Medindia
Advertisement

Cancer Prevention Drug Reduces Virulence of H. Pylori Bacterium

by Ramya Rachamanti on March 29, 2019 at 7:43 PM
Font : A-A+

Cancer Prevention Drug Reduces Virulence of H. Pylori Bacterium

New chemoprevention drug named DFMO(difluoromethylornithine) which blocks the production of cell growth compounds, was also found to reduce the virulence of Helicobacter pylori, the primary cause of gastric cancer, according to Vanderbilt researchers.

The findings, reported in the Proceedings of the National Academy of Sciences, support further studies of DFMO for the prevention of stomach cancer, the third leading cause of cancer deaths worldwide.

Advertisement


H. pylori infects the stomachs of half of the human population, but only about 1 percent of infected individuals develop stomach cancer. Although it's possible to treat the infection to prevent stomach cancer, it's not clear whom to treat. Plus, the bug may be conferring beneficial effects -- esophageal reflux diseases, asthma and other allergic disorders occur more frequently in people who are not infected with H. pylori.

"H. pylori has co-evolved with humans for at least 60,000 years, probably longer, and attempting to prevent stomach cancer by eliminating the infection with widespread use of antibiotics is not necessarily a good idea," said Keith Wilson, MD, Thomas F. Frist Sr. Professor of Medicine and professor of Pathology, Microbiology and Immunology.
Advertisement

"Our study suggests that it might be possible to reduce the virulence of the bacteria, without having to eliminate it. It's a speculative and unusual way to think about an infection, but it could be an interesting strategy."

Wilson, who also directs the Vanderbilt Center for Mucosal Inflammation and Cancer, and his team previously linked the production of cell growth compounds called polyamines to the development of stomach cancer in an H. pylori-infected animal model. They demonstrated that treatment of the animals with DFMO, which inhibits an enzyme that is key to the production of polyamines, prevents stomach cancer.

Their findings are the basis for an ongoing clinical trial of DFMO for stomach cancer prevention in Honduras and Puerto Rico.

Patients with pre-malignant lesions in the stomach, as determined by endoscopy, are enrolled in the trial of DFMO and will be studied for disease progression.

To further explore how DFMO works, J. Carolina Sierra, PhD, research instructor in Medicine, collected H. pyloribacteria from infected animals that had been treated (or not) with DFMO. Using an in vitro test, she assessed the activity of one of the main H. pylori virulence factors, a protein called CagA. CagA is "injected" into stomach epithelial cells, where it contributes to oncogenic signaling pathways.

"What we noticed is that bacterial strains coming from DFMO-treated animals have reduced ability to move this virulence factor into epithelial cells," Sierra said.

The researchers discovered that DFMO treatment -- in animals or in vitro -- caused mutations in the H. pylori gene that encodes CagY, part of the translocation machinery that injects CagA into cells.

They demonstrated that animals infected with H. pylori strains containing mutations in the CagY gene did not develop stomach cancer.

This finding, Wilson said, supports using DFMO or other tools to reduce H. pylori virulence for cancer prevention.

"This drug (DFMO), which inhibits a very specific enzymatic pathway, also has what some might call 'off target' effects: it causes mutations in an H. pylori gene that affects the translocation of CagA," Wilson said. "The vast majority of gastric cancer is associated with strains that are CagA-positive. If this drug interferes with CagA activity, that's an added bonus."

The investigators will analyze H. pylori strains isolated from the DFMO trial participants in Honduras and Puerto Rico to determine if there is a similar reduction of bacterial virulence in people.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
World Alzheimer's Day 2021 - 'Know Dementia, Know Alzheimer's
'Hybrid Immunity' may Help Elude COVID-19 Pandemic
Stroop Effect
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Drug Toxicity Cancer and Homeopathy Signature Drug Toxicity Cancer Facts Cancer Tattoos A Body Art Drugs Banned in India Acid Peptic Disease Common Lifestyle Habits that Cause Diseases Health Benefits of Dandelion Plant 

Recommended Reading
Gastric Cancer
Stomach (gastric) cancer develops from the stomach lining. It is the third most common cause for ......
Acid Peptic Disease
Acid peptic diseases are a collective disorder affecting millions of people worldwide. A general des...
Common Lifestyle Habits that Cause Diseases
Cigarette smoking, unhealthy diets, overuse of alcohol, and physical inactivity are some of the most...
Drug Toxicity
Drug toxicity is an adverse reaction of the body towards a drug that results as a side effect of a d...
Drugs Banned in India
Several drugs are either banned or withdrawn after introduction in the market....
Health Benefits of Dandelion Plant
What is dandelion? Dandelion greens are nutrition powerhouses with a wide range of health benefits. ...
Tattoos A Body Art
Tattoos are a rage among college students who sport it for the ‘cool dude’ or ‘cool babe’ look...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use