tbuckley/cabot-search huggingface dataset:
Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen
Authors: Yan Zhuang, Xiang Wang, Hong T Nguyen, Ying Zhuo, Xinpeng Cui, Claire Fewell, Erik K Flemington, Bin Shan
Journal: Journal of Hematology & Oncology (2013)

Abstract Background The tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms. Findings We investigated whether the expression of lincRNAs was regulated by the tumor promoting Col-1. In a three-dimensional organotypic culture model using the reconstituted basement membrane ECM Matrigel (rBM 3-D), supplementation of Col-1 disrupted acini, a differentiation feature of well-differentiated lung adenocarcinoma cells, and concurrently induced the expression of a tumor-promoting lincRNA, HOX transcript antisense RNA (HOTAIR). Induction of HOTAIR by Col-1 was diminished by a neutralizing antibody against the Col-1 receptor α2β1 integrin. Col-1 activates the expression of a reporter gene controlled by the human HOTAIR promoter. Moreover the expression of HOTAIR and Col-1 was concurrently up-regulated in human non-small cell lung cancer. Conclusions Our findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. These initial results warrant further investigation of HOTAIR and other lincRNA genes in lung tumorigenesis.
A mouse model of juvenile hemochromatosis
Authors: F. W. Huang
Journal: Journal of Clinical Investigation (2005)

Hereditary hemochromatosis is an iron-overload disorder resulting from mutations in proteins presumed to be involved in the maintenance of iron homeostasis. Mutations in hemojuvelin (HJV) cause severe, early-onset juvenile hemochromatosis. The normal function of HJV is unknown. Juvenile hemochromatosis patients have decreased urinary levels of hepcidin, a peptide hormone that binds to the cellular iron exporter ferroportin, causing its internalization and degradation. We have disrupted the murine Hjv gene and shown that Hjv–/– mice have markedly increased iron deposition in liver, pancreas, and heart but decreased iron levels in tissue macrophages. Hepcidin mRNA expression was decreased in Hjv–/– mice. Accordingly, ferroportin expression detected by immunohistochemistry was markedly increased in both intestinal epithelial cells and macrophages. We propose that excess, unregulated ferroportin activity in these cell types leads to the increased intestinal iron absorption and plasma iron levels characteristic of the juvenile hemochromatosis phenotype.
Differential response to right and left ansae subclaviae stimulation of early afterdepolarizations and ventricular tachycardia induced by cesium in dogs.
Authors: J Ben-David, D P Zipes
Journal: Circulation (1988)

Early afterdepolarizations (EADs) are depolarizing potentials that occur before complete repolarization. They may be important in the acquired and possibly the idiopathic long QT syndrome and associated ventricular tachycardia (VT). The purpose of these experiments was to study in 20 open-chest dogs the effects of sympathetic stimulation on EADs and VT produced with cesium chloride (84 mg/kg i.v.) alone or combined with left (LAS), right (RAS), or bilateral (BAS) ansae subclaviae stimulation (2 Hz, 4 msec, 2 mA). We compared the EAD amplitude and area as a percentage of monophasic action potential amplitude and area, respectively, recorded simultaneously with contact electrodes from right (RV) and left ventricular (LV) endocardium and recorded the prevalence of VT induction during each intervention. Both LAS and BAS produced left ventricular EADs with larger amplitudes and areas than did RAS or cesium alone. BAS and LAS produced larger EADs recorded from the LV than from the RV. Cesium produced VT in six of 20 dogs, RAS in three of 20, BAS in 12 of 20, and LAS in 16 of 20. Norepinephrine (0.1-1.5 micrograms/kg/min) caused VT in all dogs by producing a dose-related increase in EAD amplitude that was similar in RV and LV, suggesting that the response of RV and LV EADs to catecholamine stimulation was not intrinsically different. During stimulation of left ansae subclaviae at increasing frequencies (1, 2, 4, and 6 Hz), EADs were significantly larger in LV than in RV at all stimulus frequencies, and the amplitude of EADs in both ventricles increased with increasing stimulus frequencies. Based on the increased LV amplitude and area of cesium chloride-induced EADs during LAS and BAS, with EAD amplitude dependent on the frequency of LAS but with an equal RV and LV EAD amplitude during norepinephrine infusion, it is possible that more norepinephrine released into the LV during LAS and BAS compared with RAS causes larger amplitude LV EADs that reach threshold to cause VT more often. Thus, quantitative differences between the effects of left and right stellate ganglia stimulation rather than qualitative differences or imbalance may account for the arrhythmogenic potential of the left stellate ganglion.
Mechanisms and markers of airway inflammation in cystic fibrosis: Fig. 1.—
Authors: V. De Rose
Journal: European Respiratory Journal (2002)

Airway inflammation is now recognized as a major factor in the pathogenesis of lung disease in cystic fibrosis (CF). Its most characteristic feature is a marked and persistent influx into the airways of neutrophils, which damage the lung by releasing noxious mediators, such as reactive oxygen species and proteolytic enzymes. Recent studies suggest that inflammation occurs very early and may even happen in the absence of infection. Furthermore, links between CF transmembrane conductance regulator dysfunction and both infection and inflammation are postulated; dysregulation of cytokine production and abnormal epithelial host defences have been regarded as causes of sustained inflammation. Bronchoalveolar lavage and the evaluation of neutrophils and inflammatory mediators provide the most accurate picture of airway inflammation. Routine bronchoscopy with bronchoalveolar lavage, however, is unpleasant for the patient and usually is of no immediate benefit to the management of individual cases. Therefore, surrogate markers collected by noninvasive procedures would be of great assistance in the follow-up of cystic fibrosis patients. Several markers have been evaluated in the sputum, serum and urine of cystic fibrosis patients and related to the degree of airway inflammation. Long-term studies are needed to confirm their potential clinical utility and specificity, and to determine which can be used clinically to monitor disease outcome and efficacy of treatment.
Development of a Multiplex RNA Urine Test for the Detection and Stratification of Transitional Cell Carcinoma of the Bladder
Authors: Andrew Holyoake, Paul O'Sullivan, Rob Pollock, Terry Best, Jun Watanabe, Yoichiro Kajita, Yoshiyuki Matsui, Masaaki Ito, Hiroyuki Nishiyama, Natalie Kerr, Fernanda da Silva Tatley, Lisa Cambridge, Tumi Toro, Osamu Ogawa, Parry Guilford
Journal: Clinical Cancer Research (2008)

New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage > or =T1 disease.RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases.A combination of the RNAs CDC2, MDK, IGFBP5, and HOXA13 detected 48%, 90%, and 100% of stage Ta, T1, and >T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% for Ta tumors > or =1 cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage > or =T1 TCCs with approximately 80% specificity and sensitivity.Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.
Microscale mechanical properties of single elastic fibers: The role of fibrillin–microfibrils
Authors: Mieke M.J.F. Koenders, Lanti Yang, Ronnie G. Wismans, Kees O. van der Werf, Dieter P. Reinhardt, Willeke Daamen, Martin L. Bennink, Pieter J. Dijkstra, Toin H. van Kuppevelt, Jan Feijen
Journal: Biomaterials (2009)
Phase III Trial Comparing a Defined Duration of Therapy Versus Continuous Therapy Followed by Second-Line Therapy in Advanced-Stage IIIB/IV Non-Small-Cell Lung Cancer
Authors: Mark A. Socinski, Michael J. Schell, Amy Peterman, Kamal Bakri, Steven Yates, Robert Gitten, Paul Unger, Joanna Lee, Ji Hyun Lee, Maureen Tynan, Martha Moore, Merrill S. Kies
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To compare four cycles of therapy versus continuous therapy to determine the optimal duration of chemotherapy in advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB/IV NSCLC patients were randomized to arm A (four cycles of carboplatin at an area under the curve of 6 and paclitaxel 200 mg/m2 every 21 days) or arm B (continuous treatment with carboplatin/paclitaxel until progression). At progression, all patients on both arms were to receive second-line weekly paclitaxel at 80 mg/m2/wk. The primary end points were survival and quality of life (QOL). RESULTS: Two hundred thirty patients were randomized. Fifty-seven percent of arm A patients completed four courses of therapy. In the 116 arm B patients, the median number of cycles delivered was four (range, zero to 19 cycles). Forty-two percent received five or more cycles; 18% received eight or more cycles. Overall response rates were 22% and 24% for arms A and B, respectively (P = .80). Median survival time and 1-year surv...
Blockade of nuclear factor-κB activation prevents hypodynamic shock and gastric hypoperfusion induced by endotoxin in anesthetized dogs
Authors: Chieko Mitaka, Yukio Hirata, Yutaka Narumi, Kuninori Yokoyama, Koshi Makita, Koichi Katsuyama, Takasuke Imai
Journal: Intensive Care Medicine (2005)
Intragenomic Spread of Plastid-Targeting Presequences in the Coccolithophore Emiliania huxleyi
Authors: Fabien Burki, Yoshihisa Hirakawa, Patrick J. Keeling
Journal: Molecular Biology and Evolution (2012)

Nucleus-encoded plastid-targeted proteins of photosynthetic organisms are generally equipped with an N-terminal presequence required for crossing the plastid membranes. The acquisition of these presequences played a fundamental role in the establishment of plastids. Here, we report a unique case of two non-homologous proteins possessing completely identical presequences consisting of a bipartite plastid-targeting signal in the coccolithophore Emiliania huxleyi. We further show that this presequence is highly conserved in five additional proteins that did not originally function in plastids, representing de novo plastid acquisitions. These are among the most recent cases of presequence spreading from gene to gene and shed light on important evolutionary processes that have been usually erased by the ancient history of plastid evolution. We propose a mechanism of acquisition involving genomic duplications and gene replacement through non-homologous recombination that may have played a more general role for equipping proteins with targeting information.
Hybrid Open Endovascular Technique for Aortic Thoracoabdominal Pathologies
Authors: Konstantinos G. Moulakakis, Spyridon N. Mylonas, Efthimios D. Avgerinos, John D. Kakisis, Jan Brunkwall, Christos D. Liapis
Journal: Circulation (2011)

Background— Many authors using a hybrid debranching strategy for the treatment of thoracoabdominal pathologies have reported disappointing results and the initial enthusiasm for the technique has given way to criticism and ambiguity. The aim of the present meta-analysis study was to assess the safety and efficacy of the technique in patients with thoracoabdominal aortic aneurysms or other aortic pathologies. Methods and Results— A multiple electronic search was performed on all articles describing hybrid open endovascular repair. Separate meta-analyses were conducted for technical success, visceral graft patency, spinal cord ischemia symptoms, renal insufficiency, and other complications as well as 30-day/in-hospital mortality. Nineteen publications with a total of 507 patients were analyzed. The pooled estimates for primary technical success and visceral graft patency were 96.2% (95% CI, 93.5%–98.2%) and 96.5% (95% CI, 95.2%–97.8%) respectively. A pooled rate of 7.5% (95% CI, 5.0%–11.0%) for overall spinal cord ischemia symptoms was observed; whereas for irreversible paraplegia the pooled rate was 4.5% (95% CI, 2.5%–7.0%). The pooled estimate for renal failure was 8.8% (95% CI, 3.9%–15.5%). The pooled 30-day/in-hospital mortality rate was 12.8% (95% CI, 8.6%–17.0%). During the mean follow-up period of 34.5 (95% CI, 31.5–37.5) months, a total of 119 endoleaks were identified in 111 patients (22.7%). Conclusions— The repair of thoracoabdominal pathologies by means of hybrid procedures in patients who are poor surgical candidates is still associated with significant morbidity and mortality rates. Future studies may substantiate whether the technique is amenable to amelioration and improvement.
Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial
Authors: Charles Butts, Mark A Socinski, Paul L Mitchell, Nick Thatcher, Libor Havel, Maciej Krzakowski, Sergiusz Nawrocki, Tudor-Eliade Ciuleanu, Lionel Bosquée, José Manuel Trigo, Alexander Spira, Lise Tremblay, Jan Nyman, Rodryg Ramlau, Gun Wickart-Johansson, Peter Ellis, Oleg Gladkov, José Rodrigues Pereira, Wilfried Ernst Erich Eberhardt, Christoph Helwig, Andreas Schröder, Frances A Shepherd
Journal: The Lancet Oncology (2013)
An in vivo patient-derived model of endogenous IDH1-mutant glioma
Authors: H. A. Luchman, O. D. Stechishin, N. H. Dang, M. D. Blough, C. Chesnelong, J. J. Kelly, S. A. Nguyen, J. A. Chan, A. M. Weljie, J. G. Cairncross, S. Weiss
Journal: Neuro-Oncology (2011)

Somatic mutations in the catalytic domain of isocitrate dehydrogenase (IDH) 1/2 and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG) appear to be among the earliest events in gliomagenesis and may contribute to malignant transformation. The lack of cell lines with endogenous mutations has been one of the major challenges in studying IDH1/2-mutant glioma and developing novel therapeutics for these tumors. Here, we describe the isolation of a glioma brain tumor stem cell line (BT142) with an endogenous R132H mutation in IDH1, aggressive tumor-initiating capacity, and 2-HG production. The neurosphere culture method was used to establish a brain tumor stem cell line from an IDH1-mutant anaplastic oligoastrocytoma sample, and an orthotopic xenograft system was developed to allow its rapid expansion. Production of 2-HG by glioma cells with endogenous IDH1 mutations was confirmed by mass spectrometry. BT142 retained an endogenous R132H IDH1 mutation in culture and possessed aggressive tumor-initiating capacity, allowing it to be readily propagated in orthotopic xenografts of nonobese diabetic/severe combined immune deficiency (NOD SCID) mice. Endogenous 2-HG production by BT142 was detectable in both cell culture medium and xenograft animal serum. BT142 is the first brain tumor cell line with an endogenous IDH1 mutation and detectable 2-HG production both in vitro and in vivo, which thus provides a unique model for studying the biology of IDH1-mutant glioma and in vivo validation of compounds targeting IDH1-mutant cells.
Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma
Authors: Michel Attal, Valerie Lauwers-Cances, Gerald Marit, Denis Caillot, Philippe Moreau, Thierry Facon, Anne Marie Stoppa, Cyrille Hulin, Lofti Benboubker, Laurent Garderet, Olivier Decaux, Serge Leyvraz, Marie-Christiane Vekemans, Laurent Voillat, Mauricette Michallet, Brigitte Pegourie, Charles Dumontet, Murielle Roussel, Xavier Leleu, Claire Mathiot, Catherine Payen, Hervé Avet-Loiseau, Jean-Luc Harousseau
Journal: New England Journal of Medicine (2012)

High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation.We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival.Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001).Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).
An Official American Thoracic Society Policy Statement: Managing Conflict of Interest in Professional Societies
Authors: Holger J. Schünemann, Molly Osborne, Joel Moss, Constantine Manthous, Gregory Wagner, Leonard Sicilian, Jill Ohar, Shane McDermott, Lance Lucas, Roman Jaeschke
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Section:ChooseTop of pageAbstract <<CONTENTSEXECUTIVE SUMMARYINTRODUCTIONMETHODSTHE POLICYCONCLUSIONSAPPENDIX 1APPENDIX 2APPENDIX 3APPENDIX 4APPENDIX 5ReferencesCITING ARTICLES
ASAS recommendations for collecting, analysing and reporting NSAID intake in clinical trials/epidemiological studies in axial spondyloarthritis
Authors: M. Dougados, S. Paternotte, J. Braun, R. Burgos-Vargas, W. P. Maksymowych, J. Sieper, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2010)

The amount of NSAID intake could be considered as a clinically relevant outcome measure in ankylosing spondylitis. The information should include at least the following: (1) the type of NSAID; (2) the dose; (3) the number of days taking NSAID during the period of interest. The objectives of this initiative were to propose both an NSAID equivalent score and a way of collecting and analysing this information in longitudinal clinical studies/trials. For the NSAID equivalent scoring system, the recommendations are (1) to refer to a scale in which 0 = no intake, 100 = 150 mg diclofenac, 1000 mg naproxen, 200 mg aceclofenac, 400 mg celecoxib, 600 mg etodolac, 90 mg etoricoxib, 200 mg flurbiprofen, 2400 mg ibuprofen, 150 mg indometacin, 200 mg ketoprofen, 15 mg meloxicam, 400 mg phenylbutazone, 20 mg piroxicam, 20 mg tenoxicam; (2) to present the results as mean daily intake by considering the number of days on which NSAID has been taken during a period of interest. This initiative should facilitate the conduct and analysis of clinical studies/trials.
Effects of euthanasia on the bereaved family and friends: a cross sectional study
Authors: Nikkie B Swarte, Marije L van der Lee, Johanna G van der Bom, Jan van den Bout, A Peter M Heintz
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To assess how euthanasia in terminally ill cancer patients affects the grief response of bereaved family and friends. <b>Design</b> Cross sectional study. <b>Setting</b> Tertiary referral centre for oncology patients in Utrecht, the Netherlands. <b>Participants</b> 189 bereaved family members and close friends of terminally ill cancer patients who died by euthanasia and 316 bereaved family members and close friends of comparable cancer patients who died a natural death between 1992 and 1999. <b>Main outcome measures</b> Symptoms of traumatic grief assessed by the inventory of traumatic grief, current feelings of grief assessed by the Texas revised inventory of grief, and post-traumatic stress reactions assessed by the impact of event scale. <b>Results</b> The bereaved family and friends of cancer patients who died by euthanasia had less traumatic grief symptoms (adjusted difference −5.29 (95% confidence interval −8.44 to −2.15)), less current feeling of grief (adjusted difference 2.93 (0.85 to 5.01)); and less post-traumatic stress reactions (adjusted difference −2.79 (−5.33 to −0.25)) than the family and friends of patients who died of natural causes. These differences were independent of other risk factors. <b>Conclusions</b> The bereaved family and friends of cancer patients who died by euthanasia coped better with respect to grief symptoms and post-traumatic stress reactions than the bereaved of comparable cancer patients who died a natural death. These results should not be interpreted as a plea for euthanasia, but as a plea for the same level of care and openness in all patients who are terminally ill.
Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice
Authors: Ainhoa Iglesias, Matilde Murga, Usua Laresgoiti, Anouchka Skoudy, Irantzu Bernales, Asier Fullaondo, Bernardino Moreno, José Lloreta, Seth J. Field, Francisco X. Real, Ana M. Zubiaga
Journal: Journal of Clinical Investigation (2004)

E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.