: Neue EPA-Studie zeigt Wirkung auf Krebszellen!
Eicosapentaenoic Acid Activates RAS/ERK/C/EBPb Pathway through H-Ras Intron 1 CpG Island Demethylation in U937 Leukemia Cells
Abstract Epigenetic alterations, including aberrant DNA methylation, contribute to tumor development and progression. Silencing of tumor suppressor genes may be ascribed to promoter DNA hypermethylation, a reversible phenomenon intensely investigated as potential therapeutic target. Previously, we demonstrated that eicosapentaenoic acid (EPA) exhibits a DNA demethylating action that promotes the re-expression of the tumor suppressor gene CCAAT/enhancer-binding protein d (C/EBPd). The C/EBPb/C/EBPd heterodimer formed appears essential for the monocyte differentiation commitment. The present study aims to evaluate the effect of EPA on RAS/extracellular signal regulated kinases (ERK1/2)/C/EBPb pathway, known to be induced during the monocyte differentiation program. We found that EPA conditioning of U937 leukemia cells activated RAS/ERK/C/EBPb pathway, increasing the C/EBPb and ERK1/2 active phosphorylated forms. Transcriptional induction of the upstream activator H-Ras gene resulted in increased expression of H-Ras protein in the active pool of non raft membrane fraction. H-Ras gene analysis identified an hypermethylated CpG island in intron 1 that can affect the DNA- protein interaction modifying RNA polymerase II (RNAPII) activity. EPA treatment demethylated almost completely this CpG island, which was associated with an enrichment of active RNAPII. The increased binding of the H-Ras transcriptional regulator p53 to its consensus sequence within the intronic CpG island further confirmed the effect of EPA as demethylating agent. Our results provide the first evidence that an endogenous polyunsaturated fatty acid (PUFA) promotes a DNA demethylation process responsible for the activation of RAS/ERK/C/EBPb pathway during the monocyte differentiation commitment. The new role of EPA as demethylating agent paves the way for studying PUFA action when aberrant DNA methylation is involved.
Blöde Formulierung. Meinte damit natürlich, dass die Wirkung nicht in allen Krebszellen erforscht wurde, sondern ausschliesslich in Leukämie-Zellen. Dennoch ist der Weg frei für weitere Studien in dieser Richtung. Wäre doch ein Hammer, wenn das zu den Anwendungsgebieten von Vascepa dazukäme...
: Könnte das Auswirkungen auf ANCHOR haben?
Um nicht das Gesicht zu verlieren, wird die FDA höchstwahrscheinlich dem sNDA stattgeben, allerdings mit einer geringeren Population - vllt 300-500? Wenn dann noch die Spekulationen zur Wirksamkeit bei Leukämie dazukommen, wo seht ihr dann die Aktie?
Die Verzögerung ist besser als ein klares no! Die FDA hat großen Druck von allen Seiten und das betrügerische Panel sorgt weltweit für Entsetzen!
Ich habe die Hoffnung daß ein erweitertes Label genehmigt wird, Amarin hat alle primary and secondary endpoints für das Anchor label erreicht ohne Nebenwirkungen!
Amarin Announces FDA Review Division Response on ANCHOR SPA Agreement Reinstatement Request Will Be Delayed GlobeNewswire Amarin Corporation plc 14 minutes ago BEDMINSTER, N.J., and DUBLIN, Ireland, Jan. 15, 2014 (GLOBE NEWSWIRE) -- Amarin Corporation plc (AMRN), a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health, announced today that the Division of Metabolism and Endocrinology Products (DMEP) within the U.S. Food and Drug Administration (FDA) notified the company today that a determination on Amarin's request for reconsideration of DMEP's October 2013 decision to rescind the ANCHOR clinical trial Special Protocol Assessment (SPA) agreement will be delayed. FDA previously notified the company that it planned to convey its decision to Amarin no later than January 15, 2014. In today's communication, DMEP provided no definitive date for its planned response. Based on dialogue with DMEP, Amarin does not expect the delay to be for a significant period of time.
There can be no assurance that Amarin will be successful in its effort to reinstate the ANCHOR SPA agreement or obtain a label expansion reflecting the ANCHOR clinical trial data.
Vascepa is FDA approved for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>=500 mg/dL) hypertriglyceridemia. The ANCHOR Supplemental New Drug Application (sNDA) seeks approval of Vascepa for use as an adjunct to diet and exercise for adult patients on statin therapy with mixed dyslipidemia (one or more lipid disorder) and triglyceride levels between 200 and 499 mg/dL.
About Vascepa(R) (icosapent ethyl) capsules
Vascepa(R) (icosapent ethyl) capsules, known in scientific literature as AMR101, is a highly pure-EPA omega-3 prescription product in a 1 gram capsule.
Indications and Usage
Vascepa (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (>=500 mg/dL) hypertriglyceridemia. The effect of Vascepa on the risk for pancreatitis and cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined. Important Safety Information for Vascepa
Vascepa is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to Vascepa or any of its components and should be used with caution in patients with known hypersensitivity to fish and/or shellfish. The most common reported adverse reaction (incidence > 2% and greater than placebo) was arthralgia (2.3% for Vascepa, 1.0% for placebo). FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.
Vascepa is under various stages of development for potential use in indications that have not been approved by the FDA. Nothing in this press release should be construed as promoting the use of Vascepa in any indication that has not been approved by the FDA.
Amarin Corporation plc is a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health. Amarin's product development program leverages its extensive experience in lipid science and the potential therapeutic benefits of polyunsaturated fatty acids. Vascepa(R) (icosapent ethyl), Amarin's first FDA approved product, is a patented, ultra pure omega-3 fatty acid product comprising not less than 96% EPA. For more information about Vascepa visit www.vascepa.com. For more information about Amarin visit www.amarincorp.com.
This press release contains forward-looking statements, including statements about anticipated FDA review of the ANCHOR SPA rescission decision and the timing of such review. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include the following: uncertainties associated generally with regulatory review and approvals; the risk that SPA agreements with the FDA are not a guarantee that FDA will approve a product candidate; the risk associated with the FDA's rescinding of the ANCHOR SPA agreement; the risk that FDA will follow the recommendation of the advisory committee against ANCHOR sNDA approval; the risk that the FDA may not complete its review of the ANCHOR SPA reinstatement in the timing expected; and the risk that Amarin's interpretation of the applicable legal standards and scientific information related to the SPA agreement rescission may not be determinative or adjudicated in Amarin's favor or at all. A further list and description of these risks, uncertainties and other risks associated with an investment in Amarin can be found in Amarin's filings with the U.S. Securities and Exchange Commission, including its most recent Quarterly Report on Form 10-Q. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Amarin undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.
Availability of other information about Amarin
Investors and others should note that we communicate with our investors and the public using our company website (www.amarincorp.com), our investor relations website (http://www.amarincorp.com/investor-splash.html), including but not limited to investor presentations and investor FAQs, Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that we post on these channels and websites could be deemed to be material information. As a result, we encourage investors, the media, and others interested in Amarin to review the information that we post on these channels, including our investor relations website, on a regular basis. This list of channels may be updated from time to time on our investor relations website and may include social media channels. The contents of our website or these channels, or any other website that may be accessed from our website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.
das,ganze wurde schon mal verschoben wie gesagt auf heute.Naja wenn man gerade after Hours sieht war es wohl nur ein Kurzer schreck sie erholt sich bereits wieder wie das Ende wird ja hoffe bei 10 Doller ;-)
es bleibt in der Tat spannend.Das die verschiebung erneut,mittgeteilt wurden ist hat vielleicht im ersten moment Angst aus gelöst aber finde dafür hat die Aktie sich sehr schnell wieder Stabiliesiert ;-).Charttech.ist auch alles OK.
monate naja die Böersen laufen im Biotec momentan sehr gut kann mir also nicht vorstellen das der Wert egal was passiert nicht solange mehr oder weniger seitlich laufen wir.Wenn man dran glaubt das die FDA ein Positives Signal gibt dann wird Sie mindest wieder 30-40 teuerer werden bin mit ner Kleinen Posi von 2500 St dabei.aktuell 19 Prozent plus alo einen kleinen puffer habe ich bereit´s für kleine News die weniger gut sind ;-).Bei einer ablehnung ist fraglich wie weit es down gehen wird deshalb momentan schon Sehr Spekulativ aber mit guten Chancen