Click here to close now.

SYS-CON MEDIA Authors: AppDynamics Blog, Roger Strukhoff, Pat Romanski, Elizabeth White, Liz McMillan

News Feed Item

Study Identifies Targeted Molecular Therapy for Untreatable NF1 Tumors

CINCINNATI, Dec. 10, 2012 /PRNewswire-USNewswire/ -- Researchers conducting a preclinical study in mice successfully used targeted molecular therapy to block mostly untreatable nerve tumors that develop in people with the genetic disorder Neurofibromatosis 1 (NF1).

(Logo: http://photos.prnewswire.com/prnh/20110406/MM79025LOGO)

Scientists from Cincinnati Children's Hospital Medical Center report their findings online Dec. 10 in the Journal of Clinical Investigation.

"We can for the first time shrink the large majority of neurofibromas, at least in mice, by using a molecularly targeted treatment," said Nancy Ratner, PhD, principal investigator and program leader for the Cancer Biology and Neural Tumors Program in the Cancer and Blood Disorders Institute at Cincinnati Children's. "At present there is no treatment for these tumors and our data provide strong rationale for testing this therapy in clinical trials for NF1."

Neurofibromas are benign tumors that grow along peripheral nerves in the body. They affect up to half of the people who have NF1. In the United States alone there are 10,000 people with NF1. Fueled initially by mutation of the tumor-suppressing gene NF1, the tumors can grow to become quite large and compress vital organs. They can also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs), the leading cause of death in people with NF1.

The researchers tested an existing experimental drug from Pfizer called PD0325901, which in the current study shrank NF1 tumors in over 80 percent of the mice treated. Study authors report it was "the most dramatic result described to date for neurofibroma bearing mice."

The drug inhibits a protein called MEK, part of a molecular signaling chain that relays genetic instructions to the cell nucleus to promote cell growth. Researchers decided to test the drug after conducting a cross-species bioinformatics computer analysis of mouse and human NF1 tumors. The analysis identified genes and molecules that regulate cell signals driving the growth of neurofibromas and MPNSTs in both species.

The drug is currently being tested in human clinical trials for cancers that involve molecular components similar to those in NF1, in particular the MEK protein.

MEK is a downstream molecular target for a group of cell signaling proteins called Ras-GTPase. The proteins work together in a molecular relay to activate normal cell growth. In the instance of genetic mutation, Ras-GTPase can get stuck in the "on" position and promote hyperactive cell growth, tumor formation or cancer. Overactive Ras-GTPase signaling has been linked to a number of cancers.

In the case of mouse and human NF1 tumors, bioinformatics computer analysis suggested that deregulated Ras-GTPase signaling prompted MEK to stimulate the sustained activity of an enzyme called ERK. To confirm whether this molecular pathway is critical to NF1 tumor growth, researchers tested the MEK-blocking drug in genetically engineered mice.

The mice lacked expression of the NF1 gene and its tumor suppressing protein, causing the animals to develop benign neurofibromas. Scientists also transplanted human malignant peripheral nerve sheath tumor cells into a separate group of genetically receptive mice, which developed their own cancerous tumors.

Researchers then tested different doses of the drug to identify an optimal dose – one that would achieve the maximum amount of tumor shrinking efficiency with the least amount of toxicity. Treatment with PD0325901 reduced the abnormal growth of cells in both benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). It also reduced the volume of tumor feeding blood vessels.

Treated mice with benign neurofibromas had significant shrinkage of their tumors after 60 days, compared to untreated mice. In mice implanted with human MPNSTs, the drug diminished cancerous tumor growth and doubled survival time to 52 days, as compared to untreated animals.

Researchers said overall shrinkage of MPNSTs was modest compared to that achieved in benign tumors, possibly because additional molecular pathways are involved in their formation. They said this suggests that MPNSTs may require a combinatory treatment that includes PD0325901 in conjunction with other therapies.

Mutations of the NF1 gene are frequently found in other cancers, such as glioblastoma, lung adenocarcinoma and ovarian cancer. The researchers said this could open the possibility of studying the Ras-MEK-ERK pathway as molecular target for treating these diseases.

Funding for the study came from: the DAMD Program on Neurofibromatosis for the NF1 Microarray Consortium (DODW81XWH-09-1-0135 and W81XWH-04-1-0273); the Children's Tumor Foundation for support to the NF1 Preclinical Consortium; a National Institutes of Health Bench to Bedside Award for MRI Analyses (NIH-P50-NS05753) and an American Recovery and Reinvestment Act supplement to NIH grant R01-NS28840. The drug was provided by the manufacturer, Pfizer Inc.

About Cincinnati Children's
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2012 Best Children's Hospitals ranking. It is ranked #1 for neonatology and in the top 10 for all pediatric specialties. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health and a research affiliate of the University of Cincinnati College of Medicine. It is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org.

SOURCE Cincinnati Children's Hospital Medical Center

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
The 17th International Cloud Expo has announced that its Call for Papers is open. 17th International Cloud Expo, to be held November 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, brings together Cloud Computing, APM, APIs, Microservices, Security, Big Data, Internet of Things, DevOps and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding bu...
Operational Hadoop and the Lambda Architecture for Streaming Data Apache Hadoop is emerging as a distributed platform for handling large and fast incoming streams of data. Predictive maintenance, supply chain optimization, and Internet-of-Things analysis are examples where Hadoop provides the scalable storage, processing, and analytics platform to gain meaningful insights from granular data that is typically only valuable from a large-scale, aggregate view. One architecture useful for capturing...
Actifio, the copy data virtualization company, today announced a series of new features and functional enhancements to better support the growing number of customers leveraging its virtual data pipeline technology in support of DevOps use cases. While infrastructure is increasingly seen as a commodity inside large enterprises, applications – where the technology touches the business – are becoming more strategic. Managing the flow of data that powers those applications presents a range of cha...
Cloud services are the newest tool in the arsenal of IT products in the market today. These cloud services integrate process and tools. In order to use these products effectively, organizations must have a good understanding of themselves and their business requirements. In his session at 15th Cloud Expo, Brian Lewis, Principal Architect at Verizon Cloud, outlined key areas of organizational focus, and how to formalize an actionable plan when migrating applications and internal services to the ...
Most companies hope for rapid growth so it's important to invest in scalable core technologies that won't demand a complete overhaul when a business goes through a growth spurt. Cloud technology enables previously difficult-to-scale solutions like phone, network infrastructure or billing systems to automatically scale based on demand. For example, with a virtual PBX service, a single-user cloud phone service can easily transition into an advanced VoIP system that supports hundreds of phones and ...
The explosion of connected devices / sensors is creating an ever-expanding set of new and valuable data. In parallel the emerging capability of Big Data technologies to store, access, analyze, and react to this data is producing changes in business models under the umbrella of the Internet of Things (IoT). In particular within the Insurance industry, IoT appears positioned to enable deep changes by altering relationships between insurers, distributors, and the insured. In his session at @Things...
Since 2008 and for the first time in history, more than half of humans live in urban areas, urging cities to become “smart.” Today, cities can leverage the wide availability of smartphones combined with new technologies such as Beacons or NFC to connect their urban furniture and environment to create citizen-first services that improve transportation, way-finding and information delivery. In her session at @ThingsExpo, Laetitia Gazel-Anthoine, CEO of Connecthings, will focus on successful use c...
The recent trends like cloud computing, social, mobile and Internet of Things are forcing enterprises to modernize in order to compete in the competitive globalized markets. However, enterprises are approaching newer technologies with a more silo-ed way, gaining only sub optimal benefits. The Modern Enterprise model is presented as a newer way to think of enterprise IT, which takes a more holistic approach to embracing modern technologies.
DevOps Summit, taking place Nov 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 17th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long developmen...
Security can create serious friction for DevOps processes. We've come up with an approach to alleviate the friction and provide security value to DevOps teams. In her session at DevOps Summit, Shannon Lietz, Senior Manager of DevSecOps at Intuit, will discuss how DevSecOps got started and how it has evolved. Shannon Lietz has over two decades of experience pursuing next generation security solutions. She is currently the DevSecOps Leader for Intuit where she is responsible for setting and driv...
Software-driven innovation is becoming a primary approach to how businesses create and deliver new value to customers. A survey of 400 business and IT executives by the IBM Institute for Business Value showed businesses that are more effective at software delivery are also more profitable than their peers nearly 70 percent of the time (1). DevOps provides a way for businesses to remain competitive, applying lean and agile principles to software development to speed the delivery of software that ...
“Oh, dev is dev and ops is ops, and never the twain shall meet.” With apoloies to Rudyard Kipling and all of his fans, this describes the early state of the two sides of DevOps. Yet the DevOps approach is demanded by cloud computing, as the speed, flexibility, and scalability in today's so-called “Third Platform” must not be hindered by the traditional limitations of software development and deployment. A recent report by Gartner, for example, says that 25% of Global 2000 companies will b...
Big Data is amazing, it's life changing and yes it is changing how we see our world. Big Data, however, can sometimes be too big. Organizations that are not amassing massive amounts of information and feeding into their decision buckets, smaller data that feeds in from customer buying patterns, buying decisions and buying influences can be more useful when used in the right way. In their session at Big Data Expo, Ermanno Bonifazi, CEO & Founder of Solgenia, and Ian Khan, Global Strategic Positi...
JFrog on Thursday announced that it has added Docker support to Bintray, its distribution-as-a-service (DaaS) platform. When combined with JFrog’s Artifactory binary repository management system, organizations can now manage Docker images with an end-to-end solution that supports all technologies. The new version of Bintray allows organizations to create an unlimited number of private Docker repositories, and through the use of fast Akamai content delivery networks (CDNs), it decreases the dow...
More organizations are embracing DevOps to realize compelling business benefits such as more frequent feature releases, increased application stability, and more productive resource utilization. However, security and compliance monitoring tools have not kept up and often represent the single largest remaining hurdle to continuous delivery. In their session at DevOps Summit, Justin Criswell, Senior Sales Engineer at Alert Logic, Ricardo Lupo, a Solution Architect with Chef, will discuss how to ...