Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse brain tumors mimic those in human genetic disorder

03.01.2005


A recently developed mouse model of brain tumors common in the genetic disorder neurofibromatosis 1 (NF1) successfully mimics the human condition and provides unique insight into tumor development, diagnosis and treatment, according to researchers at Washington University School of Medicine in St. Louis.



After validating their animal model, the team made two important discoveries: New blood vessels and immune system cells may be essential to the initial formation of tumors and therefore may be promising drug targets; and brain images often used to determine the need for treatment may not actually be diagnostically informative. "These mice develop brain tumors with many of the same features as those seen in children with NF1, and studying those tumors has helped us understand the cellular events involved in NF1 brain tumor development," says principal investigator David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology.

The study appears online and will be published in the January 2005 issue of the journal Annals of Neurology.


NF1 is one of the most common neurological disorders caused by a single gene mutation. The disorder can lead to a variety of complications including brain cancer. To supplement their clinical research, Gutmann’s team developed a mouse model in which the animals, like humans with the disease, have one abnormal copy of the gene for NF1 in every cell in their body, while specific support cells in the brain called astrocytes have two abnormal copies of this same gene. Their latest paper shows that brain tumor formation in these mice has several of the same distinguishing clinical characteristics as tumor development in children with NF1.

First, the mice developed tumors along the optic nerve and optic chiasm, which transmit visual information from the eye to the brain. This type of tumor, called an optic pathway glioma, is the most common tumor in children with NF1.

Second, the time course of tumor development was similar to that seen in humans. Unlike most tumors, optic pathway gliomas associated with NF1 typically stop growing after a few years. Moreover, they almost always occur in children -- these tumors generally start growing in children younger than 5 years old and usually do not progress after age 10. A similar pattern occurred in the mice: The optic nerve and chiasm were enlarged and astrocytes along the optic pathway began multiplying and growing when the animals were around three weeks old, developing into optic pathway gliomas by two months of age. After that time-period, which is roughly equivalent to teenage years in humans, the cells slowed down to the same growth speed as astrocytes in control mice. "The fact that cell growth is dramatically reduced after a few months in mice and after a few years in humans tells us there may be growth signals that are produced early in life, which are critical for tumor formation and expansion," Gutmann explains.

Optic pathway gliomas in humans are typically surrounded by blood vessels and microglia, which are immune system cells in the brain. But it was unclear whether the development of blood vessels and recruitment of microglia helped trigger tumor formation or if they appeared only after the tumor was fully developed. The researchers found that by three weeks of age, the mutant mice had about four times the number of small blood vessels in the optic nerves and chiasm as control mice. Similarly, microglia were also found in the nerve and chiasm of mutant mice prior to tumor formation. "In our judgment, the fact that recruitment of new blood vessels and infiltration of immune system cells occurs before actual tumor formation suggests that these events are important for the development of tumors," Gutmann says. "These findings raise the possibility that targeted therapies for NF1 brain tumors may involve agents that prevent the supply of growth promoting factors provided by new blood vessels and microglia."

Next, the researchers used the mouse model to investigate a clinical concern. Physicians rely on several tests to determine whether a child with an optic pathway glioma should undergo treatment for the tumor, including the tumor’s size and the patient’s clinical symptoms. But often those tests aren’t sufficiently informative, so experts also examine pictures of the patient’s brain taken with magnetic resonance imaging (MRI). To capture such brain images, physicians inject a contrast dye into a patient’s bloodstream and look for accumulation of dye around the tumor. Though dye accumulation may be a sign of tumor progression, it is unclear whether that is always the case, particularly in optic pathway gliomas associated with NF1.

Results from this latest study suggest that the two are not necessarily correlated. Gutmann’s team found that optic pathway gliomas lit up just as brightly in 2-month-old mice as in 8-month-old mice, despite the fact that the tumors were actively growing only in the younger mice. "If this finding is also true in humans, this strongly argues that contrast enhancement on MRI alone is not a reliable test of tumor progression," Gutmann says. "If we rely on contrast enhancement in children with NF1 optic pathway gliomas, we may be treating kids who don’t need to be treated. Using this mouse model, we hope to continue to hone in on more accurate diagnostic, prognostic and treatment approaches."

Gila Z. Reckess | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>