Minnesota - April 2012 Archives

ROCHESTER, Minn. — April 3, 2012.  Add lower gastrointestinal (GI) problems such as ulcers, bleeding and perforations to the list of serious complications facing many rheumatoid arthritis patients. They are at greater risk for GI problems and gastrointestinal-related death than people without the disease, a Mayo Clinic study shows. Researchers say their findings point out the need for new ways to prevent and treat lower GI disease in rheumatoid arthritis patients; the incidence of lower gastrointestinal complications is rising even as upper GI problems decrease significantly among rheumatoid arthritis patients. Smoking, the use of steroids known as glucocorticoids, prior upper GI disease and abdominal surgery were associated with lower GI problems in rheumatoid arthritis patients, the study found. The research was published online this week in The Journal of Rheumatology. Rheumatologists have long recognized that rheumatoid arthritis patients are at higher risk for upper GI problems such as stomach ulcers and bleeding. The study suggests increased awareness of that and likely, modern treatment strategies that emphasize the need to prevent ulcers and bleeding and control rheumatoid arthritis without relying as much on nonsteroidal drugs and corticosteroids have reduced upper GI complications, says co-author Eric Matteson, M.D., Chair of the Department of Rheumatology at Mayo Clinic in Rochester. "What we are also seeing for the first time in a systematic way is that patients with rheumatoid arthritis also are at risk for problems of bleeding and ulcers in the lower gut, especially the colon," Dr. Matteson says. Lung disease, heart problems, osteoporosis and carpal tunnel syndrome are among other potential complications for patients with rheumatoid arthritis, an often debilitating disorder in which the immune system attacks tissues, inflaming joints. To study the incidence of GI problems in rheumatoid arthritis patients, Mayo researchers identified 813 patients with rheumatoid arthritis and 813 without it, using data from 1980-2008 in the Rochester Epidemiology Project, a National Institutes of Health-supported effort in which Mayo and other Olmsted County, Minn., health care providers pool medical records. The incidence of upper GI problems in rheumatoid arthritis patients declined over the years but was still higher in that group: 2.9 for every 100 person years compared with 1.7 in non-rheumatoid arthritis patients. The rate of lower GI problems in rheumatoid arthritis patients was 2.1, compared with 1.4 in others, the study found. Of the arthritis patients studied, 229 died. GI problems were significantly associated with their deaths, including bleeds, perforations and obstructions.

ROCHESTER, Minn. — The dietary supplement gamma-linolenic acid can inhibit the growth of a subset of pancreatic cancer cells and selectively promote cancer cell death in mice, a Mayo Clinic study has found. The supplement, a fatty acid also known as GLA, worked particularly well when combined with the chemotherapy drug gemcitabine, the researchers say. The findings were presented today by Mayo Clinic pathologist Ruth Lupu, Ph.D., at the American Association for Cancer Research (AACR) Annual Meeting 2012. "One of the most devastating facts about pancreatic cancer is the paucity of effective drugs that exist to halt a tumor," Dr. Lupu says. "We knew from studies done about 20 years ago that polyunsaturated fatty acids such as GLA could influence cancers in general, but we didn't know which type of fatty acids and to what degree." Dr. Lupu's team first tested GLA against a variety of pancreatic cancer cell lines, and found that it was effective only against a subtype, expressing a gene for fatty acid synthase (FASN). Earlier studies by Dr. Lupu's team had demonstrated that FASN is highly expressed in pancreatic adenocarcinomas and appears to be a marker for poor overall survival in patients. "This was very exciting finding, because we realized that GLA was working selectively and had a particular target within cells," Dr. Lupu says. As researchers tested the GLA against cells with high levels of FASN, they found GLA inhibited about 85 percent of cell growth, while gemcitabine alone, the standard chemotherapy for pancreatic cancer, had a modest effect on cell inhibition. When researchers combined GLA with gemcitabine, the cell growth was inhibited completely. Then the team investigated the combination in mouse models of pancreatic cancer and found GLA in combination with gemcitabine significantly inhibited tumor growth. "The two treatments worked synergistically, and we achieved a significantly higher inhibition of cell growth and higher incidence of dead pancreatic carcinoma cells," Dr. Lupu says. "We don't yet know why the combination works better, but we know that many drugs work better when used together." Dr. Lupu says that because GLA targets FASN, which is present in high levels in certain pancreatic cancers, the supplement has real potential for individualized therapy. Dr. Lupu cautions that patients or healthy individuals should not rush to take GLA or alter their chemotherapy without consulting their oncologist. Her next stage of research will be to develop a Phase I clinical trial to test the GLA-gemcitabine combination in human patients. Her group will also test GLA in combination with other chemotherapy drugs currently used to treat pancreatic cancer.