News Article | November 7, 2016
Today's release of the U.S. Department of Health and Human Services 14th Report on Carcinogens includes seven newly reviewed substances, bringing the cumulative total to 248 listings. The chemical trichloroethylene (TCE), and the metallic element cobalt and cobalt compounds that release cobalt ions in vivo, are being added to the list, as well as five viruses that have been linked to cancer in humans. The five viruses include human immunodeficiency virus type 1, human T-cell lymphotropic virus type 1, Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, and Merkel cell polyomavirus. "Given that approximately 12 percent of human cancers worldwide may be attributed to viruses, and there are no vaccines currently available for these five viruses, prevention strategies to reduce the infections that can lead to cancer are even more critical," said Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences (NIEHS) and National Toxicology Program (NTP). "The listings in this report, particularly the viruses, bring attention to the important role that prevention can play in reducing the world's cancer burden. There are also things people can do to reduce their exposure to cobalt and TCE." The Report on Carcinogens is a congressionally mandated report prepared for the HHS Secretary by NTP. The report identifies many different types of environmental factors, collectively called substances, including chemicals; infectious agents, such as viruses; physical agents, such as X-rays and ultraviolet radiation; mixtures of chemicals; and exposure scenarios in two categories -- known to be a human carcinogen and reasonably anticipated to be a human carcinogen. It's important to note that a listing in the report indicates a cancer hazard, but does not by itself mean that a substance or a virus will cause cancer. Many factors, including an individual's susceptibility to a substance, and the amount and duration of exposure, can affect whether a person will develop cancer. In the case of viruses, a weakened immune system may also be a contributing factor. People should talk to their health care providers about decreasing their cancer risk from viruses. All five viruses are being added to the category of known to be a human carcinogen. Collectively, these viruses have been linked to more than 20 different types of cancers. Trichloroethylene (TCE) is an industrial solvent used primarily to make hydrofluorocarbon chemicals. It is being listed in the Report on Carcinogens as a known human carcinogen. Since 2000, TCE had been listed as a reasonably anticipated human carcinogen. However, numerous human studies showing a causal association between TCE exposure and an increased risk for kidney cancer have led NTP to reevaluate and reclassify TCE as known to be a human carcinogen. There are many ways people can be exposed to TCE. It can be released into the air, water, and soil at places where it is produced or used. It breaks down slowly and can move readily through soil to make its way into underground drinking water sources. Because of its widespread use as a metal degreasing agent to maintain military equipment, it has been found in the groundwater at many military and Superfund sites. Cobalt and cobalt compounds that release cobalt ions in vivo Cobalt and cobalt compounds that release cobalt ions in vivo are being listed as reasonably anticipated to be a human carcinogen. The listing for cobalt includes different types of cobalt compounds that release ions into the body. It does not include vitamin B-12, because cobalt in this essential nutrient is bound to protein and does not release cobalt ions. Cobalt is a naturally occurring element used to make metal alloys and other metal compounds, such as military and industrial equipment, and rechargeable batteries. The highest exposure occurs in the workplace and from failed surgical implants. The listing for this metal and its compounds is based largely on studies in experimental animals. The new report is available at http://ntp.niehs.nih.gov/go/roc14.
News Article | November 16, 2016
New Johns Hopkins Bloomberg School of Public Health-led research suggests that some workers at industrial hog production facilities are not only carrying livestock-associated, antibiotic-resistant bacteria in their noses, but may also be developing skin infections from these bacteria. The findings are published Nov. 16 in PLOS ONE. "Before this study, we knew that many hog workers were carrying livestock-associated and multidrug-resistant Staphylococcus aureus strains in their noses, but we didn't know what that meant in terms of worker health," says study leader Christopher D. Heaney, PhD, an assistant professor at the Bloomberg School's departments of Environmental Health and Engineering, and Epidemiology. "It wasn't clear whether hog workers carrying these bacteria might be at increased risk of infection. This study suggests that carrying these bacteria may not always be harmless to humans." Because the study was small, the researchers say there is a need to confirm the findings, but the results highlight the need to identify ways to protect workers from being exposed to these bacteria on the job, and to take a fresh look at antibiotic use and resistance in food animal production. Hogs are given antibiotics in order to grow them more quickly for sale, and the overuse of antibiotics has been linked to the development of bacteria that are resistant to many of the drugs used to treat staph infections. The researchers, involving collaborators at the University of North Carolina at Chapel Hill, the Rural Empowerment Association for Community Help in Warsaw, NC, and the Statens Serum Institut in Copenhagen, enrolled 103 hog workers in North Carolina and 80 members of their households (either children or other adults) to have their noses swabbed to determine whether they were carrying strains of S. aureus in their nasal passages. Each person was also shown pictures of skin and soft tissue infections caused by S. aureus and asked if they had developed those symptoms in the previous three months. The researchers found that 45 of 103 hog workers (44 percent) and 31 of 80 household members (39 percent) carried S. aureus in their noses. Nearly half of the S. aureus strains being carried by hog workers were mutidrug-resistant and nearly a third of S. aureus strains being carried by household members were. Six percent of the hog workers and 11 percent of the children who lived with them reported a recent skin and soft tissue infection (no adult household members reported such infections). Those hog workers who carried livestock-associated S. aureus in their noses were five times as likely to have reported a recent skin or soft tissue infection as those who didn't carry those bacteria in their noses. The association was stronger among hog workers who carried multidrug-resistant S. aureus in their noses, who were nearly nine times as likely to have reported a recent skin or soft tissue infection. Multidrug-resistant S. aureus infections can be difficult to treat because the antibiotic drugs that doctors typically prescribe don't work. Researchers are concerned about what might happen if these bacteria develop the capacity to spread more broadly between animals and humans. While the study is small, Heaney says the findings suggest that more work is needed to figure out how to mitigate S. aureus exposure and the risk of infection among workers and to track the extent to which these livestock-associated bacteria may spread into the community at large. Since the study found that those hog workers who never wore protective masks over their nose and mouth were more likely to be carriers of the bacteria than those who did, Heaney says recommendations about wearing personal protective equipment might be prudent. Heaney says 89 percent of the hog workers in the study were Hispanic and that many are likely without health insurance. Studies like this, he says, can help focus on risks to a population that is vulnerable and may otherwise fall through the cracks. According to a Duke University analysis of U.S. Bureau of Labor Statistics data, roughly 327,350 people were employed in hog farming in the United States in 2012. Most evidence about the burden of human infections associated with drug-resistant S. aureus nasal colonization comes from studying strains that circulate in hospital settings, where patients are often tested upon admission so that medical staff can take precautions. Less is known about whether generally healthy people in the community, such as hog workers, are at increased risk of developing S. aureus infections. The rise of multidrug-resistant bacteria - often called superbugs - is a global crisis according to the World Health Organization and the use of antibiotics in food animal production has been highlighted as an important contributor. Roughly 80 percent of antibiotics sold in the United States are used in animals, with heavy nontherapeutic uses in food animal production. "This issue isn't going away and there are many more research questions that need to be answered," he says. "Livestock-associated, antibiotic-resistant Staphylococcus aureus nasal carriage and recent skin and soft tissue infection among industrial hog operation workers" was written by Maya Nadimpalli, Jill R. Stewart, Elizabeth Pierce, Nora Pisanic, David C. Love, Devon Hall, Jesper Larsen, Karen C. Carroll, Tsigereda Tekle, Trish M. Perl and Christopher D. Heaney. Funding for this study was provided by the National Institute for Occupational Safety and Health (1K01OH010193-01A1), the Johns Hopkins NIOSH Education and Research Center, the Johns Hopkins Center for a Livable Future, the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program at the Johns Hopkins University School of Medicine (018HEA2013), the National Science Foundation (1316318), the National Institute of Environmental Health Sciences (5T32ES007141-30), the Royster Society fellowship, an Environmental Protection Agency Science to Achieve Results fellowship the GRACE Communications Foundation and the National Institute for Allergy and Infectious Diseases (1R01AI101371-01A1).
News Article | January 21, 2017
Zika Virus - What You Should Know The adverse health effects of synthetic chemicals usually found in common household or agricultural products like insecticides are being revealed. A new research from the University at Buffalo adds another reason why it's best to steer clear from these types of chemicals at all cost. Insecticides are actually a type of pesticide specific to insects. They are frequently used in agriculture, industrial, public health, and household setting to ward off or totally eliminate undesirable bugs, such as roaches, mosquitoes, and termites. Other forms of pesticides include herbicides (non-beneficial plants or weeds), fungicides (molds, mildew, and rust), rodenticides (rats, mice, gophers), algaecides (algae), disinfectants and antimicrobials (bacteria and viruses). Insecticides are available in various formulations and ways of applications. Some of these include sprays, baits, and slow-release diffusion. According to EPA, the most commonly used insecticides are the organophosphates, pyrethroids, and carbamates. Based on a 2001 report by the U.S. Department of Agriculture (USDA) insecticides accounted for 12 percent of total pesticides applied to the surveyed crops. Corn and cotton, on the other hand, account for the largest shares of insecticide use in the United States. A study published in Chemical Research in Toxicology discovered alarming health consequences humans are at risk of when exposed to active chemical ingredients in insecticides. "No one was thinking that the melatonin system was affected by these compounds, but that's what our research shows," Marina Popovska-Gorevski, co-author, now a scientist with Boehringer Ingelheim Pharmaceuticals, stated. "We found that both insecticides are structurally similar to melatonin and that both showed affinity for the melatonin, MT2 receptors, that can potentially affect glucose homeostasis and insulin secretion," Popovska-Gorevski said. "That means that exposure to them could put people at higher risk for diabetes and also affect sleeping patterns," she added. Funded by a grant from the National Institute of Environmental Health Sciences, under the National Institutes of Health (NIH), the study centers on two chemicals: carbaryl (which despite being banned in many countries, is currently the third most extensively used insecticide in the United States), and carbofuran (which is considered as the most lethal carbamate insecticide prohibited from all forms of applications on food crops for human consumption since 2009). Pesticides are everywhere, but with a conscious effort, it's possible to reduce risks of being exposed to them. Go for green and chemical-free alternatives when addressing pest issues at home or garden. Opt for organic fruits and vegetables. Diet plays a big part, too, since most crops in the country are notorious for being heavily sprayed with chemical fertilizers and pesticides. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
News Article | January 14, 2016
Scientists have shown that a process known as oxidative stress is at work during encounters between certain nanoparticles and immune cells, selectively modifying proteins on macrophages, a type of immune cell. The findings, by researchers at the Department of Energy's Pacific Northwest National Laboratory, were published in the journal ACS Nano. While oxidative stress is a common way for cell damage to occur, the findings were a surprise in some ways. "Oxidative stress is occurring selectively even at low levels of exposure to nanoparticles," said Brian Thrall, a nanotoxicology expert at PNNL and a corresponding author of the study. "We've demonstrated an approach that is sensitive enough to detect effects of nanoparticles on macrophages long before those cells die. This gives us the opportunity to understand the most sensitive cellular targets of oxidative stress and the pathways involved more completely than before. "This is important information for understanding how nanoparticles can alter cell function and for beginning to identify functions that allow cells to adapt versus those that are potentially involved in adverse effects," Thrall added. Nanoparticles are typically smaller than 100 nanometers wide, less than one one-thousandth the width of a human hair. If a standard basketball were blown up to the size of the Earth, a nanoparticle enlarged proportionately would be roughly the size of a beach ball in comparison. The particles are used broadly in biomedical applications, clothing, the electronics industry, cosmetics, food packaging and sunscreens; they're also a component in many forms of air pollution. As scientists have refined their ability to make a diversity of nanoparticles used in manufactured goods, there is a greater need to study their potential effects. Oftentimes, these studies look at whether or not exposure to the particles results in cell death. The PNNL study is more nuanced, looking in more depth at specific proteins in cells that are the targets of oxidative damage caused by nanoparticles. "This study shows that some nanoparticles which we consider non-toxic can have many effects on macrophages," said analytical chemist Wei-Jun Qian, also a corresponding author of the study. The findings depend on a method recently developed by PNNL scientists to measure protein oxidation at very specific sites in cells like macrophages. Qian developed a very sensitive measure of protein modifications in cells to allow scientists to look at specific sites in the cell where scientists know certain functions are carried out. The method, known as a quantitative redox proteomics approach, utilizes an advanced mass spectrometer to look at thousands of sites involved in redox reactions simultaneously. Thrall's and Qian's teams worked together to analyze modifications in all the proteins in mouse cells. The group looked at the effects of three types of nanoparticles which vary in their potential to cause oxidative stress and cell death: The team took a close look at more than 2,000 cellular hotspots where a process known as S-glutathionylation, a specific type of protein modification known to be involved in immune functions when a cell is under oxidative stress, occurs. In macrophages exposed to nanoparticles, the team found molecular "footprints" of activity — an increase in S-glutathionylation. However, the specific pattern of oxidative modifications on proteins varied depending on the type of nanoparticle. By looking at these modifications, researchers were able to identify specific molecular pathways that were most sensitive to low levels of oxidative stress, and distinguish those from other pathways that were associated with high levels of oxidative stress linked to cell death. The idea that a nanoparticle would damage the body's macrophages is no surprise: Macrophages are the body's first responders when it comes to recognizing and neutralizing an invader. Some nanoparticles can weaken macrophages' ability to recognize, hold onto and engulf the particles. Two years ago, Thrall's team showed that when macrophages are exposed to nanoparticles, the cells don't work as well and are less able to recognize and remove Streptococcus pneumonia, the leading cause of community-acquired pneumonia. The pattern of protein changes identified in this study provides new clues to the types of nanoparticles that cause these effects and the proteins involved. Qian developed the method as part of his work studying redox reactions which play an important role regulating photosynthesis in plants. Understanding how plants capture, process and funnel the Sun's energy naturally helps scientists develop efficient new energy systems to do the same. Qian has used the system to discover more than 2,100 molecular locations where redox reactions are likely to occur in cyanobacteria, which are important for producing biofuels. The work by Qian's group is funded in part by an Early Career Research Award from the Department of Energy, as well as an NIH Director's New Innovator Award. The spectrometric analyses took place at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science User Facility at PNNL. Support for this study came from the National Institute of Environmental Health Sciences.
News Article | December 8, 2016
AMHERST, Mass. - A new study led by environmental health scientist Richard Pilsner at the University of Massachusetts Amherst, one of the first to investigate whether preconception exposures to phthalates in fathers has an effect on reproductive success via embryo quality, found that exposures from select chemicals tested were associated with "a pronounced decrease in blastocyst quality" at an early stage in embryo development. Phthalates are compounds found in plastics and personal care products that are estimated to be detectable in nearly 100 percent of the U.S. population. The authors believe theirs is the first prospective study to assess associations between paternal exposure to phthalates and embryo quality through the blastocyst stage in humans. Pilsner and colleagues say their prospective study of 761 oocytes, or immature eggs, from 50 couples undergoing in vitro fertilization (IVF) "provides the first data demonstrating associations between preconception paternal phthalate and phthalate alternatives and embryo development, in a critical step towards our understanding of the paternal contributions to reproductive success." Details appear in the current issue of Human Reproduction from Oxford University Press. For this investigation, the researchers recruited 50 couples from the Baystate Medical Center's Fertility Center in Springfield, Mass., as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). They measured phthalate exposure in urine from male and female partners on the same day as semen sample procurement and oocyte retrieval, and assessed embryo quality at the cleavage (day 3) and blastocyst (day 5) stages. The 50 couples contributed 761 oocytes, of which 423 progressed to the cleavage stage, 261 were high quality cleavage stage embryos, 137 were transferrable quality blastocysts and 47 were high quality blastocysts. The researchers quantified concentrations of 17 urinary metabolites by liquid chromatography mass spectrometry, estimated odds ratios (OR) and confidence intervals with urinary phthalates and phthalate alternatives fitted as continuous variables and embryo quality as a binary variable. At the cleavage stage, there were no overall significant associations for male or female phthalate exposures. Concentrations of male urinary monoethyl phthalate were positively associated with high quality cleavage stage embryos, with an OR=1.20 and no other significant associations were observed at this stage. At the blastocyst stage, ORs for male urinary concentrations of monobenzyl phthalate was 0.55 for mono-3-hydroxybutyl phthalate 0.37, for mono-n-butyl phthalate 0.55 and for monomethyl phthalate 0.39, all inversely associated with high-quality blastocysts. "Although our results do not show altered embryo development associated with urinary metabolites at day 3, it is possible that the molecular changes associated with phthalates and phthalate alternatives were too subtle to be detected morphologically during these early cleavage stages and that such early molecular changes manifest at the morphological level during later stages of development," the authors say. "Our modest sample included only 50 couples contributing one cycle each. In addition, non-differential misclassification of exposure remains a concern given the single spot urine collection and the short half-life of phthalates," they add. Overall, results support "the growing evidence that the preconception paternal environmental health may contribute to reproductive potential." They add that "future studies are needed to investigate the long-term effects of altered embryo development" and to identify a mechanism by which a father's preconception exposure to phthalates may affect embryo development. "If corroborated with other studies, such findings will have public health and clinical significance for both the general population and those undergoing IVF." This work was supported by a grant from the National Institute of Environmental Health Sciences. Pilsner collaborated with Dr. Cynthia Sites, director of the in vitro fertilization clinic at Baystate Medical Center, Springfield, Mass., to conduct this research.
News Article | December 8, 2016
The Cardiac & Vascular Institute Research Foundation (TCAVIRF) has been named a participating clinical site for the second Trial to Assess Chelation Therapy (TACT2). TACT2 will examine the use of intravenous chelation treatments in combination with oral vitamins in diabetic patients with a prior heart attack to determine if they reduce recurrent heart episodes, such as heart attacks, stroke, death, and others, by removing toxins from the blood. Funding for TACT2 was announced in September of 2016 when The National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health (NIH) awarded $37M to initiate the trial. The trial is also co-funded by the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences. Chelation is a process by which a medication, such as edetate disodium (Na2EDTA), can “grab” and remove toxic metal pollutants - like lead or cadmium - which are present in most individuals. TACT2 follows up on the positive results of TACT, an NIH-sponsored multicenter, double-blind safety and efficacy study, which took place from 2002- 2012 and was conducted in 134 sites across the United States and Canada. During TACT, 1,708 heart attack patients were randomly assigned to receive 40 infusions of an edetate disodium-based chelation solution or a placebo (inactive) infusion. Patients also received an oral vitamin and mineral regimen, or an oral placebo. TACT demonstrated an 18% reduction in recurrent heart events by chelation in patients who already had sustained a heart attack. Recurrent heart events measured in the study were death, heart attack, stroke, heart bypass or stent, and hospitalization for angina (chest pains). In 633 diabetic patients, there was an even larger benefit with a 41% reduction in recurrent heart events and a 43% reduction in deaths. Based on these results, the Mount Sinai and Duke scientists who conducted the trial felt that a repeat study was important to carry out. TACT2 will narrow its focus to the group with the greatest benefit in the original study - diabetic patients 50- years of age or older who have survived a prior heart attack. The original TACT clinical results were published in the Journal of the American Medical Association in 2013, Circulation: Quality and Outcomes in 2014, and the American Heart Journal in 2014. “If TACT2 is positive, it will forever change the way we treat heart attack patients and view toxic metals in the environment,” said Gervasio Lamas, M.D., study chairman and chief of the Columbia Division of Cardiology at Mount Sinai Medical Center in Miami Beach, Florida. “Therefore, with NIH support and in collaboration with the Duke Clinical Research Institute, Columbia University, New York University, Mount Sinai (NYC), and hundreds of physicians and nurses throughout the U.S. and Canada, we are moving forward with TACT2.” "The results of the initial TACT study were very impressive in the diabetic population, in fact, better than many other recommended medications,” said Michael Dillon, M.D., cardiologist at The Cardiac & Vascular Institute. “This certainly raises important questions about management of CAD in diabetics. I am very excited about the opportunity to see if the results of the initial trial can be confirmed in TACT 2." Although not approved by the Food and Drug Administration for treating heart disease, some practitioners have used chelation therapy for nearly 60 years in the absence of clinical trial data supporting its use. Because of the lack of data, it has generally been believed by conventional medical practitioners and cardiologists to be without value, although TACT results suggest otherwise. A definitive answer on chelation therapy in diabetic patients that will be embraced by the cardiology community will require positive results from TACT2. The Cardiac & Vascular Institute Research Foundation is currently recruiting patients for participation in the study. Candidates must be 50 years of age or older, have diabetes and experienced a prior heart attack. Patients interesting in participating may contact the study team through http://www.tact2.org, or by calling TCAVIRF at 352-244-0208. This work is supported by the following grants: R01AT009273 and UH3AT009149. Oral vitamins are provided by Xymogen (Orlando FL).
News Article | April 21, 2016
Having a lot of green around your home might help you live longer, according to a new study of more than 100,000 U.S. women. Women in the study with the most greenness near their homes — whether it was plants, trees and other vegetation — had a 12 percent lower death rate during the study period, compared with women who had the least amount of vegetation near their homes, the researchers found. "It is important to know that trees and plants provide health benefits in our communities, as well as beauty," Linda Birnbaum, director of the National Institute of Environmental Health Sciences, which funded the study, said in a statement. "The finding of reduced mortality suggests that vegetation may be important to health in a broad range of ways." For the study, researchers at the Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital in Boston looked at the level of vegetation around the homes of about 110,000 women who were registered nurses living across the United States, and were participating in a large ongoing research effort called the Nurses' Health Study. The participants had given their home addresses, and the researchers used satellite imagery to determine the amount of vegetation within 250 meters (820 feet) of their homes. Then, the researchers tracked the women from 2000 to 2008, during which there were 8,604 deaths. [Extending Life: 7 Ways to Live Past 100] Living in an area with a lot of vegetation was linked with a lower rate of death from any cause (excluding accidental injuries). Women living near areas with the most vegetation had a 41 percent lower death rate from kidney disease, a 34 percent lower death rate from respiratory disease and a 13 percent lower death rate from cancer, compared with women living in areas with the least vegetation, the study found. There are a number of reasons why vegetation near the home could lead to a longer life span, including providing space for physical activity or social gatherings, or decreasing stress and depression through contact with nature, the researchers said. Indeed, the study showed that women with lots of vegetation near their homes had lower levels of depression, and spent more hours participating in social groups such as charities, than people with less vegetation near their homes, suggesting that these were the biggest factors driving the link. The researchers took into account changes in vegetation around the home during the study period, as well as other factors that can affect mortality, such as a person's age, ethnicity or income level. The study was published April 14 in the journal Environmental Health Perspectives. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
News Article | August 22, 2016
Researchers at MIT and the University of California at San Diego (UCSD) have recruited some new soldiers in the fight against cancer — bacteria. In a study appearing in the July 20 of Nature, the scientists programmed harmless strains of bacteria to deliver toxic payloads. When deployed together with a traditional cancer drug, the bacteria shrank aggressive liver tumors in mice much more effectively than either treatment alone. The new approach exploits bacteria’s natural tendency to accumulate at disease sites. Certain strains of bacteria thrive in low-oxygen environments such as tumors, and suppression of the host’s immune system also creates favorable conditions for bacteria to flourish. “Tumors can be friendly environments for bacteria to grow, and we’re taking advantage of that,” says Sangeeta Bhatia, who is the John and Dorothy Wilson Professor of Health Sciences and Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and its Institute for Medical Engineering and Science. Bhatia and Jeff Hasty, a professor of bioengineering at UCSD, are the senior authors of the paper. Lead authors are UCSD graduate student Omar Din and former MIT postdoc Tal Danino, who is now an assistant professor of biomedical engineering at Columbia University. The research team began looking into the possibility of harnessing bacteria to fight cancer several years ago. In a study published last year focusing on cancer diagnosis, the researchers engineered a strain of probiotic bacteria (similar to those found in yogurt) to express a genetic circuit that produces a luminescent signal, detectable with a simple urine test, if liver cancer is present. These harmless strains of E. coli, which can be either injected or consumed orally, tend to accumulate in the liver because one of the liver’s jobs is to filter bacteria out of the bloodstream. In their new study, the researchers delivered artificial genetic circuits into the bacteria, that allow the microbes to kill cancer cells in three different ways. One circuit produces a molecule called hemolysin, which destroys tumor cells by damaging their cell membranes. Another produces a drug that induces the cell to undergo programmed suicide, and the third circuit releases a protein that stimulates the body’s immune system to attack the tumor. To prevent potential side effects from these drugs, the researchers added another genetic circuit that allows the cells to detect how many other bacteria are in their environment, through a process known as quorum sensing. When the population reaches a predetermined target level, the bacterial cells self-destruct, releasing their toxic contents all at once. A few of the cells survive to begin the cycle again, which takes about 18 hours, allowing for repeated release of the drugs. “That allows us to maintain the burden of the bacteria in the whole organism at a low level and to keep pumping the drugs only into the tumor,” Bhatia says. The researchers tested the bacteria in mice with a very aggressive form of colon cancer that spreads to the liver. The bacteria accumulated in the liver and began their cycle of growth and drug release. On their own, they reduced tumor growth slightly, but when combined with the chemotherapy drug 5-fluorouracil, often used to treat liver cancer, they achieved a dramatic reduction in tumor size — much more extensive than if the drug was used on its own. This approach is well suited to liver tumors because bacteria taken orally have high exposure there, Bhatia says. “If you want to treat tumors outside the gut or liver with this strategy, then you would need to give a higher dose, inject them directly into the tumor, or add additional homing strategies,” she says. In previous studies, the researchers found that engineered bacteria that escape from the liver are effectively cleared by the immune system, and that they tend to thrive only in tumor environments, which should help to minimize any potential side effects. Martin Fussenegger, a professor of biotechnology and bioengineering at ETH Zurich, calls the new approach “unconventional” and “highly promising.” “This is a fascinating, refreshing, and beautiful concept,” says Fussenegger, who was not involved in the study. “In a world of mainstream cancer therapy concepts with often limited success, new therapy strategies are badly needed.” The researchers are now working on programming the bacteria to deliver other types of lethal cargo. They also plan to investigate which combinations of bacterial strains and tumor-targeting circuits would be the most effective against different types of tumors. The study was funded by the San Diego Center for Systems Biology, the National Institute of General Medical Sciences, the Ludwig Center for Molecular Oncology at MIT, an Amar G. Bose Research Grant, the Howard Hughes Medical Institute, a Koch Institute Support Grant from the National Cancer Institute, and a Core Center Grant from the National Institute of Environmental Health Sciences.
News Article | November 10, 2016
CHAMPAIGN, Ill. -- A study of mouse reproductive tissues finds that exposure to isoliquiritigenin, a compound found in licorice, disrupts steroid sex hormone production in the ovary, researchers report. This is the first study to examine the effects of this chemical on the ovary. Exposure to high levels of the compound, which the researchers call "iso," lowered the expression of key genes involved in hormone production, the researchers found. In particular, expression of a gene for aromatase, an enzyme that converts testosterone to estrogen, dropped by 50 percent or more. The findings are reported in the journal Reproductive Toxicology. Though preliminary - more research must be done to determine iso's effects in living animals - the discovery is concerning, said University of Illinois comparative biosciences professor Jodi Flaws, who led the study with researcher Sharada Mahalingam. "In general, when you start to have lower hormone levels, you could start to have problems with reproduction," Flaws said. "And because estrogen is also important for healthy brains, healthy bones, a healthy cardiovascular system, if the levels are depleted for too long, you could have problems with those systems. We haven't shown that to be the case. That's just a possibility. "I would say, though, that a 50-plus percent drop in aromatase in humans would be a serious problem for fertility and for other things," Flaws said. Whole licorice root and purified forms of iso are used in herbal supplements, teas, candies and as flavoring agents in tobacco products. Iso is sometimes marketed to women for the relief of hot flashes or other symptoms of menopause, and studies have found that the root has anti-cancer properties for some types of breast, prostate and colon cancer, Mahalingam said. The same properties that make iso effective against some cancers also might make it toxic to the normal growth and development of the ovary, Flaws said. Other aromatase inhibitors are already in use in oncology to stop the growth of tumors that respond to estrogen, but doctors warn of potential effects on fertility in women of child-bearing age. Use of iso to inhibit aromatase could have the same effects as other aromatase inhibitors, Flaws said. "This could lead to a good outcome in certain tissues, depending on dose and timing of exposure," she said. "In the ovary, though, if you reduce aromatase, you're also reducing estrogen, so you could be interfering with fertility." "Botanical estrogens are quite complex, and different tissues may have differential responses, depending on dosage," said food science and human nutrition professor William Helferich, the director of the Botanical Estrogen Research Center at the U. of I. and a co-author of the study. The new findings are only the first step in understanding iso's role, if any, in influencing fertility, the researchers said. The National Institutes of Health funded this research through the National Institute of Environmental Health Sciences, the National Center for Complementary and Alternative Medicine, and via a grant from the Office of the Director to veterinary student and study co-author Jacqueline Eisner. The National Cancer Institute Office of Dietary Supplements also supported this research. The paper "Effects of isoliquiritigenin on ovarian antral follicle growth and steroidogenesis" is available online and from the U. of I. News Bureau.
News Article | January 8, 2016
A team of researchers from Colorado State University has been studying DNA damage in living cells to learn more about how genetic abnormalities arise. It has long been known that DNA molecules in every cell get constantly damaged by things from the outside environment, like sunlight, cigarette smoke and radiation. However, more recently researchers have discovered that sources from within the cell itself can sometimes be even more damaging. DNA, or deoxyribonucleic acid, is found in the nucleus of every cell. It is the code for the traits we have as human beings, and it serves as the warehouse of information needed to make a cell work. When something goes wrong with DNA, it can lead to a mutation and changes in the cell, and can sometimes lead to disease. In a study highlighted in a recent issue of Genetics, the team -- led by J. Lucas Argueso, CSU assistant professor and Boettcher Investigator in the Department of Environmental & Radiological Health Sciences -- found that RNA, or ribonucleic acid, has a new and important part in this process. CSU researchers worked in close in collaboration with scientists from the National Institute of Environmental Health Sciences in North Carolina. RNA is a molecule that plays a central role in the function of genes. It is the "business" end of a genome. The building blocks that cells use for making RNA are knows as ribonucleotides, which was the focus of the research paper. "You don't hear as much about RNA, but cells actually have much more RNA than DNA," Argueso said. Cells also have more ribonucleotides than deoxyribonucleotides, the building blocks for making DNA. Since the two are chemically very similar, it is quite common for cells to mistakenly incorporate RNA pieces into DNA. Argueso and his team -- including Hailey Conover, Ph.D. student in Cell & Molecular Biology and lead author of the study, and Deborah Afonso Cornelio, a post-doctoral researcher -- are looking at what happens to yeast cells when they are unable to accurately remove RNA from DNA. "The same problem happens in humans, carrots, butterflies, and yeast cells, the model organism used in our lab," Argueso said. "The same yeast that is used to bake bread and to brew beer is an incredibly useful biomedical research model." Findings from this study have direct implications for children with Aicardi-Goutieres syndrome, a devastating disorder that affects the brain, the immune system and the skin. "This is a very serious disease that affects children born without a critical enzyme that removes the RNA building blocks from DNA," Argueso said. "Our model yeast cells have been engineered to have the same basic genetic defect as Aicardi-Goutieres children so that we can investigate this problem at its very core." What's next for the team? Argueso said they want to extend their work to cancer research. The team wants to determine how ribonucleotides increase chromosome abnormalities and whether those increases are asymmetric, depending on which of the two strands of DNA the ribonucleotides are introduced. Most cancers have some form of alteration in chromosomal structure, though Argueso said that breast and ovarian cancers are by far the most affected by this issue. In addition, with some forms of chemotherapy that have been used for a long time, the mechanism of action is to decrease the production of DNA building blocks. "Cancer cells reproduce quickly," Argueso said. "To do that, the cells need DNA building blocks. Chemotherapy is used to decrease the building blocks. However, when you reduce the number of DNA building blocks, you push the cancer cells into a corner, where they end up putting in more RNA building blocks into the DNA." In other words, the very thing that the chemotherapy agent is encouraging cancer cells to incorporate causes them to acquire even more mutations. This could help explain why cancers often recur in more aggressive forms after someone goes into remission. "This unintended consequence could be one of the mechanisms making that happen," Argueso said.