Cancer

JACKSONVILLE, Fla. — May 17, 2012.  By simply shining a tiny light within the small intestine, close to that organ's junction with the pancreas, physicians at Mayo Clinic's campus in Florida have been able to detect pancreatic cancer 100 percent of the time in a small study. The light, attached to a probe, measures changes in cells and blood vessels in the small intestine produced by a growing cancer in the adjoining pancreas. VIDEO ALERT: Video of Dr. Michael Wallace discussing the study is available on the Mayo Clinic News Network, our new method for delivering embargoed media content. The network requires a username and password, which can be obtained at http://NewsNetwork.MayoClinic.org. Learn about this new network by watching this short video. This minimally invasive technique, called Polarization Gating Spectroscopy, will now be tested in a much larger international clinical trial led by the Mayo Clinic researchers. The preliminary study suggests it may be possible, one day, to use a less invasive endoscope to screen patients for early development of pancreatic cancer. The findings are being highlighted in a special address by Mayo Clinic gastroenterologist Michael Wallace, M.D., at the international Digestive Disease Week 2012, the world's largest gathering of physicians and researchers who treat, and study, disorders of the gastrointestinal tract. The pancreas is notoriously hard to reach and see due to its very deep location in the abdomen, surrounded by intestines. The study investigators theorized that there may be changes in the nearby "normal appearing" tissue of the small intestine which is much more accessible. "No one ever thought you could detect pancreatic cancer in an area that is somewhat remote from the pancreas, but this study suggests it may be possible," says Dr. Wallace, the chairman of the Division of Gastroenterology at Mayo Clinic in Florida. "Although results are still preliminary, the concept of detection field effects of nearby cancers holds great promise for possible early detection of pancreatic cancer." Pancreatic cancer is one of the most deadly of human tumors. It is only curable in 5 percent of cases, and even when it is surgically removed, 70 percent of patients have a recurrence that is fatal, Dr. Wallace says. There are no ways currently to detect the cancer early enough to cure a substantial number of patients, he says. Pancreatic cancer is now usually detected through an imaging scan, followed by an invasive biopsy. Tumors found in this way are usually at an advanced stage. In this study, the Mayo Clinic physicians tested a light probe developed by their long-time collaborators at Northwestern University.

Shining a tiny light in the small intestine, close to where it meets with the pancreas, can help detect pancreatic cancer.  In a small study at the Mayo ...

ROCHESTER, Minn. — The 25th annual National Cancer Survivors Day event will be held on Sunday, June 3, 2012. The event is sponsored by Mayo ...

The “on-off” switches of genes that occur early in the development of prostate cancer could be used as biomarkers to detect the disease months or even ...

ROCHESTER, Minn. — May 14, 2012.  Alterations to the "on-off" switches of genes occur early in the development of prostate cancer and could be used as biomarkers to detect the disease months or even years earlier than current approaches, a Mayo Clinic study has found. These biomarkers — known as DNA methylation profiles — also can predict if the cancer is going to recur and if that recurrence will remain localized to the prostate or, instead, spread to other organs. The study, published in the journal <ahref="http://www.aacr.org/home/scientists/meetings--workshops/educational-workshops--special-courses.aspx?utm_source=googlegr&utm_medium=searchad&utm_campaign=2012workshops"> Clinical Cancer Research, is the first to capture the methylation changes that occur across the entire human genome in prostate cancer. MULTIMEDIA ALERT: Video of interview excerpts is available on the Mayo Clinic News Network. The discovery could someday help physicians diagnose prostate cancer earlier and make more effective treatment decisions to improve cure rates and reduce deaths. It also points to the development of new drugs that reverse the DNA methylation changes, turning the "off" switch back "on" and returning the genetic code to its normal, noncancerous state. "Our approach is more accurate and reliable than the widely used PSA (prostate-specific antigen) test," says senior author <ahref="http://mayoresearch.mayo.edu/mayo/research/staff/Donkena_KV.cfm"> Krishna Donkena, Ph.D., a Mayo Clinic molecular biologist. The PSA test detects any prostate abnormality, whether inflammation, cancer, infection or enlargement, while the DNA methylation changes are specific to prostate cancer, she says. Though the instructions for all the cell's activities lie within the genes, whether a particular gene is turned "off" or "on" is determined by the presence or absence of specific chemical tags or methyl groups — methylation — along the underlying DNA of cells. When this process of DNA methylation turns off the activity of tumor suppressor genes, cancer develops. Dr. Donkena and her colleagues analyzed the methylation status of 14,495 genes from 238 prostate cancer patients. The patients included people who remained cancer-free after treatment, those who had a localized tumor recurrence and those whose cancer spread. The researchers found that the DNA methylation changes that occurred during the earliest stages of prostate cancer development were nearly identical in all patients. Having discovered DNA methylation patterns that could distinguish between healthy and cancerous tissue, the researchers then searched for similar biomarkers that could distinguish between patients with varying levels of recurrence risk. They found distinct methylation alterations that corresponded to whether a patient had a slow-growing tumor known as an indolent tumor, or had a more aggressive one.

Instead of stimulating immune cells to battle cancerous tumors, treatment with a protein called interleukin-12 (IL-12) is having the opposite effect, driving the cells to exhaustion. The results ...

ROCHESTER, Minn. — May 9, 2012.  Rather than stimulating immune cells to more effectively battle cancerous tumors, treatment with the protein interleukin-12 (IL-12) has the opposite effect, driving these intracellular fighters to exhaustion, a Mayo Clinic study has found. The findings appear in the Journal of Clinical Investigation. The study helps explain the negative results of clinical trials testing the treatment's ability to ramp up the body's natural immune response to destroy cancer cells. The study also demonstrates that the same "T cell exhaustion" that plagues specialized immune cells during chronic viral infections also affects cells fighting long bouts of cancer. MULTIMEDIA ALERT:: Video of interview excerpts is available on the Mayo Clinic News Network. The results suggest a change in therapeutic tactics for lymphomas and other cancers by dampening, rather than fueling, the effects of cell-signaling molecules such as IL-12. The study focused on a type of cancer called Follicular B-cell non-Hodgkin's lymphoma (FL), the second most frequent type of non-Hodgkin's lymphoma. Previously, senior author Stephen Ansell, M.D., Ph.D., a Mayo Clinic hematologist, had shown that tumors biopsied from patients with FL and other similar cancers are a 50-50 mixture of cancer cells and immune cells. Although those immune cells are genetically programmed to kill cancer, instead, they seemed content to cohabitate with their deadly neighbors. Dr. Ansell wondered if a phenomenon known as T cell exhaustion may be the cause. The study findings suggest it is. "It is like beating a dead horse," says Dr. Ansell. "Our study suggests that many immunotherapy approaches are futile, because these cells are already past the point where they can do their job of targeting and killing malignant cells. Before we can stimulate the immune system, we have to reverse this state of exhaustion so the body's T cells can get back to work." T cell exhaustion was discovered a few years ago in the context of chronic viral infections such as cytomegalovirus (CMV), hepatitis and HIV. Researchers found that constant unrelenting combat with these viruses caused a key contingent of the immune response, known as T cells, to wear out. Even when artificially stimulated, these exhausted cells were unable to proliferate, recruit other members of the immune army, or kill enemy cells. In addition, these T cells began to carry cellular marks of exhaustion, most notably the cell surface proteins PD1 and Tim-3. In this study, Dr. Ansell and his colleagues tested whether exposing isolated human T cells to IL-12 would induce T cell exhaustion. They found that treatment with IL-12 brought the Tim-3 marker of exhaustion to the cell surface. When they tried experimentally to stimulate those immune cells into action, they discovered that the T cells couldn't proliferate and couldn't make the immune system signaling molecules known as cytokines.

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.

A new class of molecular mutation, in various forms of breast cancer, has been discovered by Mayo Clinic researchers in Florida.   This finding may shed new ...

MEDIA ALERT: Experts Discuss Emotional Coping Strategies for Survivors There are more than 11 million cancer survivors in the United States, and during April, which is National ...

ROCHESTER, Minn. — April is National Cancer Control Month, which focuses on the prevention, detection, and treatment of cancer and on efforts to improve the ...

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.