TY - JOUR A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Häggström, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort JF - International journal of cancer N2 - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood. KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - https://doi.org/10.1002/ijc.33339 SN - 0020-7136 SN - 1097-0215 VL - 148 IS - 7 SP - 1637 EP - 1651 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Schürmann, Robin Mathis A1 - Vogel, Stefanie A1 - Ebel, Kenny A1 - Bald, Ilko T1 - The physico-chemical basis of DNA radiosensitization BT - implications for cancer radiation therapy JF - Chemistry - a European journal N2 - High-energy radiation is used in combination with radiosensitizing therapeutics to treat cancer. The most common radiosensitizers are halogenated nucleosides and cisplatin derivatives, and recently also metal nanoparticles have been suggested as potential radiosensitizing agents. The radiosensitizing action of these compounds can at least partly be ascribed to an enhanced reactivity towards secondary low-energy electrons generated along the radiation track of the high-energy primary radiation, or to an additional emission of secondary reactive electrons close to the tumor tissue. This is referred to as physico-chemical radiosensitization. In this Concept article we present current experimental methods used to study fundamental processes of physico-chemical radiosensitization and discuss the most relevant classes of radiosensitizers. Open questions in the current discussions are identified and future directions outlined, which can lead to optimized treatment protocols or even novel therapeutic concepts. KW - cancer KW - dissociative electron attachment KW - low-energy electrons KW - radiation therapy KW - radiosensitizers Y1 - 2018 U6 - https://doi.org/10.1002/chem.201800804 SN - 0947-6539 SN - 1521-3765 VL - 24 IS - 41 SP - 10271 EP - 10279 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Kühne, Franziska A1 - Hermann, Myriel A1 - Preisler, Martina A1 - Rohrmoser, Amy A1 - Letsch, Anne A1 - Goerling, Ute T1 - Prognostic Awareness in Advanced Disease BT - A Review Update and Concept Analysis JF - Frontiers in Psychology N2 - Purpose: Although subjective knowledge about the prognosis of an advanced disease is extremely important for coping and treatment planning, the concept of prognostic awareness (PA) remains inconsistently defined. The aims of the scoping review were to synthesize a definition of PA from the most recent literature, describe preconditions, correlates and consequences, and suggest a conceptual model. Methods: By using scoping review methodology, we searched the Web of Science and PubMed databases, and included publications, reviews, meta-analyses or guidelines on all physical diagnoses, as well as publications offering a conceptual or an operational definition of PA. The data were analyzed by means of content analysis techniques. Results: Of the 24 included publications, 21 referred exclusively to cancer, one to patients with hip fractures and two to palliative care in general. The deduced definition of PA comprised the following facets: adequate estimation of chances for recovery, knowledge of limited time to live, adequate estimation of life expectancy, knowledge of therapy goals, and knowledge of the course of the disease. Further content analysis results were mapped graphically and in a detailed table. Conclusion: There appears to be a lack of theoretical embedding of PA that in turn influences the methods used for empirical investigation. Drawing on a clear conceptual definition, longitudinal or experimental studies would be desirable. KW - prognosis KW - cancer KW - oncology KW - palliative care KW - patient-centered care KW - systematic review KW - advanced disease Y1 - 2020 U6 - https://doi.org/10.3389/fpsyg.2021.629050 SN - 1664-1078 VL - 12 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Galbete, Cecilia A1 - Kröger, Janine A1 - Jannasch, Franziska A1 - Iqbal, Khalid A1 - Schwingshackl, Lukas A1 - Schwedhelm, Carolina A1 - Weikert, Cornelia A1 - Boeing, Heiner A1 - Schulze, Matthias Bernd T1 - Nordic diet, Mediterranean diet, and the risk of chronic diseases BT - the EPIC-Potsdam study JF - BMC Medicine N2 - Background: The Mediterranean Diet (MedDiet) has been acknowledged as a healthy diet. However, its relation with risk of major chronic diseases in non-Mediterranean countries is inconclusive. The Nordic diet is proposed as an alternative across Northern Europe, although its associations with the risk of chronic diseases remain controversial. We aimed to investigate the association between the Nordic diet and the MedDiet with the risk of chronic disease (type 2 diabetes (T2D), myocardial infarction (MI), stroke, and cancer) in the EPIC-Potsdam cohort. Methods: The EPIC-Potsdam cohort recruited 27,548 participants between 1994 and 1998. After exclusion of prevalent cases, we evaluated baseline adherence to a score reflecting the Nordic diet and two MedDiet scores (tMDS, reflecting the traditional MedDiet score, and the MedPyr score, reflecting the MedDiet Pyramid). Cox regression models were applied to examine the association between the diet scores and the incidence of major chronic diseases. Results: During a follow-up of 10.6 years, 1376 cases of T2D, 312 of MI, 321 of stroke, and 1618 of cancer were identified. The Nordic diet showed a statistically non-significant inverse association with incidence of MI in the overall population and of stroke in men. Adherence to the MedDiet was associated with lower incidence of T2D (HR per 1 SD 0.93, 95% CI 0.88-0.98 for the tMDS score and 0.92, 0.87-0.97 for the MedPyr score). In women, the MedPyr score was also inversely associated with MI. No association was observed for any of the scores with cancer. Conclusions: In the EPIC-Potsdam cohort, the Nordic diet showed a possible beneficial effect on MI in the overall population and for stroke in men, while both scores reflecting the MedDiet conferred lower risk of T2D in the overall population and of MI in women. KW - Mediterranean diet KW - Nordic diet KW - regional diets KW - chronic diseases KW - diabetes KW - myocardial infarction KW - stroke KW - cancer KW - EPIC-Potsdam study KW - longitudinal analysis Y1 - 2018 U6 - https://doi.org/10.1186/s12916-018-1082-y SN - 1741-7015 VL - 16 PB - BMC CY - London ER - TY - JOUR A1 - Kangas, Maria A1 - Heissel, Andreas T1 - Mental health literacy, treatment preferences and the lived experience of mental health problems in an Australian cancer sample JF - Psycho-oncology N2 - Objectives: The prevalence rates for mental health (MH) problems in cancer patients is high, although reduced uptake of services may be influenced by mental health literacy (MHL). The objective of this study was to investigate the MHL for depression and panic disorder (PD), including treatment preferences in Australian adults who had been diagnosed and treated for cancer, and whether MHL and treatment preferences was influenced by sex, age, and individuals' lived MH experience. Method: A total of 421 cancer survivors (n = 378 females) completed a self-report survey. Participants were asked to specify whether they had a lived experience with anxiety and/or depression, and to indicate treatment preferences for managing cancer-related distress. Two vignettes were administered to assess MHL for depression and PD. Results: The MHL accuracy for depression was higher than PD. Accuracy rates were higher for females with a lived experience with anxiety and/or depression; although the accuracy rate for PD was significantly lower in males. A high proportion of individuals preferred exercise and in-person counselling to manage depression and PD. Internet-based therapies were not strongly preferred for managing MH problems. Conclusions: The MHL for depression and PD is moderate for adult cancer survivors, with higher levels indicated for individuals with a personal lived experience with anxiety and/or depression. Public health campaigns for enhancing MHL should broaden to include individuals experiencing comorbid physical health conditions. Health providers also need to take into account client preferences for evidence-based therapies. KW - anxiety KW - cancer KW - exercise KW - major depression KW - mental health KW - preferences KW - psycho-oncology KW - treatment Y1 - 2020 U6 - https://doi.org/10.1002/pon.5520 SN - 1057-9249 SN - 1099-1611 VL - 29 IS - 11 SP - 1883 EP - 1894 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Dreymann, Nico A1 - Wuensche, Julia A1 - Sabrowski, Wiebke A1 - Moeller, Anja A1 - Czepluch, Denise A1 - Vu Van, Dana A1 - Füssel, Susanne A1 - Menger, Marcus M. T1 - Inhibition of Human Urokinase-Type Plasminogen Activator (uPA) Enzyme Activity and Receptor Binding by DNA Aptamers as Potential Therapeutics through Binding to the Different Forms of uPA JF - International journal of molecular sciences N2 - Urokinase-type plasminogen activator is widely discussed as a marker for cancer prognosis and diagnosis and as a target for cancer therapies. Together with its receptor, uPA plays an important role in tumorigenesis, tumor progression and metastasis. In the present study, systematic evolution of ligands by exponential enrichment (SELEX) was used to select single-stranded DNA aptamers targeting different forms of human uPA. Selected aptamers allowed the distinction between HMW-uPA and LMW-uPA, and therefore, presumably, have different binding regions. Here, uPAapt-02-FR showed highly affine binding with a K-D of 0.7 nM for HMW-uPA and 21 nM for LMW-uPA and was also able to bind to pro-uPA with a K-D of 14 nM. Furthermore, no cross-reactivity to mouse uPA or tissue-type plasminogen activator (tPA) was measured, demonstrating high specificity. Suppression of the catalytic activity of uPA and inhibition of uPAR-binding could be demonstrated through binding with different aptamers and several of their truncated variants. Since RNA aptamers are already known to inhibit uPA-uPAR binding and other pathological functions of the uPA system, these aptamers represent a novel, promising tool not only for detection of uPA but also for interfering with the pathological functions of the uPA system by additionally inhibiting uPA activity. KW - biomarker KW - cancer KW - cancer therapy KW - DNA aptamer KW - microscale thermophoresis (MST) KW - SELEX KW - surface plasmon resonance spectroscopy (SPR) KW - uPA KW - uPAR KW - urokinase Y1 - 2022 U6 - https://doi.org/10.3390/ijms23094890 SN - 1661-6596 SN - 1422-0067 VL - 23 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Li, Chen A1 - Stoma, Svetlana A1 - Lotta, Luca A. A1 - Warner, Sophie A1 - Albrecht, Eva A1 - Allione, Alessandra A1 - Arp, Pascal P. A1 - Broer, Linda A1 - Buxton, Jessica L. A1 - Boeing, Heiner A1 - Langenberg, Claudia A1 - Codd, Veryan T1 - Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length JF - American Journal of Human Genetics N2 - Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease. KW - Mendelian randomization KW - risk KW - variants KW - disease KW - cancer KW - loci KW - database KW - genes KW - heart KW - gwas Y1 - 2019 VL - 106 IS - 3 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Tzoneva, Rumiana A1 - Stoyanova, Tihomira A1 - Petrich, Annett A1 - Popova, Desislava A1 - Uzunova, Veselina A1 - Momchilova, Albena A1 - Chiantia, Salvatore T1 - Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models JF - Biomolecules N2 - Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid–lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells. KW - alkylphospholipids KW - fluorescence microscopy KW - fluorescence correlation spectroscopy KW - lipids KW - plasma membrane KW - cancer KW - lipid–lipid interactions KW - membrane microdomains KW - membrane biophysics Y1 - 2020 U6 - https://doi.org/10.3390/biom10050802 SN - 2218-273X VL - 10 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Haß, Ulrike A1 - Herpich, Catrin A1 - Norman, Kristina T1 - Anti-Inflammatory Diets and Fatigue JF - Nutrients N2 - Accumulating data indicates a link between a pro-inflammatory status and occurrence of chronic disease-related fatigue. The questions are whether the observed inflammatory profile can be (a) improved by anti-inflammatory diets, and (b) if this improvement can in turn be translated into a significant fatigue reduction. The aim of this narrative review was to investigate the effect of anti-inflammatory nutrients, foods, and diets on inflammatory markers and fatigue in various patient populations. Next to observational and epidemiological studies, a total of 21 human trials have been evaluated in this work. Current available research is indicative, rather than evident, regarding the effectiveness of individuals’ use of single nutrients with anti-inflammatory and fatigue-reducing effects. In contrast, clinical studies demonstrate that a balanced diet with whole grains high in fibers, polyphenol-rich vegetables, and omega-3 fatty acid-rich foods might be able to improve disease-related fatigue symptoms. Nonetheless, further research is needed to clarify conflicting results in the literature and substantiate the promising results from human trials on fatigue. KW - chronic fatigue KW - cancer KW - fatigue reduction diet KW - probiotics KW - polyphenols KW - omega-3 fatty acids KW - anti-inflammatory nutrition KW - cytokines KW - inflammation KW - myalgic encephalomyelitis Y1 - 2019 U6 - https://doi.org/10.3390/nu11102315 SN - 2072-6643 VL - 11 IS - 10 PB - MDPI CY - Basel ER - TY - JOUR A1 - Guo, Ranran A1 - Tian, Ye A1 - Yang, Yueqi A1 - Jiang, Qin A1 - Wang, Yajun A1 - Yang, Wuli T1 - A Yolk-Shell nanoplatform for gene-silencing-enhanced photolytic ablation of cancer JF - Advanced functional materials N2 - Noninvasive near-infrared (NIR) light responsive therapy is a promising cancer treatment modality; however, some inherent drawbacks of conventional phototherapy heavily restrict its application in clinic. Rather than producing heat or reactive oxygen species in conventional NIR treatment, here a multifunctional yolk-shell nanoplatform is proposed that is able to generate microbubbles to destruct cancer cells upon NIR laser irradiation. Besides, the therapeutic effect is highly improved through the coalition of small interfering RNA (siRNA), which is codelivered by the nanoplatform. In vitro experiments demonstrate that siRNA significantly inhibits expression of protective proteins and reduces the tolerance of cancer cells to bubble-induced environmental damage. In this way, higher cytotoxicity is achieved by utilizing the yolk-shell nanoparticles than treated with the same nanoparticles missing siRNA under NIR laser irradiation. After surface modification with polyethylene glycol and transferrin, the yolk-shell nanoparticles can target tumors selectively, as demonstrated from the photoacoustic and ultrasonic imaging in vivo. The yolk-shell nanoplatform shows outstanding tumor regression with minimal side effects under NIR laser irradiation. Therefore, the multifunctional nanoparticles that combining bubble-induced mechanical effect with RNA interference are expected to be an effective NIR light responsive oncotherapy. KW - cancer KW - gene silencing KW - near-infrared absorption KW - photolytic ablation KW - yolk-shell nanoparticles Y1 - 2018 U6 - https://doi.org/10.1002/adfm.201706398 SN - 1616-301X SN - 1616-3028 VL - 28 IS - 14 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Jannasch, Franziska A1 - Nickel, Daniela V. A1 - Bergmann, Manuela M. A1 - Schulze, Matthias Bernd T1 - A new evidence-based diet score to capture associations of food consumption and chronic disease risk JF - Nutrients / Molecular Diversity Preservation International (MDPI) N2 - Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases. KW - diet score KW - dietary guidelines KW - food groups KW - chronic disease KW - type 2 KW - diabetes KW - cardiovascular disease KW - cancer KW - prevention KW - reliability; KW - validity Y1 - 2022 U6 - https://doi.org/10.3390/nu14112359 SN - 2072-6643 VL - 14 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Christakoudi, Sofa A1 - Tsilidis, Konstantinos K. A1 - Muller, David C. A1 - Freisling, Heinz A1 - Weiderpass, Elisabete A1 - Overvad, Kim A1 - Söderberg, Stefan A1 - Häggström, Christel A1 - Pischon, Tobias A1 - Dahm, Christina C. A1 - Zhang, Jie A1 - Tjønneland, Anne A1 - Schulze, Matthias Bernd T1 - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort JF - Scientific Reports N2 - Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring. KW - all-cause mortality KW - anthropometric measures KW - mass index KW - overweight KW - cancer KW - prediction KW - adiposity KW - size Y1 - 2020 VL - 10 IS - 1 PB - Springer Nature CY - Berlin ER -