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News Article | May 23, 2017
Site: www.eurekalert.org

Boston, MA - Consuming moderate amounts of chocolate was associated with significantly lower risk of being diagnosed with atrial fibrillation (AF)--a common and dangerous type of irregular heartbeat--in a large study of men and women in Denmark led by researchers at Harvard T.H. Chan School of Public Health and in Denmark. The study will be published online May 23, 2017 in Heart. "Our study adds to the accumulating evidence on the health benefits of moderate chocolate intake and highlights the importance of behavioral factors for potentially lowering the risk of arrhythmias," said Elizabeth Mostofsky, instructor in the Department of Epidemiology at Harvard Chan School, a postdoctoral fellow at Beth Israel Deaconess Medical Center, and lead author of the study. Previous studies have suggested that cocoa and cocoa-containing foods--in particular, dark chocolate, which has a higher cocoa content than milk chocolate--confer cardiovascular benefits, perhaps because of their high content of flavanols, which may promote healthy blood vessel function. But there has been only limited research on the association between consuming chocolate and the occurrence of AF--which affects millions of people around the world and is linked with higher risk of stroke, heart failure, cognitive decline, dementia, and death. The study included 55,502 men and women participating in the Danish Diet, Cancer, and Heath Study. Researchers considered study participants' body mass index, blood pressure, and cholesterol, which were measured at the time participants were recruited, between December 1993 and May 1997. They also looked at participants' health conditions, including high blood pressure, diabetes, or cardiovascular disease, and data on their diet and lifestyle, from questionnaires. Diagnoses of AF were identified from the Danish National Patient Register. There were 3,346 cases of AF among the study participants over a 13.5-year follow-up period. Compared with those who ate a one-ounce serving of chocolate less than once per month, men and women who ate one to three servings per month had a 10% lower rate of AF; those who ate one serving per week had a 17% lower rate; and those who ate two to six servings per week had a 20% lower rate. The benefit leveled off slightly with greater amounts of chocolate consumption, with those eating one or more servings per day having a 16% lower AF rate. Results were similar for men and women. "Despite the fact that most of the chocolate consumed by the study participants likely had relatively low concentrations of potentially protective ingredients, we still observed a significant association between eating chocolate and a lower risk of AF--suggesting that even small amounts of cocoa consumption can have a positive health impact," Mostofsky said. "Eating excessive amounts of chocolate is not recommended because many chocolate products are high in calories from sugar and fat and could lead to weight gain and other metabolic problems. But moderate intake of chocolate with high cocoa content may be a healthy choice." Senior author of the study was Kim Overdad of Aalborg University Hospital in Denmark. Murray Mittleman, professor of epidemiology at Harvard Chan School, was a co-author. Funding for the study came from grants from the National Heart, Lung, and Blood Institute (HL-115623), the European Research Council (ERC), EU 7th Research Framework Program (281760), a KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100) and the Danish Cancer Society and the Danish Council for Strategic Research (Aalborg AF-Study Group). "Chocolate Intake and Risk of Clinically Apparent Atrial Fibrillation: the Danish Diet, Cancer, and Health Study," Elizabeth Mostofsky, Martin Berg Johansen, Anne Tjønneland, Harpreet S. Chahal, Murray A. Mittleman, Kim Overvad, Heart, online May 23, 2017, doi: 10.1136/heartjnl-2016-310357 Visit the Harvard Chan School website for the latest news, press releases, and multimedia offerings. Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people's lives--not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America's oldest professional training program in public health.


Lukanidin E.,Danish Cancer Society | Sleeman J.P.,University of Heidelberg | Sleeman J.P.,Karlsruhe Institute of Technology
Seminars in Cancer Biology | Year: 2012

Communication between cancer cells and stromal cells, often mediated by extracellular molecules in the tumor microenvironment, plays a central role in tumorigenesis and metastasis. The establishment of a pro-inflammatory milieu is increasingly recognized as an important consequence of these interactions. The family of S100 Ca2+-binding proteins has been implicated in many aspects of the interaction between cancer cells and stromal cells, and contributes to the formation of an inflammatory tumor microenvironment. Focusing on S100A4, S100A8 and S100A9, in this review we discuss the role these proteins play in primary tumors and in the development of metastases, in particular during the formation of pre-metastatic niches. © 2012 Elsevier Ltd.


Barisic M.,Danish Cancer Society | Maiato H.,University of Porto
Trends in Cell Biology | Year: 2016

Before chromosomes segregate during mitosis in metazoans, they align at the cell equator by a process known as chromosome congression. This is in part mediated by the coordinated activities of kinetochore motors with opposite directional preferences that transport peripheral chromosomes along distinct spindle microtubule populations. Because spindle microtubules are all made from the same α/β-tubulin heterodimers, a critical longstanding question has been how chromosomes are guided to specific locations during mitosis. This implies the existence of spatial cues/signals on specific spindle microtubules that are read by kinetochore motors on chromosomes and ultimately indicate the way towards the equator. Here, we discuss the emerging concept that tubulin post-translational modifications (PTMs), as part of the so-called tubulin code, work as a navigation system for kinetochore-based chromosome motility during early mitosis. © 2016 Elsevier Ltd


Aits S.,Danish Cancer Society | Jaattela M.,Danish Cancer Society
Journal of Cell Science | Year: 2013

Lysosomes serve as the cellular recycling centre and are filled with numerous hydrolases that can degrade most cellular macromolecules. Lysosomal membrane permeabilization and the consequent leakage of the lysosomal content into the cytosol leads to so-called "lysosomal cell death". This form of cell death is mainly carried out by the lysosomal cathepsin proteases and can have necrotic, apoptotic or apoptosis-like features depending on the extent of the leakage and the cellular context. This article summarizes our current knowledge on lysosomal cell death with an emphasis on the upstream mechanisms that lead to lysosomal membrane permeabilization. © 2013. Published by The Company of Biologists Ltd.


Hansen J.,Danish Cancer Society | Lassen C.F.,Danish Cancer Society
Occupational and Environmental Medicine | Year: 2012

Objectives: Growing but limited evidence suggests that night shift work is associated with breast cancer. The authors conducted a nationwide case-control study nested within a cohort of 18 551 female military employees born in 1929-1968 to investigate the risk for breast cancer after night shift work and to explore the role of leisure time sun exposure and diurnal preference. Methods: The authors documented 218 cases of breast cancer (1990-2003) and selected 899 age-matched controls from the cohort by incidence density sampling. Information on shift work, sun exposure habits, diurnal preference and other potential confounders was obtained from a structured questionnaire. ORs were estimated by multivariate conditional logistic regression. Results: Overall, the authors observed an adjusted OR of 1.4 (95% CI 0.9 to 2.1) among women with ever compared with never night shifts. The RR for breast cancer tended to increase with increasing number of years of night shift work (p=0.03) and with cumulative number of shifts (p=0.02),with a neutral risk for fewer than three night shifts per week. The OR for the group with the highest tertile of cumulative exposure was 2.3 (95% CI 1.2 to 4.6). The most pronounced effect of night shift work on breast cancer risk was observed in women with morning chronotype preference and intense night shifts (OR=3.9, 95% CI 1.6 to 9.5). Night shift workers tended to sunbathe more frequently than day workers. Conclusions: The results indicate that frequent night shift work increases the risk for breast cancer and suggest a higher risk with longer duration of intense night shifts. Women with morning preference who worked on night shifts tended to have a higher risk than those with evening preference.


Hansen J.,Danish Cancer Society
Journal of the National Cancer Institute | Year: 2013

Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.


Jaiswal J.K.,Center for Genetic Medicine Research | Nylandsted J.,Danish Cancer Society
Cell Cycle | Year: 2015

Mechanical activity of cells and the stress imposed on them by extracellular environment is a constant source of injury to the plasma membrane (PM). In invasive tumor cells, increased motility together with the harsh environment of the tumor stroma further increases the risk of PM injury. The impact of these stresses on tumor cell plasma membrane and mechanism by which tumor cells repair the PM damage are poorly understood. Ca2+ entry through the injured PM initiates repair of the PM. Depending on the cell type, different organelles and proteins respond to this Ca2+entry and facilitate repair of the damaged plasma membrane. We recently identified that proteins expressed in various metastatic cancers including Casup>2+ -binding EF hand protein S100A11 and its binding partner annexin A2 are used by tumor cells for plasma membrane repair (PMR). Here we will discuss the involvement of S100, annexin proteins and their regulation of actin cytoskeleton, leading to PMR. Additionally, we will show that another S100 member - S100A4 accumulates at the injured PM. These findings reveal a new role for the S100 and annexin protein up regulation in metastatic cancers and identify these proteins and PMR as targets for treatingmetastatic cancers. © 2015 Taylor & Francis Group, LLC.


Kallunki T.,Danish Cancer Society | Olsen O.D.,Danish Cancer Society | Jaattela M.,Danish Cancer Society
Oncogene | Year: 2013

Rapidly dividing and invasive cancer cells are strongly dependent on effective lysosomal function. Accordingly, transformation and cancer progression are characterized by dramatic changes in lysosomal volume, composition and cellular distribution. Depending on one's point of view, the cancer-associated changes in the lysosomal compartment can be regarded as friends or foes. Most of them are clearly transforming as they promote invasive growth, angiogenesis and drug resistance. The same changes can, however, strongly sensitize cells to lysosomal membrane permeabilization and thereby to lysosome-targeting anti-cancer drugs. In this review we compile our current knowledge on cancer-associated changes in lysosomal composition and discuss the consequences of these alterations to cancer progression and the possibilities they can bring to cancer therapy. © 2013 Macmillan Publishers Limited All rights reserved.


Lukas J.,Danish Cancer Society | Lukas C.,Danish Cancer Society | Bartek J.,Danish Cancer Society | Bartek J.,Palacky University
Nature Cell Biology | Year: 2011

Following the discovery in 1998 of Î 3-H2AX, the first histone modification induced by DNA damage, interest in the changes to chromatin induced by DNA damage has exploded, and a vast amount of information has been generated. However, there has been a discrepancy between our rapidly advancing knowledge of how chromatin responds to DNA damage and the understanding of why cells mobilize large segments of chromatin to protect the genome against destabilizing effects posed by tiny DNA lesions. Recent research has provided insights into these issues and suggests that chromatin responses induced by DNA damage are not simply the accumulation of 'nuclear foci' but are mechanisms required to guard genome integrity. © 2011 Macmillan Publishers Limited. All rights reserved.


Andersen K.K.,Danish Cancer Society | Olsen T.S.,Frederiksberg University Hospital
International Journal of Stroke | Year: 2015

Background: Although associated with excess mortality and morbidity, obesity is associated with lower mortality after stroke. The association between obesity and risk of recurrent stroke is unclear. Aims: The study aims to investigate the association in stroke patients between body mass index and risk of death and readmission for recurrent stroke. Methods: An administrative Danish quality-control registry designed to collect a predefined dataset on all hospitalized stroke patients in Denmark 2000-2010 includes 45615 acute first-ever stroke patients with information on body mass index in 29326. Data include age, gender, civil status, stroke severity, computed tomography, and cardiovascular risk factors. Patients were followed up to 9·8 years (median 2·6 years). We used Cox regression models to compare risk of death and readmission for recurrent stroke in the four body mass index groups: underweight (body mass index<18·5), normal weight (body mass index 18·5-24·9), overweight (body mass index 25·0-29·9), obese (body mass index≥30·0). Results: Mean age 72·3 years, 48% women. Mean body mass index 23·0. Within follow-up, 7902 (26·9%) patients had died; 2437 (8·3%) were readmitted because of recurrent stroke. Mortality was significantly lower in overweight (hazard ratio 0·72; confidence interval 0·68-0·78) and obese (hazard ratio 0·80; confidence interval 0·73-0·88) patients while significantly higher in underweight patients (hazard ratio 1·66; confidence interval 1·49-1·84) compared with normal weight patients. Risk of readmission for recurrent stroke was significantly lower in obese than in normal weight patients (hazard ratio 0·84; confidence interval 0·72-0·92). Conclusionsx: Obesity was not only associated with reduced mortality relative to normal weight patients. Compared with normal weight, risk of readmission for recurrent stroke was also lower in obese stroke patients. © 2013 World Stroke Organization.

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