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 Remdesivir prevents MERS coronavirus disease in monkeys
14.02.2020 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Recent advances in addressing tuberculosis give hope for future
12.02.2020 | NIH/National Institute of Allergy and Infectious Diseases

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: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

Im Focus: Quantum fluctuations sustain the record superconductor

Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected

Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...

Im Focus: New coronavirus module in SORMAS

HZI-developed app for disease control is expanded to stop the spread of the pathogen

At the end of December 2019, the first cases of pneumonia caused by a novel coronavirus were reported from the Chinese city of Wuhan. Since then, infections...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Electric solid propellant -- can it take the heat?

14.02.2020 | Physics and Astronomy

Pitt study uncovers new electronic state of matter

14.02.2020 | Physics and Astronomy

Researchers observe quantum interferences in real-time using a new extreme ultra-violet light spectroscopy technique

14.02.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>