Genome-wide expression patterns of invasion front, inner tumor mass and surrounding normal epithelium of colorectal tumors

Colorectal tumors have characteristic genome-wide expression patterns that allow their distinction from normal colon epithelia and facilitate clinical prognosis. The expression heterogeneity within a primary colorectal tumor has not been studied on a genome scale yet. Here we investigated three compartments of colorectal tumors, the invasion front, the inner tumor mass, and surrounding normal epithelial tissue by microdissection and microarray-based expression profiling. In both tumor compartments many genes were differentially expressed when compared to normal epithelium. The sets of significantly deregulated genes in both compartments overlapped to a large extent and revealed various interesting known and novel pathways that could have contributed to tumorigenesis. Cells from the invasion front and inner tumor mass, however, did not show significant differences in their expression profile, neither on the single gene level nor on the pathway level. Instead, gene expression differences between individuals are more pronounced as all patient-matched tumor samples clustered in close proximity to each other. With respect to invasion front and inner tumor mass we conclude that the specific tumor cell micro-environment does not have a strong influence on expression patterns: largely similar genome-wide expression programs operate in the invasion front and interior compartment of a colorectal tumor

An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types

Wiskott–Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Chiparray based gene expression analysis in colorectal carcinoma after laser captured microdissection

Titelblatt und Inhaltsverzeichnis Einleitung Zielsetzung Material und Methoden Ergebnisse Diskussion Zusammenfassung Anhang Publikationsliste Literaturverzeichnis Danksagung LebenslaufDie differenzielle Genexpression als Folge der molekularen Alteration in Karzinomen spielt eine entscheidende Rolle für das Verständnis der Tumorbiologie und bildet die Grundlage für die Entdeckung neuer diagnostischer Biomarker und therapeutischer Zielgene. Ziel dieser Arbeit war die Identifikation von differenziell exprimierten Genen (DES) beim kolorektalen Karzinom durch die vergleichende Analyse Chiparray basierter Genexpressionsdaten von korrespondierenden Normal- und Tumorgeweben nach Laser gestützter Mikrodissektion. Zudem wurde die Homogenität der Expression der identifizierten DES innerhalb des Tumorgewebes untersucht, indem definierte Tumorareale mittels Laser gestützter Mikrodissektion getrennt voneinander aufgearbeitet wurden. Des weiteren wurde unter Verwendung der Clusteranalyse untersucht, inwiefern die kolorektalen Tumor- und Normalgewebe anhand der Genexpressionsdaten nach histopathologischen Kriterien klassifiziert werden konnten. Die in dieser Arbeit verwendeten GeneChips von Affymetrix ermöglichten es, die Expression von ca. 33.000 bekannten Genen in den kolorektalen Tumor- und Normalgeweben von 25 Patienten zu messen. Gemäß eines heuristischen Verfahrens wurde eine Rangfolge der detektierten Sequenzen berechnet, anhand derer mittels eines arbiträr gewählten cut-offs 200 DES identifiziert wurden, die in den untersuchten kolorektalen Karzinomgeweben überexprimiert waren, sowie 200 weitere, die unterexprimiert waren. Unter den identifizierten DES fanden sich 42 Gene, die bereits aus der Literatur als im kolorektalen Karzinom differenziell exprimiert bekannt waren, und weitere 43 Gene, die in anderen Tumorentitäten als differenziell exprimiert beschrieben wurden. Der Vergleich der identifizierten DES aus der Tumorinvasionsfront und aus der zentralen Tumorregion ergab eine gemeinsame Schnittmenge von nur ca. 50 % der DES. Die restlichen 50% erfüllten zwar nicht in beiden Tumorarealen die in dieser Arbeit festgelegten heuristischen Kriterien der differenziellen Expression, waren aber dennoch in den unterschiedlichen Tumorregionen ähnlich exprimiert. Die untersuchten kolorektalen Gewebeproben ließen sich anhand ihrer Expressionsprofile in der Clusteranalyse eindeutig einer Tumor- und einer Normalgewebegruppe zuordnen. Es gelang nicht, die untersuchten Gewebeproben anhand ihrer Expressionsprofile in der Clusteranalyse reproduzierbar entsprechend anderer histopathologischer Eigenschaften zu gruppieren. Die Clusteranalysen ergaben zudem, dass die Gewebe unterschiedlicher Tumorareale, der Tumorinvasionsfront (IT) und der zentralen Tumorregionen (RT), keine eigenständigen Gruppen bildeten, sondern die IT und RT Proben des gleichen Patienten innerhalb des Tumorgewebeclusters in den meisten Fällen korrespondierende Dupletts bildeten und somit bezüglich ihrer Genexpression einander ähnlicher waren als im interindividuellen Vergleich. Um die statistische Aussagekraft dieser Arbeit weiter zu stärken, wurde das Patientenkollektiv auf 75 Patienten erweitert. Des weiteren werden einzelne identifizierte DES, wie z.B. Claudin 1, auf RNA- und Proteinebene validiert. Inwiefern die in dieser Arbeit identifizierten DES als neue potenzielle Tumormarker bedeutsam sind oder potenziell therapeutische Zielgene darstellen, muss noch weiter evaluiert werden.Differential gene expression as a result of molecular alterations in cancer plays an important role for defining new diagnostic biomarkers and treatment targets. Chiparray technology enabling expression analysis of thousands of genes simultaneously has already been successfully applied for the identification of differentially expressed genes (DEGs) in several tumor entities. The aim of this study was to identify DEGs in colorectal cancer by comparing chiparray based expression data from normal and corresponding cancerous epithelium after laser captured microdissection. The intratumor heterogeneity of gene expression was investigated by separating definitive tumor areas using laser captured microdissection. Characteristic expression profiles for pathological parameters were searched by means of cluster analysis. Affymetrix Gene Chips were applied to monitor the gene expression of about 33.000 genes in 25 patients with colorectal cancer. 200 up- and 200 down-regulated genes were identified to be differentially expressed by generating a rank for all detected genes based on statistical tests and an arbitrary chosed cut off. Among those identified DEGs 42 genes were already associated with colorectal cancer and 43 genes with other tumor entities. Nearly 50% of the identified DEGs were differentially expressed in both tumor areas, the central tumor and the invasion front. The other half of the DEGs was similarly expressed in both investigated tumor areas but did not fulfil the defined heuristic criterias of differential expression in this study. Hierarchical cluster analysis clearly discriminated between normal and cancerous colorectal tissues but did not identify reproducible characteristic expression profiles according to pathological parameters like e.g. UICC. Moreover gene expression profiling showed that tissues from different tumor areas of the same patient were stronger related concerning gene expression than the different tumor areas in the interindividual comparison. To support the statistical significance of this study the patient collective has currently been enlarged to 75 patients and selected genes, e.g. Claudin 1, have been validated on RNA and protein level. Whether the identified DEGs encode new potential tumor markers or potential novel therapeutic targets in colorectal cancer has to be further evaluated

Für das Spielen lernen wir – Konzept und Evaluation des internationalen Medizinstudierendenwettbewerbs "Benjamin Franklin Contest" [Learning for the game – concept and evaluation of the international medical student competition "Benjamin Franklin Contest"]

[english] Objective: In 1998 an international contest for medical students called “Benjamin Franklin Contest” was initiated by the former university hospital of Freie Universität Berlin on the occasion of the 30th anniversary of its foundation in 1968. Since then, seven teams from Germany, Austria, and Switzerland have been competing against each other every year. Five medical students per team match up in paper cases, diagnosis of medical images, multiple choice tests, and practical skills.Methods: All participants of the 11th Benjamin Franklin Contest (2009) were asked about their motivation, preparation strategy, and experience with the contest. Results: In total 92% (32 of 35) participated in the evaluation study. We show that improvement of medical knowledge is one of the key motivating factors behind participation in the competition. The teams were trained by self-study, tutorials, and learning groups. Remarkably, students invested 54.2 hours (SD 32 hours) of their free time to prepare for the contest. Conclusions: The Benjamin Franklin Contest is an innovative approach to facilitate self-directed learning and develope medical competencies. <br>[german] Zielsetzung: Im Jahr 1998 wurde am damaligen Universitätsklinikum Benjamin Franklin der Freien Universität (FU) in Berlin der internationale Medizinstudierendenwettbewerb „Benjamin Franklin Contest“ (BFC) initiiert. Anlass war damals der 30. Jahrestag der Gründung der Universitätsmedizin an der FU. Seitdem findet jedes Jahr ein Wettbewerb zwischen sieben Teams von medizinischen Fakultäten aus Deutschland, Österreich und der Schweiz statt. Jeweils fünf Studierende messen sich in den Kategorien Papierfälle, Blickdiagnosen, Auswahlfragen und praktische Fähigkeiten.Methodik: Ziel dieser Arbeit ist die Beschreibung des Projektes BFC und eine erste Evaluation der Erfahrung von Teilnehmenden. Dazu wurden alle Teilnehmenden des 11. BFC (2009) mittels eines selbst entwickelten Fragebogens hinsichtlich ihrer Motivation, Art und Aufwand der eigenen Vorbereitung und der Erfahrung mit dem Wettbewerb befragt. Ergebnisse: Insgesamt beteiligten sich 92% (32/35) der Teilnehmenden im Jahr 2009 an der Evaluation des Wettbewerbs. Es zeigte sich, dass die Erweiterung medizinischen Wissens zu den Hauptmotiven für eine Teilnahme am BFC gehört. Zur Vorbereitung auf den Wettbewerb wurden neben dem Selbststudium insbesondere Tutorien und Lerngruppen eingesetzt. Der Aufwand lag bei durchschnittlich 54,2 Stunden (Standardabweichung 32 Stunden). Schlussfolgerungen: Das Konzept des BFC kann als innovativer Ansatz selbstmotivierten Lernens verstanden werden. Die Teilnahme am BFC hat das Potential, neben medizinischen Kompetenzen auch die Fähigkeit zur Teamarbeit zu fördern

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020