Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

’Energy blocker’ kills big tumors in rats

18.10.2004


Building on their earlier work, Johns Hopkins researchers have discovered that an apparently nontoxic cellular "energy blocker" can eradicate large liver tumors grown in rats. Six months to more than a year after treatment was stopped, the rats are still cancer free.


Female rat "R4" before treatment with 3-bromopyruvate (left) and 4 weeks after treatment with the compound. The tumor is gone from the animal’s right shoulder. [Credit: Johns Hopkins Medicine/Young Ko]



While the results are dramatic, clinical trials with the chemical, 3-bromopyruvate, are likely some years away, says the study’s leader, Young Ko, Ph.D., assistant professor of radiology and biological chemistry. If tests in the lab continue to be promising, however, the chemical or one like it may become an option for treating advanced liver cancers and perhaps other tumors in people.

"Liver cancer usually isn’t detected in people until it’s difficult or impossible to treat, and many other aggressive cancers spread to the liver, so we need more treatment options," says Peter Pedersen, Ph.D., professor of biological chemistry in the Institute for Basic Biomedical Sciences at Johns Hopkins. "The compound Dr. Ko tested in animals targets a fundamental process cancer cells need to survive, can kill big tumors, and appears so far to have little or no effect on normal tissues."


In fact, Ko says she hasn’t been able to find a toxic dose of the compound, which blocks the two ways cancer cells make energy. In earlier experiments with rabbits with liver cancer, reported in 2002, no obvious toxic effects were seen, either. There is a patent pending on possible cancer applications of the compound.

While the details of normal cells’ protection are still unclear, the scientists suggest cancer cells well-known appetite for sugar might be behind their demise. Ko, who first studied the compound as a graduate student at Washington State University in 1990 and initiated its study at Hopkins, has shown that it completely blocks cancer cells’ conversion of sugar into usable energy, a process necessary to fuel the cells’ functions and growth.

"We believe this is the first time that a drug has blocked both ways cancer cells make energy and are very happy that it seems so effective against advanced liver cancers," says Ko. "Usually researchers don’t try to attack advanced cancers because success seems unlikely. But these are the very cancers we must learn to defeat if we are to win the war on cancer."

Sugar, or glucose, is brought into cells and converted into useable energy, a molecule called ATP, by either of two processes. Another product of this conversion, a molecule called lactate, is then taken out of the cell by specialized transporters. But because cancer cells use so much more sugar and make so much more lactate than normal cells, the researchers suggest cancer cells may be riddled with more of the "two-way streets" that transport lactate. And because 3-bromopyruvate looks very similar to lactate, it might travel those same roads, sneaking into cancer cells like a Trojan horse, suggests Ko.

In her latest experiments, described in the Nov. 5 issue of Biochemical and Biophysical Research Communications and available online now, Ko found that treating rat liver cancer cells with 3-bromopyruvate halted the cells’ production of ATP within 30 minutes, and visual evidence of the cells’ self-destruction was apparent almost immediately. Four times as much of the compound was necessary to begin decreasing ATP production in normal liver cells.

Turning to animal studies, Ko injected rat liver cancer cells into either the abdomen or the upper back of 33 rats. Nineteen of the animals received daily injections of the compound into the tumor site for five days or longer, which caused all of the cancers to disappear within four weeks. The rats otherwise appeared unaffected, although Ko will examine the animals when they are euthanized -- probably for old age. The 14 untreated animals that served as controls were euthanized within 10 days because of their tumors’ rapid growth.

To be sure that the compound had completely eradicated the tumors in the treated animals, Ko and Pedersen collaborated with radiologist Martin Pomper, M.D., Ph.D., Yuchuan Wang, Ph.D., and James Fox. They used radioactive glucose to take PET scans of four of the rats and found that "hot spots" of high uptake disappeared within a few weeks of treatment. PET scans are commonly used to diagnose or stage cancers in people because of tumors’ appetite for glucose.

Ko is now studying the compound’s effects on human cancer cell lines in the lab, and will begin studying it in animal models of breast cancer shortly. The researchers also are planning to examine the compound’s effects in an animal model of an aggressive non-liver cancer that spreads to the liver.

The research was funded by the National Cancer Institute and the Johns Hopkins Department of Radiology. Authors on the paper are Ko, Wang, Pomper, Pedersen, Barbara Smith, David Rini, Michael Torbenson and Joanne Hullihen, all of Johns Hopkins.

Joanna Downer | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

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

Im Focus: Highly precise wiring in the Cerebral Cortex

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...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>