@article{DreymannWuenscheSabrowskietal.2022, author = {Dreymann, Nico and Wuensche, Julia and Sabrowski, Wiebke and Moeller, Anja and Czepluch, Denise and Vu Van, Dana and F{\"u}ssel, Susanne and Menger, Marcus M.}, title = {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}, series = {International journal of molecular sciences}, volume = {23}, journal = {International journal of molecular sciences}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {1661-6596}, doi = {10.3390/ijms23094890}, pages = {22}, year = {2022}, abstract = {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.}, language = {en} } @article{JannaschNickelBergmannetal.2022, author = {Jannasch, Franziska and Nickel, Daniela V. and Bergmann, Manuela M. and Schulze, Matthias Bernd}, title = {A new evidence-based diet score to capture associations of food consumption and chronic disease risk}, series = {Nutrients / Molecular Diversity Preservation International (MDPI)}, volume = {14}, journal = {Nutrients / Molecular Diversity Preservation International (MDPI)}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu14112359}, pages = {16}, year = {2022}, abstract = {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.}, language = {en} } @article{KangasHeissel2020, author = {Kangas, Maria and Heissel, Andreas}, title = {Mental health literacy, treatment preferences and the lived experience of mental health problems in an Australian cancer sample}, series = {Psycho-oncology}, volume = {29}, journal = {Psycho-oncology}, number = {11}, publisher = {Wiley}, address = {New York, NY}, issn = {1057-9249}, doi = {10.1002/pon.5520}, pages = {1883 -- 1894}, year = {2020}, abstract = {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.}, language = {en} } @article{ChristakoudiPagoniFerrarietal.2020, author = {Christakoudi, Sofia and Pagoni, Panagiota and Ferrari, Pietro and Cross, Amanda J. and Tzoulaki, Ioanna and Muller, David C. and Weiderpass, Elisabete and Freisling, Heinz and Murphy, Neil and Dossus, Laure and Turzanski Fortner, Renee and Agudo, Antonio and Overvad, Kim and Perez-Cornago, Aurora and Key, Timothy J. and Brennan, Paul and Johansson, Mattias and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Artaud, Fanny and Severi, Gianluca and Kaaks, Rudolf and Schulze, Matthias Bernd and Bergmann, Manuela M. and Masala, Giovanna and Grioni, Sara and Simeon, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Skeie, Guri and Rylander, Charlotta and Borch, Kristin Benjaminsen and Quiros, J. Ramon and Rodriguez-Barranco, Miguel and Chirlaque, Maria-Dolores and Ardanaz, Eva and Amiano, Pilar and Drake, Isabel and Stocks, Tanja and H{\"a}ggstr{\"o}m, Christel and Harlid, Sophia and Ellingjord-Dale, Merete and Riboli, Elio and Tsilidis, Konstantinos K.}, title = {Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {International journal of cancer}, volume = {148}, journal = {International journal of cancer}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0020-7136}, doi = {10.1002/ijc.33339}, pages = {1637 -- 1651}, year = {2020}, abstract = {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.}, language = {en} } @article{KuehneHermannPreisleretal.2021, author = {K{\"u}hne, Franziska and Hermann, Myriel and Preisler, Martina and Rohrmoser, Amy and Letsch, Anne and Goerling, Ute}, title = {Prognostic Awareness in Advanced Disease}, series = {Frontiers in Psychology}, volume = {12}, journal = {Frontiers in Psychology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-1078}, doi = {10.3389/fpsyg.2021.629050}, pages = {6}, year = {2021}, abstract = {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.}, language = {en} } @article{GuoTianYangetal.2018, author = {Guo, Ranran and Tian, Ye and Yang, Yueqi and Jiang, Qin and Wang, Yajun and Yang, Wuli}, title = {A Yolk-Shell nanoplatform for gene-silencing-enhanced photolytic ablation of cancer}, series = {Advanced functional materials}, volume = {28}, journal = {Advanced functional materials}, number = {14}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1616-301X}, doi = {10.1002/adfm.201706398}, pages = {11}, year = {2018}, abstract = {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.}, language = {en} } @article{GalbeteKroegerJannaschetal.2018, author = {Galbete, Cecilia and Kr{\"o}ger, Janine and Jannasch, Franziska and Iqbal, Khalid and Schwingshackl, Lukas and Schwedhelm, Carolina and Weikert, Cornelia and Boeing, Heiner and Schulze, Matthias Bernd}, title = {Nordic diet, Mediterranean diet, and the risk of chronic diseases}, series = {BMC Medicine}, volume = {16}, journal = {BMC Medicine}, publisher = {BMC}, address = {London}, issn = {1741-7015}, doi = {10.1186/s12916-018-1082-y}, pages = {13}, year = {2018}, abstract = {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.}, language = {en} } @article{LiStomaLottaetal.2020, author = {Li, Chen and Stoma, Svetlana and Lotta, Luca A. and Warner, Sophie and Albrecht, Eva and Allione, Alessandra and Arp, Pascal P. and Broer, Linda and Buxton, Jessica L. and Boeing, Heiner and Langenberg, Claudia and Codd, Veryan}, title = {Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length}, series = {American Journal of Human Genetics}, volume = {106}, journal = {American Journal of Human Genetics}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, pages = {16}, year = {2020}, abstract = {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.}, language = {en} } @article{ChristakoudiTsilidisMulleretal.2020, author = {Christakoudi, Sofa and Tsilidis, Konstantinos K. and Muller, David C. and Freisling, Heinz and Weiderpass, Elisabete and Overvad, Kim and S{\"o}derberg, Stefan and H{\"a}ggstr{\"o}m, Christel and Pischon, Tobias and Dahm, Christina C. and Zhang, Jie and Tj{\o}nneland, Anne and Schulze, Matthias Bernd}, title = {A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {Berlin}, pages = {15}, year = {2020}, abstract = {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.}, language = {en} } @article{SchuermannVogelEbeletal.2018, author = {Sch{\"u}rmann, Robin Mathis and Vogel, Stefanie and Ebel, Kenny and Bald, Ilko}, title = {The physico-chemical basis of DNA radiosensitization}, series = {Chemistry - a European journal}, volume = {24}, journal = {Chemistry - a European journal}, number = {41}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0947-6539}, doi = {10.1002/chem.201800804}, pages = {10271 -- 10279}, year = {2018}, abstract = {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.}, language = {en} } @article{TzonevaStoyanovaPetrichetal.2020, author = {Tzoneva, Rumiana and Stoyanova, Tihomira and Petrich, Annett and Popova, Desislava and Uzunova, Veselina and Momchilova, Albena and Chiantia, Salvatore}, title = {Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models}, series = {Biomolecules}, volume = {10}, journal = {Biomolecules}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {2218-273X}, doi = {10.3390/biom10050802}, pages = {17}, year = {2020}, abstract = {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.}, language = {en} } @misc{WiesnerReinholdSchreinerBaldermannetal.2017, author = {Wiesner-Reinhold, Melanie and Schreiner, Monika and Baldermann, Susanne and Schwarz, Dietmar and Hanschen, Franziska S. and Kipp, Anna Patricia and Rowan, Daryl D. and Bentley-Hewitt, Kerry L. and McKenzie, Marian J.}, title = {Mechanisms of Selenium Enrichment and Measurement in Brassicaceous Vegetables, and Their Application to Human Health}, series = {Frontiers in plant science}, volume = {8}, journal = {Frontiers in plant science}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-462X}, doi = {10.3389/fpls.2017.01365}, pages = {20}, year = {2017}, abstract = {Selenium (Se) is an essential micronutrient for human health. Se deficiency affects hundreds of millions of people worldwide, particularly in developing countries, and there is increasing awareness that suboptimal supply of Se can also negatively affect human health. Selenium enters the diet primarily through the ingestion of plant and animal products. Although, plants are not dependent on Se they take it up from the soil through the sulphur (S) uptake and assimilation pathways. Therefore, geographic differences in the availability of soil Se and agricultural practices have a profound influence on the Se content of many foods, and there are increasing efforts to biofortify crop plants with Se. Plants from the Brassicales are of particular interest as they accumulate and synthesize Se into forms with additional health benefits, such as methylselenocysteine (MeSeCys). The Brassicaceae are also well-known to produce the glucosinolates; S-containing compounds with demonstrated human health value. Furthermore, the recent discovery of the selenoglucosinolates in the Brassicaceae raises questions regarding their potential bioefficacy. In this review we focus on Se uptake and metabolism in the Brassicaceae in the context of human health, particularly cancer prevention and immunity. We investigate the close relationship between Se and S metabolism in this plant family, with particular emphasis on the selenoglucosinolates, and consider the methodologies available for identifying and quantifying further novel Se-containing compounds in plants. Finally, we summarize the research of multiple groups investigating biofortification of the Brassicaceae and discuss which approaches might be most successful for supplying Se deficient populations in the future.}, language = {en} } @article{HassHerpichNorman2019, author = {Haß, Ulrike and Herpich, Catrin and Norman, Kristina}, title = {Anti-Inflammatory Diets and Fatigue}, series = {Nutrients}, volume = {11}, journal = {Nutrients}, number = {10}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu11102315}, pages = {24}, year = {2019}, abstract = {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.}, language = {en} }