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.
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
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Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
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23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy