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.
Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State
NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
08.12.2016 | Life Sciences
08.12.2016 | Physics and Astronomy
08.12.2016 | Materials Sciences