Barrett

Other investigations are studying how dietary constituents that inhibit COX-2 -- such as resveratrol (found in red wine and the skin of red grapes), and omega-3 fatty acids (found in fish like salmon) -- can prevent cancer.

Celecoxib and COX-2

Studies have shown that levels of COX-2 are markedly elevated in many different types of cancer versus adjacent normal tissue. Celecoxib, an anti-inflammatory drug commonly used to treat arthritis, has been shown to inhibit COX-2, and in turn, reduce the formation, growth and metastasis of several types of experimental cancers. Celecoxib also has been shown to suppress angiogenesis, the process by which tumors create new blood vessels needed to obtain nutrients for their growth and spread.

Additionally, because standard cancer therapies like chemotherapy and radiation induce COX-2, selective COX-2 inhibitors such as Celecoxib may prove useful as a supplemental, or adjuvant, therapy. In 1999, the drug was approved by the FDA for use to reduce the number of polyps in familial adenomatous polyposis (FAP), a rare and devastating genetic condition that results in colorectal cancer.

Oxidative stress plays a role in malignant transformation of Barrett's esophagus
Source: Reuters News
Publish Date: 01/04/2003

NEW YORK (Reuters Health) - Increased myeloperoxidase activity and decreased antioxidant capacity appear to contribute to the pathogenesis and malignant transformation of Barrett's esophagus, according to findings published in the December 20th issue of the International Journal of Cancer.

To examine whether oxidative stress and radical scavenger capacity play a role in the malignant transformation of Barrett's esophagus, researchers measured myeloperoxidase activity, superoxide dismutase activity, glutathione content, and total DNA adducts from mucosal specimens taken from 52 patients with various stages of esophageal disease.

Included were patients with symptomatic gastroesophageal reflux disease (GORD) without (n = 8) and with (n = 5) endoscopic esophagitis, Barrett's epithelium without (n = 8) and with (n = 5) dysplasia, adenocarcinoma in the esophagus (n = 19), and controls (n= 7).

"In the GORD-esophagitis-metaplasia-dysplasia-adenocarcinoma sequence, glutathione content [antioxidant capacity] was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barrett's epithelium without dysplasia," Dr. Jarmo A. Salo, of Helsinki University Central Hospital, Finland, and colleagues report.

Compared with controls, superoxide dismutase activity increased significantly only in Barrett's epithelium with dysplasia.

Mean DNA adduct levels were significantly higher in all patient groups compared with controls, the researchers found. Pooled data showed that glutathione content was negatively correlated with DNA adducts.

Dr. Salo and colleagues point out that the findings are in line with recent epidemiologic data showing that higher antioxidant intake is associated with decreased risk for esophageal adenocarcinoma. "This insight may prove useful for preventive measures against carcinogenesis in Barrett's esophagus."

Red wine component to be studied against cancer
Source: Reuters News
Publish Date: 11/06/2002

LONDON (Reuters Health) - Scientists in Britain and the US announced plans on Tuesday to begin studying a possible new cancer prevention drug based on resveratrol, a natural compound found in red wine.

Researchers at the University of Leicester in England and the University of Michigan will begin testing tablets of pure resveratrol in healthy volunteers early next year, the British university said in a statement. The US National Cancer Institute (NCI) is funding the research.

Leicester's Professor Will Steward said resveratrol is found in peanuts and several berries, as well as grape skins and wine--particularly red wine.

"Consumption of resveratrol has been proposed as one possible explanation for the low incidence of cardiovascular disease in Southern European countries with high red wine consumption, and resveratrol has been shown to possess anti-inflammatory and anti-cancer activity in experimental models," he said.

"Since resveratrol may be of value in preventing cancer, the NCI are funding early clinical studies of pure resveratrol capsules in healthy volunteers and patients with early cancer," Steward added.

The 20 or so healthy volunteers in the study will initially be given one tablet containing 0.5 grams of resveratrol--equivalent to the amount in dozens and dozens of bottles of wine, Leicester researcher Professor Andreas Gescher told Reuters Health. Later trials will look at repeated doses.

The point of these preliminary studies is to analyze how long the compound stays in the body and how much circulates in the blood. The researchers will also look for evidence of biochemical changes that might suggest a protective effect.

"You obviously have to know that you're taking enough to get to the places that you want to prevent cancer," Gescher said.

Several studies have found that wine drinkers seem to be less likely to develop cancer. Resveratrol has been suggested as one possible reason, but the benefits of wine may be due to a combination of reasons.

"It is quite possible that after all this work we find resveratrol isn't active alone," Gescher said. "But first you have to look at what these single agents do and then you look at the next step."

Strawberries, raspberries halt cancer in rats
Source: Reuters News
Publish Date: 09/03/2002

BOSTON (Reuters Health) - If animal studies are correct, black raspberries and strawberries may be "very, very powerful" inhibitors of cancer growth, an Ohio researcher reported here this month at the American Chemical Society's annual meeting.

People should make berries one of their daily fruit servings, or at least try to eat berries two or three times a week, Dr. Gary D. Stoner of Ohio State University told Reuters Health.

Animal studies by Stoner and his colleagues found the berries were potent inhibitors of cancer development in rodents given cancer-promoting chemicals. The team is now planning studies in people to investigate the effect of berries on both esophageal and colon cancer.

Stoner and his team are studying squamous cell carcinoma (SCC) of the esophagus, which makes up 95% of cases of esophageal cancer worldwide. Overall, survival is very poor, with 10% of patients living 5 years after diagnosis.

Esophageal SCC is particularly common in China, Japan, the Transkei region of South Africa, Iran, France and Puerto Rico. Men are more likely than women to develop the disease, and African Americans also face an increased risk compared with whites.

Smoking, alcohol, salt, and hot and spicy foods are known to promote the development of esophageal SCC. Fungal toxins and chemicals called nitrosamines--both found in the Chinese diet--and vitamin and mineral deficiencies have also been implicated.

To investigate strategies for blocking esophageal SCC growth, Stoner and his team fed rats two types of cancer-promoting nitrosamine chemicals. While chemicals called isothiocyanates proved to be the best way to stop tumors from forming in the first place, strawberries and black raspberries from an Ohio farm worked best for preventing tumors from growing.

Isothiocyanates are found in many foods, including cruciferous vegetables like broccoli and wasabi, a pungent Japanese condiment.

Rats that consumed 5% to 10% of their diet as freeze-dried black raspberries and strawberries showed dramatic reductions in the growth of precancerous cells and tumor progression, the researchers found. And in other animal tests, Stoner told Reuters Health, the berries reduced colon cancer growth by 80%.

The Ohio Department of Agriculture supported the research Stoner presented at the meeting.

Eating berries could be a way to help people at risk of esophageal SCC protect themselves from the disease, Stoner said.

But there are obstacles. For one, he pointed out, berries are a seasonal food in most of the world, which has also made it difficult to conduct epidemiological studies of their effects on cancer. And in some countries where esophageal SCC is a major problem--like China--people rarely eat berries. Finally, berries are expensive.

One way to get around these problems, Stoner said, might be to use extracts of the freeze-dried berries. He and his colleagues have been able to develop some potent berry extracts, he added.

Stoner and his team have completed Phase I trials to investigate the toxicity of the berries and whether berry components reach the bloodstream. People who ate two large bowls of berries a day showed no toxic effects, and many fruit components were absorbed into the blood, according to Stoner.

The researchers, in partnership with a food company, are now launching Phase II clinical trials to investigate whether berries have a cancer-protecting effect on esophageal cancer among people in China and the US. They also plan to investigate the effect of berries on colon cancer.

Barrett's Esophagus and Acid Reflux