RESEARCHERS DISCOVER BLOOD MARKER THAT BETTER DEFINES WHO WILL RESPOND TO DRUG USED IN METASTATIC COLORECTAL CANCER
Newswise — Cancer researchers have identified a marker that shows up in a blood test that determines which patients with colorectal cancer that has spread would benefit from receiving the drug cetuximab. The research, published online today in Clinical Cancer Research, a journal of the American Association for Cancer Research, solves one of the mysteries of why receiving cetuximab was futile for up to half of incurable colorectal cancer patients who did not respond to treatment, says principal investigator Dr. Geoffrey Liu, clinician-scientist at Princess Margaret Cancer Centre, University Health Network, in collaboration with the Canadian Cancer Trials Group and the Australasian Gastro-Intestinal Trials Group. Dr. Liu holds the Alan B. Brown Chair in Molecular Genomics and is Associate Professor of Medicine, Medical Biophysics, and Epidemiology, Dalla Lana School of Public Health, University of Toronto. He talks about his research at https://www.youtu.be/jyntlRqqizQ. “Our research discovered that the blood marker FCGR2A identifies a new group of patients that will benefit from taking cetuximab. With this finding, we believe we are now on the way to move it into the clinical setting to provide patients targeted, effective treatment,” says Dr. Liu. The new research builds on an international clinical trial of about 10 years ago led by Canadians, in which the Princess Margaret participated (DOI: 10.1056/NEJMoa071834) “In a group of metastatic colorectal cancer patients who were running out of treatment options, the previous clinical trial determined that cetuximab was most effective in a certain group of patients with tumours carrying a RAS mutation. But it certainly didn’t work for everyone and so the race was on to find out how to better identify which patients would benefit from this drug,” says Dr. Liu. “Our finding, which resulted from analyzing archived tumor and normal tissue samples from some of the 572 patients enrolled in that trial, further refines this quest and defines another subset of patients who will respond to the drug. “We need to find other ways to personalize cancer medicine for people with colorectal disease, keeping in mind that cetuximab is an expensive drug and can have side effects.” “So instead of looking at aspects in the tumour, which is where RAS mutations show up, we looked at certain things in the blood and normal tissues that we could measure for heritable genetic variations.” Dr. Liu, a medical oncologist who specializes in lung cancer, describes the pathway to today’s discovery as an ideal example of what can happen when you follow the drug and wherever the research may lead. “When we followed the drug, first in lung cancer and then in other cancers, it led us to colorectal cancer where the drug was also being used, and directly onto this new finding.” Dr. Liu’s research was funded by the Ontario Institute of Cancer Research, the Alan B. Brown Chair in Molecular Genomics, the Cancer Care Ontario Chair in Experimental Therapeutics and Population Studies, the Canadian Cancer Society, and The Princess Margaret Cancer Foundation.
Newswise — ANN ARBOR, Mich. — Dominic Pangborn’s artwork is always changing and he’s fearless in his approach, which is never the same twice. Over his decades-long career, the designer has received many awards and recognitions. His signature ties are ubiquitous in the Detroit business community. Not for the wallflower, his ties, like all his designs, combine bold patterns and beautiful colors that are aesthetically pleasing and serve as statement pieces that make the wearer stand out. Now, Pangborn is making a statement about research on mental health. He has designed a new scarf and tie based on images generated by University of Michigan scientists. Those who add it to their wardrobe will be helping that science move ahead. “One of my greatest joys is to ‘pay it forward’ and give back to the community,” said Pangborn. Released just in time for May, National Mental Health Awareness Month, Pangborn’s creations are in partnership with the Heinz C. Prechter Bipolar Research Fund. The silk scarves and ties bear images of neural stem cells generated in Prechter-funded research, together with the hopeful shapes of butterflies. The Prechter Bipolar Research Program, part of the University of Michigan Depression Center, includes research into the basic mechanisms underlying bipolar disorder. Its scientists generate stem cells from skin cells donated by people with the illness, and those without, and then grow the kinds of neural cells found in the brain. This process allows scientists to understand — in the laboratory — what’s different between the two kinds of cells, at the genetic and molecular level. Scientists can manipulate these ‘brain cells in a dish’ to test different medications. “The scientists at the University of Michigan Center for Pluripotent Stem Cell Research monitor the cells daily and have learned that cells taken from bipolar patients fire more intensively and in a way that is significantly different than cells from an individual who doesn't have bipolar disorder," said Melvin McInnis, M.D., the Prechter Fund research director. "By understanding the causes of bipolar disorder, we will be able to develop new treatments for the illness and most importantly, we’ll be able to prevent destructive mood episodes. Our ultimate goal is to allow people to live happy, normal lives.” The stem cell center, headed by Sue O’Shea, Ph.D., is based in the U-M Medical School’s Department of Cell and Developmental Biology. Bipolar disorder is an illness that affects millions of Americans and is marked by the highs of mania and the lows of depression. Also known as manic-depressive illness, the disorder causes shifts in mood, energy and activity levels, making day-to-day tasks difficult and sometimes impossible. The illness is marked by a high suicide rate and impacts the whole family. The Prechter Fund scarf and tie project aims to call attention to research being done in this area of mental illness – research that is vitally necessary. Dominic Pangborn believes that art should reflect a current mood, expression, and point in time. “I decided to add butterflies to the design because they signify metamorphosis. Our society is finally at a point where mental illness is openly talked about and research is taking a turn for the better,” he says. Beginning in May, the Pangborn Collection store at 335 S. Main Street in Ann Arbor, and the Pangborn Collection web store at pangborncollection.com, will sell the special edition of scarves and ties for the Prechter Fund, priced at $95.00. All net proceeds will go directly to Prechter bipolar research projects at the University of Michigan Depression Center. For more information on the Heinz C. Prechter Bipolar Research Fund, please visit prechterfund.org. To learn more about Pangborn Design, go to pangborndesign.com.
Newswise — In 2014, a team of researchers in the Lewis Katz School of Medicine at Temple University became the first to successfully eliminate the HIV-1 virus from cultured human cells. Fewer than two years later, the team has made further strides in its research by eliminating the virus from the genome of human T-cells using the specialized gene editing system they designed. In a new study published in Scientific Reports, the researchers show that the method can both effectively and safely eliminate the virus from the DNA of human cells grown in culture. How this research differsIn previous work, the team—led by Kamel Khalili, professor and chair of the Department of Neuroscience at Temple—had demonstrated the ability of their technology to snip out HIV-1 DNA from normal human cells. The newest findings used that same technology to snip out the virus from latently and productively infected CD4+ T-cells, which host the virus in persons infected with HIV. In this round of research, the scientists used blood drawn from actual patients living with HIV. These ex vivo experiments allowed T-cells from patients infected with HIV to be grown in cell culture and treated with the gene editing system. Results showed that the treatment system can eliminate the virus and protect cells against reinfection. Another major component of the study addressed questions about potential side effects and toxicity. The researchers used the gold standard in genomic assessment known as ultra-deep whole-genome sequencing to analyze the genomes of HIV-1-eradicated cells for mutations in genes outside the region targeted by the process. Their analyses ruled out off-target effects on genes and showed that HIV-1-eradicated cells were growing and functioning normally. What the research means“The findings are important on multiple levels,” said Khalili, also director of the Center for Neurovirology and director of the Comprehensive NeuroAIDS Center at Temple. “They demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of CD4+ T-cells and, by introducing mutations into the viral genome, permanently inactivate viral replication. Further, they show that the system can protect cells from reinfection and that the technology is safe for the cells, with no toxic effects.” “These experiments had not been performed previously to this extent,” he added. “But the questions they address are critical, and the results allow us to move ahead with this technology.” The research was funded by grants from the National Institutes of Health.
Newswise — A new study from IMC researchers Kristian Tylén, Riccardo Fusaroli, and Andreas Roepstorff, published in the scientific journalNeuroImage, used LEGO bricks to investigate the neurocognitive underpinnings of our engagements with symbolic objects. The study suggests that we experience symbolic objects as social entities. Sometimes objects are just objects, that is, static, material things. But some objects are relevant to us due to their particular role or value in our social lives. Symbolic artifacts such as road signs, national flags, wedding rings, and artworks are imbued with social significance as they are developed, negotiated and engaged in a variety of everyday cultural practices. More than mere physical objects, we thus experience them as vehicles of social meaning: although a red traffic light does not present any physical impediment to movement, it still (most often) stops us from crossing the street. LEGO Bricks to illustrate A new study conducted by IMC researchers Kristian Tylén, Riccardo Fusaroli and Andreas Roepstorff, and just published in the high-ranking scientific journal NeuroImage, investigates the neurocognitive underpinnings of our engagements with such symbolic artifacts. In a two-day experimental study, participants in groups first built collective models of LEGO bricks to illustrate their understanding of abstract concepts such as 'justice', 'safety' and 'collaboration'. Later they went into an fMRI brain scanner where they would be presented with pictures of their own and others' LEGO models. Interestingly, when participants attended to the meaning of the models, brain areas associated with social cognition and language were activated. These areas are often found in studies where participants watch social stimuli or are instructed to think about other people's mental states. Lead researcher Kristian Tylén explains: "It is really interesting that brain areas associated with social interaction and reasoning are also active when our participants look at static, dead objects. It tells us that these objects have gained symbolic meaning through social interaction in the preceding group interventions". Furthermore, special activation patterns in brain areas related to social empathy were found when participants saw LEGO models that they had built with their own group in contrast to models made by other groups. Riccardo Fusaroli continues: "Activation in these areas were found to depend on how closely the participants felt related to their fellow group members after the LEGO construction sessions." Together these finding shed new light on the special status of symbolic objects in human cognition. More than simple material structures these objects are experienced as an extension of our social engagements with each other, as trails of social and cultural interactions.
Newswise — It’s time for your primary care check-up, and the doctor asks you to list any known drug allergies. “Penicillin,” you say immediately, although you can’t remember actually taking the drug or having a reaction to it—it was your parents who said so. According to a Texas A&M Health Science Center allergist, many people who believe they’re allergic to this antibiotic may not actually be allergic at all. “Hypersensitivity reactions are the major problem in the use of penicillin,” said Thomas Leath, M.D., an allergist with the Texas A&M College of Medicine. “Many people who report a penicillin allergy don’t even know why. It could be because they had a reaction when they were very young, or, because a family member had an allergic reaction and told their children not to take penicillin.” Penicillin, which has been around since 1928, is used to treat a variety of conditions, from strep throat to ear infections. It’s also the base of many front-line drugs. When you are allergic to penicillin, you’re often forced to take more expensive alternatives, which can have more side effects. Penicillin allergies are widely listed in patient histories, but, a Mayo Clinic study found 80 to 90 percent of patients who listed a penicillin allergy had no real evidence of a true reaction and avoided the drug unnecessarily. Moreover, anaphylaxis (a severe, potentially life-threatening allergic reaction) to penicillin is still quite rare. Inappropriate prescribing of antibiotics for conditions they cannot treat (cold, flu etc.,) has led to a rise in deadly ‘superbugs’—bacteria that can’t be killed with standard antibiotics—and could be another reason why people suspect they have a penicillin allergy. “Penicillin will not treat viruses like the common cold,” Leath said. “When someone is prescribed an antibiotic for a virus they may break out in a rash, or experience other side effects, falsely attributed to penicillin.” An actual allergic reaction to penicillin can cause symptoms along a wide spectrum. A person with a mild reaction to the drug may break out in hives, but more severe signs can occur, including swelling of the lips, tongue and throat, as well as asthma-like symptoms. Vomiting, nausea and diarrhea also indicate a true allergic reaction. “Penicillin allergies can even drop your blood pressure, cause dizziness or loss of consciousness,” Leath said. “If you experience almost all these symptoms listed, and at the same time, you’re having an anaphylactic (life-threatening) reaction and need to see a health care provider immediately.” According to Leath, it’s important to recognize the difference between an allergic reaction to penicillin and the drug’s reported side effects. “True allergic reactions happen quickly after exposure—usually within 10 to 15 minutes or within an hour or two of taking the drug,” he said. “If you have a reaction, like an upset stomach, three days after beginning a penicillin regimen, you probably aren’t allergic.” That sort of reaction would be considered a side effect, not an allergy. Worth noting: Penicillin is the only antibiotic with a skin test protocol—there’s really no standard way to test and confirm allergies to other antibiotics. However, experts can often discover what’s wrong. “As an allergist, I can frequently tease out the real reason for the problem just by talking with the patient about how and when certain symptoms occurred,” Leath said. “We can then discern if they are truly allergic or not.” This skin test protocol helps determine if a patient’s penicillin allergy actually exists if they have outgrown the allergy. If a penicillin reaction was reported when a patient was very young, the immune system may ‘forget’ the allergy if the antibiotic is never taken again. Leath said 10 years later, up to 90 percent of people will have outgrown a penicillin allergy. “This is because the immune system doesn’t receive the stimulus that prompts an allergic reaction,” he said. “Even if a patient did have a true allergy, the chances of it still being present in the next 10 years is very low.” Nonetheless, this doesn’t always mean it’s safe to take penicillin after reporting an allergic reaction to it. “If patients have an allergic reaction to penicillin—even a mild one—it ups the potential for having another more severe reaction,” Leath said. “This is always a conversation to have with your health care provider to discuss the best options for your health and treatment.”
Newswise — Researchers report in the journal Cancer Cell an experimental therapy that in laboratory tests on human cells and mouse models stops aggressive, treatment-resistant and deadly brain cancers called glioblastoma and high-grade gliomas. A multi-institutional team led by researchers at Cincinnati Children’s Hospital Medical Center publishes their results on May 9. Testing a multi-step therapeutic strategy, the scientists found a way to use a gene therapy to shut down a gene long-implicated in the formation of high-grade gliomas called Olig2. The protein encoded by Olig2 is expressed in the majority of gliomas. Removing the Olig2 gene halts tumor growth, while elimination of Olig2-producing cells blocks tumor formation. “We find that elimination of dividing Olig2-expressing cells blocks initiation and progression of glioma in animal models and further show that Olig2 is the molecular arbiter of genetic adaptability that makes high-grade gliomas aggressive and treatment resistant,” said Qing Richard Lu, PhD, lead investigator and scientific director of the Brain Tumor Center at Cincinnati Children’s. “By finding a way to inhibit Olig2 in tumor forming cells, we were able to change the tumor cells’ makeup and sensitize them to targeted molecular treatment. This suggests a proof of principle for stratified therapy in distinct subtypes of malignant gliomas.” The current study may apply to high-grade brain gliomas and a fatal brainstem tumor called DIPG (Diffused Intrinsic Pontine Glioma), which expresses Olig2 and is inoperable because of its location in a brain region controlling vital functions. Even if these cancers do initially respond to a specific targeted treatment, they adapt by finding genetic/molecular workarounds, evade treatment and continue growing. Researchers caution the experimental therapeutic approach they describe requires extensive additional research and remains years away from possible clinical testing. Still, Dr. Lu said the data are a significant research breakthrough. The current study finds a potential chink in the molecular armor of these stubborn cancers that – even after an initial round of successful treatment – almost always relapse and kill the patients who get them. The cancers form from precursors of supporting brain cells called oligodendrocytes, which help generate insulation for neural connections. Olig2 appears at the early stages of brain cell development. Through extensive analysis of human brain cancer cells and mouse models, the researchers observed Olig2 expression in early-stage dividing and replicating cells in tumors. Olig2 contributes to the transformation of normal precursor cells into abnormal malignant cells that divide uncontrollably. In the context of cancer cell formation, the researchers saw Olig2 drive molecular processes that allow forming glioma cells to be highly adaptable and susceptible to the tumor-promoting effects of additional genetic changes. Researchers then decided to eliminate Olig2-positive dividing cells during tumor formation. To use an approach more rapidly translatable from the laboratory bench to clinical bedside, they successfully tested a gene therapy that uses an engineered herpes simplex virus (viral vector) to deliver a suicide gene into replicating Olig2-positive cancer cells. They next administered an anti-herpes drug already in clinical use, ganciclovir (GCV). The Olig2-deleted tumors were not able to grow. Researchers also found that after Olig2 was inhibited, the forming brain cancer cells switched directions and molecular composition– going from the cells resembling oligodendrocyte precursors to assume astrocyte-like brain cell characteristics. They continued to form tumors, however these newly formed astrocyte-like brain cancer cells produce the epidermal growth factor receptor (EGFR) gene at high levels. EGFR is a common and effective target for chemotherapy drugs used clinically to treat tumors such as breast cancers. In repeated tests in mouse models, Olig2 inhibition prompted the glioma-forming cells to transform into EGFR-expressing astrocyte-like cells. Then, in subsequent and repeated testing on the transformed human and mouse model astrocyte-like cancer cells, the researchers treated the cells with an EGFR-targeted chemotherapy drug called gefitinib. The treatment stopped the growth of new tumor cells and tumor expansion. Dr. Lu said that with additional testing, verification and refinement the experimental therapy could be especially helpful in preventing a recurrence of brain cancer in patients who have undergone an initial round of successful treatment. He added the new treatment approach would likely be used in combination with other existing therapies like radiation, surgery, other chemotherapies and targeted molecular treatments. The scientists continue their research with additional testing in human cell lines and “humanized” mouse models of high-grade glioma. The mouse models are engineered to grow brain tumors derived from the tumor cells of specific patients whose families have donated biopsy samples for research. This allows researchers to test different targeted drugs in their therapeutic protocol that may best match the genetic makeup of tumors from specific individuals. Funding support for the study came in part from the National Institutes of Health (R01NS078092, R01NS075243).About Cincinnati Children’sCincinnati Children’s Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report’s 2015 Best Children’s Hospitals. It is also ranked in the top 10 for all 10 pediatric specialties, including a #1 ranking in pulmonology and #2 in both cancer and nephrology. Cincinnati Children’s, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati’s College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally-recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org. Connect on the Cincinnati Children’s blog, viaFacebook and on Twitter.
Newswise — A new registry that launches this month gives women who have uterine fibroids the opportunity to help determine which strategies are most effective in treating the common condition. The registry, called Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF), will enroll more than 10,000 women at clinics affiliated with nine medical centers across the country. Participating women will be asked at annual intervals specific questions about the treatments they’ve elected to receive, and how well the treatments seem to be working for them. Approximately three years after initial treatment, researchers at the Duke Clinical Research Institute (DCRI) will analyze the patients’ feedback to determine which procedures provide the greatest benefit to women – insights that have been lacking for both women and their physicians. Specifically, studies will focus on symptom relief, reproductive effects, and effectiveness among different patient subgroups, including African-American women, who are disproportionately affected by uterine fibroids. “This is a common condition – it affects up to 75 percent of women to varying degrees and is the leading cause of hysterectomies in the country – yet we don’t know which treatment works best for a given patient,” said the study’s principal investigator, Evan Myers, M.D., professor in the Department of Obstetrics and Gynecology at Duke University School of Medicine. “Patients have clearly stated that they wanted these questions answered, but preferred a registry to randomized trials, particularly because hysterectomy is one of the current options,” Myers said. The registry was funded in 2013 with a $20 million funding award from the Patient-Centered Outcomes Research Institute (PCORI), in partnership with the Agency for Healthcare Research and Quality (AHRQ), which provides scientific oversight and administration. The DCRI serves as the research and data coordinating center for the five-year project. Enrollments sites include Mayo Clinic Collaborative Network, University of California Fibroid Network, Henry Ford Health System, University of Mississippi Medical Center, University of North Carolina, Brigham and Women/Harvard Clinical Center, Inova Health Systems and the Department of Defense Clinical Consortium. The University of Michigan will become an enrollment site later this year. Potential participants must have a documented diagnosis of uterine fibroids and be older than 18 and young enough to still have menstrual periods. Current treatments to be evaluated are hysterectomy (removal of the uterus), myomectomy (removal of the fibroids within the uterus), endometrial ablation (laser or heat treatments to destroy the uterine lining), radiofrequency ablation (using radio waves to destroy the fibroid), uterine artery embolization (blocking blood supply to the uterus), and magnetic resonance guided focused ultrasound (using ultrasound to destroy the fibroids). The study will add other treatments, including medications. “Uterine fibroids have a big impact on women’s quality of life, affecting their ability to work and to participate in the things that they enjoy,” Myers said. “There are also high costs, both in treatments and in managing the pain and heavy bleeding that many women experience. “One of the things that makes fibroids difficult to study is that they cause lots of different kinds of symptoms, and the symptoms can be complex, ranging from fairly minor discomfort to infertility,” Myers said. “This registry for the first time will help us collect strong, relevant information from the patients themselves that can then be analyzed to determine what treatments work best for which women.” Patient advocacy groups, which had been integral in helping design the study, said the registry launch this month is a much-anticipated milestone. "There are far too many women suffering with complications from uterine fibroids. This research effort initiated by AHRQ and PCORI is groundbreaking and crucial,” said Sateria Venable, founder & executive director of the Fibroid Foundation. “My hope is that COMPARE-UF will lead the way to more consistently and adequately funded fibroid research. If we focus our efforts, we will reap the rewards - health, fertility and quality of life."
Newswise — It is well known that men and women differ in terms of cancer susceptibility, survival and mortality, but exactly why this occurs at a molecular level has been poorly understood. A study at The University of Texas MD Anderson Cancer Center reviewed 13 cancer types and provided a molecular understanding of sex effects in diverse cancers. The research revealed two cancer-type groups associated with cancer incidence and mortality, suggesting a “pressing need” to develop sex-specific therapeutic strategies for some cancers. The research findings are published in the May 9 online issue of Cancer Cell. Using data from The Cancer Genome Atlas, a team led by Han Liang, Ph.D., associate professor of Bioinformatics and Computational Biology, found more than half of the genes studied that were related to clinical practice of cancer treatment showed sex-biased signatures in certain cancer types. “Our study helps elucidate the molecular basis for sex disparities in cancer and lays a critical foundation for the future development of precision cancer medicine that is sex-specific,” said Liang. “This is a crucial finding as currently, male and female patients with many cancer types often are treated in a similar way without explicitly considering their gender.” Liang’s group performed a comprehensive analysis of molecular differences between male and female patients, revealing two sex-effect groups associated with distinct incidence and mortality profiles and accounting for 53 percent of clinically actionable genes. Those genes are informative for clinical decisions and are either therapeutic targets or biomarkers that can help predict patient survival or tumor response. In the study, Liang found one group contained a small number of sex-affected genes (weak group), while the other showed a much greater number of sex-biased molecular signatures (strong group). Liang said the current equal treatment of both genders may be appropriate for those in the “weak” group, but observations in the “strong” group are clinically significant. “Special consideration should be given to those in the strong sex-effect group in terms of both drug development and practice,” said Liang. “For a therapeutic target with a strong sex-biased signature, sex-specific clinical trials may be more likely to succeed. This new information is vital as the fundamental issue of sex differences for cancer prevention and therapy has not been investigated systematically.” Liang’s team analyzed data in patient cohorts of 30 or greater samples for each sex for various cancers of the bladder, colon, kidney, brain, rectum, thyroid, liver and lung as well as acute myeloid leukemia. They looked for specific molecular data including somatic mutations, copy alterations, protein and gene expression and DNA methylation. The study included controls for other factors such as race, age, disease stage, smoking status and tumor purity. “Interestingly, our analysis also suggested that sex bias might be amplified during the tumor formation process,” said Liang. “However this observation should be interpreted with caution at this early stage as further efforts are needed to determine the relative contributions of other factors, including tumorigenesis, sex chromosomes and hormones.” MD Anderson members of the study team included Yuan Yuan, Ph.D., and Jun Li, Ph.D., of Bioinformatics and Computational Biology; Huzhang Ma, Ph.D., and Liang Li, Ph.D., Biostatistics; and Gordon Mills, M.D., Ph.D., Systems Biology. Other participating institutions included Baylor College of Medicine, Houston; Johns Hopkins University, Baltimore; The University of Texas Health Science Center at Houston; and Nanjin Medical University, Nanjing, China. The study was funded by the National Institutes of Health (CA175486 and CA016672), the Cancer Prevention and Research Institute of Texas (RP140462), the Jeanne F. Shelby Scholarship Fund, the Lorraine Dell Program in Bioinformatics for Personalization of Cancer Medicine, the National Natural Science Foundation of China (81472782), the Natural Science Foundation of Jiangsu Province (BK20141491), Six Talent Peaks Foundation of Jiangsu Province (2012-WS-026) and the “333” Talents Project of Jiangsu Province.
Newswise — Consuming a high-fructose diet during pregnancy may cause defects in the placenta and restrict fetal growth, potentially increasing a baby’s risk for metabolic health problems later in life, according to research in mice and people by a team at Washington University School of Medicine in St. Louis. However, giving the mice allopurinol, a generic drug frequently prescribed to treat gout and kidney stones, appears to mitigate the negative maternal and fetal effects. The findings suggest it may be possible to devise a prenatal screening test and treatment plan for pregnant women with high fructose levels. The study is available online in Scientific Reports, a journal affiliated with Nature Publishing Group. Fructose, a sugar occurring naturally in fruits and honey, has been popular for decades among food manufacturers who process it into high-fructose corn syrup used to sweeten food and beverages. In fact, researchers have reported that the refined sugar accounts for more than half of all sweeteners used in the U.S. food-supply chain. And in recent years, there’s growing concern that fructose in processed foods and sugary drinks may be linked to diabetes and obesity. “Since the early 1970s, we’ve been eating more fructose than we should,” said Kelle H. Moley, MD, the School of Medicine’s James P. Crane Professor of Obstetrics and Gynecology and the study’s senior author. “It is becoming increasingly critical to understand how fructose consumption is impacting human health. This study shows potentially negative effects of a high-fructose diet during pregnancy.” Fructose is processed differently than other sugars such as glucose, which the body converts into energy. Instead, fructose is broken down by liver cells that turn the sugar into a form of fat known as triglycerides while also driving high levels of uric acid, a normal waste product found in urine and stool. Too much uric acid can create metabolic mayhem resulting in obesity, type 2 diabetes and other health conditions. Studying mice, the researchers found elevated uric acid and triglycerides in otherwise healthy mice who were fed a high-fructose diet during pregnancy. Additionally, the mice developed smaller fetuses and larger placentas than those fed standard rodent chow. Genetically, Moley said, a small fetus may become wired to grow more after birth than a normal-sized fetus. “The body tries to compensate for the small growth in utero,” Moley said. “These babies can become kids and then adults struggling with obesity and other health problems.” Maternal health also may suffer. Metabolic problems caused by high levels of uric acid and fat increase a woman’s risk of developing pregnancy complications such as preeclampsia — a potentially serious condition in pregnancy often marked by high blood pressure, swelling and high protein levels in the urine — and gestational diabetes, Moley said. To assess the relevance of the mouse data in pregnant women, the researchers examined the association between fructose and placental uric acid levels in a small controlled group of 18 women who underwent scheduled cesarean sections. The women had no disorders that would have caused elevated uric acid. “We found a correlation suggesting similar maternal and fetal effects occur in humans,” Moley said. In the mouse model, researchers found that giving mice with high-fructose levels the common drug allopurinol – a prescription medication that reduces uric acid — reversed the refined sugar’s negative maternal and fetal effects by reducing the levels of uric acid in the placenta. “The negative effect of excess fructose in humans is likely to lead to an exacerbation of the problems seen in the mice,” said Moley, who believes additional research may lead to a prenatal screening test for measuring fructose levels. This can be determined by simple blood work. Besides advising pregnant women to limit fructose in their diets, treatment for those with high-fructose levels may include administering allopurinol, which crosses the placenta and generally is considered safe to take late in the second trimester or third trimester during pregnancy, Moley said. “One of the best ways to ensure healthy maternal and fetal outcomes is by eating natural foods,” she said. Future studies will test the effectiveness of giving allopurinol to pregnant women when there is concern about fetal growth, Moley added. The study’s lead author was Zeenat Asghar, a graduate student in molecular cell biology in the university’s Division of Biology and Biomedical Sciences.
Newswise — Pterostilbene (PS), a component of blueberries, have been found to protect against dry eye disease according to a new study. The research is being presented at the 2016 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) this week in Seattle, Wash. When introduced to human corneal epithelial cells, PS significantly reduced the levels of oxidative damage, which in turn reduced inflammation. Inflammation can contribute to dry eye disease, a condition that becomes increasing common with age. PS is a molecule chemically related to resveratrol. Abstract Title: Blueberry Component Pterostilbene Protects Corneal Epithelial Cells from Inflammatory and oxidative stress The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include nearly 12,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders.All abstracts accepted for presentation at the ARVO Annual Meeting represent previously unpublished data and conclusions. This research may be proprietary or may have been submitted for journal publication. Embargo policy: Journalists must seek approval from the presenter(s) before reporting data from paper or poster presentations. Press releases or stories on information presented at the ARVO Annual Meeting may not be released or published until the conclusion of the presentation.