Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Purdue scientists hunt for ’secret X’ to treat liver cancer

14.12.2004


Identifying the link between chronic hepatitis B infection and liver cancer may one day help cancer patients sidestep the poison of chemotherapy, a Purdue University study suggests.



The research group of Ourania M. Andrisani (oo-RAHN-ee-ah an-dri-SAH-nee) has shown that a protein the hepatitis virus instructs chronically infected liver cells to produce – known as the X protein – under certain conditions instructs precancerous infected liver cells to die. The discovery of how the X protein influences liver cell behavior could be harnessed as an anticancer therapy, turning the X protein’s presence in the liver to patients’ advantage.

"Instead of chemotherapy, drugs that influence the X protein’s behavior might become an alternative cancer therapy," said Andrisani, a professor of basic medical sciences in Purdue’s School of Veterinary Medicine. "Rather than give a patient chemicals that damage every cell in the body, therapy based on the X protein could potentially target only cancerous cells, slowing their growth."


The research, which Andrisani conducted with first author Wen Horng Wang, and Gérald Gregori and Ronald L. Hullinger, all of Purdue, appears in the current issue of Molecular and Cellular Biology.

Viruses like the hepatitis B virus incorporate their genes into a healthy cell’s genetic material. This way, many viruses not only instruct the cell to make proteins necessary to assemble more virus particles, but they also change or deregulate the normal production of proteins by the healthy cell. One of the genes hepatitis B introduces into liver cells is called the X gene, a short sequence of DNA that "expresses," or creates, the X protein – a building block essential for creating hepatitis B. Scientists have suspected the gene and its corresponding protein to be accomplices in cancer development as well.

"The X protein is present in the livers of all chronic hepatitis B patients, and several past studies have implicated it in liver cancer development," Andrisani said. "We decided to look at the effect of the X protein on liver cells in isolation to find out what it was doing to the cells’ life cycle."

As a molecular biologist, Andrisani studies how cells receive chemical messages from the body that instruct them to grow, differentiate and die at proper times – actions that are necessary for health in highly specialized bodies like our own. Andrisani’s team theorized that the X protein was the chemical messenger that caused the liver cells to behave erratically, putting them out of step with healthy liver tissue.

"To find out what instructions the X protein was feeding the cells, we worked with samples of mouse liver tissue in the lab," she said. "We first took the X gene from hepatitis B and inserted it into liver cell nuclei. Then, after the gene started producing the X protein in the cells, we watched the behavior of these mouse liver samples to see whether they conformed to healthy liver cell life cycles."

To ease observation, they used samples that were only a single layer of cells thick. Observing these modified cells, the team found that the effects of the X gene were a bit complicated.

"The gene does different things to cells at different stages of their lives," Andrisani said. "We found, for example, that liver cells in the beginning of their life cycle will grow vigorously when the X protein is around, but under conditions of stress, it encourages them to die. We have other data, as yet unpublished, that shows the X protein can essentially ’rescue’ cells from dying at the appropriate time. Of course, if you see cells growing uncontrollably and refusing to die, then you are looking at the mechanisms of cancer development."

Andrisani likens the X gene to a driver going downhill who doesn’t use the car’s brakes, allowing the vehicle to accelerate to breakneck speed. But before cells with the X gene can begin proliferating at such an unhealthy rate, it could be possible to counter this behavior with drugs. Andrisani said that it is currently within medicine’s power to devise treatments that can eliminate precancerous X-expressing cells, based on their increased tendency to die. Researchers at other institutions also are optimistic about this aspect of the work’s implications.

"In fact, some drugs already exist that could help slow the effects of the X protein within the livers of cancer patients," said Spiro Hiotis, a surgeon at New York University who is not affiliated with the study. "While a great deal of further research still needs to be done, Andrisani’s team has shown that work with the X gene could someday lead to liver cancer treatments, and managing the gene’s effects with drugs could be a viable approach."

This approach could mean that liver cancer could be treated at least in part without chemotherapy, Andrisani said, making for far less overall stress on a patient’s body.

"This is what we in the business would call a mechanism-based treatment," she said. "Rather than kill all rapidly-dividing cells in the body – the healthy ones along with the cancerous ones – we would like to target the cancer cells alone. We are taking the next steps toward that goal now."

That next step involves work with live animals instead of tissue samples, she said, and work is now in progress in the labs of Marie-Annick Buendia and Pierre Tiollais of the Louis Pasteur Institute in France.

"In our lab, we are continuing with liver tissue culturing as well," Andrisani added. "We are now trying to work with 3-D cultures of many cell layers, which more closely resemble a normal liver. We hope that with a few years’ effort, our work will pay off in the clinic."

Funding for this work was provided in part by the National Institutes of Health.

Andrisani is associated with the Purdue Cancer Center. One of just eight National Cancer Institute-designated basic-research facilities in the United States, the center attempts to help cancer patients by identifying new molecular targets and designing future agents and drugs for effectively detecting and treating cancer.

Chad Boutin | EurekAlert!
Further information:
http://www.purdue.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>