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 Malaria Already Endemic in the Mediterranean by the Roman Period
27.07.2017 | Universität Zürich

nachricht Serious children’s infections also spreading in Switzerland
26.07.2017 | Universitätsspital Bern

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: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

Satellite data for agriculture

28.07.2017 | Information Technology

Abrupt motion sharpens x-ray pulses

28.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>