UF scientists work to develop simple
bladder cancer test
|By Melanie Fridl Ross
GAINESVILLE, Fla. - University of Florida researchers have identified a set of proteins that appear to signal the presence of bladder cancer, a discovery they hope will lead to a simple, fast and noninvasive test that can detect the disease early.
Working with colleagues at the University of Michigan, the scientists used advances in technology to isolate nearly 200 proteins from the urine of patients with and without bladder cancer. Several appear promising as potential biomarkers, including one that studies conducted elsewhere have already linked to liver and ovarian cancer. The findings, available online, are scheduled to be published in the July 6 print edition of the American Chemical Society's Journal of Proteome Research.
Developing a simple "dipstick" test that would better single out patients whose symptoms are linked to cancer would enable those who simply have an infection to avoid a battery of screenings that typically include cystoscopy, a painful procedure that uses a small camera threaded through the urethra to image the bladder's interior. Such a test also could be used to detect cancer sooner, possibly before its signs even surface.
"With any cancer, the earlier you find it the better because it's not as aggressive in its early stages, and of course it's much easier to remove any cancer anywhere in the body if you catch it while it's relatively small," said Steve Goodison, Ph.D., an associate professor of surgery at the UF College of Medicine-Jacksonville.
"What would really help in this disease would be a test you could use to monitor these patients just by monitoring their urine," he added. "If we could develop this test to try to narrow down those who've got infections versus something more serious, that would relieve the patient from pain and worry and (cut health-care costs). The final aim would be to make a test cheap and convenient enough that you can start to think of screening people who don't have any symptoms."
Bladder cancer ranks among the five most common malignancies. The American Cancer Society estimates that in 2007 there will be about 67,160 new cases of bladder cancer diagnosed in the United States. Four times more men than women contract the disease, and smoking as well as exposure to industrial toxins increases the risk. Although the five-year survival rate is about 94 percent when it is detected early, bladder cancer is extremely difficult to cure because it tends to recur.
"Imagine the bladder like a balloon, and the tumors grow into the interior of the balloon," Goodison said. "So the surgeons go in and want to be as least disruptive as possible, so they nip these growths off from the inside, but unfortunately once it's happened it's very likely going to happen again - once you have bladder cancer you are at a high risk of recurrence for the rest of your life, which makes monitoring it a real problem."
As a result patients need to be closely monitored, with most undergoing cystoscopy every few months in the first year after diagnosis and as frequently as every six months thereafter. Meanwhile, the urine tests currently used to detect recurrent bladder cancer miss 60 percent to 75 percent of all malignancies, especially those that are low-grade or early stage.
"They haven't proven to be accurate enough to make the urologists confident to use them instead of doing manual inspection to date (using cystoscopy)," Goodison said. "The trouble is, a lot of tests tend to look at only one biomarker, and one biomarker is never really going to do it, you need to do a panel. You need something like six biomarkers on a dipstick and if four of the six come up then you have an accurate answer. Tests that look at one protein are not going to do it because cancer is so different between individuals."
In the current study, scientists used a technique to search for glycoproteins - a subset of proteins naturally secreted into the urine from the bladder lining - in urine samples from 10 individuals, five of whom had bladder cancer. Each sample was small, on average about 30 milliliters, equivalent to a fluid ounce. In contrast, previous urine protein profiles required large-volume samples.
Of the 186 proteins identified in the study, five were present only in the patients with cancer. The findings also substantially add to the urinary proteome database, which until now only contained 146 proteins. Additional studies are planned to screen samples from a larger number of bladder cancer patients with a variety of disease stages and grades, Goodison said.
"Even though our study involved a small number of patients so far, this was really a proof of principle that we can use these new techniques to detect proteins in the urine," Goodison said. "Nobody could do that at this (degree of) sensitivity until now."
The study was funded through a grant from the Florida Department of Health. Goodison's collaborators included UF urologic surgeon Charles Rosser, M.D., and David Lubman, Ph.D., a protein chemist at the University of Michigan.
"The development of novel non-invasive methods for early detection of bladder cancer is very exciting and represents a major step in (making) routine screening of patients with urological disease feasible in the future," said Nicholas C. Popescu, Ph.D., chief of the molecular cytogenetics section at the National Cancer Institute's Laboratory of Experimental Carcinogenesis. "In addition, interactions among specific proteins could lead to the development of effective therapy of bladder cancer, a major cause of cancer death worldwide."
Outdoor alcohol ads boost kids' urge to drink
By April Frawley Birdwell
GAINESVILLE, Fla. - In the world depicted in an alcohol billboard, bikini-clad babes clutch icy bottles, frothy beer flows over frosty mugs and the slogan reads, "Life is good." Ads like these may target adults, but children are getting the message too, a University of Florida and University of Minnesota study shows.
Adolescents attending schools in neighborhoods where alcohol ads litter the landscape tend to want to drink more and, compared with other children, have more positive views of alcohol, researchers report in this month's issue of the Journal of Studies on Alcohol and Drugs.
UF and UM researchers counted the number of alcohol ads within a two-block radius of 63 Chicago schools and compared students' opinions on drinking when they were in sixth grade and again two years later. The result? The more ads for alcohol there were in a neighborhood, the more students were interested in drinking alcohol, the findings show.
Most of the ads researchers found were beer signs in storefronts, although they also counted billboards, bus stop signs and other types of ads. In total, there were about 931 ads for alcohol around the schools. On average, there were about 28 ads in each neighborhood, after excluding 22 schools where there were no ads. One school had more than 100.
"The majority of the ads were just brand information only," said UF epidemiologist Kelli A. Komro, Ph.D., who studied these more subtle logo-only signs as well as more elaborate, image-laden billboards. "Sometimes we think that those as are not so powerful, but the majority of the ads we found were those kinds of ads and still we found the association with increased intentions to use alcohol."
About half of all teens sample their first alcoholic drink by the time they are 15, according to the U.S. Surgeon General, which released a report on teen drinking earlier this year. Teens who start drinking this early are more likely to have trouble in school, become addicted to alcohol, smoke cigarettes and use drugs than adolescents who don't drink, the report states.
Prior research has shown that adolescents' intentions and attitudes about alcohol generally predict their later behavior, said Komro, an associate professor of epidemiology and child health policy in the UF College of Medicine. To gauge students' thoughts on drinking, the researchers asked them a series of questions, such as whether they planned on drinking in high school or if they thought drinking made teens popular.
By eighth grade, the students who attended schools with more alcohol advertising in the surrounding neighborhood had more intentions to drink alcohol and gave fewer reasons for not drinking when researchers surveyed them, the study shows.
The ads also seemed to have the same effect on teens who were already drinking in sixth grade and those who had not yet imbibed, Komro said.
"A lot of times advertisers say ads are targeted to people who are already drinking, so we looked at kids who were already drinking in sixth grade and kids who were not," she said. "Among those kids who were not drinking, we still found the association between exposure to the outdoor ads and increased intentions to use alcohol. The ads are working even for the kids who are not drinking."
Ads like these influence children by changing their perceptions of what is normal, said Steven Thomsen, Ph.D., a professor of communication at Brigham Young University who studies the effects of advertising on children. If kids believe that most people drink and all their peers drink, the chances are greater they will also drink, Thomsen said.
"The importance of this (study) is they determined that these messages have an impact on normative beliefs, which are the assumptions we make about how the world works," Thomsen said. "It doesn't have to be a (TV) commercial (to be effective)."
Restrictions that limit or eliminate alcohol advertising around schools could help students stay alcohol-free, Komro said.
"I think results from this study and studies like this study clearly indicate that there should be policies to ban alcohol advertising near the schools," Komro said. "It clearly shows that exposure is dangerous for our children."