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April 4, 2002


Common treatment for endometriosis linked to ovarian cancer

A commonly prescribed medication for treating endometriosis appears to increase the risk of ovarian cancer, according to findings presented recently by a Pitt Graduate School of Public Health (GSPH) researcher at the 33rd annual meeting of the Society of Gynecologic Oncologists in Miami.

In the study, women taking danazol, a synthetic version of the male hormone androgen, were nearly three times more likely to develop ovarian cancer than were women taking leuprolide, an anti-androgenic, gonadotropin-releasing hormone agonist. Both drugs are used to treat endometriosis, a painful disease in which pieces of uterine tissue migrate to other parts of the body.

"Our previous studies have found that women with endometriosis are already at a 50 percent increased risk for ovarian cancer, and treating them with danazol appears to further increase their risk. This new result, even though it is preliminary, may factor into the equation when clinicians and their patients with endometriosis are deciding on the best treatment," said presenter Roberta B. Ness, associate professor of epidemiology at GSPH and director of the school's Epidemiology of Women's Health Program.

The study analyzed pooled data from two case-control studies that examined the relationships among endometriosis, endometriosis treatments and ovarian cancer. Among women with endometriosis, 17 took danazol and 15 took leuprolide. Analysis showed that the study participants who took danazol were 2.7 times more likely to have ovarian cancer than were other women with endometriosis who did not take danazol. Women taking leuprolide had no significant elevation in risk.

"While the number of women studied is small, the results are telling, and they warrant further studies on a larger scale," said the study's principal investigator, Carrie Cottreau, assistant professor of obstetrics and gynecology at Pitt's School of Medicine.

Additional research studies are planned at Pitt to further investigate the link between androgens and ovarian cancer.

Earlier this year, Ness and colleagues published results of a study showing that there is no association between fertility drugs and ovarian cancer. However, the study showed that the risk of ovarian cancer is 50 percent higher in women with endometriosis than it is for women without endometriosis.


Findings reported on tissue engineering, cellular therapies

Clinical and basic science research findings of nearly a dozen studies were presented by Pitt School of Medicine researchers at the Engineering Tissue Growth International Conference and Exposition, March 19-21 at the Westin Convention Center Hotel in downtown Pittsburgh.

Now in its second year, the Engineering Tissue Growth International Conference and Exposition is designed to bring scientists and researchers from around the world together with industry representatives to present current research and products in regenerative medicine.

Regenerative medicine focuses on ways to develop treatments to repair or replace damaged tissues or treat disease by using engineered tissues, cellular therapies, artificial organs or other biohybrid devices.

Highlights of the findings included the following:

Genetically engineered stem cells show promise Using genetically engineered stem cells shows promise in treating mice with a disease similar to Duchenne muscular dystrophy, Johnny Huard, associate professor of orthopaedic surgery, molecular genetics and biochemistry, and his colleagues reported.

These adult, or somatic, stem cells are derived from skeletal muscle and may be coaxed to form blood-cell precursors. Working with a strain of "mdx" mice, a rodent model for Duchenne muscular dystrophy, Huard's group found reason to believe that genetically engineered stem cells may be used to deliver the essential missing protein dystrophin to musculature wasted by the congenital disease.

Experiments injecting cultured skeletal muscle cells into mdx mice revealed that while some cells migrated to the muscles, others found their way into bone marrow. Those in bone marrow showed evidence of being able to produce new blood cells. Muscle function also improved.


Research continues to combine man-made, living tissue

Bioengineered materials research is continuing to find ways to combine man-made materials and living tissue, Michael Sacks, associate professor in the bioengineering department, and his colleagues report.

Sacks' group is studying the geometry, mechanical properties and compatibility of engineered biomaterials to native tissues. The challenge, Sacks says, is developing a thorough understanding of structure and function so replacement tissues can reach optimal efficiency. For example, no one has yet been able to build a replacement heart valve that can match the performance of a natural aortic valve, which functions to prevent blood from flowing backward from the aorta to the left ventricle.

The natural valve represents a masterful interaction of fluid and solid tissue, and can withstanding as many as 40 million cycles a year — up to three billion or more in a lifetime. Current tissue engineering materials, including biodegradable polymer scaffolds, require much more work in order to provide both structure and functional mechanics.


Repairing liver may become easier

Repairing liver disease or damage may become easier thanks to research being undertaken by George Michalopoulous, professor and chairman of the pathology department, and his colleagues.

They are studying ways to use differentiated liver cells, called hepatocytes, to reconstruct liver tissue. Using several cell growth factors, liver cells were encouraged to proliferate in culture. After eight days, tissue growth was sufficient to cover the surface of the culture.

Examination showed that the cultured tissue displayed patterns of cell division and cell death similar to the natural growth cycle. In addition, layers of differentiated liver cells were observed, including connective tissue, bile ducts and other cells that would naturally be associated with blood vessels within the liver.

These experiments could lead to further understanding of ways to use such engineered liver tissue to repair liver damage and disease.

Healing of common sports injury may be significantly improved Healing of a common sports injury may be significantly improved by using a tissue-engineered scaffold made of cellular components found in the small intestine, reports Volker Musahl, a fellow in the Musculoskeletal Research Center.

Musahl presented findings of a study using elements of small intestinal submucosa, or SIS, to boost healing of injuries to the knee joint's medial collateral ligament (MCL). A common sports injury, MCL tears account for some 40,000 injuries a year in the United States. Most such injuries can be treated without surgery, but the healed ligament remains weak and is susceptible to re-injury.

Using a rabbit model, Musahl and his colleagues used a tissue-engineered scaffold made up of SIS, a collagen layer in the small bowel that already has been approved by the U.S. Food and Drug Administration for clinical use in vascular surgery, urology and some orthopaedic cases. After 12 weeks of healing, the ligament tissue was carefully examined for strength and quality. Both strength and quality were doubled when compared to ligament healing without SIS treatment.


Research suggests genes for depression differ in men, women

Pitt researchers have found evidence that men and women have different genes that anchor the roots of depression, a revelation that could have a major impact on the way doctors treat patients in the future.

The researchers are the first to report the results of a systematic search for chromosomal regions that harbor genes that affect susceptibility to severe depression, the second leading cause of disability worldwide. Their results were published in the April American Journal of Medical Genetics, and posted on the journal's Web site.

"We suspected there were at least a few different genes involved in making women and men susceptible to major depression," said lead author George S. Zubenko, professor of psychiatry at Pitt's School of Medicine and adjunct professor of biological sciences at Carnegie Mellon University.

"The results of this study suggest that sex-specific genes for recurrent major depression may actually be the rule rather than the exception."

For the study, funded by the National Institute of Mental Health, Zubenko and his colleagues compared genetic markers from 100 men and women with recurrent, early-onset major depressive disorder (RE-MDD) and 100 people with no history of this disorder, to find out which chromosomal regions were associated with the illness. RE-MDD is a severe form of clinical depression that runs in families and impairs the health and life span of family members.

Out of 19 chromosomal regions that were associated with the development of RE-MDD, 16 were significantly associated with the disorder in either men or women — but not both.

According to Zubenko, these findings suggest important differences in the molecular basis of clinical depression in men and women, or sex-specific differences that determine resistance to stressful events. These genetic factors also may contribute to differences in the symptoms of clinical depression in men and women, differential treatment responses, and the development of additional psychiatric disorders such as anxiety disorders, alcoholism and other substance use disorders that frequently accompany major depression and run in the same families.

Zubenko said this research may provide an important step toward changing the way doctors diagnose and treat major depression, which affects nearly 10 percent of the population.

"Studies such as this one are providing us with a better understanding of the biology of complicated disorders such as major depression, which is unlikely to represent a single disease with a unitary cause," Zubenko said. "Instead, clinical depression is probably more like anemia. Both of these disorders are defined by a collection of clinical features that result from different causes in different people. Treatment or prevention efforts are usually most successful when they are aimed at the specific causes of a disorder."

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