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Saturday, May 3, 2008

MIT researchers find early treatment of stomach infection may prevent cancer

Prompt treatment of a microbe that causes stomach ulcers and other ailments can reverse damage to the lining of the stomach and ultimately prevent one of the most lethal forms of cancer from developing there, MIT researchers have concluded.

In the May 1 issue of Cancer Research, a journal of the American Association for Cancer Research, the scientists say their study results should lay to rest any question about whether--and when--antibiotic treatment of Helicobacter pylori (H. pylori) can eliminate or reduce risk of developing gastric, or stomach cancer.

The findings are important, the researchers say, because stomach cancer is the second leading cause of cancer death worldwide, and approximately half of the world's population is infected with H. pylori. Although H. pylori infection is now recognized as the major cause of both peptic ulcers and gastric cancer, and has been classified as a group I carcinogen by the World Health Organization, physicians are not sure whom to screen and treat with costly antibiotics, aside from first degree relatives of gastric cancer patients and those with peptic ulcer disease.

Since it typically takes several decades for gastric cancer to develop in those who are susceptible - which is estimated to be up to 3 percent of infected people - researchers also do not know when to treat the infection for maximum benefit. Human studies that tested treatment in patients who had already developed tumors had mixed results, but one previous study showed that giving antibiotics before premalignant lesions develop was successful in preventing cancer, said the study's lead author, James G. Fox, D.V.M., a professor in the Department of Biological Engineering, director of MIT's Division of Comparative Medicine, and member of the MIT Center for Environmental Health Sciences.

"We concluded that H. pylori eradication prevented gastric cancer to the greatest extent when antibiotics were given at an early point of infection, but that eradication therapy given at a later time point also delayed the development of severe lesions that can lead to cancer," Fox says.

The current study, which used a new mouse model of gastritis and stomach cancer, examined the effects of treating and eliminating H. pylori at different stages of progression from gastritis, an inflammation of the mucous membrane layer of the stomach, to development of gastric cancer. To do this, Fox and colleagues from MIT and Columbia University developed transgenic "INS-GAS" mice that over-expressed gastrin, a hormone that controls secretion of gastric acid by the stomach's parietal cells. "If you lose these cells over time, they stop secreting gastric acid, and this is, in and of itself, a risk factor for development of cancer, but gastric acid also helps protect against commensal bacterial colonization of the stomach," Fox says.

With increasing age, parietal cells in INS-GAS mice stopped producing gastric acid and underwent precancerous changes. By 20 months of age, the mice spontaneously developed invasive gastric cancer. Infection by H. pylori and progression to gastric cancer was accelerated in these mice, the researchers discovered.

They then treated the mice with antibiotics and looked for cellular changes. They found that, at every stage of advancing infection, mice that were treated with antibiotics had less severe disease. Treating mice that were eight weeks post-infection reduced risk of developing cancer to the same level seen in uninfected mice. But using antibiotics at 12 and 22 weeks post-infection did not reverse the damaging changes, such as inflammation and development of precancerous lesions, to the levels seen in uninfected mice.

"Our mouse model mimics the progressive process we know occurs in development of human gastric cancer," Fox says. "This shows early intervention provides the maximum benefit."

Of added benefit, Fox says, is the associated finding that antibiotic treatment also reduces the level of other bacterial species that have invaded the stomach. "Gastric acid is a barrier to bacteria, and if there is no barrier, bacteria can move into the stomach from the lower bowel and colonize it, producing inflammation and progression to cancer," he says. "Findings in humans and mice now suggest that antibiotic treatment potentially changes gastric microbiota and may impact gastric carcinogenesis."

The first author of this paper is Chung-Wei Lee, M.D. Lee recently received his PhD under the supervision of Fox in the Department of Biological Engineering. Additional authors are Barry Rickman, Arlin B. Rogers, and Zhongming Ge, all of the Division of Comparative Medicine, and Timothy C. Wang of Columbia University.

This work was funded by the National Institutes of Health.

Blu-ray player sales down

Looks like it wasn't the HD DVD/Blu-ray battle that was keeping potential customers away from high-definition video players after all.

The NPD Group released some of its retail sales tracking data Wednesday that showed sales of Blu-ray standalone players (not a PlayStation 3, combo player, or PC with Blu-ray drive) had mostly decreased since the beginning of the year.

Standalone Blu-ray player unit sales in the U.S. decreased 40 percent from January to February and saw a very slight increase (2 percent) between February and March, according to NPD.

The industry appeal of Sony’s Blu-ray high definition video format may have beaten back the challenge of Toshiba’s HD DVD alternative, leaving Blu-ray to be crowned as the official HD standard, but that victory clearly hasn’t yet secured Sony the true success that it seeks.

Specifically, market research company NPD Group has indicated that sales of standalone Blu-ray players have thus far failed to impress following the demise of HD DVD on February 19, which is in stark contrast to the market reaction industry watchers expected.

While having not yet released the actual figures that support the poor sales performance (due to the likelihood of easy retailer identification), NPD Group notes that Blu-ray sales plunged some 40 percent from January to February, before rising by a mere 2 percent between February and March -- when HD DVD was no longer a competitive force.

According to Ross Rubin, NPD’s director of industry analysis, Blu-ray’s superior digital performance is not yet registering at the consumer level, with cheaper DVD players equipped with up-scaling technology (a marginal visual enhancement) thus far proving a bigger hit in the living room and a smaller hit on the pocket.

For example, DVD players offering an up-scaling feature are presently available for below $100 USD, while standalone Blu-ray players are generally pegged in excess of $300 USD. That cost-based disparity is compounded by a recent report from ABI Research, which revealed that the majority of consumers are still not able to discern the visual differences between Blu-ray and standard DVD.

In terms of Blu-ray’s market future, NPD offers that its relative lack of popularity growth will likely remain shackled to its pricing, at least until this year’s Christmas period, which should see Blu-ray players drop to around $200 USD. Unlike NPD, the research team at API believes that Blu-ray will continue to struggle for widespread acceptance until the end of Q3, 2009.

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