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Archive - Nov 2013

November 7th

Harvard Study Associates Nut Consumption with Reduced Pancreatic Cancer Risk in Women

In a large prospective study published online on October 22, 2013 in the British Journal of Cancer, researchers looked at the association between nut consumption and risk of pancreatic cancer among 75,680 women in the Nurses' Health Study, with no previous history of cancer. Consumption of nuts, including tree nuts (such as almonds, Brazil nuts, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios, and walnuts), was inversely associated with risk of pancreatic cancer, independent of other potential risk factors for pancreatic cancer. Women who consumed a one-ounce serving of nuts two or more times per week had a significantly reduced risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47-0.92; P=0.007) compared to those who largely abstained from nuts. "This reduction in risk was independent of established or suspected risk factors for pancreatic cancer including age, height, obesity, physical activity, smoking, diabetes, and dietary factors," stated lead author, Ying Bao, M.D., Sc.D., from the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School. Pancreatic cancer is the fourth most common cause for cancer-related mortality in the U.S., yet very few modifiable risk factors have been identified. According to the 2009 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) report, aside from cigarette smoking, body fatness was the only convincing modifiable risk factor for pancreatic cancer. While there may be concern that frequent nut consumption may result in weight gain and thereby increase the risk of developing pancreatic cancer, the opposite seems to be true. "In our cohort, women who consumed the most nuts tended to weigh less," reported Dr. Bao. Moreover, in a recent analysis of this same cohort, higher nut consumption was associated with a slightly lower risk of weight gain and obesity.

Drug-Filled Nanoparticles Can Overcome Drug Resistance in Breast Cancer Cells

Nanoparticles filled with chemotherapeutic drugs can kill drug-resistant breast cancer cells, according to an open-access study published online on November 6, 2013 in Biomaterials. Nanoparticles are just as small, or even smaller, than many blood proteins. They can therefore pass through the walls of healthy and sick cells, which make them interesting carriers of drugs against cancer and other diseases. In the present study, researchers from the Karolinska Institutet in Sweden have shown that nanoparticles made from biodegradable plastics can overcome drug resistance in breast cancer cells. Such resistance is especially common in relapsing cancer patients and depresses, even neutralizes, the effect of the therapy against the tumour in many instances. In their experiments, the researchers used breast cancer cells that responded poorly to drugs owing to their high concentrations of the enzyme microsomal glutathione S-transferase-1 (MGST-1). Abnormally high levels of MGST-1 have been associated with poor responses to several cancer drugs. The team treated the resistant breast cancer cells with nanoparticles filled with doxorubicin, a chemotherapeutic used clinically to treat bladder, lung, ovarian, and breast cancers, amongst others. "Our experiments on cultivated cells showed that the particles themselves are harmless," says research team member Dr. Andreas Nyström, Associate Professor at the Institute of Environmental Medicine, Karolinska Institutet. "We made it possible for the nanoparticles carrying the drug to kill resistant cancer cells by controlling where in the cancer cell they delivered their payload.

November 6th

Research Reveals Possible Cause of Diabetic Cardiomyopathy

Researchers from the University of Texas Medical Branch (UTMB) at Galveston have discovered one of the pathogenic components of diabetes in the heart, as published onine on October 22, 2013 in the Journal of Biological Chemistry. While both heart disease and diabetes are widely studied, how diabetic cardiomyopathy develops is not well understood, other than that it seemed to be linked to protein kinase C (PKC) — a family of enzymes that controls the functions of other proteins by using phosphates to turn them on and off. Researchers at UTMB, led by assistant professor of biochemistry Dr. Muge Kuyumcu-Martinez, studied the effects of PKC signals in the hearts of diabetic mice. "We now know that the leading cause of diabetic cardiomyopathy can be attributed to PKC activation and its downstream effects on gene expression," said Dr. Kuyumcu-Martinez. "Knowing how cardiomyopathy manifests, further research can use these results to concentrate on the prevention and treatment of heart failure in diabetics." Cardiomyopathy, a known symptom of diabetes, occurs when the muscles of the heart weaken, and the heart is no longer strong enough to pump blood and properly circulate it throughout the body. Adults with diabetes are two to four times more likely to die of heart failure than the rest of the population. The researchers discovered that when PKC is over-activated, the cells of the adult heart revert to splicing methods used during the embryonic stages. Genes contain codes for certain processes and products, such as proteins, and they send signals to the body to complete these processes and products through messenger RNA. Alternative splicing occurs when one gene contains the codes for multiple proteins.

Genetic Aberration in TOP2A Paves the Way for New, Potentially Rapidly Implemented Treatment for Some Colorectal Cancer Patients

Researchers from the Faculty of Health and Medical Sciences, University of Copenhagen, have characterized a genetic aberration in a group of colorectal cancer patients. The discovery gives hope for a new and efficient treatment of colorectal cancer, which is a frequent and often fatal disease. The research was recently published online on October 21, 2013 in the Scandinavian Journal of Gastroenterology. Approximately 600,000 patients die of colorectal cancer each year worldwide. 12-15 years of development and millions of dollars are typically the costs, when companies develop a new anti-cancer drug. Therefore all short-cuts to a treatment are welcome. Researchers at Department of Veterinary Disease Biology, University of Copenhagen, recently discovered such a potential short-cut. “Our new research shows that we might be able to introduce a treatment faster and cheaper than usual in the development of cancer treatment, and we estimate that it will be efficient in around 10 per cent of patients with colorectal cancer," says M.D. and Ph.D. student Sune Nygård, Department of Veterinary Disease Biology, University of Copenhagen. In the new study, the researchers have shown that approximately 10 per cent of colorectal cancer patients harbor an aberration in the gene called TOP2A (DNA topoisomerase 2-) in their cancer cells. These tumors could potentially benefit from treatment with a specific chemotherapeutic drug, a so-called “anti-TOP2A treatment,” which is already used in breast cancer patients with this gene aberration. “If the first treatment doesn’t cure a patient with colorectal cancer, the possibilities of additional treatment are limited,” says Nils Brünner, M.D., professor at the University of Copenhagen. “Therefore it is very important to find a new, efficient treatment,” he adds.

November 5th

Study Links Intestinal Bacteria to Rheumatoid Arthritis

Researchers have linked a species of intestinal bacteria known as Prevotella copri to the onset of rheumatoid arthritis, the first demonstration in humans that the chronic inflammatory joint disease may be mediated in part by specific intestinal bacteria. The new findings by laboratory scientists and clinical researchers in rheumatology at the New York University (NYU) School of Medicine add to the growing evidence that the trillions of microbes in our body play an important role in regulating our health. Using sophisticated DNA analysis to compare gut bacteria from fecal samples of patients with rheumatoid arthritis and healthy individuals, the researchers found that P. copri was more abundant in patients newly diagnosed with rheumatoid arthritis than in healthy individuals or patients with chronic, treated rheumatoid arthritis. Moreover, the overgrowth of P. copri was associated with fewer beneficial gut bacteria belonging to the genera Bacteroides."Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases," says Dan R. Littman, M.D., Ph.D., the Helen L. and Martin S. Kimmel Professor of Pathology and Microbiology at NYU School of Medicine and a Howard Hughes Medical Institute investigator. "Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association," says Dr. Littman, whose basic science laboratory at NYU School of Medicine's Skirball Institute of Biomolecular Medicine collaborated with clinical investigators led by Steven Abramson, M.D., senior vice president and vice dean for education, faculty, and academic affairs; the Frederick H.

“Zone in with Zon”—Aptamers May Be Superior to Antibodies

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated November 4, 2013, and published by TriLink BioTechnologies of San Diego, suggests that aptamers may actually be superior to Mother Nature’s antibodies. Dr. Zon said that aptamers were first discovered approximately 20 years ago and are nucleic acids or peptides that bind to a specific target molecule. RNA or DNA aptamers are usually created from a large pool (library) of random sequences. However, he also pointed out that natural RNA aptamers exist in riboswitches. Dr. Zon noted that aptamers have “been used for an impressively wide variety of applications in either basic research or, especially, health-related diagnostics and therapeutics. This remarkable utility is clearly reflected in the publication statistics—since their discovery in 1990, there have been ~11,000 publications indexed to DNA or RNA aptamers in SciFinder with a projected average rate of ~5 per day in 2013! More than 1,600 of these publications are patents, which is a stunning testament to the commercial potential of aptamers.” Dr. Zon went on to describe how in 1990, two independent laboratories separately described different methods for RNA selection, without using an RNA replicase. One method was published in Science by Drs. Craig Turk and Larry Gold, and the other was published in Nature by Drs. Andrew D. Ellington and Jack W. Szostak Dr. Zon went on to note that the vast body of literature covering basic research and numerous applications of nucleic acid aptamers is a stunning testament to the enabling power of these molecules, and to the myriad of expanded types of aptamers and aptamer-generation methods.

How Pigeons May Smell Their Way Home

Homing pigeons, like other birds, are extraordinary navigators, but how they manage to find their way back to their lofts is still debated. To navigate, birds require a ‘map’ (to tell them home is south, for example) and a ‘compass’ (to tell them where south is), with the sun and the Earth’s magnetic field being the preferred compass systems. A new paper provides evidence that the information pigeons use as a map is in fact available in the atmosphere: odors and winds allow them to find their way home. The results were published online on November 4, 2013 in Biogeosciences, an open-access journal of the European Geosciences Union (EGU). Experiments over the past 40 years have shown that homing pigeons get disoriented when their sense of smell is impaired or when they don’t have access to natural winds at their home site. But many researchers were not convinced that wind-borne odors could provide the map pigeons need to navigate. Now, Dr. Hans Wallraff of the Max Planck Institute for Ornithology in Seewiesen, Germany, has shown that the atmosphere does contain the necessary information to help pigeons find their way home. In previous research, Dr. Wallraff collected air samples at over 90 sites within a 200 km radius around a former pigeon loft near Würzburg in southern Germany. The samples revealed that the ratios among certain ‘volatile organic compounds’ (chemicals that can be a source of scents and odors) in the atmosphere increase or decrease along specific directions. “For instance, the percentage of compound A in the sum A+B or A+B+C+D increases the farther one moves from north to south,” Dr. Wallraff explains. These changes in compound ratios translate into changes in perceived smell. But a pigeon that has never left its loft does not know in what directions what changes occur – unless it has been exposed to winds at its home site.

November 4th

Mutated Gene for Rare Hereditary Cancer Syndrome Also Disrupts Critical Growth-Regulating Pathway

Whitehead Institute scientists report that the gene mutated in the rare hereditary disorder known as Birt-Hogg-Dubé cancer syndrome also prevents activation of mTORC1, a critical nutrient-sensing and growth-regulating cellular pathway. This is an unexpected finding, as some cancers keep this pathway turned on to fuel their unchecked growth and expansion. In the case of Birt-Hogg-Dubé syndrome, the mutated gene prevents mTORC1 pathway activation early in the formation of tumors. Reconciling these opposing roles may give scientists a new perspective on how cancer cells can distort normal cellular functions to maintain their own harmful ways. Cells use the mTORC1 (an abbreviation for "mechanistic target of rapamycin complex 1") pathway to regulate growth in response to the availability of certain nutrients, including amino acids. Whitehead Member Dr. David Sabatini and other researchers have teased apart many components of this pathway, but the precise mechanism by which nutrient levels are actually sensed has remained elusive. Recently, Dr. Sabatini and his lab determined that a family of proteins known as Rag GTPases act as a switch for the pathway—when nutrients are present, the Rag proteins turn on the mTORC1 pathway. Now, several members of the Sabatini lab, including graduate student Zhi-Yang Tsun, have determined that the FLCN (folliculin) protein acts as a trigger to activate the Rag protein switch. Their work was published online on October 3, 2013 in Molecular Cell. "Zhi has ascribed a molecular function to this protein, and that's a major contribution," says Dr. Sabatini, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. "For the first time, we have a biochemical function that's associated with it.

New Method to Create Membrane Pores with DNA Nanotechnology

A new way to build membrane-crossing pores, using Lego-like DNA building blocks, has been developed by scientists at University College London (UCL), in collaboration with colleagues at the University of Cambridge and the University of Southampton. The approach provides a simple and low-cost tool for synthetic biology and the technique has potential applications in diagnostic devices and drug discovery. The research was published online on October 2, 2013 in Angewandte Chemie. Membrane pores are the gateways controlling the transport of essential molecules across the otherwise impermeable membranes that surround cells in living organisms. Typically made from proteins, pores of different sizes control the flow of ions and molecules both and in and out of the cell as part of an organism's metabolism. Our understanding of membrane pores comes both from the study of natural pores, and from equivalent structures built in the lab by synthetic biologists. But synthetic proteins are notoriously difficult to handle due to the complex and often unpredictable ways in which their structures can fold. Even minor protein misfolding changes a protein's properties, meaning that building synthetic pores out of proteins can be risky and time-consuming. A more straightforward approach is so-called 'rational engineering' using Lego-like DNA building blocks. Although generally known as life's genetic code, DNA strands, which are chemically much simpler than proteins, are far easier and more predictable to work with than proteins. As such they are a useful material for building nanoscale structures in the lab. "DNA is a construction material that follows very simple rules," said Dr. Stefan Howorka (UCL Chemistry). "New nanostructures can be easily designed using a computer program, and the elements fit together like Lego bricks.

Post-Treatment Mutations in Estrogen Receptor Gene Linked to Breast Cancer Treatment Resistance

Researchers at the University of Michigan (U-M) Comprehensive Cancer Center, together with colleagues, have used DNA and RNA sequencing to identify a type of mutation that develops after breast cancer patients take anti-estrogen therapies. The mutations explain one reason why patients often become resistant to this therapy. The discovery stems from a program at the U-M Comprehensive Cancer Center called Mi-ONCOSEQ in which patients with advanced cancer have their DNA and RNA sequenced to identify all types of genetic mutations that could play a role in the cancer. Researchers use the findings to help direct therapies they think will work best. But they also use the data to find new genetic links. The detailed analysis means that researchers can identify anomalies among a small number of patients. In this study, they looked at 11 patients with metastatic breast cancer that was classified as estrogen-receptor-positive, meaning the cancer is influenced by the hormone estrogen. This is the most common type of breast cancer. The study was published online on November 3, 2013 in Nature Genetics. The analysis found that six patients had mutations in the estrogen receptor. All of them had been treated with an aromatase inhibitor, a type of drug that blocks estrogen production. What’s more, the researchers found that the mutations were not present before the patients started their treatment, which implied it was the therapy itself that caused the mutations to develop or be selected. “This is the tumor’s way of evading hormonal therapy. These mutations activate the estrogen receptor when there is no estrogen – as is the case when a patient takes an aromatase inhibitor.