Cancer Research Tip Sheet
This information tip sheet highlights research news from the Kimmel Cancer Center at Johns Hopkins* that are the subject of presentations at the annual meeting of the American Association of Cancer Research.
EMBARGOED FOR RELEASE UNTIL TIME OF PRESENTATION.To arrange interviews, or for more information, please contact Vanessa Wasta (phone: 410-955-1287, email: [email protected])
Smart Bomb Therapy for Prostate CancerHopkins Kimmel Cancer Center researchers are exploring new ways to deliver targeted prostate cancer therapy by linking anti-cancer drugs to protein carriers that are activated by prostate specific antigen (PSA). When these so-called "pro-drugs" reach prostate tumors, PSA clips off the protein carrier freeing the drug to kill cancer cells. Pro-drugs may be most helpful in reaching prostate cancers that have spread to other parts of the body. PSA, produced only by prostate cells and prostate cancer cells, is shut down when it gets into the blood, but is found in high levels surrounding prostate tumors.
Researchers are testing PSA-based pro-drugs made with standard chemotherapy agents like taxol and 5-flourodeoxyuridine (5-FU) as well as new agents currently too toxic for patients if given systemically. One such drug is Thapsigargin, an extract from the seed of a Mediterranean plant in the carrot family, called Thapsia garganica L. Thapsigargin causes cell death by blocking a critical energy pump within the cell and, unlike many standard therapies, can kill prostate cancer cells that are not dividing rapidly. Animal studies by Hopkins Kimmel Cancer Center researchers show that PSA-based pro-drugs made with Thapsigargin destroy more than 80 percent of prostate cancer cells after two weeks of injections directly into the tumor. *Embargoed for release until presentation on Tuesday, April 9, 2002, 9:00 am, PDT, in Hall E, Room 134; Abstract numbers 364 and 2058.
Prostate Cancer May Result from Chronic InflammationThe earliest stages of prostate cancer may develop in lesions generally associated with chronic inflammation and might be reversible with anti-inflammatory drugs and dietary supplements, new research suggests. Hopkins Kimmel Cancer Center researchers screened several stages of normal and cancerous prostate cells for changes in a key gene, called glutathione S-transferase p (GSTP1), that detoxifies environmental carcinogens and protects against cancer. In prostate cancer, this gene is deactivated through a biochemical process known as hypermethylation. Methylation acts like the safety on a gun, causing a gene to stop working. Too much or "hyper"methylation on the GSTP1 gene shuts off its cancer-preventing properties as the prostate stops producing critical protective enzymes. Hopkins Kimmel Cancer Center researchers looked at GSTP1 hypermethylation in normal and prostate cancers tissue samples as well as in inflammatory prostate lesions known as PIA (proliferative inflammatory atrophy) and PIN (prostate intraepithelial neoplasia). They found GSTP1 methylation in three of 17 (17.6 percent) of PIA lesions, six of ten (60 percent) of high-grade PIN lesions and seven of seven (100 percent) prostate cancers. No GSTP1 methylation was detected in seven samples of normal prostate tissue.
The increasing levels of GSTP1 methylation may show how prostate cancer develops. The starting point may be PIA lesions, which are associated with inflammation and produce high levels of the GSTP1 gene suggesting that the gene has kicked into high gear from some kind of environmental stress. It is in these PIA lesions that researchers believe the first genetic mistakes are made leading to hypermethylation of the GSTP1 gene leaving prostate cells unable to repair damage from carcinogens. With an onslaught of carcinogens from the environment and diet, researchers believe more gene mistakes are made, making PIA lesions progress to PIN lesions, funny-looking cells strongly linked to cancer and considered by some to be pre-cancerous. Investigators will test the prostate cancer preventive effects of anti-inflammatory agents and antioxidant nutrients on PIA lesions in animal models.
*Embargoed for release until poster presentation on Sunday, April 7, 2002, 8:00 am, PDT, Exhibit Hall A-C, Abstract number 1.
*Notice: Our name has changed to the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Please use our new name or the shortened version -- Kimmel Cancer Center at Johns Hopkins -- when identifying our scientists and cancer center.
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