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Like to eat meat? Consider this unappetizing truth: When you gulp down a nice juicy steak or hamburger, you are contributing to tumor-fueling inflammation in your body.In fact, eating a diet rich in red meat has long been linked to a host of ills including an increased risk of several types of cancer. But what is it about meat consumption that could impact cancer growth? Now scientists at the University of California, San Diego School of Medicine, have found a mechanism that explains how eating red meat, as well as milk, could spur the growth of malignancies. The new study, headed by Ajit Varki, M.D., suggests that inflammation resulting from a molecule introduced through eating these foods could make cancer grow. The research is set for upcoming publication in the Proceedings of the National Academy of Sciences (PNAS).Dr.Varki, UC San Diego School of Medicine distinguished professor of medicine and cellular and molecular medicine and co-director of the UCSD Glycobiology Research and Training Center, and his research team studied a non-human glycan, or sugar molecule, known as N-glycolylneuraminic acid (Neu5Gc). Although this molecule is not produced naturally in the human body, it’s incorporated into human tissues if you eat red meat. The body then develops antibodies against Neu5Gc – and this immune response could potentially trigger a low-grade chronic inflammation, spurring the growth of cancer. In a statement prepared for the media, Dr. Varki explained it has been recognized by scientists for some time that chronic inflammation can stimulate cancer progression."We've shown that tumor tissues contain much more Neu5Gc than is usually found in normal human tissues. We therefore surmised that Neu5Gc must somehow benefit tumors,” Dr. Varki said in the press statement. So the scientists came up with this hypothesis: The fact that Neu5Gc accumulates in human tumors despite circulating anti-Neu5Gc antibodies suggests a low-grade, chronic inflammation has developed, and caused the tumor to grow. To test this idea, the researchers worked with specially bred mice. The animals lacked the Neu5Gc molecule , just as humans do before they eat red meat and the molecule is absorbed into their bodies, and they had tumors.Anti-Neu5Gc antibodies were given to half of the mice . In those animals, the antibodies induced inflammation and their cancers started growing faster. In the control group comprised of mice that were not treated with antibodies, their tumor growth was far less aggressive.Building on previous research that has shown that humans who take non-steroidal anti-inflammatory drugs (commonly known as NSAIDs) have a reduced risk of cancer, the researchers tried giving NSAIDs to the mice with cancerous tumors fueled by anti-Neu5Gc antibodies. The result? The anti-inflammatory treatment blocked the effect of the Neu5Gc antibodies and the tumors became smaller."Taken together, our data indicate that chronic inflammation results from interaction of Neu5Gc accumulated in our bodies from eating red meat with the antibodies that circulate as an immune response to this non-human molecule – and this may contribute to cancer risk," Varki said in the media statement.For anyone interested in reducing inflammation through natural, non-drug methods, here are seven top strategies to incorporate into your lifestyle:1. Stop eating meat and dairy products.2. Concentrate on a Mediterranean flavored style of eating with lots of fruits, vegetables, whole grains , olive oils and nuts. Research has shown these foods lower inflammation levels.3. Don’t smoke and avoid those who do – second hand smoke can contribute to inflammation.4. Know your oils. Avoid all inflammation-causing trans-fats, hydrogenated and partially hydrogenated oils as well as saturated animal fats. Instead, add inflammation-fighting omega-3 oils like flaxseed, canola and walnut oil to your diet.5. Lose weight if you need to. Research has shown that a waist that measures over 40 inches in a man or over 35 inches in a woman is a sign of probable high inflammation.6. Don’t skimp on sleep. Previous studies have concluded less than six hours of sleep can result in inflammation .7. De-stress. Try yoga, meditation, walking and other forms of exercise. Staying continually stressed out means your body is releasing excess, inflammation-promoting stress hormones . Schedule a minimum of 20 minutes a day to let your worries go.

US and Israeli scientists have found evidence that a family history of brain cancer may increase a person's chances of developing the disease.
Researchers at the University of Utah and Tel Aviv University analysed the medical records of nearly 1,500 people from Utah and tracked back for between three and ten generations of family members.
Their findings are published in the journal Neurology.
They found that a family history of brain tumours - including the aggressive glioblastoma - increases a person's likelihood of developing the disease, sometimes as much as fourfold.
Dr Deborah Blumenthal, co-director of Tel Aviv University's Neuro-oncology Service and an affiliate associate professor at the University of Utah Huntsman Cancer Institute, said that the study is unique as it was able to track genealogy records back so far.
She recommended that people with a family history of brain cancer should report this to their family doctor at routine medical checks.
"Until now, brain tumours were not thought to be an inheritable disease," said Dr Blumenthal. "A few earlier studies did find an increased risk in immediate relatives, but in such cases it is hard to distinguish between the effects of a shared environment and heredity."
However, Dr Blumenthal emphasised that the risks of having a hereditary brain tumour are still "very low" as the majority of primary brain tumours are not inheritable.
Less than five per cent of rare primary brain tumours are hereditary and the risk of inheriting genes that may increase the risk of a brain tumour is therefore low.
She explained: "Reporting to your family doctor that brain cancer runs in the family just gives a more comprehensive picture of your medical history. It may provide doctors and family members with useful information."
The researchers now hope to use blood and tissue samples from high-risk families to try to identify genes associated with brain tumours so that, in future, it may be possible to screen people with a family history of the disease and identify those whose genes place them at greater risk

Cancer Genetics: Massive cancer gene search finds potential new targets in brain tumors

Results validate ambitious NIH-funded project to uncover cancer mutationsBOSTON--An array of broken, missing, and overactive genes -- some implicated for the first time -- have been identified in a genetic survey of glioblastoma, the most common and deadly form of adult brain cancer, report scientists from Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard, together with their collaborating investigators at 18 institutions and organizations.The large-scale combing of the brain cancer genome confirms the key roles of some previously known mutated genes and implicates a variety of other genetic changes that may be targets for future therapies.The findings, posted online by Nature on Thursday, Sept. 4, help solidify and expand the "parts list" of genetic flaws linked to glioblastoma multiforme (GBM), the incurable brain tumor that Sen. Edward M. Kennedy is battling. Lynda Chin, MD, at Dana-Farber and Harvard Medical School (HMS) and Matthew Meyerson, MD, PhD, at Dana-Farber, HMS, and Broad, co-led the writing effort for the first summary of data from the $100 million pilot project of The Cancer Genome Atlas (TCGA), funded by the National Institutes of Health (NIH). The data are released to the public at TCGA's website as they are generated.Systematic multi-dimensional genomic studies of patient samples of glioblastoma began in 2006 as the first TCGA program. The pilot is designed to determine the feasibility of a full-scale effort to systematically explore the universe of genomic changes involved in all types of human cancer and to demonstrate the values of such efforts in advancing cancer research and improving patient care.The current report in Nature summarizes the interim analyses of data gathered in the GBM pilot study. "The findings of significant mutations in genes that have implications for therapeutic development illustrate precisely how unbiased and systematic cancer genome analyses can lead to paradigm-shifting discoveries," said Chin, who chairs the GBM disease working group within TCGA.An exciting example, Chin said, is an unanticipated observation of a link between DNA methylation of specific genes and DNA repair defects, leading to a hypothesis about a potential mechanism of resistance to a common chemotherapy drug used for brain cancer.The Nature paper complements a parallel study by Johns Hopkins researchers of 22 GBM tumors, which was also published on Sept. 4 in the journal Science."These data show that this approach, of looking at large numbers of tumors and a large number of genetic factors, can be done and the results are really valuable," said Meyerson. "We have made significant novel findings, and the reproducibility of the data is high."Collaborating teams analyzed 206 specimens of glioblastoma tissue donated by patients at four medical centers. Their approach was "multidimensional" -- looking for several categories of flaws simultaneously. These included mutations -- "typos" in the DNA code of a gene that alters its function; too many or too few copies of a given gene; damage to chromosomes causing loss or dislocation of pieces; gene activity that is higher or lower than normal; and changes in DNA methylation -- turning genes on or off without affecting their structure.The researchers also had access to information on how the patients who donated the samples had fared, including how they responded to certain drugs.Automated machines at three Genome Sequencing Centers, including the Broad Institute center led by Eric S. Lander, Broad Institute director, were set to work reading the DNA messages in the cancer cells' nuclei. Of the roughly 20,000 protein-coding genes in the tumor cells, 601 genes were selected by the GBM disease working group for detailed sequencing -- determining the order of chemical "letters" in the DNA -- and comparison. A second installment of genes is already being sequenced, and Chin and her group are working on additional gene lists for mutational analyses.Five major gene mutations have previously been identified in glioblastoma cells; the new sequencing effort revealed three that hadn't been discovered. One mutation affects the NF1 gene, which causes neurofibromatosis. A second mutation is in the ERBB2 gene known to be involved in breast cancer. The third affects a gene in the PIK3 signaling pathway that is abnormally activated in a number of cancers, but this particular gene, PIK3R1, had been only rarely implicated in any cancer. "Each of these mutated genes defines a new target for glioblastoma treatment," said Meyerson.As they examined the data, the researchers found that three signaling pathways -- networks of genes and proteins that act together to carry out a cellular function -- were disrupted in more than three-quarters of the GBM tumors. They are known as the cyclin-dependent kinase/retinoblastoma pathway that regulates cell division; the p53 tumor suppressor pathway, which is involved in response to DNA damage and cell death; and the receptor tyrosine kinase pathway that carries signals that control cell growth.Chin said that the most exciting finding is that this multipronged study design also enabled the scientists to make a potentially important connection between a methylation change in the glioblastoma cells and which drugs should be used for treatment. Brain tumors that contain a methylated, or silenced, form of a gene known as MGMT are known to be more susceptible to cancer drug temozolomide (Temodar). Therefore, Temodar is routinely given along with radiation to patients with MGMT methylation.But the analysis of methylation in the glioblastoma tumors, when matched with the patients' medical history, revealed a cautionary sign. When such patients were treated with Temodar and subsequently had a recurrence of the tumor, it was very likely to become resistant to treatment because of "hypermutation" -- an increased rate of gene changes that led to the tumor's ability to evade the drugs."This could have immediate clinical applications," said Chin.The discoveries in the paper are only the tip of an expected iceberg, said the authors. The "most powerful impact" is expected to come from further research studies carried out by scientists who make use of the data released freely by TCGA, they said.More than 21,000 new cases of brain cancer are expected to be diagnosed in the United States this year, and more than 13,000 people are likely to die from the disease."These impressive results from TCGA provide the most comprehensive view to date of the complicated genomic landscape of this deadly cancer," said NIH Director Elias A. Zerhouni, M.D. "The more we learn about the molecular basis of glioblastoma multiforme, the more swiftly we can develop better ways of helping patients with this terrible disease. Clearly, we should move ahead and apply the power of large-scale, genomic research to many other types of cancer."Chin is co-principal investigator of a TCGA center with Raju Kucherlapati of HMS, and Meyerson is principal investigator of a TCGA Cancer Genome Characterization Center at the Broad Institute. Chin is the scientific director of the Belfer Cancer Genomics Center in the Center for Applied Cancer Science at Dana-Farber, and Meyerson directs the Center for Cancer Genome Discovery at Dana-Farber.The research was funded by grants from the NIH.Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.The Broad Institute of MIT and Harvard was founded in 2003 to bring the power of genomics to biomedicine. It pursues this mission by empowering creative scientists to construct new and robust tools for genomic medicine, to make them accessible to the global scientific community, and to apply them to the understanding and treatment of disease. The Institute is a research collaboration that involves faculty, professional staff and students from throughout the MIT and Harvard academic and medical communities. It is jointly governed by the two universities. Organized around Scientific Programs and Scientific Platforms, the unique structure of the Broad Institute enables scientists to collaborate on transformative projects across many scientific and medical disciplines. For further information about the Broad Institute, go to http://www.broad.mit.edu.

Researchers Find Mechanism To Target Brain Tumor Cells

Researchers at Duke University Medical Center and the University of North Carolina, Chapel Hill are exploiting an "Achilles Heel" of brain tumors that may selectively kill tumor cells while sparing surrounding brain tissue. Although most cancer cells thrive by avoiding the normal process of programmed cell death, or apoptosis, the researchers found a way to turn this normal cell suicide way up for brain cancer cells. "In collaboration with Dr. Deshmukh's lab at UNC, we attempted to come up with a way to specifically target tumor cells without damaging surrounding cells," said Sally Kornbluth, Ph.D., Professor of Pharmacology and Cell Biology and Vice Dean of Basic Sciences. In addition to turning off normal cell death, brain cancers, such as glioblastomas and medulloblastomas, are generally resistant to traditional chemotherapy. And chemotherapy and radiation can also lead to significant neurological defects because they kill both cancerous and healthy brain. In their study, published in the December issue of the Proceedings of the National Academy of Sciences, the researchers found that brain tumor cells are particularly sensitive to a protein called cytochrome c, which is involved in programmed cell death. Because of this difference, lab-cultured, human brain tumor cells treated with cytochrome c were killed, while mature neurons were not affected. "This work highlights a previously unappreciated vulnerability within tumor cells. It also suggests a powerful technique by which new chemotherapeutic agents could act," Kornbluth said. "Apoptosis could be induced within brain tumors by small molecules that mimic cytochrome c," said Mohanish Deshmukh of UNC, co-seniorauthor of the study. All types of brain tumors appear to share this vulnerability, Kornbluth said. The next step toward a real-world treatment would be to determine how to deliver cytochrome c directly to brain cells without affecting other cells in the body. Indeed, much of conventional chemotherapy's more debilitating side effects, including extreme fatigue and low blood-cell counts, come from the inadvertent elimination of healthy cells. The study was supported by grants from the National Institutes of Health and the Pediatric Brain Tumor Foundation.

Cancer Stem Cells Linked to Radiation Resistance

Information courtesy of Duke University Medical Center News Office

DURHAM, N.C. - Certain types of brain cancer cells, called cancer stem cells, help brain tumors to buffer themselves against radiation treatment by activating a "repair switch" that enables them to continue to grow unchecked, researchers at Duke University Medical Center have found. The researchers also identified a method that appears to block the cells' ability to activate the repair switch following radiation treatment. This finding may lead to the development of therapies for overcoming radiation resistance in brain cancer as well as other types of cancer, the researchers said. Working with animal and cell culture models, the researchers found that a specific cellular process called the "DNA damage checkpoint response" appears to enable cancer stem cells to survive exposure to radiation and to switch on a signal to automatically repair any damage caused to their DNA. "In recent years, people have hypothesized that cancer stem cells are responsible for the resistance of malignant tumors to radiation treatment," said Jeremy Rich, M.D., senior investigator of the study and an associate professor of neurology at Duke. "We have shown, for the first time, that this is indeed the case." The findings appear Oct. 18, 2006, in the advance online edition of the journal Nature. The research was supported by the National Institutes of Health and a number of philanthropic organizations [complete list below]. The type of cancer that the researchers studied, glioblastoma, is highly resistant to radiation and other forms of treatment and is the most deadly form of brain cancer worldwide. Although aggressive treatments can destroy the majority of the cancerous cells, a small fraction of them remain and often regenerate into even larger masses of tumor cells. Until recently, scientists knew little about what made these resistant cells different from those that succumb to radiation treatment. It was clear, however, that the cells shared characteristics similar to those of normally functioning nerve stem cells, Rich said. In the current study, the researchers used glioblastoma tissue removed from patients during neurosurgery and created two separate models. For one model, the researchers extracted cells from the tissue and grew them in cultures in the laboratory. For the second model, they transplanted the glioblastoma tissue into the frontal lobes of the brains of mice. The researchers first measured the number of glioma stem cells present in the original tissue and then administered set doses of ionizing radiation to the cell cultures and to the mice. In both cases, the researchers observed a roughly fourfold jump in the number of glioma stem cells present in the tumor tissue following radiation treatment. Because ionizing radiation works primarily by causing permanent damage to the key genetic material of cells, DNA, the researchers hypothesized that the glioma stem cells survive and multiply by somehow fixing radiation-induced DNA damage better than the other cancer cells. To test this, the researchers searched the tissue samples for specific proteins that are responsible for detecting DNA damage. Using cell samples taken from both study models, the team examined the DNA damage checkpoint response both before and after use of ionizing radiation treatments by testing for activation of the key proteins that detect DNA damage. The researchers wanted to know whether the cells, following exposure to radiation treatment, would repair the DNA damage by activating the checkpoint response or whether they would instead die. The team found that after ionizing radiation, the DNA damage checkpoint proteins in glioma stem cells were more highly activated than in other cancer cells. This heightened activation, the researchers said, leads cancer stem cells to more effectively repair DNA damage and thus render the cells less likely to die as a result of the treatment. In another set of experiments, the researchers treated both the test animals and the cell cultures with a drug, called debromohymenialdisine, which is known to inhibit the proteins involved in the activation process. They added the drug before and after radiation treatment and measured the number of surviving cancer stem cells. They found that administering the drug before radiation did little to change the number of cancer stem cells, but giving the drug in conjunction with radiation appeared to halt the resistance of cancer stem cells to radiation. This finding, the researchers said, suggests that use of a checkpoint inhibitor during radiation ruins the cells' potential to repair themselves and increases the likelihood that the cells will die. "Our findings show one pathway in cancer stem cells that promotes the radiation resistance of glioblastomas," said Rich. "Treatments that target DNA damage checkpoint response in cancer stem cells may overcome the radiation resistance and eventually allow us to help even greater numbers of cancer patients." Other researchers involved in the study were Shideng Bao, Qiulian Wu, Roger McLendon, Yueling Hao, Qing Shi, Anita Hjelmeland, Mark Dewhirst and Darell Bigner. The philanthropic organizations that supported the research include the Childhood Brain Tumor Foundation, the Pediatric Brain Tumor Foundation of the United States, the Damon Runyon Cancer Research Foundation, the Sidney Kimmel Foundation for Cancer Research, Accelerate Brain Cancer Cure, and the Duke Comprehensive Cancer Center Stem Cell Initiative.