Skip to Navigation
University of Pittsburgh
Print This Page Print this pages

May 13, 2004

Research Notes

Researchers report at AUA meeting

Pitt researchers have presented findings from 25 studies at the annual meeting of the American Urological Association, May 8-13, in San Francisco.
Highlights of the findings included the following:

Women with overactive bladders less likely to enjoy sex Women who experience overactive bladder are less likely to enjoy sexual activity, according to a Pitt study. Overactive bladder, a condition where the muscle surrounding the bladder contracts spastically causing frequent urination and incontinence, affects more than 8 million women worldwide.

Prostate cancer marker could lead to earlier diagnosis Prostate cancer could be detected as many as five years earlier than it is currently being diagnosed by testing for a protein in tissue that indicates the presence of early disease. Pitt researchers suggest that testing for the protein called early prostate cancer antigen could serve as an adjunct to the current diagnostic approach to patients with elevated levels of prostate-specific antigen who undergo repeat needle biopsies.

Botox injections effective for lower urinary tract dysfunctions Botox injections continue to be a safe and effective, although temporary, treatment for a number of lower urinary tract dysfunctions, including incontinence. Pitt professor Michael Chancellor, who has performed the largest number of these procedures in North America, presented results on the efficacy and safety of this treatment.

Potential biomarker could lead to early detection of renal cell carcinoma

Pitt researchers have identified a potential biomarker that could lead to the early detection of renal cell carcinoma. Renal cell carcinoma is the most common form of kidney cancer in adults. Due to the lack of a sensitive test for the disease, it often goes undetected until the cancer is in an advanced stage.

Muscle-derived cells, gene therapy restore erectile function Nearly 80 percent of men who undergo radical prostatectomy experience some type of erectile dysfunction due to damage to the nerves essential for achieving and maintaining an erection. In two separate studies of animal models, Pitt researchers have found novel approaches to facilitate the healing of these nerves, restoring erectile function – one by using muscle-derived cells, the other through gene therapy.

Botox improves enlarged prostate symptoms

In a preliminary study, researchers from Pitt and Chang Gung Memorial Hospital in Kaohsiung, Taiwan, have found that injections of botulinum toxin A (botox) significantly reduces symptoms of benign prostatic hyperplasia, commonly known as enlarged prostate. This offers the potential of a promising new alternative treatment for the millions of men with enlarged prostates.

Anti-depression drug helps to treat irritable bowel syndrome

Paroxetine, a drug commonly used to treat depression, can improve symptoms in people with irritable bowel syndrome (IBS), according to a study in the May issue of the American Journal of Gastroenterology.
In a randomized double-blind, placebo-controlled study, researchers at Pitt’s School of Medicine found that the drug relieved some symptoms of IBS and improved the well-being of people with IBS.
“This study points out the benefits of this drug as a potential new and improved treatment for IBS, a disease that is very difficult for physicians to manage,” said George Arnold, a Pitt clinical professor of medicine and principal investigator in the study.
IBS is a chronic gastrointestinal disorder that affects 14-24 percent of women and 5-19 percent of men in Western populations. It is characterized by abdominal pain, altered bowel habits and abdominal bloating. It generally has been treated with high-fiber diet, drugs or both.
The study found that the percentage of participants experiencing an improvement in overall well-being was significantly greater (63.3 percent) in the paroxetine group than the placebo group (26.3 percent). The percentage of participants experiencing an improvement in bowel movements was significantly greater in the paroxetine recipients (58.6 percent) than the placebo recipients (32.4 percent). There was a significant improvement in food avoidance and work function for those on paroxetine. There was no significant improvement in abdominal pain or bloating between the paroxetine and placebo groups. “This study showed that in absence of depression, paroxetine helped irritable bowel syndrome,” said Arnold. “This is a medicine that has been in use for some years and is safe with no long term side effects, which is a problem with current medications for IBS.”
The effectiveness of paroxetine, a selective serotonin reuptake inhibitor (SSRI), has been reported in case reports but not in controlled studies. SSRIs are considered first line treatments in psychiatric illnesses such as major depression and generalized anxiety disorder, which are found in 50 to 90 percent of patients with IBS, according to Arnold, who is a gastroenterologist at the University of Pittsburgh Medical Center’s (UPMC) Shadyside Hospital. The study was funded by the Competitive Research Fund of the Shadyside Hospital Foundation of Pittsburgh.

Breast cancer researcher gets $250,000 award

Robert W. Sobol Jr., assistant professor of pharmacology at Pitt’s School of Medicine, has received a $250,000 award from the Susan G. Komen Breast Cancer Foundation for a project that seeks to identify the mechanisms that trigger tumor cell death in order to improve the ability of a promising breast cancer treatment.
Sobol, who joined the University of Pittsburgh Cancer Institute (UPCI) in 2002, focuses his research on the identification of mechanisms that may improve the ability of a frequently used chemotherapy agent, temozolomide (TMZ), to damage the DNA of cancer cells. While TMZ is an effective treatment for many cancers, its ability to destroy cancer cells depends on how effectively it can damage the DNA of these cells, preventing them from multiplying and causing them to eventually die.
“Tumor cells, unfortunately, are quite robust and can often repair the damage that chemotherapy causes to their DNA,” said Sobol. “In order to improve the efficacy of chemotherapeutic agents for breast cancer, we need to develop ways to subvert the ability of cancer cells to repair themselves. I am hopeful that our project will lead to discoveries of promising new approaches that improve the efficacy of therapy by identifying the mechanisms that control cancer cells’ ability to survive.”

People seek comfort in scent of partners’ clothing

We are all familiar with the image of a woman picking up her husband’s shirt and putting it to her face to detect his scent. Pitt researchers now have documented just how often this practice occurs.
A survey of 108 Pitt undergraduate students who were or had been in a committed relationship revealed that 72 percent of the women and 27percent of the men surveyed had slept in or with their partners’ clothing while separated from their partners. Additionally, 87 percent of the women and 56 percent of the men deliberately smelled their partners’ shirts or blouses.
Many participants reported that the odor comforted them. The data was presented recently by the researchers at the national conference of the Association for Chemoreception Scientists in Sarasota, Fla.
“We were surprised at how common this occurs,” said Pitt psychology professor Donald McBurney, who was assisted in the research by two Pitt psychology majors, graduate student Sybil Streeter and undergraduate student Melanie Shoup. “Men are just as interested in their partners’ odor when present, but they do not seek it out as much when absent,” McBurney said, noting that this study marks the first research into the prevalence of the activity.
“We know from other studies that women prefer partners with certain genetic traits that can be distinguished by smell,” said Shoup, who is using the research as the basis for her thesis for the Department of Psychology Honors Program. “It is possible that smelling a piece of clothing is one way people evaluate their partners’ genetic quality. Alternatively, a partner provides a sense of safety and security, especially to a woman. The odor may be a sign of that security.”

Mechanism may impact stem cells’ ability to fight disease

Adult stem cell transplantation offers great therapeutic potential for a variety of diseases due to their ability to replenish diseased cells and tissue. While they are unique in this ability, it remains a challenge to effectively treat disease long-term with stem cells because of our inability to grow them in the laboratory.
Defining the molecular switch in the stem cell replication process, or cell cycle, is a key step to stimulating their growth for broader clinical use. In the May issue of Nature Cell Biology, Tao Cheng, assistant professor in the Pitt medical school’s Department of Radiation Oncology, and colleagues report the discovery of a molecular mechanism in the cell cycle that appears to impact the replicating ability of stem cells from bone marrow and blood to fight disease. They found that blood stem cells from mice missing a gene called p18 were much better able to multiply and grow; p18 is a molecule in a class of so-called “cyclin-dependent kinase inhibitors” that are critical inhibitors of cell cycle control.
Cheng and his team isolated p18-deficient stem cells from mice and found that these cells were much more efficient at repopulating injured bone marrow tissue. As a result, they concluded that blocking the function of p18 may be a productive way to enhance the efficacy of stem cell transplantation as a treatment for diseases.
“Stem cells have great potential, but we need to develop novel strategies to help them proliferate to better fight diseases,” said Cheng, who also is a stem cell biologist at the University of Pittsburgh Cancer Institute. “By using stem cells deficient in p18, we found a strikingly improved long-term engraftment of stem cells in bone marrow leading us to the conclusion that p18 is a strong inhibitor to stem cell self-renewal. This is an exciting finding because it may lead to a new medical invention that can improve the ability of stem cells to self-renew, and thus, more effectively treat a wide range of diseases including cancer.”
Stem cells give rise to blood cells with various essential functions, from carrying oxygen to providing immunity against disease. Preserving the function of stem cells and correcting any defects is essential to fighting disease and maintaining health. Stem cell transplantation is a common treatment for patients with advanced or recurrent cancers of the blood, such as leukemia and lymphoma.
The study was funded in part by grants from the National Institutes of Health. Co-first-authors include Youzhong Yuan and Hongmei Shen of the University of Pittsburgh Cancer Institute.

NASA technology may help to preserve fertility after cancer treatment

Using technology borrowed from the National Aeronautics and Space Administration, scientists at Pitt’s McGowan Institute for Regenerative Medicine have taken the first steps toward successfully preserving ovarian tissue from rats and mice in culture, including immature egg follicles, according to a study in the current issue of the journal Tissue Engineering.
Such techniques may prove to be valuable in protecting the fertility of a woman with cancer whose future childbearing potential is threatened by the very chemotherapy or radiation treatments necessary to save her life.
“While it is possible for ovaries to be removed and frozen before cancer treatment, there is currently no reliable way to generate mature eggs once the stored tissue is thawed,” said Alan J. Russell, director of the McGowan Institute and senior author of the study. “Finding a safe, dependable way to produce healthy eggs from preserved ovaries will be a significant advance toward conserving fertility for cancer patients.”
In the most recent study using ovarian tissue in rats and mice, Pitt scientists focused their efforts on ovarian tissue structures, including immature eggs and follicles, the main functional portion of the ovary. Under normal circumstances, follicles remain dormant until triggered at puberty to cycle through several stages of development before reaching full maturity. Eggs are nurtured within the follicle. Once all the follicles are gone, ovaries fail and a woman enters menopause.
“We looked at using suspension culture systems to provide a uniform setting for follicles that is similar to the natural ovarian environment,” said Russell, who also is a professor of surgery at the Pitt medical school.
Custom-designed rotating wall vessels and orbiting test tubes were the suspension systems used, explained Elizabeth McGee, a study co-author who is assistant professor of obstetrics, gynecology and reproductive sciences at the Pitt medical school and a McGowan Institute faculty member.
“Test tubes are housed in an orbiting device designed to gently agitate a special growth medium just enough to prevent follicles from settling on the surface – to keep them surrounded by fluid,” added McGee, who also is an assistant investigator at Pittsburgh’s Magee-Womens Research Institute. “Ovarian follicles are highly fragile. We wanted to eliminate as much opportunity for mechanical damage as possible.”
For comparison purposes, some ovarian tissue was encapsulated in a special protective polymer gel and some was not, McGee said. Culture wells, test tubes and rotating wall vessels were incubated for 72 hours, and follicle diameters were measured daily. Between 25 and 60 follicles were analyzed for each treatment group.
In addition, follicles were cultured in the presence and absence of follicle-stimulating hormone (FSH) in the specially designed systems and in a conventional culture system to evaluate resulting changes in egg structure and maturation using the different mediums and culture systems.
“Our goal is to understand which features of the artificial environment contribute significantly to egg cell changes,” said Russell.
At the end of the 72-hour culture period, follicles were evaluated for changes in shape and levels of development. There were vastly different rates of growth depending on culture conditions. Follicles cultured in a growth medium that included FSH using the NASA-inspired techniques developed larger diameters, growing at roughly double the rate of those in conventional culture, the authors report. In addition, these follicles were more likely to maintain their normal spherical shape than those supported in other ways.
“This study is the first to look at this new environment for the culture of immature rat and mouse follicles,” said Russell. “We found that a suspension culture in combination with micro-encapsulation does a better job of promoting follicular growth than more conventional methods.”
“More studies are needed to evaluate these techniques in the longer term as well as to discover optimum conditions for follicle growth,” Russell said. “Still, the results represent a promising step in the right direction.”
In addition to Russell and McGee, study authors included Neshat Rowghani and Matthew Heise of Pitt’s School of Engineering; Dan McKeel, McGowan Institute faculty, and Richard Koepsel of the engineering school and the McGowan Institute.

New device may help people with emphysema breathe better

Physicians at Pitt’s School of Medicine are leading a national, multi-center research study of a valve, implanted in the lung, that may help people with emphysema breathe better.
Emphysema is caused primarily by smoking and leads to a gradual, irreversible breakdown of lung tissue. This causes the lungs to lose the ability to move air in and out normally and to efficiently absorb oxygen. Eventually, breathing becomes harder as the damaged lungs trap air.
As the disease advances, the damaged areas of the lung progressively expand within the chest cavity, leaving patients constantly feeling out-of-breath since there is not enough room available for the lungs to function normally.
“Previous studies have shown that lung volume reduction surgery (LVRS) offers relief to patients suffering from emphysema by surgically removing the most diseased portion of the lung. This allows the remaining lung tissue to function better,” said Frank Sciurba, associate professor of medicine at the Pitt medical school’s division of pulmonary, allergy and critical care medicine and principal investigator for the national study.
“The goal of this research study is to test a new, bronchoscopic approach to lung volume reduction by implanting one-way valves in the bronchial lumen, the large air tubes leading from the trachea to the lungs that convey air to and from the lungs. This procedure may involve fewer risks and reduced recovery time than surgery,” said Rodney Landreneau, co-investigator of the study, a Pitt professor of surgery and director of the Comprehensive Lung Center at UPMC Shadyside.
The one-way valve, called the Emphasys Endobronchial Valve (EBV), is supported by a stent-like, self-expanding retainer that secures the implant to the walls of the lumen during all physiological conditions, including coughing.
The EBV allows air to be vented from the isolated lung segment under normal exhalation pressure and prevents air from refilling the isolated lung area during inhalation. The valve can be removed if medically necessary.
Sciurba said: “The EBV was developed as a bronchoscopic approach to block airflow into targeted, hyperinflated regions of the lung, while redirecting the inhaled air to healthier portions of the lung and permitting exhaled air to escape. This approach may provide some of the clinical benefits of LVRS without the high risks and costs associated with such an invasive surgical procedure.”
The multi-center study will enroll 270 participants with 180 participants randomly assigned to undergo pre-implant pulmonary rehabilitation and have valves implanted in their lungs. The remaining 90 participants will be randomly assigned to the control group and will receive optimized medical management, but no valves. There will be 25 randomized participants in the University of Pittsburgh arm of the study. Prior to randomization, both the control and study device groups will participate in a pulmonary rehabilitation program, which involves exercise training and optimized care.
To participate in this research study, participants must have been diagnosed with emphysema, a condition characterized by poor flow of air in and out of the lungs. Men or women between 40 and 75 years of age, who have been nonsmokers for 4 months prior to screening are eligible.
For additional information on the study, call the Emphysema Research Center in Pitt’s division of pulmonary, allergy and critical care medicine at 412/692- 4800.

Leave a Reply