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.
Piet J.,University of Aarhus |
Wurtzen H.,Danish Cancer Society |
Zachariae R.,Aarhus University Hospital
Journal of Consulting and Clinical Psychology | Year: 2012
Objective: The use of mindfulness-based therapy (MBT) in oncology settings has become increasingly popular, and research in the field has rapidly expanded. The objective was by means of a systematic review and meta-analysis to evaluate the current evidence for the effect of MBT on symptoms of anxiety and depression in adult cancer patients and survivors. Method: Electronic databases were searched, and researchers were contacted for further relevant studies. Twenty-two independent studies with a total of 1,403 participants were included. Studies were coded for quality (range: 0-4), and overall effect size analyses were performed separately for nonrandomized studies (K = 13, n = 448) and randomized controlled trials (RCTs; K = 9, n = 955). Effect sizes were combined using the random-effects model. Results: In the aggregated sample of nonrandomized studies (average quality score: 0.5), MBT was associated with significantly reduced symptoms of anxiety and depression from pre-to posttreatment corresponding to moderate effect sizes (Hedges\'s g) of 0.60 and 0.42, respectively. The pooled controlled effect sizes (Hedges\'s g) of RCTs (average quality score: 2.9) were 0.37 for anxiety symptoms (p <.001) and 0.44 for symptoms of depression (p <.001). These effect sizes appeared robust. Furthermore, in RCTs, MBT significantly improved mindfulness skills (Hedges\'s g = 0.39). Conclusion: While the overall quality of existing clinical trials varies considerably, there appears to be some positive evidence from relatively high-quality RCTs to support the use of MBT for cancer patients and survivors with symptoms of anxiety and depression. © 2012 American Psychological Association.
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.