The researchers discovered that the compound, indirubin, both blocks the migration of glioblastoma cells, preventing their spread to other areas of the brain, and the migration of endothelial cells, preventing them from forming the new blood vessels that the tumor needs to grow.
Glioblastomas occur in about 18,500 Americans annually and kill nearly 13,000 of them yearly. Glioblastoma multiforme is the most common and lethal form of the malignancy, with an average survival of 15 months after diagnosis.
The research is published online in the journal Cancer Research.
"We have pretty good methods to stop glioblastoma from growing in the human brain, but these therapies fail because tumor cells migrate from the original site and grow elsewhere in the brain," says co-principal investigator Dr. E. Antonio Chiocca, professor and chair of neurological surgery and co-director of the Dardinger Center for Neuro-oncology and Neurosciences.
"Our findings suggest that indirubins offer a novel therapeutic strategy for these tumors that simultaneously targets tumor invasion and angiogenesis," Chiocca says.
"This study shows for the first time that drugs of the indirubin family may improve survival in glioblastoma, and that these agents inhibit two of the most important hallmarks of this malignancy – tumor-cell invasion and angiogenesis," says co-principal investigator Dr. Sean Lawler, senior scientist and group leader of the Translational Neurooncology Group at the Leeds Institute of Molecular Medicine.
Indirubin is derived from the Indigo plant. It is the active ingredient in the Chinese herbal remedy called Dang Gui Long Hui Wan, which is used to treat chronic myeloid leukemia.
Chiocca, Lawler and their collaborators used multiple glioblastoma cell lines and two animal models to examine three derivatives of indirubin. Key findings include the following:
When human glioblastoma cells were transplanted into one brain hemisphere of mice, indirubin-treated animals survived significantly longer than controls and showed no migration of tumor cells to the opposite hemisphere.
In a separate experiment, indirubin reduced the migration of tumor cells by 40 percent in treated animals versus controls.
Treated tumors showed a lower density of blood vessels, and new blood-vessel growth was reduced up to three-fold in intracranial tumors, depending on the tumor-cell line.
A laboratory assay showed that indirubins reduced endothelial-cell migration by 52 to 41 percent compared with untreated controls.
"Overall, our findings suggest that indirubins reduce tumor invasion and tumor vasculature because of their antimigratory effects on both tumor and endothelial cells," Chiocca says.
Darrell E. Ward | EurekAlert!
Usher syndrome: Gene therapy restores hearing and balance
25.09.2017 | Institut Pasteur
MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University
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
26.09.2017 | Life Sciences
26.09.2017 | Physics and Astronomy
26.09.2017 | Information Technology