Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein stops growth of brain tumor

28.01.2005


Herstatin blocks signaling inside cells that leads to deadly glioblastoma growth



A protein developed by scientists at Oregon Health & Science University blocks the growth of glioblastoma, an aggressive and deadly brain tumor, in laboratory rats, a new study shows. Herstatin inhibits the activation of a family of enzymes responsible for signaling inside tumor cells that tells the cells to proliferate and display other malignant properties, said Gail Clinton, Ph.D., professor of biochemistry and molecular biology in the OHSU School of Medicine who co-authored the study appearing this month in the journal Clinical Cancer Research. "The growth is completely blocked in the intracranial model," said Clinton, a member of the OHSU Cancer Institute.

Over-expression of the epidermal growth factor (EGF) receptors results in a cascade of signals in the glioblastoma cells that drives their growth. But herstatin, a naturally occurring product, blocks growth of the cells by binding to EGF receptors and turning signaling off. Clinton said human clinical trials for herstatin could begin as early as next year. In fact, the technology is part of a patent portfolio that OHSU has licensed exclusively to San Francisco-based pharmaceutical company Receptor BioLogix Inc., which is developing herstatin as a cancer therapeutic for a variety of cancer types under the name Dimercept.


According to the nonprofit Central Brain Tumor Registry of the United States, glioblastomas account for the majority - 52 percent - of all gliomas, which are tumors that arise from glial cells and include astrocytomas, oligodendrocytomas, ependymomas, mixed gliomas, malignant gliomas NOS (nitric oxide synthase), and neuroepithelial tumors. Glioblastomas make up 23 percent of all brain and central nervous system tumors.

Between 1995 and 1999, there were 8,690 reported cases of glioblastomas in the United States. The median age at diagnosis was 65, and men make up the majority of cases. The disease is most deadly within the first year after diagnosis. Study co-author Edward Neuwelt, M.D., professor of neurology and neurological surgery, OHSU School of Medicine and the Portland Veterans Affairs Medical Center, called the results "very exciting."

Treating glioblastomas, which can be several millimeters to several centimeters wide, has been tricky. Radiation and chemotherapy "help a little bit, but nothing helps very much," Neuwelt said, and getting chemotherapy drugs past the blood-brain barrier, the brain’s protective wall of tightly knit endothelial cells, always is difficult.

However, herstatin shows promise as a viable alternative to traditional brain tumor treatment methods, he said. "That herstatin gene Gail developed is very powerful on this tumor, as the paper shows," said Neuwelt, a member of the OHSU Cancer Institute who directs the OHSU Blood-Brain Barrier Program and pioneered a method for getting most drugs past the barrier. "I think this is a very significant approach."

But Neuwelt added that "One should always view with caution new and exciting results in rodent models since they may or may not translate in humans." Scientists used herstatin to treat human glioblastoma cells grown in culture and implanted in rats. "We saw a few tumor cells at the injection site, but they never proliferated," Clinton said.

Herstatin was not effective on a mutant form of the EGF receptor, called EGF receptor delta. The mutant receptor causes even more aggressive tumor growth in a subset of glioma. "We found our inhibitor targets the full-length EGF receptor, but not the mutant EGF receptor," Clinton said. "So a patient with a glioma generated by the mutant EGF receptor would not be expected to respond to herstatin."

She added, "This inhibitor we have is a naturally occurring one, and it’s possible that the mutant EGF receptor may have developed to confer resistance to the class of inhibitors that blocks the extracellular domain" on the glioblastoma cells. About a third of all glioblastomas derive from the mutant receptor, Neuwelt said.

Although herstatin is not effective against the mutant EGF receptor, the study’s results demonstrate highly selective molecules can be developed to target pathogen cells, reducing the chance that other complications will crop up when treating diseases. "It gives new information about which tumors to target, what molecular profile is important to look at up front, but it also tells us that herstatin is a specific inhibitor," Clinton noted. "This is another step in proving it doesn’t kill all cells, and the more specific and tailored it is to a particular molecular profile, the less likely you’re going to have a lot of side effects."

Jonathan Modie | EurekAlert!
Further information:
http://www.ohsu.edu

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>