics) is a novel ablative therapy that uses cycles of freezing and thawing to induce cell death by intra and extracellular ice formation, vascular injury, and apoptosis.  Aim:  Single centre study to evaluate the feasibility of the focal cryoablation for the treatment of areas of refractory oesophageal neoplasia in patients who had undergone first line EET. Endpoints were CR-D and CR-IM in those with BE related neoplasia. The rate of stenosis and adverse events were also studied.  Method  A total of 10 cases (7male, 3female; mean age=71; range:55–83) were treated by a single experienced endoscopist. Baseline histology included 3 Low Grade Dysplasia LGD, 5 High Grade Dysplasia HGD, 1 Intramucosal cancer (IMC) and 1 patient with ESCN. The mean length of dysplastic BE treated was 3 cm (Range: 1–9) in 9 cases and 4 cm of a visible lugols-voiding-mucosa in 1 patient with ESCN. An average of 9 ablations applied per patient; range 2–22. Each selected area of visible dysplasia received 10 s of ablation. Only 1 session of cryoablation per patient. Endoscopy and re-biopsy from the treated sites were taken at 3 months post ablation to assess for end points.  Results  CR-D achieved in 70% (7/10) of all patients. In those with BE the CR-D was 78% (7/9) and CR-IM 44% (4/9). The patient with ESCN did not respond to Cryoablation and was referred for radiotherapy. There was progression from LGD to HGD in 1 BE case that was treated with EMR. Technical difficulty due to challenging anatomy was noted in 1 case with tortuous and dilated oesophagus. There were no device malfunction or adverse events. There was no recorded stenosis post procedure.  Conclusion  In this feasibility study, Cryoablation with the cryoballoon device appears to be a good option in patients with refractory neoplasia after sequential first line EET. It is well tolerated and partially successful in obtaining CR-D and CR-IM in “treatment-refractory” patients with BE dysplasia. Further trials of dosimetry, efficacy and safety in “treatment-naive” patients with randomised controlled trials is recommended and are underway.  Disclosure of Interest  None Declared
Chronic vertigo: treat with exercise, not drugs
Authors: Vincent A van Vugt, Henriëtte E van der Horst, Rupert A Payne, Otto R Maarsingh
Journal: BMJ (2017)

#### What you need to know Chronic vertigo is a challenging problem. Currently patients are generally treated in general practice with betahistine (off-label use), while stronger evidence exists for the effectiveness of vestibular rehabilitation. Vertigo is the most common type of dizziness.1 Each year around 1 in 20 people in the general population experiences vertigo.2 Around 80% of these people affected by vertigo find that it severely impairs their daily functioning.2 Since the symptoms of vertigo prevent many people from working, as well as resulting in an increase in the risk of falling and a high use of healthcare services, vertigo also represents a substantial economic cost.2 Most cases of vertigo are caused by peripheral vestibular disorders such as vestibular neuronitis, benign paroxysmal positional vertigo, vestibular migraine, and Ménière's disease.2 Initial treatment varies, depending on the most likely vestibular disorder. Box 1 provides an overview of specific treatments for the most common peripheral vestibular disorders. #### Box 1: Specific treatments for the most common peripheral vestibular disorders ##### Vestibular neuronitis ##### Benign paroxysmal positional vertigo (BPPV)