A team of Johns Hopkins researchers has identified and successfully tested in animals a potential new treatment for liver cancer, a disease for which there are few effective treatments.
Writing in the July 15 issue of Cancer Research, the scientists report that only cancer cells were killed when the compound, 3-bromopyruvate, was given to rabbits with experimental liver tumors.
"Its very exciting because we expected the compound to be pretty toxic, but somehow normal cells in the rabbit protect themselves against it," says Peter Pedersen, Ph.D., professor of biological chemistry who has spent two decades studying energy production in cells and how it relates to cancer growth. "We even injected it into a vein so it was distributed throughout the rabbit, and we still didnt see any apparent toxicity. Its sort of amazing."
A single injection of the compound directly into the artery that feeds the tumor killed a lot of the cancer cells, but left healthy liver alone. The researchers compared 3-bromopyruvate to a currently used treatment for human liver cancer, called chemoembolization, which delivers a dose of chemotherapy to the tumor and also blocks off the artery that feeds it.
"With 3-bromopyruvate in the rabbits, healthy liver seems to be spared, but sections of healthy liver were damaged by chemoembolization," says first author Jeff Geschwind, M.D., associate professor of radiology and director of interventional radiology. "The difference was quite dramatic."
Pedersen cautions that before 3-bromopyruvate could be tested in humans, scientists would need to learn how normal cells protect themselves, whether the compound causes long-term damage to normal tissues, and how increasing the dose affects the animals.
"We assume some level of the compound would be toxic," adds Pedersen. "Any drug can be toxic, its a matter of determining the limits."
Some 16,600 new cases of primary liver cancer are expected this year in the United States, but tumors that spread to the liver from elsewhere (so-called metastatic tumors) frequently hasten death from other, more prevalent types of cancer, such as skin, colon, breast and prostate cancers. If laboratory tests with other cancer cell types are promising, the compound might be useful for treating any tumor in the liver, not just ones originating there, the researchers say.
Two years ago, frustrated because most patients die within six months, Geschwind approached Pedersen with the idea of finding a new way to treat liver cancer. The plan: Identify potential new drugs and use intra-arterial delivery, a procedure with which Geschwind has considerable expertise, to get them directly into the tumor.
The timing was right, because Pedersen had learned enough about the role of energy production in liver cancer over the previous two decades to warrant looking for a possible new drug. Biological chemist Young Ko, Ph.D., now an assistant professor of radiology, tested a dozen or so possible energy-blocking molecules in the lab to find ones that could kill liver cancer cells.
In 2001, the team reported that already-available 3-bromopyruvate was head and shoulders above the rest, in part because it blocks both ways cells make energy (in the form of a molecule called ATP). "3-Bromopyruvate looks like a chemical found in our own body," says Ko, who used 3-bromopyruvate in her graduate work years ago. "It shows a possible drug doesnt have to be fancy or expensive; this is just as simple and as good as can be."
Building on those laboratory studies, the researchers now have tested the compounds effects in an animal model of liver cancer. Team member and pathologist Michael Torbenson, M.D., saw damage only to the tumor when he examined the tumor, liver, and other possibly affected organs from the rabbits. The researchers dont understand how normal cells resist the compounds effects, but cancer cells greater use of glucose to make energy may play a role.
In another experiment, the researchers discovered that small tumors in the lungs, buds from the original tumor in the liver, werent affected by arterial delivery of 3-bromopyruvate, but were substantially reduced by intravenous injection.
"It might be logical to treat tumors in the liver by direct intra-arterial injection, and then use an intravenous injection to kill cancer cells that have spread," suggests Pedersen, "but knowing whether this is so is still a long way off."
Joanna Downer | EurekAlert
Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin
One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
26.06.2017 | Life Sciences
26.06.2017 | Physics and Astronomy
26.06.2017 | Information Technology