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A LOSS OF $0.07 PER SHARE EXPECTED FOR PEREGRINE PHARMACEUTICAL'S (PPHM) FOURTH QUARTER
UPT
10/07/2017 10:04 AM
The only analyst covering Peregrine Pharmaceutical currently calls for losses of $-0.07 per share for the fourth quarter that ended in April 2017. RECOMMENDATIONS
Recommendations by the two analysts evaluating the company include one strong buy and one buy
The peer group has an average consensus recommendation of a strong buy. FORECAST CHANGES
At the present time, one analyst is providing Thomson Reuters I/B/E/S with earnings estimates.
YEAR OVER YEAR
The consensus expected loss of $0.07 per share would be a reduction of 80.00% from the same quarter last year when the company lost $0.35 per share.
Peer group earnings are projected to fall over the the corresponding quarter last year and have been revised downward over the last four weeks. EARNINGS HISTORY
In the past four quarters, the company did not match the Thomson Reuters I/B/E/S consensus estimate.
This is a computer-generated article from Thomson Reuters I/B/E/S News. For information or comments, please contact us via https://customers.reuters.com/kccontactus/support.aspx.
Copyright (C) 2016 Thomson Reuters. All rights reserved. Republication or redistribution of Thomson Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Thomson Reuters. 'Thomson Reuters' and the Thomson Reuters logo are registered trademarks and trademarks of Thomson Reuters and its affiliated companies.
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© Thomson Reuters 2017. All rights reserved.
Sorry JJ it's only a french publication
http://www.e-cancer.fr/Expertises-et-publications/Catalogue-des-publications/Le-prix-des-medicaments-anticancereux
No sorry but mayby CP can translate ; -)
PRIX DES MÉDICAMENTS ANTICANCÉREUX
May 2017 with Bavi and PS.....and Monday coming soon...uurrrggg
https://www.google.at/url?sa=t&source=web&rct=j&url=http://www.canceraquitaine.org/sites/default/files/ddblock/Les_prix-des_medicaments_anticancereux_mel_20170619.pdf&ved=0ahUKEwj5nvyT4_zUAhUGkRQKHecYD3sQFgg0MAc&usg=AFQjCNF0SPBLz2-IONd5xhnL_WCkXJcvHA
What every that means. All or nothing.
PEREGRINE TO REPORT FINANCIAL RESULTS FOR QUARTER AND FISCAL YEAR ENDED APRIL 30, 2017 AFTER MARKET CLOSE ON JULY 14, 2017
GNW
07/07/2017 10:05 PM
For best results when printing this announcement, please click on link below: http://pdf.reuters.com/htmlnews/htmlnews.asp?i=43059c3bf0e37541&u=urn:newsml:reuters.com:20170707:nGNXNYVGPa
TUSTIN, Calif., July 07, 2017 (GLOBE NEWSWIRE) -- Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, today announced that it will report financial results for the quarter and fiscal year (FY) ended April 30, 2017 on July 14, 2017 after market close, and will host a conference call and webcast at 1:30 PM PDT (4:30 PM EDT). Peregrine's senior management will discuss financial results for the quarter and FY ended April 30, 2017 and review recent corporate developments.
To listen to the live webcast, or access the archived webcast, please visit: http://ir.peregrineinc.com/events.cfm.
To listen to the conference call, please dial (877) 312-5443 or (253) 237-1126 and request the Peregrine Pharmaceuticals call.
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of patients by delivering high quality pharmaceutical products through its contract development and manufacturing organization (CDMO) services and through advancing and licensing its investigational immunotherapy and related products. Peregrine's in-house CDMO services, including cGMP manufacturing and development capabilities, are provided through its wholly-owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and third-party customers. The company is also working to evaluate its lead immunotherapy candidate, bavituximab, in combination with immune stimulating therapies for the treatment of various cancers, and developing its proprietary exosome technology for the detection and monitoring of cancer. For more information, please visit http://www.peregrineinc.com.
Contacts:
Stephanie Diaz (Investors)
Vida Strategic Partners
415-675-7401
sdiaz@vidasp.com
Tim Brons (Media)
Vida Strategic Partners
415-675-7402
tbrons@vidasp.com
GlobeNewswire, Inc. 2017
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© Thomson Reuters 2017. All rights reserved.
No. That's a fact .
+24% from day low . Not so bad.
Green in one hour? And on monday some news....... Just a dream
Who bought that 5 mil pphm and why?
PEREGRINE SAYS COMMON STOCK TO TRADE ON JULY 10 ON A SPLIT-ADJUSTED BASIS
RINB
07/07/2017 6:56 PM
July 7 (Reuters) - Peregrine Pharmaceuticals Inc PPHM.O: *Peregrine pharmaceuticals announces reverse stock split *Peregrine pharmaceuticals -previously approved 1-for-7 reverse split of its outstanding shares of common stock will take effect on july 7, 2017 *Peregrine pharmaceuticals -common stock will open for trading on nasdaq capital market on july 10, on a split-adjusted basis
((Reuters Investor Briefs; email: reutersinvestor.briefs@thomsonreuters.com)) Source Date/Time = 07-JUL-201714:25:00 GMT
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© Thomson Reuters 2017. All rights reserved.
And who is buying pphm today.......ronin....known something. ....
Or another dream of mine.
Platelets and cancer angiogenesis Nexus
http://paperity.org/p/80090219/platelets-and-cancer-angiogenesis-nexus
Report explores the human papillomavirus (hpv) associated cancer vaccine pipeline therapeutics 2017
Published: 05 July 2017
https://www.whatech.com/market-research/medical/331253-human-papillomavirus-hpv-associated-cancer-vaccine-pipeline-therapeutics-2017
Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
Published online:27 June 2017
http://www.nature.com/articles/s41598-017-04494-y?WT.feed_name=subjects_biochemistry
26,44 mio pphm or 8,88%
Immunotherapy holds promise of turning blood into cancer drugs
http://www.cbsnews.com/news/cancer-drugs-blood-treatment-immunotherapy-car-t/
Overriding Phosphatidylserine-mediated Tumor Immune Suppression to Enhance Immune Checkpoint Therapies
Bruce Freimark
Research Director, Preclinical Oncology
Peregrine
http://precisionlungcancer.com/agenda--day-one.html
http://cancergrace.org/lung/
Dr. Luis Raez, MD FACP FCCP
Yes. Pphm could be one target . But there are hundreds out there. And stock price says: no hurry
Anti-vaccination messages spread easier than positive ones on Twitter.Posted on June 9, 2017 at 1:36 am
Second, additional research might reveal why positive communications seem to encourage unfavorable tweeting; maybe there's something about the manner in which the message is being conveyed. For example, public health officials might use that info to send positive communications in a way that would be more likely to really have the intended effect. .. Anti-vaccination messages spread easier than positive ones on Twitter, researchers find On Twitter, a popular microblogging and social-networking program, statements about vaccines may have unexpected effects – – positive messages may backfire, according to a team of Penn State University experts led by Marcel Salath-, an assistant professor of biology.Durvalumab can be a monoclonal antibody directed against programmed cell loss of life ligand 1 . Indicators from PD-L1 help tumours prevent detection by the disease fighting capability. Preclinical data possess demonstrated that by merging the improved T-cell mediated anti-tumour activity of bavituximab with checkpoint inhibitors like PD-L1 antibodies, the power of tumour-particular T-cells to keep attacking the tumor can be prolonged. Robert Iannone, Mind of Immuno-Oncology, Global Medications Development, at AstraZeneca stated: We think that mixture therapy in immuno-oncology gets the potential to be always a novel and impressive approach to treating tumor. Our partnership with Peregrine supplies the chance to explore a thrilling, novel combination which could deliver important scientific benefit to sufferers across a variety of cancers.
http://innovationigniter.com/anti-vaccination-messages-spread-easier-than-positive-ones-on-twitter.html
REUTERS INSIDER - IMMUNOTHERAPY TO END CANCER -IMMUNOVACCINE
RITPC
30/06/2017 6:27 PM
Click the following link to watch video: https://share.insider.thomsonreuters.com/link?entryId=0_lh5yt1t5&referenceId=7367_808&pageId=ReutersNews Source: BTV
Description: Frederic Ors, CEO and Director of Immunovaccine speaks on the company's solution to ending cancer. Short Link: http://reut.rs/2t2QIWP
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© Thomson Reuters 2017. All rights reserved.
It does NOT mean that pphm is the object of beauty. ........but I have heard that Gilead is looking for such objects this year......they have to invest. IMO
PEREGRINE PHARMACEUTICALS INC -- SC 13D/A - Edgar Filings
29-Jun-2017 23:26:15
http://pdf.reuters.com/htmlnews/8knews.asp...
Hutchison China Meditech Limited - Chi-Med and AstraZeneca Initiate SAVOIR, a Global Phase III Trial of Savolitinib in Papillary Renal Cell Carcinoma - PUBT
29-Jun-2017 08:08
AstraZeneca PLC ('AstraZeneca') (LON/STO/NYSE: AZN) Hutchison China MediTech Limited ('Chi-Med') (AIM/Nasdaq: HCM)
London: Thursday, June 29, 2017: Chi-Med and AstraZeneca today announce that they have initiated a global pivotal Phase III, open-label, randomized multi-center registration study of the highly selective inhibitor of c-MET receptor tyrosine kinase, savolitinib, in c-MET-driven papillary renal cell carcinoma ('PRCC'). This is the first pivotal study ever conducted in c-MET-driven PRCC and the first molecularly selected trial in renal cell carcinoma ('RCC').
'The launch of the SAVOIR trial, designed to support product registration in the U.S. and Europe, continues to advance our strategy to deliver innovative medicines to major markets worldwide,' said Christian Hogg, Chief Executive Officer of Chi-Med. 'Based on the results of our Phase II study, we believe savolitinib has the potential to bring meaningful clinical benefit to patients with c-MET-driven PRCC. We also expect to further understand the correlations between c-MET alterations and patient outcomes through epidemiological analyses using our newly developed companion diagnostic assay.'
Susan Galbraith, SVP IMED Oncology, AstraZeneca commented that 'It is exciting to achieve this milestone in savolitinib's development. The data building across our early development studies are encouraging, that savolitinib has the potential to be an important treatment option for c-MET driven cancers including kidney, lung and gastric cancers.'
The initiation of this Phase III trial has triggered a US$5 million milestone payment to Hutchison MediPharma Limited (a 99.8% subsidiary of Chi-Med) from AstraZeneca under the terms of the license and collaboration agreement signed between them in 2011 (as amended).
In addition to SAVOIR, Chi-Med and AstraZeneca are conducting a number of Phase Ib and II studies of savolitinib in kidney cancer, lung cancer and gastric cancer. These studies involve savolitinib as a monotherapy or in combination with other targeted therapy, such as Tagrisso (osimertinib) or Iressa (gefitinib). Additional studies combining with Imfinzi (durvalumab) and Taxotere (docetaxel) are also in progress.
About SAVOIR
SAVOIR is a global Phase III, open-label, randomized, controlled trial evaluating the efficacy and safety of savolitinib, compared with sunitinib, in patients with c-MET-driven, unresectable, locally advanced or metastatic PRCC. Approximately 180 patients will be randomized at 50 to 75 sites across five to ten countries. c-MET status is confirmed by the novel targeted next-generation sequencing (NGS) assay developed for savolitinib. Patients will be randomized in a 1:1 ratio to receive either continuous treatment with savolitinib 600 mg (400 mg if <50 kg) orally, once daily, or intermittent treatment with sunitinib 50 mg orally once daily (4 weeks on/2 weeks off), on a 6-week cycle.
The primary objective is to evaluate the primary efficacy endpoint progression free survival ('PFS') of savolitinib as compared with sunitinib. Secondary endpoints include overall survival, objective response rate ('ORR'), duration of response, best percentage change in tumor size, disease control rate, and safety and tolerability. The impact of savolitinib compared with sunitinib on disease symptoms and quality of life, along with the pharmacokinetics of savolitinib will also be assessed. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03091192 (https://clinicaltrials.gov/ct2/show/NCT03091192).
About Savolitinib
Savolitinib (AZD6094/HMPL-504) is a potential first-in-class selective inhibitor of c-MET (also known as mesenchymal epithelial transition factor) receptor tyrosine kinase, an enzyme which has been shown to function abnormally in many types of solid tumors. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with other selective c-MET inhibitors, such as renal toxicity.
Savolitinib was discovered by Chi-Med and is being developed in collaboration with AstraZeneca. Savolitinib is currently being studied in multiple tumor types worldwide including kidney, lung and gastric cancers, both as a monotherapy or in combination with other targeted and immunotherapy agents.
About c-MET-Driven PRCC
Worldwide, about 366,000 new patients are diagnosed with kidney cancer annually. RCC accounts for approximately 80-85% of kidney cancer and has several histological sub-types with different genetic and biochemical characteristics. PRCC is the most common of the non-clear cell renal carcinomas accounting for 10-15% of RCC. However, the biology and molecular characteristics of PRCC are different from those of clear cell RCC ('ccRCC'). Multiple studies indicate that PRCC is c-MET-driven in 40-70% of patients.
There are no therapies approved for patients with PRCC, who currently receive treatments approved for RCC such as sunitinib. These RCC agents were mostly approved on the basis of studies where the majority of subjects were ccRCC patients and where the benefits to the PRCC minority were more modest. Currently the National Comprehensive Cancer Network Guidelines advise PRCC patients to enter clinical trials.
About Savolitinib in PRCC
In February 2017, the results of a global Phase II multicenter study in advanced PRCC was presented at the 2017 American Society of Clinical Oncology Genitourinary Cancers Symposium, which indicated a clear efficacy signal with savolitinib monotherapy in c-MET-driven patients. Median PFS of 6.2 months in c-MET-driven patients as compared with 1.4 months (p <0.0001) in c-MET-independent patients. ORR was 18.2% in c-MET-driven patients vs. 0% (p=0.002) in c-MET independent patients. An encouraging durable response and safety profile were reported in savolitinib treated patients. Further details are available at www.chi-med.com/asco-gu-2017-savolitinib-ph2-in-prcc-pres/.
Studies of c-MET-driven disease in gastric cancer and lung cancer suggest that c-MET amplification and/or overexpression can be a negative prognostic for disease progression. Over the course of 2017, Chi-Med and AstraZeneca are also conducting a comprehensive molecular epidemiology study of approximately 300 PRCC patient samples to further understand the correlations between c-MET alterations and patient outcomes, including any predictive biomarkers.
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.
Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least 6 new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance new oncology as one of AstraZeneca's six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms - immuno-oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - oncology, cardiovascular & metabolic diseases and respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca.
Phosphatidylserine externalization, “necroptotic bodies” release, and phagocytosis during necroptosis
Published: June 26, 2017
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002711
Effect of Bexarotene on Platelet Activation and Apoptosis
Paper full with Phosphatidylserine
http://www.karger.com/Article/FullText/478627
Phosphatidylserine Translocation after Radiosurgery in an Animal Model of Arteriovenous Malformation
Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer
http://europepmc.org/articles/pmc5385461
Targeted Therapy in NSCLC Not Selected for Driver Mutations
Immune Checkpoints as a Target for Colorectal Cancer Treatment
Published: 21 June 2017
http://www.mdpi.com/1422-0067/18/6/1324/htm
Massachusetts General Hospital
http://www.massgeneral.org/cancer/TrialDetails.aspx?p=17-037&disease=Brain+Tumors&nct=NCT03139916
PEREGRINE PHARMACEUTICALS INC -- SC 13D/A - Edgar Filings
20-Jun-2017 23:27:10
http://pdf.reuters.com/htmlnews/8knews.asp?i=43059c3bf0e37541&u=urn:newsml:reuters.com:20170620:EDG_0001104659-17-040465
nEOLc0t7fp
(C) Thomson Reuters 2017.
Newfield Therapeutics Corporation
They work together with:
Institute of Molecular Biosciences of Leopold Franzens University in Graz, Austria and its corporate partner, Sanochemia Pharmazeutika AG, based in Vienna and having research laboratories and manufacturing facilities in Neufeld, Austria, is engaged in the development of novel diagnostic and therapeutic oncological approaches.
And have that:
Anti-Cancer Peptides
International Patents for Newfield’s anti cancer peptides have recently been issued and apply to a broad range of solid tumors, exploiting the interaction between human lactoferricin derivatives and phosphatidylserine, expressed on the outside of cancerous cells. In order to advance from the preclinical stage to clinical studies Newfield is entertaining academic and corporate partnerships.
https://newfieldthera.com/
Tumor rim cells: From resistance to vascular targeting agents to complete tumor ablation
March 2017 - with Bavituximab
http://journals.sagepub.com/doi/pdf/10.1177/1010428317691001
Antiviral Therapeutics
Technologies, Companies & Markets
By
Prof. K. K. Jain
MD, FRACS, FFPM
Jain PharmaBiotech
Basel, Switzerland
June 2017
Bavituximab is on page 39 - but can`t get the whole paper
http://pharmabiotech.ch/reports/antiviral/contents.pdf
http://webcache.googleusercontent.com/search?q=cache:d0SKWar1NUIJ:pharmabiotech.ch/reports/antiviral/contents.pdf+&cd=31&hl=de&ct=clnk&gl=at
Immunotherapies in oncology: the future of cancer treatment lies in combinations and partnerships
http://deep-dive.pharmaphorum.com/deep-dive-oncology-may-2017#!/immunotherapies-in-oncology/item/0
Bavituximab and Peregrine in there.
Fake? or what?
Purpose We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed
Posted on May 30, 2017 by cancerdir
Purpose We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed within the external surface of vascular endothelial cells in tumors, probably in response to oxidative tensions present in the tumor microenvironment. drug pharmacokinetics. Imaging systems include positron emission tomography (PET), single-photon emission computed tomography, MRI, ultrasound, and optical imaging, as examined extensively elsewhere (1, 2). Nuclear medicine approaches are relevant because extremely low concentrations of tracer/reporter are permissible particularly. Many radionuclides are in scientific use, and so many more are under advancement (3C5). Nevertheless, many isotopes decay quickly, limiting shelf lifestyle and preventing analysis of long-term natural phenomena. A specific problem develops with antibodies, which often have an extended biological half lifestyle , nor reach optimal focus on to history selectivity Bay 60-7550 for many days. For Bay 60-7550 Bay 60-7550 Family pet, common radionuclides, such as for example 64Cu (18% + positron branching, 226 keV) and 76As (1.068 keV). The decay features from the arsenic isotopes that are most relevant for imaging or therapy are presented in Supplementary Table S1. 74As was found in a number of the first radionuclide imaging research for the introduction of Family pet, at that right time, known as positrocephalography (6). Nevertheless, inefficient isotope creation, problems in isolating 100 % pure nuclides, and insufficient effective Bay 60-7550 derivatization procedures handicapped the exploitation of arsenic isotopes. Radiochemistry has evolved now, and many isolation techniques for arsenic isotopes have already been reported. Lately, R and Jennewein?sch developed effective methods for isolating real radionuclides from irradiated GeO2 focuses on on the basis of a solid phase extraction system (7, 8). Moreover, Jennewein and R?sch proposed chemistry for the effective labeling of biologically relevant molecules, while we have now exploited. Bavituximab, a chimeric antibody focusing on revealed vascular phosphatidylserine, was chosen to develop the labeling process and display the first use of arsenic isotopes for PET imaging of solid tumors. Bavituximab binds to phosphatidylserine by stabilizing a complex of two 2-glycoprotein I molecules attached to phosphatidylserine within the cell surface (9C12). Phosphatidylserine is normally tightly segregated to the internal surface of the plasma membrane in most cell types, including the vascular endothelium (10, 11, 13, 14). Phosphatidylserine asymmetry is definitely managed by ATP-dependent aminophospholipid translocases (Mg2+-ATPase) that catalyze the transport of aminophospholipids from your external to the internal leaflet of the plasma membrane (15). Loss of phosphatidylserine asymmetry happens during apoptosis (16), necrosis (17), cell activation (18), and transformation (19), resulting in the exposure of phosphatidylserine within the external surface of the cells. Phosphatidylserine exposure happens when the aminophospholipid translocases become inhibited (20) Bay 60-7550 or when transporters, such as scramblase (21) and floppases (22), become triggered by Ca2+ fluxes into the cytosol (23, 24). We previously showed that anionic phospholipids become revealed within the vascular endothelium of blood vessels in mice bearing various types of solid tumors probably in response to oxidizing tensions in the tumor (10, 11). There was no detectable exposure on vascular endothelium in normal tissues, including the ovary, a site of physiologic angiogenesis, and the pancreas, a site of high vascular permeability. Phosphatidylserine is one of the most specific markers of tumor vasculature yet found out. The murine version of bavituximab, 3G4, retards tumor growth in multiple rodent models by stimulating sponsor cells to bind to and ruin tumor blood vessels. Bavituximab is currently in phase I clinical tests in individuals with numerous solid tumors.7 Despite its verified ability to target tumor endothelium, bavituximab has not yet been explored as an imaging agent. The vascular location of phosphatidylserine ensures ready access by radiolabeled antibody in the blood. Imaging techniques could not only enable the detection of tumors and their metastases, but also verify the presence of antigen before bavituximab therapy. In the present study, we tested the hypothesis that bavituximab can be labeled with radioactive arsenic isotopes and utilized for vascular focusing on and molecular imaging of solid tumors in rats. Doses of bavituximab that are 10-fold below the doses that have significant vascular damaging activity were used (14) to prevent occlusion of tumor F11R vasculature from impeding effective imaging. Clear tumor imaging was acquired by planar -scintigraphy and PET. Materials and Methods Antibodies Bavituximab was provided by Peregrine Pharmaceuticals, Inc. Bavituximab is definitely a chimeric antibody composed of the Fv regions of the mouse antibody 3G4 (14) and the constant regions of human being IgG1. Bavituximab binds to phosphatidylserine through a cofactor protein, 2-glycoprotein I. Bavituximab recognizes.
Bay 60-7550F11R
http://www.cancerdir.com/2017/05/purpose-we-recently-reported-that-anionic-phospholipids-principally-phosphatidylserine-become-exposed/
Phosphatidylserine (PS) is an attractive focus on for imaging agencies that
Posted on June 17, 2017 by Jose Wallace
Phosphatidylserine (PS) is an attractive focus on for imaging agencies that identify tumors and assess their response to therapy. delineation from the tumors was attained by PET 48 hours after injection. Radiation of the tumors with 15 Gy or systemic treatment of the mice with 10 mg/kg docetaxel AG-1478 improved localization in the tumors. Tumor-to-normal (T/N) AG-1478 ratios were inversely correlated with AG-1478 tumor growth measured over 28 days. These data show that 124I-PGN635 F(ab)2 is definitely a promising fresh imaging agent for predicting tumor response to therapy. Intro Phosphatidylserine (PS) is an attractive target for malignancy imaging agents that can be used for disease analysis, staging and restorative planning. PS is definitely a phospholipid that is generally not found on the surface of normal cells because lipid-specific transporters sequester it in the inner leaflet of the cells plasma membrane [1,2]. When cells undergo apoptosis, as do tumor cells responding to chemotherapy, PS becomes exposed on their outer membrane surface through one or more calcium-dependent mechanisms [3,4]. PS exposure is also induced within the viable vascular endothelium in tumors by oxidative tensions within the tumor microenvironment [5-7] and improved PS exposure levels within the endothelium are consistently seen in tumors responding to therapy [8-11]. Since PS exposure on tumor endothelium and tumor cells correlates with tumor growth inhibition [8,9,12], it provides an excellent marker for predicting tumor response to therapy. Several PS-targeting strategies have been employed to image tumors and determine their response to therapy. The PS binding protein, annexin V, has been radiolabeled with numerous positron emitters for positron emission tomography (PET) of tumors in several animal models [13-15]. Technetium-99m (99mTc)-labeled annexin V has been used for solitary photon emission computed tomography (SPECT) in humans and has shown prognostic value iNOS (phospho-Tyr151) antibody for head and neck malignancy, past due stage lung lymphoma and cancers [16,17]. Others possess utilized the C2A domains of radiolabeled synaptotagmin I for Family pet and SPECT imaging of lung carcinomas in pets treated with paclitaxel [18,19]. Low molecular fat PS imaging probes, such as for example dipicolylamine-Zn2+ complexes [20], are in development also. While these probes possess demonstrated diagnostic worth, they all screen unfavorable biodistributions with high stomach background signal because of probe deposition in the liver organ and kidneys. We’ve developed a family group of PS-targeting monoclonal antibodies that reactivate tumor immunity and induce immune system cell-mediated devastation of tumor vasculature. testing methods were made to recognize antibodies that destined PS straight, but additional characterization from the antibodies uncovered that they interact with PS by forming high affinity complexes with the serum protein 2-glycoprotein I (2GP1) [21]. The family of antibodies is named after a human-mouse chimeric antibody known as bavituximab that is currently being evaluated in clinical tests in malignancy individuals as an adjuvant to chemotherapy. Unlike PS-targeting antibodies that cause antiphospholipid syndrome (APS), bavituximab does not promote thrombosis and is well-tolerated in individuals in doses as high as 4 mg/kg. Bavituximab provides higher specificity for PS than will annexin V and higher affinity than many lower molecular fat molecules recognized to bind PS [21]. These features claim that bavituximab and very similar PS-targeting antibodies may not just end up being helpful for cancers therapy, but that they might be helpful for cancers imaging also. We’ve previously proven that bavituximab tagged using the 74As (t1/2 = 17.8 times) gave apparent Family pet pictures of subcutaneous prostate tumors in rats [22]. Optimal pictures were attained 72 h after shot, when concentrations from the probe in the AG-1478 bloodstream had dropped to amounts that didn’t obscure signal in the tumor [22]. The newest addition to the bavituximab family is a human PS-targeting antibody named PGN635 fully. PGN635 (Kd = 1.8 nM) binds with very similar affinity as bavituximab but, since it does not have mouse proteins sequences, includes a higher prospect of clinical translation. To acquire shorter bloodstream residence situations than those necessary for 74As-bavituximab imaging, we used the F(ab)2 fragment of PGN635 from the unchanged antibody rather. Iodine-124 (124I) was selected to label the antibody fragment since its radioactive half-life (t1/2 = 4.2 times) has been proven to become appropriate for immuno-PET and it’s been increasingly studied in clinic [23,24]. Furthermore, 124I allows immediate labeling from the antibody fragment by electrophilic radioiodination whereas various other Family pet isotopes widely used for immuno-PET such as for example copper-64 (64Cu) and zirconium-89 (89Zr) need chelator/linker substances [25]. Here.
This entry was posted in My Blog and tagged AG-1478, iNOS phospho-Tyr151) antibody. Bookmark the permalink.
http://stopvivisection.info/phosphatidylserine-ps-is-an-attractive-focus-on-for-imaging-agencies-that/
Medical Animation Market To Represent USD 514 Million Opportunity Globally by 2024: Grand View Research, Inc.
Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.
Oyler-Yaniv J1, Oyler-Yaniv A2, Shakiba M3, Min NK4, Chen YH5, Cheng SY6, Krichevsky O7, Altan-Bonnet N5, Altan-Bonnet G8.
Author information
Abstract
Immune cells constantly survey the host for pathogens or tumors and secrete cytokines to alert surrounding cells of these threats. In vivo, activated immune cells secrete cytokines for several hours, yet an acute immune reaction occurs over days. Given these divergent timescales, we addressed how cytokine-responsive cells translate brief cytokine exposure into phenotypic changes that persist over long timescales. We studied melanoma cell responses to transient exposure to the cytokine interferon ? (IFN?) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments. We discovered that IFN? is captured by phosphatidylserine (PS) on the surface of viable cells both in vitro and in vivo then slowly released to drive long-term transcription of cytokine-response genes. This mechanism introduces an additional function for PS in dynamically regulating inflammation across diverse cancer and primary cell types and has potential to usher in new immunotherapies targeting PS and inflammatory pathways.
Published by Elsevier Inc.
https://www.ncbi.nlm.nih.gov/pubmed/28575659
Author information
1
ImmunoDynamics Group, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Program in Computational Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.