Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chemical cousin of vitamin A restores gene function in former smokers

05.02.2003


Use of a vitamin A derivative in former smokers restored production of a crucial protein believed to protect against lung cancer development, researchers at The University of Texas M. D. Anderson Cancer Center have found.



Use of a Vitamin A derivative in former smokers restored production of a crucial protein believed to protect against lung cancer development, researchers at The University of Texas M. D. Anderson Cancer Center have found.

Although they don’t have clear evidence that the three-month therapy using 9-cis retinoic acid (9-cis-RA) restored health to cells that were already precancerous, the researchers say the work demonstrates that "chemoprevention" of future lung cancer may be feasible.


"The drug we used acts to reverse a genetic abnormality associated with development of lung cancer," says Jonathan Kurie, M. D., an associate professor of medicine in the thoracic/head and neck medical oncology department. "The work is a proof of concept, suggesting that compounds like this may prove to have a protective effect against development of precancerous lesions."

The study, led by Kurie and Reuben Lotan, Ph.D., professor of thoracic/head and neck medical oncology, will be published in the February 5 issue of the Journal of the National Cancer Institute. The findings are important, Kurie says, because it is the first one to study chemoprevention in former smokers.

The 45 million people in the United States who have quit smoking have reduced their risk of developing lung cancer, but genetic damage caused by smoking does not immediately disappear, researchers say. Half of all newly-diagnosed lung cancer occurs in former smokers, and so investigators are trying to find a way to stop the genetic damage from turning into cancer.

"This work shows that we can restore the gatekeeper in those who have quit smoking," says co-author Waun Ki Hong, M.D., head of the Division of Cancer Medicine.

"It may be possible to reverse some of the genetic damage that has accumulated."

Hong, a recognized leader in the study of chemoprevention, has previously shown that a different vitamin A derivative known as 13-cis-retionic acid (13-cis-RA) can prevent development of head and neck cancer.

Retinoids are natural and synthetic compounds related to vitamin A (retinol) and retinoic acid (RA) is needed for normal function of the epithelial cells that line the lung. Retinoic acid activates retinoic acid receptors (RARs) that regulate cell growth, differentiation, and death.

Heavy smoking, however, is known to reduce levels of a key receptor, retinoic acid receptor beta (RAR-_). Because loss of RAR-_ has been linked to development of precancerous lesions in the lung - and thus is considered a biomarker of "preneoplasia" - Lotan said it was logical to look at whether retinoid therapy could restore expression of the protective protein receptor.

They randomized 226 patients who had stopped smoking for at least one year to one of three treatment arms for a daily oral treatment given over three months. One group received a placebo, or dummy, drug. A second group was given supplements of 9-cis-RA, which had been shown in laboratory work to bind to a number of different RARs, and so might be highly effective. The supplement has also been found to prevent development of breast cancer in lab animals. The third patient group received 13-cis-RA, the drug that has worked well in head and neck cancer, and it was combined with alpha-tocopherol (a synthetic form of vitamin E), in order to reduce toxicity known to be associated with 13-cis-RA therapy.

The researchers took lung biopsies from six predetermined sites in each patient before treatment, after the 3-month treatment period, and 3 months after treatment cessation. Kurie’s team then analyzed the biopsies for histological abnormalities and for RAR-_ expression in the 177 patients who completed three months of therapy.

The results show that RAR-_ gene expression had increased in patients who received 9-cis-RA; the percentage of biopsies with RAR-_ protein expression increased from 69 percent to 76 percent, a statistically significant difference compared to the other two groups. Gene expression dropped from 75 percent to 69 percent in placebo-treated patients, and there was no substantial change in RAR-_ expression in patients taking 13-cis-RA.

The multidisciplinary research team also found a statistically significant reduction in the number of biopsies with potentially precancerous lesions known as metaplasia in the 9-cis-RA group (from 8 percent to 4.7 percent) compared to patients treated with 13-cis-RA (from 5.8 percent to 3.6 percent). But, compared to placebo (9.2 percent to 7.8 percent), neither retinoic treatment had a statistically significant effect on development of metaplasia in this study. "There was a decrease in precancerous lesions in the 9-cis-RA group, but it was not statistically significant compared to the patients who didn’t receive a retinoic treatment," Kurie says.

Despite promising results, this form of vitamin A may not be the best drug for lung cancer prevention because of such side effects as headaches, skin rashes, and fatigue, Kurie says. A related form, LGD1069, is in clinical trials in the United States, and Kurie is testing celecoxib, one of the so-called "super-aspirin" drugs, to determine if it might help repair lung damage from cigarette smoking. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) known as a COX-2 inhibitor, which works to ease inflammation without causing stomach ulcers and other side effects of similar drugs. Celecoxib has already been shown to reduce the number of precancerous intestinal polyps in patients with a rare colon cancer.



###
The study was supported by the National Cancer Institute and by the Rippel Foundation, the American Cancer Society, the National Foundation for Cancer Research, and by M. D. Anderson Cancer Center.


Heather Russell | EurekAlert!

More articles from Health and Medicine:

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

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: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>