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Among 12- to 17-year-olds who have never used tobacco products, nearly half were considered receptive to tobacco marketing if they were able to recall or liked at least one advertisement, report a coalition of behavioral scientists in a new national study. Receptivity to tobacco ads is associated with an increased susceptibility to smoking cigarettes in the future. Led by researchers at University of California San Diego Moores Cancer Center and Dartmouth's Norris Cotton Cancer Center, the researchers analyzed data from the Population Assessment of Tobacco and Health (PATH) Study, which included interviews with 10,751 adolescents who reported having never used any type of tobacco product. Risk to use a tobacco product in the future was the researchers' main point of interest. The findings are published in the May 22 issue of Pediatrics. "Tobacco marketing restrictions differ by product with only e-cigarettes allowed to be advertised on television," said John P. Pierce, PhD, Professor Emeritus in the Department of Family Medicine and Public Health at UC San Diego School of Medicine and Moores Cancer Center and lead author on the study. "Previous studies have linked receptivity to cigarette advertising with susceptibility to smoke cigarettes among youth. What we're seeing in this study is that even being receptive to marketing of non-cigarette tobacco products, including e-cigarettes, is associated with susceptibility to smoke cigarettes." In this analysis of the first wave of data from the PATH Study, respondents were considered susceptible to tobacco or committed to never using these products based on responses to three questions assessing their curiosity about the product, intention to try it in the near future, and likely response if a best friend were to offer them the product. Only those with the strongest rejection to all three questions were categorized as committed to never use. All others were susceptible. This index has been validated in multiple studies. Participants were shown 20 tobacco ads chosen randomly from 959 ads representing all available recent commercials used in print, direct mail, internet or television advertisements. Each respondent was asked initially to name his or her favorite tobacco ad and then shown a random set of five ads for each of the following products: cigarettes, e-cigarettes, cigars and smokeless products. For each ad presented, they were asked if they had seen the ad in the past 12 months and whether they liked the ad. Aided recall was classified as low receptivity while image-liking or favorite ad was considered to be higher. A high proportion of under-aged adolescents in the United States are still exposed to tobacco advertising. The study found that 41 percent of 12- to 13-year-olds, and about half of both 14- to 15-year-olds and 16- to 17-year-olds were receptive to any type of tobacco advertising. "Six of the top 10 most recognized tobacco ads by adolescents were for e-cigarettes, four of which were aired on TV," said James Sargent, MD, director of the C. Everett Koop Institute at Dartmouth and co-author. "The PATH Study will continue to track these adolescents who have not used tobacco and will be able to identify if receptivity to marketing for different tobacco products during wave 1 of the study -- particularly e-cigarette marketing -- increases cigarette smoking one or two years later." Receptivity to advertising was highest for e-cigarettes with 28 to 33 percent across age groups, followed by 22 to 25 percent for cigarettes and 15 to 21 percent for cigars. E-cigarette advertising is of interest to researchers because of its presence on television and because showing people vaping is very similar to showing people smoking, said Pierce. The proportion who were susceptible to using tobacco products increased with the level of receptivity. Fifty percent of respondents considered to have low receptivity, 65 percent who were moderately receptive and 87 percent of youth who were deemed highly receptive were susceptible to use tobacco products. "Cigarette smoking is still a major problem and a major cause of lung cancer and other diseases," said Pierce. "We've had big declines in the number of people who initiated smoking, but it is important that we maintain that reduction." Co-authors include: Martha White, David R. Strong, Eric Leas, Madison Noble, Dennis Trinidad, Karen Messer, UC San Diego; Nicolette Borek, David B. Portnoy, Blair N. Coleman, US Food and Drug Administration; Victoria R. Green, National Institutes of Health and Kelly Government Solutions; Annette R. Kaufman, National Cancer Institute; Cassandra A. Stanton, Westat and Georgetown University Medical Center; Maansi Bansal-Travers, Andrew Hyland, Roswell Park Cancer Institute; Jennifer Pearson, Johns Hopkins University and Schroeder Institute for Tobacco Research and Policy Studies at Truth Initiative; Meghan B. Moran, Johns Hopkins University; and Charles Carusi, Westat.


HANOVER, NH - Pre-school age children who are exposed to child-targeted fast-food advertising on television are considerably more likely to consume fast-food products, according to a recent Dartmouth-led study published in the journal Public Health Nutrition. According to the Federal Trade Commission, the greatest exposure to food advertising in the US for children aged 2-11 years comes from fast-food restaurant chains. In 2009, the fast-food industry spent more than $580 million on child-targeted marketing, with television being the predominant medium. "In general, children's consumption of fast food is associated with increased intakes of calories, fat and sugar, making fast-food consumption an important risk factor for obesity and other health problems," says Madeline Dalton, PhD, lead author on the study, who is a professor of pediatrics at Dartmouth's Geisel School of Medicine and a researcher at the Dartmouth-Hitchcock Norris Cotton Cancer Center. "We also know that dietary practices that are formed early in life are carried throughout adolescence and adulthood." Funded by the National Institutes of Health, the study is the first research conducted in a community setting to demonstrate a significant positive association between child-directed fast-food TV ads and increased consumption of fast food among children of pre-school age. "Most parents won't be surprised by the study's findings since they probably know this from observing their own children, and the results are also consistent with food marketing influences that have been observed in highly controlled laboratory settings," Dalton says. "I think what's significant about this study is we're using scientific methods we've developed over the past two decades to measure media and advertising exposure in an objective way, so that the findings are generalizable to real life and we're able to control for influences that we know are important--like parents' fast-food consumption and the overall amount of TV that children watch," she says. In the nine-month study, the research team recruited a total of 548 parents who had a pre-school age child (average of 4.4 years) to complete a written survey during their visits to pediatric and women, infant, and children clinics in Southern New Hampshire. Parents reported their child's viewing time, channels watched, and fast-food consumption during the past week. Their responses were combined with a list of fast-food commercials that were aired on kids' TV channels during that same period to calculate the children's exposure to child-targeted TV ads from three fast-food restaurant chains: McDonald's, Subway, and Wendy's. -- 43 percent of the preschoolers ate food from these restaurants during the past week; a similar percentage (41 percent) had been exposed to the TV ads. --Moderate or high exposure to TV ads increased the likelihood of consuming the fast food by about 30 percent. --Importantly, this association was independent of the overall number of hours of TV the children watched, the frequency with which their parents ate fast food, and other factors like socioeconomic status. --McDonald's accounted for nearly three-quarters of the TV commercials and an even greater proportion (79 percent) of the children's fast-food consumption. According to Dalton, the findings are particularly concerning because children under six years of age can't distinguish between advertisements and programs when they're watching TV--which makes them very vulnerable to persuasive messaging. "These data provide empirical evidence in support of policy recommendations to limit child-directed fast-food marketing on TV," Dalton says. Meghan Longacre, PhD, a study co-author and assistant professor of biomedical data sciences at Geisel, adds, "An important part of the take-home message for parents is that there are preschool channels that don't feature fast-food advertising, and to the extent that they can direct their child's viewing to those channels exclusively, they themselves can protect their children from that exposure." While Dalton considers the findings to be "very significant," she says more research needs to be done to inform national policy around child-targeted fast-food marketing practices. "The biggest limitation of our study is that it's cross-sectional, so we're talking about association, not causality," she explains. "The next step is a longitudinal study, which will also allow us to collect and analyze data on things like the actual food choices children make and even more precise estimates of their viewing time per channel." This research was funded by the National Institutes of Health, grant number R01HD071021. Co-authors on the study include: Linda Titus, PhD, Kristy Hendricks, PhD, Keith Drake, PhD, Lauren Cleveland, MS, from the Geisel School of Medicine, and Jennifer Harris, PhD, MBA, from the Rudd Center for Food Policy and Obesity at the University of Connecticut. Founded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, health care policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America's leading medical schools, Dartmouth's Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in health care.


News Article | June 28, 2017
Site: www.eurekalert.org

Electronic (e)-cigarette use has risen rapidly among adolescents and young adults since the product was introduced to the U.S. in 2007 and now exceeds the rate of cigarette smoking in this segment of the population. E-cigarettes may harm public health and ultimately increase the burden of cancer if their use contributes to more cigarette smoking among youth. A new collaborative Dartmouth study led by Samir, Soneji, MA, PhD, and James Sargent, MD, demonstrates that this potential harm of e-cigarettes should be taken very seriously. The study focused on an important and controversial question: Does e-cigarette use increase the risk of future cigarette smoking among adolescents and young adults? The team conducted a systematic review and meta-analysis of published studies that began with nonsmoking youths and asked whether initial e-cigarettes use increased the risk they would subsequently transition to smoking cigarettes. To rule out the possibility that e-cigarette users were simply higher risk youths, the analyses adjusted for known risk factors for cigarette smoking (like having a friend that smokes). The results showed strong and consistent evidence of greater risk between initial e-cigarette use and subsequent cigarette smoking initiation, regardless of how initiation was defined and net other factors that predict cigarette smoking. Their findings, "E-Cigarette Use and Subsequent Cigarette Smoking Among Adolescents and Young Adults: A Systematic Review and Meta-Analysis" will be published in an upcoming issue of JAMA Pediatrics. The studies did not address why e-cigarette use increases risk of transitioning to cigarettes. The reason could be that e-cigarettes mimic smoking behavior through similar involvement of hand-to-mouth movements, or puffing and exhalation. E-cigarette aerosol also contains nicotine, so use of these devices could enhance exposure and eventual addiction to this substance. "The finding is very consistent across studies. That along with the strength of the association makes it probable that e-cigarette use is one cause of cigarette smoking," said James Sargent. "E-cigarette use could affect population trends in youth smoking if use becomes more common, and that is the big public health concern." "In addition to the currently enacted age restrictions on in-store sales, regulatory actions to limit e-cigarette use could include restrictions on advertising campaigns that may be viewed by adolescents, flavor restrictions for e-cigarettes that exclude fruit and candy flavors, strict standards for reporting actual nicotine content in e-liquid, and requirements for strict age verification for online and retail sales of these products" suggests Soneji. Until more effective regulatory actions are taken, the team will continue to evaluate the excess risk posed by e-cigarette use for cigarette smoking with newer generations of e-cigarettes. Samir Soneji, MA, PhD, is an Assistant Professor of The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth and member of the Cancer Control Research Program at Dartmouth-Hitchcock Norris Cotton Cancer Center. James Sargent, MD, is a Professor of Pediatrics, Biomedical Data Science, Community and Family Medicine and Pediatric Oncology at Dartmouth's Geisel School of Medicine, co-Director of the Cancer Control Research Program at Dartmouth-Hitchcock Norris Cotton Cancer Center and Director of the C. Everett Koop Institute at Dartmouth. This work was funded by the National Cancer Institute, the Food and Drug Administration, the Center for Tobacco Products and the National Institute on Drug Abuse at the National Institutes of Health. Norris Cotton Cancer Center combines advanced cancer research at Dartmouth's Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center in Lebanon, NH, at Dartmouth-Hitchcock regional locations in Manchester, Nashua and Keene, NH, and St. Johnsbury, VT, and at partner hospitals throughout New Hampshire and Vermont. It is one of 45 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.


News Article | July 7, 2017
Site: www.eurekalert.org

LEBANON, NH - Significant research funding in the form of a five-year, $12.1 million U19 Grant from the National Institutes of Health (NIH) has been awarded to a collaboration of research teams co-led by Dartmouth's Christopher Amos, PhD, to study and improve precision of lung cancer risk and screening. The title of this multiple-PI grant is "Integrative analysis of lung cancer etiology and risk" and the total award over five years totals $12,177,381. "The goal is to enhance our understanding of gene-environment interactions in lung cancer etiology and to move the observations about risk for lung cancer towards translation" said Amos. For more than 30 years lung cancer has remained the most common cancer, and carries with it the highest cancer mortality rate worldwide, largely due to late-stage diagnosis. With this grant funding, the team particularly aims to more precisely target lung cancer screening to reduce its burden and improve the yield of detection for early lung cancer. This research funding relates to and greatly extends the team's recently published Nature Genetics paper, "Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes." The paper details the results of a huge study that identified several new variants for lung cancer risk that will translate into improved understanding of the mechanisms involved in lung cancer risk. Using the OncoArray genotyping platform developed by multiple cancer consortia, the genomewide association study identifies new susceptibility loci for lung cancer. Although tobacco smoking is the main risk factor, past studies have also shown heritability of lung cancer as a concern, though much of it remains unexplained. The cooperative grant study will be arranged into three complementary projects working towards a unifying goal. Project 1, Genomic Predictors of Smoking Lung Cancer Risk, studies large samples to identify variants that affect risk through genetic factors and environmental exposures. Project 2, Biomarkers of Lung Cancer Risk evaluates a wide range of risk biomarkers that have been implicated as promising lung cancer risk biomarkers and will identify validated risk biomarkers for use in risk prediction models. Project 3, Translating Molecular and Clinical Data to Population Lung Cancer Risk Assessment establishes an integrated risk prediction model based on lung cancer CT screening populations in the United States, Canada and Europe. It combines personal health and exposure history with targeted molecular and genomic profiles and lung function data, and establishes nodule assessment models for individuals qualified by the probability models. "We believe that this level of integration will yield novel observations about lung cancer development and provide unique translational opportunities to refine screening eligibility criteria" said Amos. "Ultimately, it will help improve screening efficiency and further reduce lung cancer mortality." Christopher Amos is Chair of the Department of Biomedical Data Science, Head of the Center for Genomic Medicine, Interim Director of Norris Cotton Cancer Center, and Associate Director for Population Sciences Geisel School of Medicine at Dartmouth. He serves as the communicating PI, the PI of the administrative core and the PI of Project 1. Other Dartmouth investigators include Ivan Gorlov, PhD, Olga Gorlova, PhD, and Jiang Gui, PhD. Paul Brennan, PhD from the International Agency for Research in Cancer, part of the World Health Organization in Lyon, France is the Project 2 leader, focusing on identifying and validating biomarkers of early lung cancer. Rayjean Hung, PhD, at the University of Toronto is the PI of project 3 focusing on applying these biomarkers in all the world's largest screening cohorts. Xihong Lin, PhD, at the Chan Harvard School of Public Health is the PI of the biostatistics core. Norris Cotton Cancer Center combines advanced cancer research at Dartmouth's Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center in Lebanon, NH, at Dartmouth-Hitchcock regional locations in Manchester, Nashua and Keene, NH, and St. Johnsbury, VT, and at partner hospitals throughout New Hampshire and Vermont. It is one of 48 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.


Compton D.A.,Norris Cotton Cancer Center
Current Opinion in Cell Biology | Year: 2011

Accurate chromosome segregation during cell division is essential for genome integrity. Errors in chromosome segregation are irreversible and lead to a state of aneuploidy where the number of chromosomes in a cell or organism is not a multiple of the haploid number of chromosomes. Aneuploidy reduces fecundity and is a frequent cause of inherited birth defects. In addition, aneuploidy is very common in solid tumors where it is associated with poor patient prognosis. Recent work has revealed the most common pathways by which chromosomes mis-segregate leading to aneuploidy. Moreover, answers to the key question of how cells respond to aneuploidy are beginning to emerge. © 2010 Elsevier Ltd.


Kaur M.,Dartmouth College | Cole M.D.,Norris Cotton Cancer Center
Cancer Research | Year: 2013

The control of normal cell growth is a balance between stimulatory and inhibitory signals. MYC is a pleiotropic transcription factor that both activates and represses a broad range of target genes and is indispensable for cell growth. Whereas much is known about gene activation by MYC, there is no established mechanism for the majority of MYC-repressed genes. We report that MYC transcriptionally activates the PTEN tumor suppressor in normal cells to inactivate the phosphoinositide 3-kinase (PI3K) pathway, thus suppressing AKT activation. Suppression of AKT enhances the activity of the EZH2 histone methyltransferase, a subunit of the epigenetic repressor Polycomb Repressive Complex 2 (PRC2), while simultaneously stabilizing the protein. MYC-mediated enhancement in EZH2 protein level and activity results in local and genome-wide elevation in the repressive H3K27me3 histone modification, leading to widespread gene repression including feedback autoregulation of the MYC gene itself. Depletion of either PTEN or EZH2 and inhibition of the PI3K/AKT pathway leads to gene derepression. Importantly, expression of a phospho-defective EZH2 mutant is sufficient to recapitulate nearly half of all MYC-mediated gene repression. We present a novel epigenetic model for MYC-mediated gene repression and propose that PTEN and MYC exist in homeostatic balance to control normal growth, which is disrupted in cancer cells. © 2012 AACR.


Kisselev A.F.,Norris Cotton Cancer Center | Van Der Linden W.A.,Leiden University | Overkleeft H.S.,Leiden University
Chemistry and Biology | Year: 2012

Proteasomes are large, multisubunit proteolytic complexes presenting multiple targets for therapeutic intervention. The 26S proteasome consists of a 20S proteolytic core and one or two 19S regulatory particles. The 20S core contains three types of active sites. Many structurally diverse inhibitors of these active sites, both natural product and synthetic, have been discovered in the last two decades. One, bortezomib, is used clinically for treatment of multiple myeloma, mantle cell lymphoma, and acute allograft rejection. Five more recently developed proteasome inhibitors are in trials for treatment of myeloma and other cancers. Proteasome inhibitors also have activity in animal models of autoimmune and inflammatory diseases, reperfusion injury, promote bone and hair growth, and can potentially be used as anti-infectives. In addition, inhibitors of ATPases and deubiquitinases of 19S regulatory particles have been discovered in the last decade. © 2012 Elsevier Ltd All rights reserved.


Rolland S.G.,Norris Cotton Cancer Center | Conradt B.,Norris Cotton Cancer Center
Current Opinion in Cell Biology | Year: 2010

Mitochondria are highly dynamic organelles that constantly fuse and divide. Dynamin-related GTPases are the core components of the machineries that mediate mitochondrial fusion and fission. The role and regulation of these machineries are currently under intense investigation. Recently, members of the BCL2 family of proteins, conserved regulators of apoptosis, have been implicated in the regulation of mitochondrial dynamics. Here, we review the functions of mitochondrial fusion and fission in apoptotic and nonapoptotic cells and how members of the BCL2 family of proteins regulate these functions. © 2010 Elsevier Ltd.


Miller T.W.,Norris Cotton Cancer Center
Clinical Cancer Research | Year: 2014

Low estrogen receptor (ER) levels in breast tumors are associated with poorer response to antiestrogen therapy. Finn and colleagues identify low ER levels as a biomarker predicting benefit from the addition of the EGFR/HER2 dual inhibitor lapatinib to an antiestrogen treatment regimen in patients with metastatic ER+/HER2- breast cancer. © 2014 American Association for Cancer Research.


Sempere L.F.,Norris Cotton Cancer Center
Expert Review of Molecular Diagnostics | Year: 2011

The promise of personalized medicine is highly dependent on the identification of biomarkers that inform diagnostic decisions and treatment options, as well as on the accurate, rapid and cost-effective detection and interpretation of these biomarkers. miRNAs, which are short noncoding regulatory RNAs, are rapidly emerging as a novel class of biomarkers with a unique set of biological and chemical properties that makes them very appealing candidates for theranostic applications in cancer. Since the utility of some protein-encoding gene biomarkers is already exploited in routine clinical practice, it will be important to identify areas in which miRNAs provide complementary or superior information to these existing (and other translational) biomarkers to enhance the diagnostic, prognostic and predictive power of molecular characterization of tumors. In this article, the challenges and opportunities for integration of miRNA-based assays in the clinical toolkit to improve care and management of patients afflicted with solid tumors will be discussed. © 2011 Lorenzo F Sempere.

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