Called an "oncometabolite" for its role in cancer metabolism, the metabolite2-hydroxyglutarate (2HG) is a by-product of a gene mutation of an enzyme known as isocitrate dehydrogenase (IDH).
Says Dr. Tak Mak of the findings published today in Nature: "For the first time, we have demonstrated how a metabolite can cause cancer. This sets the stage for developing inhibitors to block the mutation and prevent the production of this disease-initiating enzyme." The research team included scientists at Weill Cornell Medical College, New York City, and Agios Pharmaceuticals, Cambridge, Massachusetts.
Dr. Mak, Director, The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital, is an internationally acclaimed immunologist renowned for his 1984 discovery of cloning the human T-cell receptor. He is also Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.
The connection between cancer and metabolism has fascinated scientists at Agios and Dr. Mak, who were the first to identify the oncometabolite in research published in Nature (2009) and The Journal of Experimental Medicine (2010). The IDH gene mutation was initially discovered in brain cancers in 2008 by American scientists at Johns Hopkins in Baltimore and subsequently also linked to leukemia.
In the lab, Dr. Mak's team genetically engineered a mouse model with the mutation in its blood system to mimic human AML. They discovered that the gene mutation launches the perfect storm for the oncometabolite to trigger the blood system to increase the stem cells pool and reduce mature blood cells in the bone marrow. The resulting condition creates a situation with similarities to myelodysplastic syndrome – one of the precursors to this type of leukemia.
"This is one of the most common mutations in AML," says Dr. Mak. "We also found that it is the common mutation in about 40% of a specific type of lymphoma." The mutation is also known to be involved in about 70-90% of low-grade brain cancers (glioblastomas gliomas) and a variety of other cancers.
About the Princess Margaret Cancer Centre, University Health Network
Princess Margaret Hospital and Ontario Cancer Institute, the hospital's research arm, have achieved an international reputation as global leaders in the fight against cancer. The Princess Margaret Cancer Centre is part of University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to www.theprincessmargaret.ca or www.uhn.ca
Jane Finlayson | EurekAlert!
eTRANSAFE – collaborative research project aimed at improving safety in drug development process
26.09.2017 | Fraunhofer-Gesellschaft
Beer can lift your spirits
26.09.2017 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy