
JACKSONVILLE, Fla. — A single gene that promotes initial development of the most common form of lung cancer and its lethal metastases has been identified by researchers at Mayo Clinic in Florida. Their study suggests other forms of cancer may also be driven by this gene, matrix metalloproteinase-10 (MMP-10). The study, published in the journal PLoS ONE on April 24, shows that MMP-10 is a growth factor secreted and then used by cancer stem-like cells to keep themselves vital. These cells then drive lung cancer and its spread, and are notoriously immune to conventional treatment. The findings raise hope for a possible treatment for non-small cell lung cancer, the leading cause of U.S. cancer deaths. Researchers discovered that by shutting down MMP-10, lung cancer stem cells lose their ability to develop tumors. When the gene is given back to the cells, they can form tumors again. The power of this gene is extraordinary, says senior investigator Alan Fields, Ph.D., the Monica Flynn Jacoby Professor of Cancer Research within the Department of Cancer Biology at Mayo Clinic in Florida. "Our data provides evidence that MMP-10 plays a dual role in cancer. It stimulates the growth of cancer stem cells and stimulates their metastatic potential," he says. "This helps explain an observation that has been seen in cancer stem cells from many tumor types, namely that cancer stem cells appear to be not only the cells that initiate tumors, but also the cells that give rise to metastases." Dr. Fields says the findings were unexpected, for several reasons. The first is that the cancer stem cells express MMP-10 themselves, and use it for their own growth. Most of the known members of the matrix metalloproteinase genes are expressed in the tumor's microenvironment, the cells and tissue that surround a tumor, he says. The enzymes produced by these genes are involved in breaking down the microenvironment that keeps a tumor in place, allowing cancer cells to spread, which is why other genes in this family have been linked to cancer metastasis. "The fact that a gene like MMP-10, which codes for a matrix metalloproteinase that has been linked to metastasis, is actually required for the growth and maintenance of cancer stem cells is very surprising. One would not have predicted that such a gene would be involved in this process," Dr. Fields says.
JACKSONVILLE, Fla. — Mayo Clinic in Florida will be one of the first health care institutions in the United States to offer a newly approved device to treat gastroesophageal reflux disease (GERD). The condition, also known as acid reflux disease, can lead to serious health problems. VIDEO ALERT: Additional video resources, including excerpts from an interview with Dr. C. Daniel Smith describing the device and procedure, are available on the Mayo Clinic News Blog. The U.S. Food and Drug Administration (FDA) approved the device and treatment procedure on March 22 for patients with GERD who continue to have chronic reflux symptoms despite taking medication. Mayo Clinic in Florida expects to offer the new treatment immediately, says C. Daniel Smith, M.D., chair of the Surgery Department at Mayo Clinic in Florida, and an internationally recognized expert on the treatment of GERD. Dr. Smith is experienced in using the system because Mayo Clinic in Florida was one of only 14 centers nationally that participated in a clinical trial that led to the FDA's approval of the device. "Mayo has been a leader in the treatment of esophageal diseases, especially GERD, and we are pleased to be offering this new treatment to our patients immediately," he says. GERD is a condition in which liquid, or food, in the stomach flows back up into the esophagus due to the inability of a ring of muscle between the lower esophagus and the top of the stomach to close properly. If drugs aimed at neutralizing the acid in the stomach fails to prevent GERD, an operation designed to correct the mechanical defect is considered. But between 1.5 million and 2 million patients of those patients could benefit from treatment that is much less complex than current surgical options, Dr. Smith says. "The new system will offer a long-needed treatment option for a large group of underserved patients," he says. The results of the clinical study that led to approval of the device have not yet been published. But "the data presented to the FDA revealed striking results when compared to other GERD treatments that have been investigated over the past 20 years," Dr. Smith says. "The system offers effective control of GERD with limited side effects and thus far an excellent safety record." The implanted device is a ring of tiny magnetic titanium beads that is wrapped around the junction between the stomach and esophagus, serving as a mechanical augmentation of the lower esophageal sphincter (the ring of muscle). The magnetic attraction between the beads is strong enough to keep the sphincter closed to refluxing acid, but weak enough so that food can pass through it into the stomach, Dr. Smith says. The device can be implanted using minimally invasive surgery methods. Dr. Smith performs about 200 GERD-related surgeries a year and has been involved with many new treatments over the past several decades. "I expect this device to be a game changer for the treatment of GERD in select patients who have failed management with drugs," says Dr. Smith.
JACKSONVILLE, Fla. — April 10, 2012. Mayo Clinic researchers have discovered a new class of molecular mutation in various forms of breast cancer, a finding that may shed new light on development and growth of different types of breast tumors. Called fusion transcripts, the mutated forms of RNA may also provide a way to identify tumor subtypes and offer new strategies to treat them, investigators say. Their study, published in the April 15 issue of Cancer Research, is the first to systematically search for fusion genes and fusion transcripts linked to different types of breast tumors. Oncologists currently recognize three basic types of breast tumors — estrogen-receptor (ER)-positive, HER2-positive, and triple negative. "But breast cancer is much more complex than indicated by these three subtypes, and one of the challenges of treating the disease is to identify gene markers that predict how a tumor will respond to a specific treatment," says senior investigator Edith Perez, M.D., deputy director of the Mayo Clinic Comprehensive Cancer Center in Florida and director of the Breast Cancer Translational Genomics Program, which involves researchers at all three Mayo Clinic campuses. "The discovery of subtype-specific fusion transcripts in breast cancer represents a step in this direction," she says. "Our findings indicate that fusion transcripts are much more common in breast cancer than had been realized. They represent a new class of mutation whose role in breast cancer is not understood at all." "Fusion transcripts have the power to produce proteins that are relevant to tumor development, growth, and sensitivity to treatment, so we may have a brand new set of genomic changes that may help us understand, and treat, breast cancer in a new way," says E. Aubrey Thompson, Ph.D., professor of Biology at Mayo Clinic's Comprehensive Cancer Center, and co-director of the Breast Cancer Translational Genomics Program. "This is a novel discovery that will now require additional investigation," he says. "We need to understand what these fusion transcripts and proteins are doing." Fusion transcripts are created when chromosomes break apart and recombine, an event that commonly occurs in cancer cells. During this process, fusion genes are created when two halves of normal genes become linked. Fusion genes (DNA) create fusion transcripts (RNA), which then produce fusion proteins. "Mistakes are made," Dr. Thompson says. "That is one of the salient properties of tumor cells, because they are defective in repairing damage to their genes." "These mutated proteins may have an entirely new, cancer-promoting function, or they may interfere with normal cellular functions." Fusion transcripts are common in blood cancers, such as leukemia and lymphoma. Before this discovery, however, few were found in solid cancers such as breast tumors. Because fusion genes, transcript, and protein are generally found only in tumors, they make ideal biomarkers to identify tumor cells, Dr. Perez says.
JACKSONVILLE, Fla. — Findings of an extensive investigation at Mayo Clinic, published in the April 3 issue of the Annals of Internal Medicine, serve as a warning to other health care institutions that drug diversion by a health care worker can spread hepatitis C, a potentially fatal viral infection, to patients. The report details the effort that Mayo Clinic in Florida undertook to find the source of a genetically related hepatitis C virus that appeared in three patients over a 2 to 3 year period of time. Investigators eventually traced the source to a radiology technician who was using a portion of narcotics contained within syringes intended for patients, and then replacing the missing fluid with saline. The process contaminated the syringes with hepatitis C. Mayo Clinic then identified 3,929 patients who were at risk for exposure to hepatitis C, and invited them to be screened. Of the 3,444 patients who were tested, two additional cases of genetically related hepatitis C infection attributed to the employee were identified. The report, written by infectious disease experts and epidemiologists at Mayo Clinic, the Florida Department of Health, and the U.S. Centers for Disease Control and Prevention, is the most thoroughly documented instance of hepatitis C transmission caused by drug diversion in an American hospital or clinic, according to the report's lead author, Walter Hellinger, M.D., a health care epidemiologist. Four other instances have been reported to date in the United States and, of these, only one in which narcotic diversion was suspected but not confirmed has been published in a peer-reviewed medical journal, he says. "We owe our patients the best care possible, which meant conducting a thorough, investigation," says Dr. Hellinger, who also serves as chair of Infection Control at the Mayo Clinic campus in Florida.
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