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Scientists At The University Of Pittsburgh Cancer Institute Present Findings At Annual Meeting Of The American Association For Cancer Research

PITTSBURGH, April 5, 2002 — Researchers at the University of Pittsburgh Cancer Institute (UPCI) will present their findings at the 93rd annual meeting of the American Association for Cancer Research being held April 6-10 at the Moscone Convention Center in San Francisco. Highlights of the presentations are outlined below:

Estrogenic activity discovered in several commonly used medicinal botanicals

Plant extracts are often used to relieve gynecological conditions such as menopausal symptoms as well as depression and other chronic illnesses. Although used widely, many of these remedies have not been thoroughly examined. Researchers at UPCI are studying several plant extracts to learn more about their safety, potency and hormonal properties. In one such study, UPCI researchers found evidence that some of these extracts interact with estrogen receptors and induce strong estrogenic responses in female rats whose ovaries were removed.

"Our results indicate that some herbal remedies demonstrate measurable estrogenic activity, in spite of the fact that they are not traditionally used as such," said Patricia Eagon, Ph.D., associate professor of medicine at the University of Pittsburgh and principal investigator of the study. "This is important since it suggests that some extracts may not be appropriate for women who have a family or personal history of cancers that are linked to higher levels of estrogen, including breast and uterine cancer. While plant extracts can alleviate symptoms for a variety of conditions, women should practice caution when using them and may want to avoid their use for conditions in which estrogens are contraindicated."

Of the extracts studied, motherwort leaf, saw palmetto berry, rhodiola rosea root and red clover blossom were the most potent in terms of their estrogenic activity, and extracts of maca root, cramp bark and tumeric root were the least potent.

Critical cells in immune response found inhibited for the first time in prostate cancer

Dendritic cells, as the pacemakers of the immune system, play a critical role in the primary immune response. They are the first cells to recognize antigens and to assist in the production of an immune response by helping to produce antibodies to fight disease. In the current study, University of Pittsburgh researchers found that prostate cancer tumors produce factors that inhibit the growth and proliferation of dendritic cells and induce apoptosis (or cell death) in dendritic cells.

"Our data may explain the strong immunological non-responsiveness that we often see in patients with advanced prostate cancer," said Michael Shurin, M.D., Ph.D., associate professor of pathology at the University of Pittsburgh and associate director of clinical immunopathology. "For the first time, we have discovered that a systemic inhibition of the dendritic cells system occurs in prostate cancer."

In the study, prostate cancer tumor cells were injected into the bones of mice and had a direct effect on stem and hematopoietic precursor cells (the basic cells from which all other cells develop). The interaction between the tumor cells and the hematopoietic precursors resulted in a significant inhibition in the cells’ ability to differentiate into functional dendritic cells. The study demonstrates that the generation and function of dendritic cells is significantly suppressed in prostate cancer and suggests that stimulating the growth of dendritic cells is a promising area for future research in prostate cancer therapies.

Protein found to play an important role as a molecular "switch" in the survival and demise of dendritic cells

University of Pittsburgh researchers have discovered that a protein, cdc42, plays an important role in the survival of dendritic cells in cancer. Their study showed that cdc42 was upregulated in dendritic cells treated with tumors, suppressing their activity, and that dendritic cells grew when the expression of cdc42 was decreased. The study further demonstrated that dendritic cells treated with tumors not only expressed higher levels of cdc42, but also expressed 15-fold less of a cdc42 inhibitor (Rho-GD-1) and 5.7-fold more of a cdc42 activator (ezrin).

"The discovery of an increasing number of genes regulating dendritic cell activity and a better understanding of the molecular interactions between immune cells has provided the molecular basis for specific approaches of active immunotherapy in cancer patients," said Michael Shurin, M.D., Ph.D., associate professor of pathology at the University of Pittsburgh and associate director of clinical immunopathology. "This new direction, which one could term ‘therapeutic molecular immunopathology,’ will allow us to identify new molecular targets in dendritic cells and to possibly design new therapeutic approaches for cancer by genetically engineering the cells to protect them from tumor-induced apoptosis. This can translate into new possibilities for the creation of highly efficient vaccines for cancer therapy."

For more information about the University of Pittsburgh Cancer Institute please visit http://www.upmccancercenters.com.

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