tbuckley/cabot-search huggingface dataset:
Abstract 99: Identification of G9a inhibitors by AlphaLisa™ technology and hit confirmation using MT-Glo™
Authors: Claudia Fromond, Xavier Espanel, Laurent Chene, Philippe Masson, Benaïssa Boubia, Christian Montalbetti, Pierre Broqua
Journal: Cancer Research (2015)

Abstract Epigenetic processes control gene expression and play a major role in cell proliferation, survival and differentiation. Dysregulation of epigenetic mechanisms may lead to alterations in gene expression, resulting in cellular transformation and malignant outgrowth. Epigenetic enzymes are recognized as promising therapeutic targets for the treatment of cancer. Inventiva has several research programs in epigenetics, with specific focus on histone lysine methyltransferases (HKMTs). Emerging evidence suggests that G9a, a HKMT, able to mono and dimethylate H3K9 leading to the inactivation of tumor suppressor genes, plays a predominant role in lung and ovarian cancers. To identify novel G9a inhibitors, we used an AlphaLisa assay, with a histone H3-derived peptide and a specific antibody against H3K9me2. The assay, in 384-well format, displayed a robust Z-factor (0.84) with a signal to noise ratio around 800. We screened Inventiva's proprietary compound library using this assay. Three hundred thirty-six hits inhibited G9a by more than 60% (Hit rate: 0.14%). Despite the advantages offered by AlphaLisa technology, such as high S/N ratios and straightforward automation, this technology has been reported to generate a high number of false positives. In order to confirm the activity of our hits, we used a different technology, the methyltransferase Glo (MT-Glo) assay, which measures the reaction product SAH by luminescence read-out. Out of the 336 identified compounds, 75 were confirmed by this orthogonal screening (Hit confirmation rate: 22%). Additional compound characterization is ongoing to allow the selection of the best hit series for chemical optimization. In conclusion, the AlphaLisa assay, coupled with MT-Glo assay allowed the identification and confirmation of potent hits against G9a, as chemical starting points for our hit-to-lead optimization program. Citation Format: Claudia Fromond, Xavier Espanel, Laurent Chene, Philippe Masson, Benaïssa Boubia, Christian Montalbetti, Pierre Broqua. Identification of G9a inhibitors by AlphaLisa™ technology and hit confirmation using MT-Glo™. [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 99. doi:10.1158/1538-7445.AM2015-99
Inhibition of the Rho GTPase Rac by resveratrol may modulate cell surface actin structures in breast cancer cells
Authors: Nicolas G. Azios, Luis A. Cubano, Su F. Dharmawardhane
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1807 

The phytoestrogen resveratrol has been shown to have numerous cancer preventive properties, however its role in metastatic breast cancer prevention is not well characterized. Our group has previously shown that resveratrol decreased directed cell migration of ERα (-) β (+) MDA-MB-231 metastatic human breast cancer cells, while 17-β estradiol (estrogen, E2) or epidermal growth factor (EGF) increased cell migration. Decreased cell migration by resveratrol may indicate a novel role for resveratrol in breast cancer metastasis prevention. We hypothesize that the inhibitory effects of resveratrol on cell migration is due to a global prolonged extension of cell surface actin structures called filopodia. In contrast, E2 and EGF formed actin structures called lamellipodia that are known to be important for cell migration. The Rho family of GTPases regulates structural changes in the actin cytoskeleton. Rac induces the formation of lamellipodia, while Cdc42 induces the formation of filopodia. To investigate a role for Rac and Cdc42 in filopodia extension in response to resveratrol, we created MDA-MB-231 cells expressing a dominant negative Rac1(T17N) or a dominant negative Cdc42(T17N). Expression of dominant negative Rac does not significantly affect filopodia formation in response to resveratrol, while dominant negative Cdc42 expression partially blocks the effect of resveratrol on filopodia extension. To further understand the role of Rac and Cdc42 in resveratrol signaling to the actin cytoskeleton, we performed activity assays for Rac or Cdc42. This method uses a GST-fusion protein of the Cdc42 and Rac binding domain of the downstream effector PAK, which only binds to the active GTP bound form of Rac or Cdc42. Resveratrol (50μM) at 10 min (same concentration and time that induces peak filopodia) inhibited Rac activity when compared to vehicle, EGF, or E2. Overall our data indicate that resveratrol may inhibit cell migration by inhibiting Rac activity, and thus, may prevent breast cancer metastasis.
Homozygosity for the C282Y mutation in the HFE gene is associated with increased risk of colorectailand breast cancer in Australian population
Authors: N. J. Osborne, L. C. Gurrin, K. J. Allen, C. C. Constantine, M. B. Delatycki, A. E. Nisselle, A. R. Fletcher, C. E. McLaren, D. R. English, J. L. Hopper, G. G. Giles, J. Olynyk, A. Nicoll, L. W. Powell, D. M. Gertig
Journal: American Journal of Hematology (2007)
LO4 : A phase 2, randomized, placebo-controlled study (IMAGO) of LUM001, a novel inhibitor of the apical sodium-dependent bile acid transporter (ASBT), in paediatric patients with alagille syndrome (ALGS)
Authors: A. Baker, D. Kelly, P. McClean, P. Karthikeyan, P. McKiernan, A. Dorenbaum, B.M. Kamath, B. Shneider, S. Barbat, S. Medendorp, A. Raychaudhuri, C.A. Kennedy, R.J. Thompson
Journal: Journal of Hepatology (2015)
Abstract 1591: Evidence For Pleiotropic Effects Of Atorvastatin In Patients With Congestive Heart Failure
Authors: Dimitris Tousoulis, Charalambos Antoniades, Kiriakoula Marinou, Emmanouil Vavuranakis, Stella Brili, Nikos Papageorgiou, Kostas Toutouzas, Costas Tsioufis, A Trikas, Christodoulos Stefanadis
Journal: Circulation (2007)

Introduction: Statins are associated with lipid reduction and improvement of outcome in patients with coronary artery disease. However the effects of statins in patients with congestive heart failu...
Abstract 303: Migration of Cardiac Progenitor Cells to the Scarred Infarcted Myocardium is Mediated by Matrix Metalloproteinases and Chemotactic Factors
Authors: Maria Elena Padin-Iruegas, Marcello Rota, Yu Misao, Antonella De Angelis, Silvia Maestroni, Granzia Esposito, Alessandro Boni, Joao Ferreira-Martins, Roberto Bolli, Konrad Urbanek, Toru Hosoda, Piero Anversa, Annarosa Leri, Jan Kajstura
Journal: Circulation (2008)

Ischemic heart disease is characterized chronically by myocardial scarring, cavitary dilation and impaired ventricular performance. These alterations can only be reversed by replacing scarred tissu...
Double Versus Standard Loading Dose of Ticagrelor
Authors: Dimitrios Alexopoulos, Vassilios Gkizas, Sotirios Patsilinakos, Ioanna Xanthopoulou, Christos Angelidis, Prodromos Anthopoulos, George Makris, Angelos Perperis, Stavros Karanikas, Nikolaos Koutsogiannis, Periklis Davlouros, Spyridon Deftereos, John Chiladakis, George Hahalis
Journal: Journal of the American College of Cardiology (2013)
Treatment of Acute Myocardial Infarction by Hepatocyte Growth Factor Gene Transfer
Authors: Isao Kondo, Koji Ohmori, Akira Oshita, Hiroto Takeuchi, Sachiko Fuke, Kaori Shinomiya, Takahisa Noma, Tsunetatsu Namba, Masakazu Kohno
Journal: Journal of the American College of Cardiology (2004)
Inhibition of bFGF activity by size-defined oligosaccharide derivatives of low molecular weight heparin in the sponge angiogenesis assay
Authors: Jurjees Hasan, Andrew Clamp, Melissa Whitworth, Richard Byers, Roy Bicknell, John Gallagher, Gordon C. Jayson
Journal: Cancer Research (2004)

4101  bFGF is a potent stimulator of tumour angiogenesis and is dependent on its interaction with heparan sulfates for its biological effect. Previous studies have shown that oligosaccharide derivatives from bovine heparin can inhibit the biological activity of bFGF in vitro, an effect that is determined by the length of the oligosaccharide chain (Jayson et al, BJC 1997). In this study we attempted to establish the potential anti-bFGF activity of size-defined oligosaccharides derived from LMWH by inhibiting bFGF induced neoangiogenesis in the sponge angiogenesis assay. Size-defined heparin oligosaccharides were obtained from Tinzaparin sodium (Innohep) by size-separation gel chromatography. Oligosaccharides ranging from tetrasaccharides to tetradecasaccharides (dp 4- dp14) were used for the study. Two experiments were performed to enable the quantification of angiogenesis at two separate time points (one week and two weeks). Cohorts of 5 mice bearing subcutaneous sponge implants (8mm x 4mm, type 611-9) were given intra-sponge injections of the following for 7 days and 14 days respectively. (i) Saline only (ii) bFGF (100ng/day) (iii) dp4 (20mg/kg/day) + bFGF (iv) dp6 (20mg/kg/day) + bFGF (v) dp8 (20mg/kg/day) + bFGF (vi) dp10 (20mg/kg/day) + bFGF (vii) dp12 (20mg/kg/day) + bFGF (viii) dp 14 (20mg/kg/day( + bFGF The animals were sacrificed and sponges harvested on the day following the last injection. Paraffin-embedded sections were stained with a pan-endothelial marker (von Willebrand factor) and neoangiogenesis quantified by light microscopy (x400 magnification). Microvessels were counted in the new granulation tissue that envelopes and invades the sponge. Microvessel counts were performed independently by two observers in a double-blinded fashion to minimise bias. The results were analysed using a linear mixed effects model. At one week no systematic differences in microvessel counts were noted between the different treatment groups (p=0.45). At the two week end point, the tetrasacccharides, octasaccharides and decasaccharides significantly inhibited neoangiogenesis compared to the bFGF control (p values: 0.01, 0.01 and 0.001 respectively). The hexasaccharide and tetradecasaccharide derivatives also demonstrated a trend towards inhibition of bFGF induced neoangiogenesis whilst the dodecasaccharides potentiated the angiogenic response at a level that was not statistically significant. Conclusion: The shorter length oligosaccharide derivatives of Tinzaparin inhibit the angiogenic effects of bFGF in an invivo angiogenesis assay and could be potentially developed as anti-FGF agents.
Lipid lowering drugs should be considered too
Authors: A Taylor, J P Reckless
Journal: BMJ (1996)

such as age and social class) are found to be associated, even after adjustment, it seems sensible to treat such associations with caution until evidence of causality can be obtained-in this case from a prospective randomised controlled trial of the eradication of H pylon infection.We therefore believe that eradication of Hpyloni infection on the grounds of the risk of cardiovascular disease alone, like that of gastric cancer alone,4 is not supported by the current evidence.
Pain on ejaculation after vasectomy [letter]
Authors: Edwards Is, Errey B
Journal: BMJ (1982)

In Any questions? (February 6 p. 408) you report a case of a man with a 2-year history of severe pain on ejaculation starting 2 years after vasectomy; and Dr. G. Barry Carruthers suggests a diagnosis of prostatitis probably unrelated to vasectomy.  Pain with ejaculation following vasectomy is fortunately very rare but several cases have been documented.  Cures have been reported after excision of a spermatic granuloma--if one can be found; or by vasovasostomy for the relief of congestive epididymitis.  We wish to report that in 7 male patients with this distressing symptom immediate relief has followed a simple maneuver which can be carried out under local anesthetic:  this is to open the closed lower end of the vas on the affected side.  Spermatozoa are from then on released into and reabsorbed from the scrotal cavity without producing any symptoms or signs of their presence there.  In none of our cases has this maneuver failed to produce relief; nor has pain recurred over a period of 1-3 years.  Fertility does not return as the upper closed end of the vas remains closed.  We suggest that others might offer this simple and harmless procedure to the occasional man unfortunate enough to suffer pain with ejaculation after his vasectomy.  (full text)
Excess mortality after human albumin administration in critically ill patients
Authors: M. Offringa
Journal: BMJ (1998)

Papers p 235 Letters p 277 Science commentary p 240 

Albumin is a medium weight colloid which plays an essential role in generating the colloid-osmotic pressure. It facilitates fluid retention in the intravascular space. Human albumin is often given to critically ill patients with life threatening hypovolaemia. Low serum albumin concentrations are seen in various disease states and may be due to leakage, increased metabolism, or insufficient synthesis in the liver. The serum albumin concentration in critically ill patients seems to be inversely related to mortality.1 Yet does this observation imply that hypoalbuminaemia should be treated with albumin? In this week's issue a systematic review—published simultaneously in the Cochrane Library2 and a sequel to a paper on the controversy of whether critically ill patients with hypovolaemia should be given colloid or crystalloid fluids3—evaluates the use of human albumin in various clinical settings (p 235).4

The paper is clinically important because it suggests that a respected and widely used treatment given to neonates, children, and adults with hypovolaemia, burns, or hypoalbuminaemia is associated with increased mortality: on average six extra deaths for every 100 patients treated. The authors conclude that human albumin should not be given any more “outside the context of a rigorously conducted randomised controlled trial.”

Can we trust these findings? As systematic overviews of the medical literature are becoming more …
Abstract 15777: Controlling Lesion Size and Incidence of Steam Pop by Controlling Contact Force and Radiofrequency Power in Canine Beating Heart
Authors: Hiroshi Nakagawa, Atsushi Ikeda, Assaf Govari, Yaron Ephrath, Tushar Sharma, Jan V Pitha, Ralph Lazzara, Warren M Jackman
Journal: Circulation (2010)

Introduction: During radiofrequency (RF) ablation at constant power, lesion size and incidence of steam pop increase strikingly with increasing contact force (CF). Catheter systems to measure CF ar...
British guidelines should have been considered
Authors: D M Jones
Journal: BMJ (1996)

series is not the method of choice: to show an association between use of penicillin and a decreased frequency of meningococcal disease in close contacts a controlled study is required.It should also be noted that a recent monograph on meningococcal disease states that the use of penicillin in Norway to prevent secondary infec- tion "is no longer recommended."3In conclusion, there is no evidence to support the use of penicillin, with or without chemoprophylaxis, to reduce the risk of close contacts developing meningococcal disease.We fear that the only effect of this editorial will be to confuse general practitioners and others who may not be well acquainted with the subject.In our opinion the BMJ should instead have given prominence to the recent guidance on meningococcal disease issued by the Public Heath Laboratory Service's Meningococcal Infections Working Group.
Prognostic factors in early-stage Hodgkin's disease.
Authors: A H Sarris
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.1.411 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8996173 Prognostic factors in early-stage Hodgkin's disease. A H SarrisxA H SarrisSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.1.411 PDF "Prognostic factors in early-stage Hodgkin's disease.." Journal of Clinical Oncology, 15(1), pp. 411–412© 1997 by American Society of Clinical Oncology
Abstract 3791: Experience with 21 French Percutaneous CoreValve Aortic Valve Replacement in Patients Unsuitable for Surgical Aortic Valve Replacement
Authors: Eberhard Grube, Jean-Claude Laborde, Raymond Cartier, Ulrich Gerckens, Patrick W Serruys, Peter Dejaegere, Gerhard Schuler, Peter den Heijer, Johan Bosmans, Carlos E Ruiz, Raoul Bonan
Journal: Circulation (2006)
P0087 : Low serum C24 ceramide is predictive of hepatic decompensation and poor overall survival in liver cirrhosis
Authors: G. Grammatikos, N. Ferreiros, O. Waidmann, D. Bon, S. Schroeter, A. Koch, E. Herrmann, S. Zeuzem, B. Kronenberger, J. Pfeilschifter
Journal: Journal of Hepatology (2015)
Abstract 15455: Endothelial Cell Specific Molecule-1 (ESM-1), a Novel Secreted Proteoglycan Stimulates Vascular Smooth Muscle Cell Proliferation and Migration
Authors: Prashanthi Menon, Olivier N Kocher, William C Aird
Journal: Circulation (2011)

Background: Vascular inflammation plays a critical role in the initiation and progression of atherosclerosis. Endothelial cell specific molecule-1 (ESM-1) or Endocan is a dermatan sulphate proteogl...
Hazards of laparoscopy.
Authors: M Cohen
Journal: BMJ (1973)

Three cases involving complications following laparoscopy are described: cardiac arrest following carbon dioxide insufflation under general anesthesia; excessive bleeding from mesosalpingeal vessels requiring laparotomy; and tearing of the  left iliac vein requiring laparotomy.  The need for aspiration prior to insufflation grasping the tubes at relatively vascular areas and extreme care in manipulation is stressed.
Abstract LB-195: Supporting cancer epidemiology research through cohort registration: NCI's cancer epidemiology cohort descriptive database
Authors: Crystal Lane, Amy Kennedy, Michelle Brotzman, Amy Miller, Gabriel Lai, Muin Khoury, Daniela Seminara
Journal: Cancer Research (2015)

Abstract Carefully designed observational studies have recognized value and efficiency in determining associations between exposures and outcomes and thereby evaluating health care. In particular, longitudinal cohorts have served as an essential research infrastructure for studies producing a wealth of information on disease etiology and prevention. The onset of the ‘omics age has compelled many funding agencies to foster collaborations across existing large cohorts, to design studies large enough to address the dynamic and interactive nature of the factors underlying common diseases. There is currently an ongoing discussion in the scientific community of whether or not observational studies should be registered, and if so what the scientific and practical benefits of the implementation would be. Cohorts are the backbone of observational studies, and making their descriptive data rapidly available to the scientific community through a centralized descriptive database is the first step necessary to increase transparency, scientific quality and collaboration. We have created the Cancer Epidemiology Descriptive Cohort Database (CEDCD) to assist the research community in identifying and accessing population resources, with the intention of maximizing the efficiency and effectiveness of existing cohorts and targeting areas of needs when establishing new ones. This public database includes many details, including cohort profiles and investigator contact information, study design and eligibility criteria, enrollment numbers broken down by race/ethnicity/gender, number and types of biospecimens and cancer diagnoses, policies, protocols and questionnaires, publications and funded research projects, and links to the cohort websites and related resources. The initial phase of this database will include cohorts focusing on cancer as their primary outcome, specifically those funded by NCI's EGRP and members of NCI's Cohort Consortium that have more than 10,000 subjects enrolled (healthy individuals or cancer survivors). The CEDCD is serving as a model for a parallel world-wide cohort registration project. The creation of a querable web-based tools for direct population of this descriptive database, which will provide a valuable resource for the scientific community in the planning and design of large, cooperative observational studies is in progress. Citation Format: Crystal Lane, Amy Kennedy, Michelle Brotzman, Amy Miller, Gabriel Lai, Muin Khoury, Daniela Seminara. Supporting cancer epidemiology research through cohort registration: NCI's cancer epidemiology cohort descriptive database. [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 LB-195. doi:10.1158/1538-7445.AM2015-LB-195
Abstract 15086: Early 18F-galacto-RGD Uptake and Left Ventricular Remodeling in a Rat Model of Myocardial Infarction
Authors: Hossam S Sherif, Antti Saraste, Stephan G Nekolla, Eliane Weidl, Sybille Reder, Arne Tapfer, Hans-Jurgen Wester, Markus Schwaiger
Journal: Circulation (2010)

Objectives: 18F-Galacto-RGD is a PET tracer that binds to βvβ3 integrin receptors. Expression of βvβ3 integrin is increased after myocardial infarction (MI) as part of the healing process, but its ...
Notch1 regulates the expression of its ligand Jagged1 in PC3 prostate cancer cells
Authors: Hefen Yu, Shentao Li, Zesheng Wang, Wei Ding, Yuxiang Zhang
Journal: Clinical Cancer Research (2008)

A8   Notch signal transduction plays an important role in prostate cancer progress. To investigate the expression notch ligand Jagged1 is influenced upon the activation of Notch1 signal pathway, we modulated the levels of Notch1 in PC3 prostate cancer cells by either knocking down Notch1 expression by RNA interference or over-expressing it through Notch1 cDNA transfections. Subsequently, the Jagged1 protein and mRNA levels were determined by Western Blot and Real-time QPCR, respectively.  We found that the down-regulation of either Notch1 or Jagged1 was able to induce growth arrest in PC3 cells. The protein levels of Jagged1 correlated with the expression levels of Notch1. Interestingly, Jagged1 was significantly decreased at the protein level following Notch1 siRNA transfection, nevertheless, its mRNA expression appeared to be increased. Our findings suggested the expression of Jagged1 was regulated by Notch1 signaling in prostate cancer cells, and certain post-transcription regulatory mechanism(s) might be involved which deserved further investigations.  *Corresponding author.  Mailing address: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, P. R. China.  E-mail: yxzhang@ccmu.edu.cn.   +  This project was supported by Beijing Natural Science Foundation (No.7062009) funded to Dr. Y Zhang, and financial supports from the Municipal Project of Beijing Advanced Higher Education Development (BAHED) to Dr. W Ding, Dr. Y Zhang and Prof. H-T Jia.
What do you think of theBMJ's POEMs?
Authors: A. Berger
Journal: BMJ (2003)

Just over six months ago the BMJ began publishing a weekly POEM (patient-oriented evidence that matters).1 You can find them next to Editor's choice in a pink tinted box. They are gobbets of evidence that should be useful to clinicians. POEMs are selected by searching the current issues of over 100 peer reviewed journals, looking for relevant studies (potential POEMs), which are then evaluated for validity. The valid POEMs are summarised, and the summary is then reviewed and revised. The service is provided by InfoPOEM, a US based medical information company. Apart from some minor editing we publish them as they come. They have sparked an intense debate among editorial staff and advisers, and we want you—our readers—to tell us what you think by answering a short questionnaire on http://www.bmj.com/

The research papers that give birth to POEMs are chosen …