Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Reversing effects of altered enzyme may fight brain tumor growth

15.04.2009
An international team of scientists from the Moores Cancer Center at the University of California, San Diego, the University of North Carolina and several institutions in China have explained how a gene alteration can lead to the development of a type of brain cancer, and they have identified a compound that could staunch the cancer's growth.

The researchers, led by Kun-Liang Guan, PhD, professor of pharmacology at the UC San Diego School of Medicine, have shown that when a mutated enzyme fails to do its job, the development of tumor-feeding blood vessels increases, allowing more nutrients and oxygen to fuel cancer growth.

They have also shown in the laboratory that they could reverse the mutant enzyme's effects, effectively blocking this process, called angiogenesis, and provide a potential future treatment strategy against some types of brain tumors. They reported their findings in the current issue of the journal Science.

According to Guan, researchers have known that a mutation in the gene encoding the enzyme, isocitrate dehydrogenase (IDH1), contributed to certain brain tumors called low grade gliomas and secondary glioblastomas, but no one understood how. Guan, Yue Xiong, PhD, at the University of North Carolina and their co-investigators have now shown that this is because alterations in a specific gene, IDH1, impairs the body's ability to keep a tumor growth-promoting protein, HIF-1 alpha, in check.

The IDH1 enzyme works to produce a compound called alpha-KG, which is required for HIF-1 breakdown. Without that control, HIF-1 can run amok, promoting angiogenesis and tumor growth. The team was able to reverse this HIF-1 alpha effect by adding a modified form of alpha-KG to brain tumor cells in culture.

"This suggests a direction to exploit cell permeable alpha-KG for potential treatment of brain cancer patients with an IDH1 mutation," Guan said.

He added that IDH1 appears to function as a tumor suppressor gene that when altered – and turned off – can contribute to tumor formation through the HIF-1 pathway. But Guan noted, "IDH1 is not your usual suspect as a cancer gene."

He explained that the alteration in IDH1 is a substitution of an amino acid in one copy of the gene without losing the other normal copy (every gene in normal human cells has two copies), which is different from most tumor suppressor genes. Most either have genetic material that is deleted or truncated – not a single amino acid substitution.

Guan, Xiong and their group are hopeful about their findings. Understanding mechanisms behind the development of such brain tumors is critical to clinical advances, Guan said. "Because of their ability to reverse HIF-1 levels, drugs mimicking alpha-KG may be worth exploring as possible therapies for these types of gliomas."

Other co-authors include: Shimin Zhao, Yan Lin, Wei Xu, Wenqing Jiang, Zhengyu Zha, Pu Wang, Wei Yu, Qunying Lei, Fudan University, Shanghai, China; Zhiqiang Li, Lingling Gong, Wuhan University, Wuhan, China; Yingjie Peng, Jianping Ding, Chinese Academy of Sciences, Shanghai. Guan and Xiong both have appointments at Fudan University.

The Moores UCSD Cancer Center is one of the nation's 41 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.

Steve Benowitz | EurekAlert!
Further information:
http://www.ucsd.edu
http://www.cancer.ucsd.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>