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Posts Tagged ‘Aviva Lev-Ari’


Novel Mechanisms of Resistance to Novel Agents

 

Curators: Larry H. Berstein, M.D. FACP & Stephen J. Williams, Ph.D.

For most of the history of chemotherapy drug development, predicting the possible mechanisms of drug resistance that ensued could be surmised from the drug’s pharmacologic mechanism of action. In other words, a tumor would develop resistance merely by altering the pathways/systems which the drug relied on for mechanism of action. For example, as elucidated in later chapters in this book, most cytotoxic chemotherapies like cisplatin and cyclophosphamide were developed to bind DNA and disrupt the cycling cell, thereby resulting in cell cycle arrest and eventually cell death or resulting in such a degree of genotoxicity which would result in great amount of DNA fragmentation. These DNA-damaging agents efficacy was shown to be reliant on their ability to form DNA adducts and lesions. Therefore increasing DNA repair could result in a tumor cell becoming resistant to these drugs. In addition, if drug concentration was merely decreased in these cells, by an enhanced drug efflux as seen with the ABC transporters, then there would be less drug available for these DNA adducts to be generated. A plethora of literature has been generated on this particular topic.

However in the era of chemotherapies developed against targets only expressed in tumor cells (such as Gleevec against the Bcr-Abl fusion protein in chronic myeloid leukemia), this paradigm had changed as clinical cases of resistance had rapidly developed soon after the advent of these compounds and new paradigms of resistance mechanisms were discovered.

speed of imitinib resistance

Imatinib resistance can be seen quickly after initiation of therapy

mellobcrablresistamplification

Speed of imatinib resistance a result of rapid gene amplification of BCR/ABL target, thereby decreasing imatinib efficacy

 

 

 

 

 

 

 

 

 

 

Although there are many other new mechanisms of resistance to personalized medicine agents (which are discussed later in the chapter) this post is a curation of cellular changes which are not commonly discussed in reviews of chemoresistance and separated in three main categories:

Cellular Diversity and Adaptation

Identifying Cancers and Resistance

Cancer Drug-Resistance Mechanism

p53 tumor drug resistance gene target

Variability of Gene Expression and Drug Resistance

 

Expression of microRNAs and alterations in RNA resulting in chemo-resistance

Drug-resistance Mechanism in Tumor Cells

Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway

 

The miRNA–drug resistance connection: a new era of personalized medicine using noncoding RNA begins

 

Gene Duplication of Therapeutic Target

 

The advent of Gleevec (imatinib) had issued in a new era of chemotherapy, a personalized medicine approach by determining the and a lifesaver to chronic myeloid leukemia (CML) patients whose tumors displayed expression of the Bcr-Abl fusion gene. However it was not long before clinical resistance was seen to this therapy and, it was shown amplification of the drug target can lead to tumor outgrowth despite adequate drug exposure. le Coutre, Weisberg and Mahon23, 24, 25 all independently generated imatinib-resistant clones through serial passage of the cells in imatinib-containing media and demonstrated elevated Abl kinase activity due to a genetic amplification of the Bcr–Abl sequence. However, all of these samples were derived in vitro and may not represent a true mode of clinical resistance. Nevertheless, Gorre et al.26 obtained specimens, directly patients demonstrating imatinib resistance, and using fluorescence in situ hybridization analysis, genetic duplication of the Bcr–Abl gene was identified as one possible source of the resistance. Additional sporadic examples of amplification of the Bcr–Abl sequence have been clinically described, but the majority of patients presenting with either primary or secondary imatinib resistance fail to clinically demonstrate Abl amplification as a primary mode of treatment failure.

This is seen in the following papers:

Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL. Science. 2001 Aug 3;293(5531):876-80. Epub 2001 Jun 21.

and in another original paper by le Coutre et. al.

Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. le Coutre P1, Tassi E, Varella-Garcia M, Barni R, Mologni L, Cabrita G, Marchesi E, Supino R, Gambacorti-Passerini C. Blood. 2000 Mar 1;95(5):1758-66

The 2-phenylaminopyrimidine derivative STI571 has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr/abl fusion protein. The activity of this inhibitor has been demonstrated so far both in vitro with bcr/abl expressing cells derived from leukemic patients, and in vivo on nude mice inoculated with bcr/abl positive cells. Yet, no information is available on whether leukemic cells can develop resistance to bcr/abl inhibition. The human bcr/abl expressing cell line LAMA84 was cultured with increasing concentrations of STI571. After approximately 6 months of culture, a new cell line was obtained and named LAMA84R. This newly selected cell line showed an IC50 for the STI571 (1.0 microM) 10-fold higher than the IC50 (0.1 microM) of the parental sensitive cell line. Treatment with STI571 was shown to increase both the early and late apoptotic fraction in LAMA84 but not in LAMA84R. The induction of apoptosis in LAMA84 was associated with the activation of caspase 3-like activity, which did not develop in the resistant LAMA84R cell line. LAMA84R cells showed increased levels of bcr/abl protein and mRNA when compared to LAMA84 cells. FISH analysis with BCR- and ABL-specific probes in LAMA84R cells revealed the presence of a marker chromosome containing approximately 13 to 14 copies of the BCR/ABL gene. Thus, overexpression of the Bcr/Abl protein mediated through gene amplification is associated with and probably determines resistance of human leukemic cells to STI571 in vitro. (Blood. 2000;95:1758-1766)

This is actually the opposite case with other personalized therapies like the EGFR inhibitor gefinitib where actually the AMPLIFICATION of the therapeutic target EGFR is correlated with better response to drug in

Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs.Ono M, Kuwano M. Clin Cancer Res. 2006 Dec 15;12(24):7242-51. Review.

Abstract

The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, including EGFR, HER2/erbB2, and HER3/erbB3, is an attractive target for antitumor strategies. Aberrant EGFR signaling is correlated with progression of various malignancies, and somatic tyrosine kinase domain mutations in the EGFR gene have been discovered in patients with non-small cell lung cancer responding to EGFR-targeting small molecular agents, such as gefitinib and erlotinib. EGFR overexpression is thought to be the principal mechanism of activation in various malignant tumors. Moreover, an increased EGFR copy number is associated with improved survival in non-small cell lung cancer patients, suggesting that increased expression of mutant and/or wild-type EGFR molecules could be molecular determinants of responses to gefitinib. However, as EGFR mutations and/or gene gains are not observed in all patients who respond partially to treatment, alternative mechanisms might confer sensitivity to EGFR-targeting agents. Preclinical studies showed that sensitivity to EGFR tyrosine kinase inhibitors depends on how closely cell survival and growth signalings are coupled with EGFR, and also with HER2 and HER3, in each cancer. This review also describes a possible association between EGFR phosphorylation and drug sensitivity in cancer cells, as well as discussing the antiangiogenic effect of gefitinib in association with EGFR activation and phosphatidylinositol 3-kinase/Akt activation in vascular endothelial cells.

 

Mutant Variants of Therapeutic Target

 

resistant subclones in tissue samples and Tyrosine Kinase tumor activity

 

Mitochondrial Isocitrate Dehydrogenase and Variants

Mutational Landscape of Rare Childhood Brain Cancer: Analysis of 60 Intercranial Germ Cell Tumor Cases using NGS, SNP and Expression Array Analysis – Signaling Pathways KIT/RAS are affected by mutations in IGCTs

 

AND seen with the ALK inhibitors as well (as seen in the following papers

Acquisition of cancer stem cell-like properties in non-small cell lung cancer with acquired resistance to afatinib.

Hashida S, Yamamoto H, Shien K, Miyoshi Y, Ohtsuka T, Suzawa K, Watanabe M, Maki Y, Soh J, Asano H, Tsukuda K, Miyoshi S, Toyooka S. Cancer Sci. 2015 Oct;106(10):1377-84. doi: 10.1111/cas.12749. Epub 2015 Sep 30.

In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.

Nanjo S, Nakagawa T, Takeuchi S, Kita K, Fukuda K, Nakada M, Uehara H, Nishihara H, Hara E, Uramoto H, Tanaka F, Yano S. Cancer Sci. 2015 Mar;106(3):244-52. doi: 10.1111/cas.12600. Epub 2015 Feb 17.

Identification of a novel HIP1-ALK fusion variant in Non-Small-Cell Lung Cancer (NSCLC) and discovery of ALK I1171 (I1171N/S) mutations in two ALK-rearranged NSCLC patients with resistance to Alectinib. Ou SH, Klempner SJ, Greenbowe JR, Azada M, Schrock AB, Ali SM, Ross JS, Stephens PJ, Miller VA.J Thorac Oncol. 2014 Dec;9(12):1821-5

Reports of chemoresistance due to variants have also been seen with the BRAF inhibitors like vemurafenib and dabrafenib:

The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological inhibition of RAF.

Watson IR, Li L, Cabeceiras PK, Mahdavi M, Gutschner T, Genovese G, Wang G, Fang Z, Tepper JM, Stemke-Hale K, Tsai KY, Davies MA, Mills GB, Chin L.Cancer Res. 2014 Sep 1;74(17):4845-52. doi: 10.1158/0008-5472.CAN-14-1232-T. Epub 2014 Jul 23

 

 

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Yay! Bloomberg View Seems to Be On the Side of the Lowly Scientist!

 

Reporter: Stephen J. Williams, Ph.D.

Justin Fox at BloombergView had just published an article near and dear to the hearts of all those #openaccess scientists and those of us @Pharma_BI and @MozillaScience who feel strong about #openscience #opendata and the movement to make scientific discourse freely accessible.

His article “Academic Publishing Can’t Remain Such a Great Business” discusses the history of academic publishing and how consolidation of smaller publishers into large scientific publishing houses (Bigger publishers bought smaller ones) has produced a monopoly like environment in which prices for journal subscriptions are rising. He also discusses how the open access movement is challenging this model and may oneday replace the big publishing houses.

A few tidbits from his article:

Publishers of academic journals have a great thing going. They generally don’t pay for the articles they publish, or for the primary editing and peer reviewing essential to preparing them for publication (they do fork over some money for copy editing). Most of this gratis labor is performed by employees of academic institutions. Those institutions, along with government agencies and foundations, also fund all the research that these journal articles are based upon.

Yet the journal publishers are able to get authors to sign over copyright to this content, and sell it in the form of subscriptions to university libraries. Most journals are now delivered in electronic form, which you think would cut the cost, but no, the price has been going up and up:

 

This isn’t just inflation at work: in 1994, journal subscriptions accounted for 51 percent of all library spending on information resources. In 2012 it was 69 percent.

Who exactly is getting that money? The largest academic publisher is Elsevier, which is also the biggest, most profitable division of RELX, the Anglo-Dutch company that was known until February as Reed Elsevier.

 

RELX reports results in British pounds; I converted to dollars in part because the biggest piece of the company’s revenue comes from the U.S. And yes, those are pretty great operating-profit margins: 33 percent in 2014, 39 percent in 2013. The next biggest academic publisher is Springer Nature, which is closely held (by German publisher Holtzbrinck and U.K. private-equity firm BC Partners) but reportedly has annual revenue of about $1.75 billion. Other biggies that are part of publicly traded companies include Wiley-Blackwell, a division of John Wiley & Sons; Wolters Kluwer Health, a division of Wolters Kluwer; and Taylor & Francis, a division of Informa.

And gives a brief history of academic publishing:

The history here is that most early scholarly journals were the work of nonprofit scientific societies. The goal was to disseminate research as widely as possible, not to make money — a key reason why nobody involved got paid. After World War II, the explosion in both the production of and demand for academic research outstripped the capabilities of the scientific societies, and commercial publishers stepped into the breach. At a time when journals had to be printed and shipped all over the world, this made perfect sense.

Once it became possible to effortlessly copy and disseminate digital files, though, the economics changed. For many content producers, digital copying is a threat to their livelihoods. As Peter Suber, the director of Harvard University’s Office for Scholarly Communication, puts it in his wonderful little book, “Open Access”:

And while NIH Tried To Force These Houses To Accept Open Access:

About a decade ago, the universities and funding agencies began fighting back. The National Institutes of Health in the U.S., the world’s biggest funder of medical research, began requiring in 2008 that all recipients of its grants submit electronic versions of their final peer-reviewed manuscripts when they are accepted for publication in journals, to be posted a year later on the NIH’s open-access PubMed depository. Publishers grumbled, but didn’t want to turn down the articles.

Big publishers are making $ by either charging as much as they can or focus on new customers and services

For the big publishers, meanwhile, the choice is between positioning themselves for the open-access future or maximizing current returns. In its most recent annual report, RELX leans toward the latter while nodding toward the former:

Over the past 15 years alternative payment models for the dissemination of research such as “author-pays” or “author’s funder-pays” have emerged. While it is expected that paid subscription will remain the primary distribution model, Elsevier has long invested in alternative business models to address the needs of customers and researchers.

Elsevier’s extra services can add news avenues of revenue

https://www.elsevier.com/social-sciences/business-and-management

https://www.elsevier.com/rd-solutions

but they may be seeing the light on OpenAccess (possibly due to online advocacy, an army of scientific curators and online scientific communities):

Elsevier’s Mendeley and Academia.edu – How We Distribute Scientific Research: A Case in Advocacy for Open Access Journals

SAME SCIENTIFIC IMPACT: Scientific Publishing – Open Journals vs. Subscription-based

e-Recognition via Friction-free Collaboration over the Internet: “Open Access to Curation of Scientific Research”

Indeed we recently put up an interesting authored paper “A Patient’s Perspective: On Open Heart Surgery from Diagnosis and Intervention to Recovery” (free of charge) letting the community of science freely peruse and comment, and generally well accepted by both author and community as a nice way to share academic discourse without the enormous fees, especially on opinion papers in which a rigorous peer review may not be necessary.

But it was very nice to see a major news outlet like Bloomberg View understand the lowly scientist’s aggravations.

Thanks Bloomberg!

 

 

 

 

 

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Twitter, Google, LinkedIn Enter in the Curation Foray: What’s Up With That?

 

Reporter: Stephen J. Williams, Ph.D.

Recently Twitter has announced a new feature which they hope to use to increase engagement on their platform. Originally dubbed Project Lightning and now called Moments, this feature involves many human curators which aggregate and curate tweets surrounding individual live events(which used to be under #Live).

As Madhu Muthukumar (@justmadhu), Twitter’s Product Manager, published a blog post describing Moments said:

“Every day, people share hundreds of millions of tweets. Among them are things you can’t experience anywhere but on Twitter: conversations between world leaders and celebrities, citizens reporting events as they happen, cultural memes, live commentary on the night’s big game, and many more,” the blog post noted. “We know finding these only-on-Twitter moments can be a challenge, especially if you haven’t followed certain accounts. But it doesn’t have to be.”

Please see more about Moments on his blog here.

Moments is a new tab on Twitter’s mobile and desktop home screens where the company will curate trending topics as they’re unfolding in real-time — from citizen-reported news to cultural memes to sports events and more. Moments will fall into five total categories, including “Today,” “News,” “Sports,” “Entertainment” and “Fun.” (Source: Fox)

Now It’s Google’s Turn

 

As Dana Blankenhorn wrote in his article Twitter, Google Try It Buzzfeed’s Way With Curation

in SeekingAlpha

What’s a challenge for Google is a direct threat to Twitter’s existence.

For all the talk about what doesn’t work in journalism, curation works. Following the news, collecting it and commenting, and encouraging discussion, is the “secret sauce” for companies like Buzzfeed, Vox, Vice and The Huffington Post, which often wind up getting more traffic from a story at, say The New York Times (NYSE:NYT), than the Times does as a result.

Curation is, in some ways, a throwback to the pre-Internet era. It’s done by people. (At least I think I’m a people.) So as odd as it is for Twitter (NYSE:TWTR) to announce it will curate live events it’s even odder to see Google (NASDAQ:GOOG) (NASDAQ:GOOGL) doing it in a project called YouTube Newswire.

Buzzfeed, Google’s content curation platform, made for desktop as well as a mobile app, allows sharing of curated news, viral videos.

The feel for both Twitter and Google’s content curation will be like a newspaper, with an army of human content curators determining what is the trendiest news to read or videos to watch.

BuzzFeed articles, or at least, the headlines can easily be mined from any social network but reading the whole article still requires that you open the link within the app or outside using a mobile web browser. Loading takes some time–a few seconds longer. Try browsing the BuzzFeed feed on the app and you’ll notice the obvious difference.

However it was earlier this summer in a Forbes article Why Apple, Snapchat and Twitter are betting on human editors, but Facebook and Google aren’t that Apple, Snapchat and Twitter as well as LinkedIn Pulse and Instragram were going to use human editors and curators while Facebook and Google were going to rely on their powerful algorithms. Google (now Alphabet) CEO Eric Schmidt has even called Apple’s human curated playlists “elitist” although Google Play has human curated playlists.

Maybe Google is responding to views on its Google News like this review in VentureBeat:

Google News: Less focused on social signals than textual ones, Google News uses its analytic tools to group together related stories and highlight the biggest ones. Unlike Techmeme, it’s entirely driven by algorithms, and that means it often makes weird choices. I’ve heard that Google uses social sharing signals from Google+ to help determine which stories appear on Google News, but have never heard definitive confirmation of that — and now that Google+ is all but dead, it’s mostly moot. I find Google News an unsatisfying home page, but it is a good place to search for news once you’ve found it.

Now WordPress Too!

 

WordPress also has announced its curation plugin called Curation Traffic.

According to WordPress

You Own the Platform, You Benefit from the Traffic

“The Curation Traffic™ System is a complete WordPress based content curation solution. Giving you all the tools and strategies you need to put content curation into action.

It is push-button simple and seamlessly integrates with any WordPress site or blog.

With Curation Traffic™, curating your first post is as easy as clicking “Curate” and the same post that may originally only been sent to Facebook or Twitter is now sent to your own site that you control, you benefit from, and still goes across all of your social sites.”

The theory the more you share on your platform the more engagement the better marketing experience. And with all the WordPress users out there they have already an army of human curators.

So That’s Great For News But What About Science and Medicine?

 

The news and trendy topics such as fashion and music are common in most people’s experiences. However more technical areas of science, medicine, engineering are not in most people’s domain so aggregation of content needs a process of peer review to sort basically “the fact from fiction”. On social media this is extremely important as sensational stories of breakthroughs can spread virally without proper vetting and even influence patient decisions about their own personal care.

Expertise Depends on Experience

In steps the human experience. On this site (www.pharmaceuticalintelligence.com) we attempt to do just this. A consortium of M.D.s, Ph.D. and other medical professionals spend their own time to aggregate not only topics of interest but curate on specific topics to add some more insight from acceptable sources over the web.

In Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison; Dr. Larry Berstein compares a museum or music curator to curation of scientific findings and literature and draws similar conclusions from each: that a curation can be a tool to gain new insights previously unseen an observer. A way of stepping back to see a different picture, hear a different song.

 

For instance, using a Twitter platform, we curate #live meeting notes and tweets from meeting attendees (please see links below and links within) to give a live conference coverage

http://pharmaceuticalintelligence.com/press-coverage/

and curation and analysis give rise not only to meeting engagement butunique insights into presentations.

 

In addition, the use of a WordPress platform allows easy sharing among many different social platforms including Twitter, Google+, LinkedIn, Pinterest etc.

Hopefully, this will catch on to the big powers of Twitter, Google and Facebook to realize there exists armies of niche curation communities which they can draw on for expert curation in the biosciences.

Other posts on this site on Curation and include

 

Inevitability of Curation: Scientific Publishing moves to embrace Open Data, Libraries and Researchers are trying to keep up

The Methodology of Curation for Scientific Research Findings

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

The growing importance of content curation

Data Curation is for Big Data what Data Integration is for Small Data

Stem Cells and Cardiac Repair: Content Curation & Scientific Reporting

Cardiovascular Diseases and Pharmacological Therapy: Curations

Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison

 

 

 

 

 

 

 

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Horizon Discovery Group plc In-licenses Oncology Programme from Servier and Enters Option Agreement

Reporter: Aviva-Lev Ari, Ph.D., R.N.; Stephen J. Williams, Ph.D.

Press release

7 October 2015

 

Horizon Discovery Group plc In-licenses Oncology Programme from Servier and Enters Option Agreement

 

  • License programme with milestone payments of up to £50 million plus royalties on product sales
  • Horizon to in-license novel kinase inhibitor programme from Servier
  • Horizon will exploit its translational genomics and combination sciences platform to define optimum approaches to treatment and identify cancer patient populations most likely to respond

 

Cambridge, UK, 7 October 2015: Horizon Discovery Group plc (LSE: HZD) (“Horizon” or “the Company”), the international life science company supplying research tools and services that power genomics research and the development of personalised medicines, announces today that its leveraged business unit has signed a programme in-licensing and option agreement with Servier, the independent French research-based pharmaceutical company. The agreement is potentially worth over £50 million to Horizon in preclinical and clinical milestones, payments linked to net sales, and tiered royalties on future product sales.

 

Horizon has in-licensed novel kinase inhibitors from Servier that exhibit great promise based on pre-clinical data for treatment of a range of cancer types but do not currently have a biomarker to define a sensitive patient population. Horizon will use its world-leading platform, comprising isogenic cell lines and in vivo models, CRISPR-Cas9 mediated gene editing technology and ultra-high-throughput combination screening, to identify the population of cancer patients most likely to respond to the in-licensed compounds, whether as single agents or in combinations with other drugs. Horizon also has the option to explore the use of the inhibitors in other therapeutic indications.

 

Under the terms of the agreement, Servier has a first option to license back the assets. Should Servier take up this option, Horizon would receive up to £50 million in milestone payments plus royalties on product sales. If Servier does not take up its option, Horizon will be free to seek another pharma partner and Horizon and Servier would then share in the success of the progression of the programme as it advances into the clinic and registration.

 

Horizon will evaluate the mechanism of action of the candidate compounds, and will verify the patient stratification hypothesis by both in vitro and in vivo preclinical experiments. Horizon will also define a path towards the development of biomarkers for both patient stratification and drug efficacy.

 

Dr. Darrin M. Disley, Chief Executive Officer of Horizon Discovery Group plc, said: “The in-license of assets with a strong pre-clinical pedigree but do not yet have a clear clinical development strategy, represents a great opportunity for companies like Horizon. Demonstrating our scientific leadership through our translational genomics, drug combination and biomarker discovery platforms; we seek to identify genetic markers that predict drug sensitivity enabling programmes like this one to be progressed rapidly into the clinic for defined patient populations. This innovative deal, as part of our strategy to drive accelerated growth, offers significant upside potential for our investors built upon the leverage of our intellectual property, technology platforms and know-how.”

 

Mr Jean Pierre Abastado, Director of Oncology Innovation, Servier, commented: “The long standing collaboration between Servier and Vernalis has led to the discovery of novel kinase inhibitors. Horizon’s technology portfolio and expertise makes them ideally positioned to progress these drug candidates into the clinic and to investigate their potential for therapeutic efficacy both alone and in combination therapies. Servier is committed to driving therapeutic progress for the benefit of patients, with partnerships such as this playing a key role.”

ENDS

 

For further information from Horizon Discovery Group plc, please contact:

 

Zyme Communications (Trade and Regional Media)

Katie Odgaard

Tel: +44 (0)7787 502 947

Email: katie.odgaard@zymecommunications.com

 

Consilium Strategic Communications (Financial Media and Investor Relations)

Amber Fennell / Jessica Hodgson / Matthew Neal / Laura Thornton

Tel: +44 (0) 20 3709 5701

Email: horizon@consilium-comms.com

 

Panmure Gordon & Co. (NOMAD)

Corporate Finance: Freddy Crossley / Duncan Monteith / Fabien Holler

Broking: Tom Salvesen

Tel: +44 20 7886 2500

 

Notes for Editors

 

About Horizon Discovery Group plc www.horizondiscovery.com/

Horizon is a revenue-generating life science group supplying research tools to organisations engaged in genomics research and the development of personalised medicines. Horizon has a diverse and international customer base of over 1,200 organisations across more than 50 countries, including major pharmaceutical, biotechnology and diagnostic companies as well as leading academic research centers. The Group supplies its products and services into multiple markets, estimated to total in excess of £29 billion by 2015.

 

Horizon’s core capabilities are built around its proprietary translational genomics platform, a high-precision and flexible suite of gene editing tools able to alter almost any endogenous gene sequence of human or mammalian cell-lines. Horizon offers over 20,000 catalogue products, almost all of which are based on the application of gene editing to generate cell lines that accurately model the disease-causing mutations found in genetically based diseases. These ‘patients-in-a-test-tube’ are being used by customers to identify the effect of individual or compound genetic mutations on drug activity, patient responsiveness, and resistance, which may lead to the successful prediction of which patient sub-groups will respond to currently available and future drug treatments.

In addition, Horizon provides custom cell line and in vivo model generation services for research and bioproduction applications, quantitative molecular reference standards, in vivo disease models, and contract research and custom screening services.

 

Horizon is headquartered in Cambridge, UK, and is listed on the London Stock Exchange’s AIM market under the ticker “HZD”, for further information please visit: www.horizondiscovery.com.

 

About Servier

Servier is an independent French research-based pharmaceutical company. Its development is driven by the pursuit of innovation in the therapeutic areas of cardiovascular, metabolic, central nervous system, psychiatric, bone, muscle and joint diseases, as well as cancer.

  • In 2014, the company recorded a turnover of 4 billion euros.
  • 92% of Servier medicines are prescribed outside of France.
  • 28% of turnover from Servier drugs was reinvested in Research and Development in 2014.

With a strong international presence in 146 countries, Servier employs more than 21,400 people worldwide.

 

Oncology is one of the key priorities of Servier in terms of research and development with currently 8 new molecular entities in clinical development in breast cancer, lung cancer, other solid tumours and various types of lymphomas and leukaemias. This portfolio of innovative cancer treatments is being developed with various partners worldwide, and covers different hallmarks of cancer including cytotoxics, pro-apoptotic, targeted, immune and cellular therapies. Hence, Servier aims at delivering a significant and positive impact on cancer patients’ lives.

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Mozilla Science Lab Promotes Data Reproduction Through Open Access: Report from 9/10/2015 Online Meeting

Reporter: Stephen J. Williams, Ph.D.

Mozilla Inc. is developing a platform for scientists to discuss the issues related to developing a framework to share scientific data as well as tackle the problems of scientific reproducibility in an Open Access manner. According to their blog

https://blog.mozilla.org/blog/2013/06/14/5992/

We’re excited to announce the launch of the Mozilla Science Lab, a new initiative that will help researchers around the world use the open web to shape science’s future.

Scientists created the web — but the open web still hasn’t transformed scientific practice to the same extent we’ve seen in other areas like media, education and business. For all of the incredible discoveries of the last century, science is still largely rooted in the “analog” age. Credit systems in science are still largely based around “papers,” for example, and as a result researchers are often discouraged from sharing, learning, reusing, and adopting the type of open and collaborative learning that the web makes possible.

The Science Lab will foster dialog between the open web community and researchers to tackle this challenge. Together they’ll share ideas, tools, and best practices for using next-generation web solutions to solve real problems in science, and explore ways to make research more agile and collaborative.

On their blog they highlight various projects related to promoting Open Access for scientific data

On September 10, 2015 Mozilla Science Lab had their scheduled meeting on scientific data reproduce ability.  The meeting was free and covered by ethernet and on social media. The Twitter hashtag for updates and meeting discussion is #mozscience (https://twitter.com/search?q=%23mozscience )

Open Access Meeting Announcement on Twitter

https://twitter.com/MozillaScience/status/641642491532283904

//platform.twitter.com/widgets.js

mozilla science lab

Mozilla Science Lab @MozillaScience

Join @khinsen @abbycabs + @EvoMRI tmrw (11AM ET) to hear about replication, publishing + #openscience. Details: https://etherpad.mozilla.org/sciencelab-calls-sep10-2015 …

AGENDA:

  • Mozilla Science Lab Updates
  • Staff welcomes and thank yous:
  • Welcoming Zannah Marsh, our first Instructional Designer
  • Workshopping the “Working Open” guide:
    • Discussion of Future foundation and GitHub projects
    • Discussion of submission for open science project funding
  • Contributorship Badges Pilot – an update! – Abby Cabunoc Mayes – @abbycabs
  • Will be live on GigaScience September 17th!
  • Where you can jump in: https://github.com/mozillascience/paperbadger/issues/17
  • Questions regarding coding projects – Abby will coordinate efforts on coding into their codebase
  • The journal will publish and authors and reviewers get a badge and their efforts and comments will appear on GigaScience: Giga Science will give credit for your reviews – supports an Open Science Discussion

Roadmap for

  • Fellows review is in full swing!
  • MozFest update:
  • Miss the submission deadline? You can still apply to join our Open Research Accelerator and join us for the event (PLUS get a DOI for your submission and 1:1 help)

A discussion by Konrad Hinsen (@khinsen) on ReScience, a journal focused on scientific replication will be presented:

  • ReScience – a new journal for replications – Konrad Hinsen @khinsen
  • ReScience is dedicated to publishing replications of previously published computational studies, along with all the code required to replicate the results.
  • ReScience lives entirely on GitHub. Submissions take the form of a Git repository, and review takes place in the open through GitHub issues. This also means that ReScience is free for everyone (authors, readers, reviewers, editors… well, I said everyone, right?), as long as GitHub is willing to host it.
  • ReScience was launched just a few days ago and is evolving quickly. To stay up to date, follow @ReScienceEds on Twitter. If you want to volunteer as a reviewer, please contact the editorial board.

The ReScience Journal Reproducible Science is Good. Replicated Science is better.

ReScience is a peer-reviewed journal that targets computational research and encourages the explicit reproduction of already published research promoting new and open-source implementations in order to ensure the original research is reproducible. To achieve such a goal, the whole editing chain is radically different from any other traditional scientific journal. ReScience lives on github where each new implementation is made available together with the comments, explanations and tests. Each submission takes the form of a pull request that is publicly reviewed and tested in order to guarantee any researcher can re-use it. If you ever reproduced computational result from the literature, ReScience is the perfect place to publish this new implementation. The Editorial Board

Notes from his talk:

– must be able to replicate paper’s results as written according to experimental methods

– All authors on ReScience need to be on GitHub

– not accepting MatLab replication; replication can involve computational replication;

  • Research Ideas and Outcomes Journal – Daniel Mietchen @EvoMRI
    • Postdoc at Natural Museum of London doing data mining; huge waste that 90% research proposals don’t get used so this journal allows for publishing proposals
    • Learned how to write proposals by finding a proposal online open access
    • Reviewing system based on online reviews like GoogleDocs where people view, comment
    • Growing editorial and advisory board; venturing into new subject areas like humanities, economics, biological research so they are trying to link diverse areas under SOCIAL IMPACT labeling
    • BIG question how to get scientists to publish their proposals especially to improve efficiency of collaboration and reduce too many duplicated efforts as well as reagent sharing
    • Crowdfunding platform used as post publication funding mechanism; still in works
    • They need a lot of help on the editorial board so if have a PhD PLEASE JOIN
  • Website:
  • Background:
  • Science article:
  • Some key features:
  • for publishing all steps of the research cycle, from proposals (funded and not yet funded) onwards
  • maps submissions to societal challenges
  • focus on post-publication peer review; pre-submission endorsement; all reviews public
  • lets authors choose which publishing services they want, e.g. whether they’d like journal-mediated peer review
  • collaborative WYSIWYG authoring and publishing platform based on JATS XML

A brief discussion of upcoming events on @MozillaScience

Meetings are held 2nd Thursdays of each month

Additional plugins, coding, and new publishing formats are available at https://www.mozillascience.org/

Other related articles on OPEN ACCESS Publishing were published in this Open Access Online Scientific Journal, include the following:

Archives of Medicine (AOM) to Publish from “Leaders in Pharmaceutical Business Intelligence (LPBI)” Open Access On-Line Scientific Journal http://pharmaceuticalintelligence.com

Annual Growth in NIH Clicks: 32% Open Access Online Scientific Journal http://pharmaceuticalintelligence.com

Collaborations and Open Access Innovations – CHI, BioIT World, 4/29 – 5/1/2014, Seaport World Trade Center, Boston

Elsevier’s Mendeley and Academia.edu – How We Distribute Scientific Research: A Case in Advocacy for Open Access Journals

Reconstructed Science Communication for Open Access Online Scientific Curation

The Fatal Self Distraction of the Academic Publishing Industry: The Solution of the Open Access Online Scientific Journals

 

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Leaders in Pharmaceutical Business Intelligence would like to announce their First Volume of their BioMedical E-Book Series A: eBooks on Cardiovascular Diseases

 

Perspectives on Nitric Oxide in Disease Mechanisms

Nitric Oxide coverwhich is now available on Amazon Kindle at

http://www.amazon.com/dp/B00DINFFYC

This book is a comprehensive review of Nitric Oxide, its discovery, function, and related opportunities for Targeted Therapy written by  Experts, Authors, Writers.  This book is a series of articles delineating the basic functioning of the NOS isoforms, their production widely by endothelial cells, and the effect of NITRIC OXIDE production by endothelial cells, by neutrophils and macrophages, the effect on intercellular adhesion, and the effect of circulatory shear and turbulence on NITRIC OXIDE production. The e-Book’s articles have been published on the  Open Access Online Scientific Journal, since April 2012.  All new articles on this subject, will continue to be incorporated, as published, in real time in the e-Book which is a live book.

 

We invite e-Readers to write an Article Reviews on Amazon for this e-Book.

 

All forthcoming BioMed e-Book Titles can be viewed at:

http://pharmaceuticalintelligence.com/biomed-e-books/

 

Leaders in Pharmaceutical Business Intelligence, launched in April 2012 an Open Access Online Scientific Journal is a scientific, medical and business multi expert authoring environment in several domains of  life sciences, pharmaceutical, healthcare & medicine industries. The venture operates as an online scientific intellectual exchange at their website http://pharmaceuticalintelligence.com and for curation and reporting on frontiers in biomedical, biological sciences, healthcare economics, pharmacology, pharmaceuticals & medicine. In addition the venture publishes a Medical E-book Series available on Amazon’s Kindle platform.

Analyzing and sharing the vast and rapidly expanding volume of scientific knowledge has never been so crucial to innovation in the medical field. WE are addressing need of overcoming this scientific information overload by:

  • delivering curation and summary interpretations of latest findings and innovations on an open-access, Web 2.0 platform with future goals of providing primarily concept-driven search in the near future
  • providing a social platform for scientists and clinicians to enter into discussion using social media
  • compiling recent discoveries and issues in yearly-updated Medical E-book Series on Amazon’s mobile Kindle platform

This curation offers better organization and visibility to the critical information useful for the next innovations in academic, clinical, and industrial research by providing these hybrid networks.

Table of Contents for Perspectives on Nitric Oxide in Disease Mechanisms

Chapter 1: Nitric Oxide Basic Research

Chapter 2: Nitric Oxide and Circulatory Diseases

Chapter 3: Therapeutic Cardiovascular Targets

Chapter 4: Nitric Oxide and Neurodegenerative Diseases

Chapter 5: Bone Metabolism

Chapter 6: Nitric Oxide and Systemic Inflammatory Disease

Chapter 7: Nitric Oxide: Lung and Alveolar Gas Exchange

Chapter 8. Nitric Oxide and Kidney Dysfunction

Chapter 9: Nitric Oxide and Cancer 

 

 

 

 

 

 

 

 

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Metabolic Genomics and Pharmaceutics, Vol. 1 of BioMed Series D available on Amazon Kindle


Metabolic Genomics and Pharmaceutics, Vol. 1 of BioMed Series D available on Amazon Kindle

Reporter: Stephen S Williams, PhD

 

Leaders in Pharmaceutical Business Intelligence would like to announce the First volume of their BioMedical E-Book Series D:

Metabolic Genomics & Pharmaceutics, Vol. I

SACHS FLYER 2014 Metabolomics SeriesDindividualred-page2

which is now available on Amazon Kindle at

http://www.amazon.com/dp/B012BB0ZF0.

This e-Book is a comprehensive review of recent Original Research on  METABOLOMICS and related opportunities for Targeted Therapy written by Experts, Authors, Writers. This is the first volume of the Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases.  It is written for comprehension at the third year medical student level, or as a reference for licensing board exams, but it is also written for the education of a first time baccalaureate degree reader in the biological sciences.  Hopefully, it can be read with great interest by the undergraduate student who is undecided in the choice of a career. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012.  All new articles on this subject, will continue to be incorporated, as published with periodical updates.

We invite e-Readers to write an Article Reviews on Amazon for this e-Book on Amazon.

All forthcoming BioMed e-Book Titles can be viewed at:

http://pharmaceuticalintelligence.com/biomed-e-books/

Leaders in Pharmaceutical Business Intelligence, launched in April 2012 an Open Access Online Scientific Journal is a scientific, medical and business multi expert authoring environment in several domains of  life sciences, pharmaceutical, healthcare & medicine industries. The venture operates as an online scientific intellectual exchange at their website http://pharmaceuticalintelligence.com and for curation and reporting on frontiers in biomedical, biological sciences, healthcare economics, pharmacology, pharmaceuticals & medicine. In addition the venture publishes a Medical E-book Series available on Amazon’s Kindle platform.

Analyzing and sharing the vast and rapidly expanding volume of scientific knowledge has never been so crucial to innovation in the medical field. WE are addressing need of overcoming this scientific information overload by:

  • delivering curation and summary interpretations of latest findings and innovations on an open-access, Web 2.0 platform with future goals of providing primarily concept-driven search in the near future
  • providing a social platform for scientists and clinicians to enter into discussion using social media
  • compiling recent discoveries and issues in yearly-updated Medical E-book Series on Amazon’s mobile Kindle platform

This curation offers better organization and visibility to the critical information useful for the next innovations in academic, clinical, and industrial research by providing these hybrid networks.

Table of Contents for Metabolic Genomics & Pharmaceutics, Vol. I

Chapter 1: Metabolic Pathways

Chapter 2: Lipid Metabolism

Chapter 3: Cell Signaling

Chapter 4: Protein Synthesis and Degradation

Chapter 5: Sub-cellular Structure

Chapter 6: Proteomics

Chapter 7: Metabolomics

Chapter 8:  Impairments in Pathological States: Endocrine Disorders; Stress

                   Hypermetabolism and Cancer

Chapter 9: Genomic Expression in Health and Disease 

 

Summary 

Epilogue

 

 

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