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UNC School of Dentistry Scientist finds chief AIDS cancer needs trauma and virus to get started


By DAVID WILLIAMSON UNC News Services CHAPEL HILL --

Kaposi's sarcoma, the most common cancer that develops as people with the HIV virus progress to full-blown AIDS, appears to require some kind of trauma such as a cut or comparable injury to get started, a University of North Carolina at Chapel Hill scientist has discovered.

"We found that there are at least three key elements central to development of this important cancer," said Dr. Jennifer Webster-Cyriaque, assistant professor of dental ecology and microbiology at the UNC schools of dentistry and medicine.

"One is suppression of the immune system, which HIV causes. The second is the presence of human herpesvirus 8, or HHV8, which Dr. Yuan Chang and her husband Dr. Peter Moore of Columbia University discovered in 1994. And the third, which is new, is trauma after which the healing process begins to take place."

Webster-Cyriaque's report on the findings appears in the current (April 18) issue of the New England Journal of Medicine.

What apparently happened to kick-start Kaposi's sarcoma in one of her patients was that the natural healing process called in certain cells to help restore the damaged tissue, she said. But since those cells already were infected with the cancer-causing HHV8, that caused a malignancy to develop.

The report describes a 38-year-old HIV-positive patient participating in a UNC study of HIV-associated salivary gland disease. Researchers collected blood and throat secretions from the man and, in minor surgery, removed a tiny amount of salivary gland tissue for analysis.

"The biopsy went fine, and we found the HHV8 virus in his throat washings, but not in his blood or salivary glands, "Webster-Cyriaque said.

"Several days after the biopsy, he came back with a significant lesion growing inside his lip at the biopsy site," she said. "We sent him home with antibiotics to make sure the growth didn't become super-infected, but it continued to grow and soon extended outward to his chin. A second biopsy revealed it to be Kaposi's sarcoma."

The rapidly growing tumor required radiation treatments and finally disappeared six weeks after radiation therapy began. It has been gone now for more than two years.

"Through studies of the biopsied tumor tissue we found virus in macrophages, which are Pac Man-like scavenger cells that fight infection and also promote wound healing," the dentist and microbiologist said. "We also found viral genes expressed for the first time in epithelial cells and in both white cells called lymphocytes and endothelial cells in tissues and blood vessels around the wound."

Endothelial cells eventually evolve into spindle cells, which are commonly seen in Kaposi's sarcoma, but not in healthy people. "This work appears to explain why -- when some people have surgery, including transplant patients -- they develop Kaposi's sarcoma at their suture sites," Webster-Cyriaque said. "It also suggests that anti-viral agents targeted specifically at HHV8 could be useful in preventing Kaposi's sarcoma in people whose immune systems have been suppressed, such as transplant patients." The research is the first demonstration that HHV8 virus can be detected in saliva prior to disease development, she said. Previous studies examined blood to detect the virus before Kaposi's sarcoma lesions developed but not saliva.

"Looking only at blood, we would have missed it," said Webster-Cyriaque, a member of UNC's Lineberger Comprehensive Cancer Center and Center for Inflammatory Diseases.

Kaposi's sarcoma is a particular problem for gay men in the United States, older, heterosexual men in countries surrounding the Mediterranean Sea, including Spain and Italy, and people in African nations. -



Posted: 12/03/2009