1,721,071 research outputs found
Role of carcinogens factors in epigenetic silencing of Rassf1a, DAPK, p16, MT1A genes in human lung
Full text linkIn der vorliegenden Arbeit haben wir zunächst die Häufigkeit von epigenetischen Inaktivierungen durch Methylierung bei den tumorassoziierten Genen (Rassf1a), (DAPK), (p16) und Metallothionein 1 A untersucht. Von 26 Lungenkrebspatienten wurden Proben mit (Methyl PCR) untersucht. Die Häufigkeit der DNA-Methylierung lag bei: 62% für Rassf1a, 46% für DAPK, 54% für p16 und 39% für MT1A. Daneben haben wir an Primärkulturen von normalen humanen Lungenzellen die Rolle einer Langzeitexposition (NHBEZ, PLZ) gegenüber den Tabakrauchkondensat und Cadmium (II). Cadmium (II) induziert die aberrante Methylierung von DAPK in PLZ (p = 0,019) und in NHBEZ (p = 0,097). CSC führte zu einer signifikanten Induktion von p16-Methylierung in PLC (p = 0,047) Die Ergebnisse zeigen, dass Zellkulturen als In-vitro-Modelle einen Beitrag zur Langzeituntersuchung der Wirkung verschiedener Umweltschadstoffe leisten können.A total of 24 out of 26 samples (92%) taken from lung cancer patients displayed hypermethylation in at least one of the genes tested (Rassf1a, DAPK, p16 or (MTIA). Rassf1a methylation was detectable in 62% of the patients. A high methylation ratio of 69% was found for Rassf1a in tumor tissue. Methylation frequency of DAPK across tissue types was (46.2%). This study showed methylation of p16 in 54%. Methylation of MT1A was observed in (39%). Explants of (NHBEC) and (PLC) from samples of 12 lung cancer patients can be cultured over a time period of up to five generations. When NHBEC and PLC are exposed to CSC (10 mg/l) or Cd (II) (5µM) Cadmium (II) significantly induces aberrant methylation of DAPK in PLC (p = 0.019) and in NHBEC (p = 0.097). Long term exposure to CSC led to significant induction of p16-methylation in PLC (p = 0.047). Human lung cell cultures as in-vitro models enable a long term follow up in studies on the effects of environmental carcinogen
Investigations on molecular mechanisms in hepatocarcinogenesis with emphasis on the role of the Ras-effector gene NORE1B and of the fibroblast growth factor-system
No full textLeberkrebs (HCC) ist weltweit unter den häufigsten Krebstodesursachen. Die für die Erkrankung verantwortlichen Mechanismen sind noch nicht aufgeklärt.NORE1A, NORE1B und RASSF1A gehören zu der Familie der Ras-Effektoren und sind vermutlich Gegenspieler des Protoonkogens Ras im wachstumsfördernden Teil des Ras-Signalweges. In dieser Arbeit konnte gezeigt werden, dass NORE1B, NORE1A und RASSF1A kaum von Mutationen betroffen sind. Hingegen wurde eine Hypermethylierung der Promoterregion von NORE1B und RASSF1A und eine dadurch bedingte epigenetische Inaktivierung der Gene beobachtet, die insgesamt 97% der HCCs betraf.Als nächstes untersuchten wir die biologische Funktion des NORE1B-Gens.Wir konnten feststellen, dass NORE1B mit seiner Ras- und SARAH-Domäne mit dem bekannten Tumorsuppressor RASSF1A interagieren kann. Außerdem konnten wir zeigen, dass NORE1B den Zellzyklus verlangsamt, und die Transformation von Zellen vermindert. Aus unseren Untersuchungen geht hervor, dass NORE1B einige Kriterien eines Tumorsuppressor-Gens erfüllt.Veränderte Regulation von Fibroblasten-Wachstumsfaktoren (FGFs) und deren Rezeptoren spielen bei zahlreichen Krankheiten und auch in der Krebsentstehung eine wichtige Rolle. Unsere Ergebnisse zeigen, dass der FGF-8 als auch FGF-18 stimulierend auf das Wachstum von prämalignen Leberzellen wirkt. Für FGF-18 konnte eine Hochregulation in humanem Leberkrebs festgestellt werden. Dies ist ein deutlicher Hinweis dafür, dass FGF-18 sowohl ein autokrin als auch ein parakrin wirkender Wachstumsfaktor ist, der bevorzugt auf prämaligne und maligne Hepatozyten wirkt. Überdies konnten wir zeigen, dass das Auftreten eines speziellen Polymorphismus (FGFR-4Arg388) in beiden Allelen des FGFR-4 mit einem erhöhten Risiko für Leberkrebs assoziiert ist.Zusammenfassend kann gesagt werden, dass NORE1B und der FGF-Signalweg für weiterführende Untersuchungen der Hepatokarzinogenese sehr vielversprechend sind.Hepatocellular carcinoma (HCC) is a major health problem worldwide and the genetic alterations involved in the development and progression of this disease are incompletely understood. NORE1A, NORE1B, and RASSF1A are part of a regulatory mechanism antagonizing the growth-enhancing effects of the proto-oncogene Ras. In the present work we could show that mutations of NORE1B, NORE1A and RASSF1A occur rarely in HCCs. Epigenetic inactivation of NORE1B was observed in 62% of the HCCs due to considerable promoter-hypermethylation of the gene. Hypermethylation of the RASSF1A-promoter was also frequently detected in HCCs resulting that epigenetic silencing of at least one of the genes occured in 97% of the HCCs studied. Next, we investigated the biological functions of NORE1B and found that it interacts via the RA- and SARAH-domain with the known tumor suppressor RASSF1A, that it leads to a cell cycle delay and suppresses transformation of cells. It therefore meets several criteria required to be addressed as a tumor suppressor gene. Deregulated expression of fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in many pathological processes including cancer. Here we show that FGF-8 and FGF-18 stimulate growth of premalignant hepatocytes and that FGF-18 is upregulated in HCCs; this factor seems to act on (pre)malignant liver cells via paracrine or autocrine mechanisms. Furthermore, the bi-allelic occurrence of a specific polymorphism in the FGFR-4 (FGFR-4Arg388) is associated with an increased incidence of HCCs.In conclusion, NORE1B and the FGF-pathway deserve further investigations for their impact on hepatocarcinogenesis
Update of the risk assessment of nickel in food and drinking water
Full text link101 p.-5 fig.-16 tab.The European Commission asked EFSA to update its previous Opinion on nickel in food and drinking water, taking into account new occurrence data, the updated benchmark dose (BMD) Guidance and newly available scientific information. More than 47,000 analytical results on the occurrence of nickel were used for calculating chronic and acute dietary exposure. An increased incidence of post‐implantation loss in rats was identified as the critical effect for the risk characterisation of chronic oral exposure and a BMDL10 of 1.3 mg Ni/kg body weight (bw) per day was selected as the reference point for the establishment of a tolerable daily intake (TDI) of 13 μg/kg bw. Eczematous flare‐up reactions in the skin elicited in nickel‐sensitised humans, a condition known as systemic contact dermatitis, was identified as the critical effect for the risk characterisation of acute oral exposure. A BMDL could not be derived, and therefore, the lowest‐observed‐adverse‐effect‐level of 4.3 μg Ni/kg bw was selected as the reference point. The margin of exposure (MOE) approach was applied and an MOE of 30 or higher was considered as being indicative of a low health concern. The mean lower bound (LB)/upper bound (UB) chronic dietary exposure was below or at the level of the TDI. The 95th percentile LB/UB chronic dietary exposure was below the TDI in adolescents and in all adult age groups, but generally exceeded the TDI in toddlers and in other children, as well as in infants in some surveys. This may raise a health concern in these young age groups. The MOE values for the mean UB acute dietary exposure and for the 95th percentile UB raises a health concern for nickel‐sensitised individuals. The MOE values for an acute scenario regarding consumption of a glass of water on an empty stomach do not raise a health concern.The Panel wishes to thank the following for the support provided to this scientific output: Elena Rovesti. The Panel wishes to acknowledge all European competent institutions,Member State bodies and other organisations that provided data for this scientific output.Peer reviewe
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Risk assessment of ochratoxin A in food
Full text linkAcknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Elena Rovesti. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.Peer reviewe
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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