Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NSAID drug protects against intestinal tumors in mice, despite poor diet and gene losses

19.04.2005


In mouse models of intestinal cancer, use of an anti-inflammatory drug eliminated all of the cancer-causing risks produced by a high-fat Western-style diet - even when several genetic brakes to cancer formation were missing in the animals, say researchers from the Albert Einstein Cancer Center.



The investigators, who presented their findings at the 96th Annual Meeting of the American Association for Cancer Research, say that while the results do not yet have relevance for preventing human colon cancer, they do illustrate the interplay between genes and common nutritional and medicinal agents in development of cancer in the intestines.

The drug they tested, sulindac, was a highly effective chemoprevention agent, the researchers say, because it worked to induce expression of the p21 gene, which they found put a firm stop on tumor formation even though the mice were missing two key tumor suppressor genes (p27 and APC) and were fed a diet high in fat and low in calcium and vitamin D.


"It appears that p21 activation through sulindac offers protection against both a lack of tumor suppressor genes as well as poor diet," says the lead author, WanCai Yang, M.D., an assistant professor of medicine. While the drug is a NSAID (non-steroidal anti-inflammatory drug) and a COX-2 inhibitor, Yang believes its chemoprotective effects come via novel pathways that affect p21 expression.

The study builds upon a body of research conducted by Yang and Leonard Augenlicht, Ph.D., at the Albert Einstein Cancer Center that has used knockout mouse models to explore the role of genes and diet, including the finding that inactivation of the p21 gene accelerated tumor formation and that loss of this gene eliminated the ability of sulindac to inhibit tumor formation. Their earlier studies also showed that mice that lacked p27, another tumor suppressor gene, had a higher risk of developing tumors in both the small and large intestine.

Now, however, they have linked that risk to a high-risk diet. In the first part of the study, they found that mice lacking a p27 gene that were fed with a corn-oil rich diet (labeled AIN-76A, also low in calcium and vitamin D) formed tumors whereas knock-out mice fed with their regular chow (which was enriched with soybean oil) did not. And p27 knock-out mice given a Western diet, full of fat and lacking calcium and vitamin D, formed the most number of tumors.

The researchers then looked at the role that diet plays when expression of two tumor suppressor genes is reduced. The researchers mated mice that had only one APC gene to p27 positive or negative mice, producing variants with no p27 genes or one or two. The APC gene is responsible for an inherited colorectal cancer condition known as FAP (familial adenomatous polyposis), in which patients develop hundreds of potentially precancerous polyps.

They found that on the AIN-76A diet, loss of one APC gene but retention of the "wild-type" (normal) p27 genes was enough to induce tumor formation in 22 percent of the mice, but that number increased to 72 percent when one allele of the p27 gene was lost, and 93 percent when both alleles of the p27 gene were lost. But all of the knock-out mice variants developed tumors in both their small and large intestines when fed a Western-style diet.

"This showed that the diet overwhelmed any protective effect the p27 genes conferred," says Yang. "It not only increased tumor size and number, but also pushed the cancer into an invasive state."

Finally, they examined what happened when the knock-out mice were fed a Western diet enhanced with sulindac, an agent they had previously found help suppress tumor formation. To their surprise, none of the knock-out mice developed cancer.

"To us this means that as long as an animal can activate the p21 gene, this can have an overriding affect on suppressing tumor formation caused by either loss of other tumor suppressor genes or diet," says Yang. "We are testing this concept further, including exactly how the p21 gene gets activated."

Warren R. Froelich | EurekAlert!
Further information:
http://www.aacr.org

More articles from Life Sciences:

nachricht Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

A CLOUD of possibilities: Finding new therapies by combining drugs

24.05.2017 | Life Sciences

Carcinogenic soot particles from GDI engines

24.05.2017 | Life Sciences

A quantum walk of photons

24.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>