Differenzierung der Komponenten des Wilms-Tumor im Kinder- und Jugendalter von den Komponenten der Nephroblastomatose

Es wurde versucht anhand von retrospektiven Präparaten aus dem Kindertumorregister der Sektion Kinderpathologie der Christian von Albrechts Universität zu Kiel, welche im Rahmen der GPOH-Nephroblastomstudie behandelt werden, eine immunhistochemische Unterscheidung von Wilms-Tumoren und der Nephroblastomatose zu finden, um die Therapie anzupassen. Die Vorläuferläsion des Wilms-Tumors, die sogenannte Nephroblastomatose ist im Gegensatz zum eigentlich Tumor benigne, sodass auf eine Chemotherapie verzichtet werden könnte. Dazu wurden Färbungen mit 4 Antikörpern angefertigt und ausgewertet. Bei den Antikörpern handelt es sich um Mitwirkende des Wnt/β-Catenin-Pathways, und zwar β-Catenin, Axin-2, MITF und APC. Mein Hauptaugenmerk liegt auf dem Onkoprotein und Transkriptionsfaktor β-Catenin. Es wird vermutet, dass dieser Pathway an der Entstehung der Tumore beteiligt ist. In den immunhistochemischen Färbungen zeigte sich, das mittels der o.g. Antikörpern allein keine solche Differenzierung möglich ist. Außnahmen bilden die unklare (bisher noch nicht beschrieben) nukleäre Positivität von Axin 2, die es nur im eigentlichen Tumor gibt sowie die nukleäre Anfärbbarkeit des Stromas bei Tumoren mit WTX- (alle Präparate) und Beta-Catenin-Mutation (5/37 Präparaten). Letzteres spricht für eine Aktivierung des Wnt-Pathways und der damit verbundenen Transkriptionsaktivierung von Protoonkogenen. Zur weiteren Suche nach Möglichkeien der Differenzierung wären molekulargenetische Untersuchungen der Antikörper und eine Ausdehnung der Präparate auf Tumore ohne WTX-Mutation nötig

The importance of thrombospondin-1 on limb regeneration of the Ambystoma mexicanum

Limb and digit loss poses a significant problem across the animal kingdom. Ambystoma mexicanum, commonly known as the axolotl, however, is one species that has achieved a remarkable ability to bypass the misfortune associated with a lost limb. Viewed as a model organism in regenerative studies, the axolotl retains extraordinary regenerative properties well into adulthood that humans severely lack. While the basics of regeneration have been described, much about the molecular processes of regeneration is still largely unknown. Thrombospondin-1 (TSP-1), an angiogenesis inhibitor, has been identified as a potential factor to play a significant role in the regrowth of limbs. Vascularization of tissues is vital to the survival of biological structures, and TSP-1 has been shown to play a regulatory role in the development and remodeling of tissue vasculature. Here, we study the effect of a loss-of-function mutation in the tsp-1 gene on the process of limb regeneration in the axolotl. Our studies reveal that tsp-1 -/- animals lag in regeneration time, developing smaller blastemas in the first three weeks of regeneration. We show that the loss of TSP-1, however, is not deleterious to the overall process of regeneration as late stage blastemas of the -/- animals catch up in size and development to the wild type animals after three weeks. Our data suggests that while TSP-1 may be important during the initial stages, it may not be required for proper regeneration

THE IMPORTANCE OF REGENERATION IN ECHINODERMS (ECHINODERMATA)

Regeneracija je važan regulatorni proces obnove oštećenih i izgubljenih dijelova tijela životinje nakon ozljede, izlaganja stresu ili uslijed bijega od predatora. U ovome radu opisan je proces regeneracije pet razreda bodljikaša, njihov regeneracijski potencijal kao i pojava i razvoj regeneracije tijekom evolucije. Dosadašnja istraživanja i najnovija saznanja o regeneraciji kod bodljikaša uvelike će doprinijeti istraživanjima regeneracije na kralježnjacima točnije sisavcima s obzirom na njihovu blisku filogenetsku povezanost.Regeneration is an important regulatory process of recovering damaged and lost body parts in animals following an injury, exposure to stress, or escape from a predator. This paper describes the regeneration process in five classes of the phylum Echinodermata, their regenerative potential as well as the occurrence and development of regeneration during the evolution. The current research and the latest findings about regeneration in echinoderms, will greatly contribute to the research regeneration on vertebrates, more specifically mammals, due to their close phylogenetic relatedness

Cell cycle re-entry and the plasticity of myotubes in newt limb regeneration

Urodele amphibians regenerate various structures including the limb, tail, lens, and heart. Underlying this regenerative ability may be the plasticity of cells at the site of injury. Muscle is a key tissue to study these issues because myogenesis proceeds by fusion of mononucleate precursor cells into a multinucleate syncytium which is in a state of stable post-mitotic arrest. Following implantation into a regenerating limb, newt myotubes re-enter the cell cycle and give rise to proliferating mononucleate progeny. In culture, generation of mononucleate cells has never been observed, but the myotube nuclei re-enter the cell cycle and arrest in G2. This is in contrast to their mammalian counterparts, which are refractory to growth factor stimulation, and suggests that cell cycle re-entry may be one aspect of myotube plasticity. In initial experiments mouse and newt myoblasts were fused to create hybrid myotubes. In these hybrids, DNA synthesis was observed in both mouse and newt nuclei demonstrating that the post-mitotic arrest of mammalian nuclei can be destabilised. Other experiments addressed the hypothesis that mononucleate cells are generated from multinucleate myotubes by fragmentation of the syncytium, as the nuclei progress through mitosis and cytokinesis. I pursued several strategies to overcome the G2 arrest of cultured myotubes. Transfection with SV-40 large T antigen induced endoreplication of DNA in myotubes, but did not lead to mitosis. Treatment with caffeine resulted in the appearance of fragmented nuclei, which are indicative of aberrant mitosis. This response was dependent on traversal of S-phase by the myotube nuclei. These observations suggested that the block to mitosis is stable in cultured myotubes. A critical question is whether cell cycle re-entry is required for generation of mononucleate cells following implantation of myotubes into regenerating limbs. Cell-cycle re-entry was blocked in myotubes by X-irradiation or expression of the cdk4/6 inhibitor pl6. These myotubes were fluorescently labelled and implanted. Both arrested and control myotubes gave rise to mononucleate progeny, demonstrating that cell cycle re-entry is not required for generation of mononucleate cells

Die prognostische Bedeutung eines genetischen Zugewinns auf Chromosom 1q bei Wilms-Tumor

In der Arbeit wurden Wilms-Tumore mit hohem Risiko sowie als Vergleich alle neu aufgetretenen Tumore in Deutschland 2007 auf einen genetischen Zugewinn auf Chromosom 1q untersucht. Dies wurde mit dem Krankheitsverlauf korreliert, um zu prüfen, ob diese genetische Alteration als prognostischer Faktor genutzt werden kann

Windows .NET Network Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST)

BACKGROUND: BLAST is one of the most common and useful tools for Genetic Research. This paper describes a software application we have termed Windows .NET Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST), which enhances the BLAST utility by improving usability, fault recovery, and scalability in a Windows desktop environment. Our goal was to develop an easy to use, fault tolerant, high-throughput BLAST solution that incorporates a comprehensive BLAST result viewer with curation and annotation functionality. RESULTS: W.ND-BLAST is a comprehensive Windows-based software toolkit that targets researchers, including those with minimal computer skills, and provides the ability increase the performance of BLAST by distributing BLAST queries to any number of Windows based machines across local area networks (LAN). W.ND-BLAST provides intuitive Graphic User Interfaces (GUI) for BLAST database creation, BLAST execution, BLAST output evaluation and BLAST result exportation. This software also provides several layers of fault tolerance and fault recovery to prevent loss of data if nodes or master machines fail. This paper lays out the functionality of W.ND-BLAST. W.ND-BLAST displays close to 100% performance efficiency when distributing tasks to 12 remote computers of the same performance class. A high throughput BLAST job which took 662.68 minutes (11 hours) on one average machine was completed in 44.97 minutes when distributed to 17 nodes, which included lower performance class machines. Finally, there is a comprehensive high-throughput BLAST Output Viewer (BOV) and Annotation Engine components, which provides comprehensive exportation of BLAST hits to text files, annotated fasta files, tables, or association files. CONCLUSION: W.ND-BLAST provides an interactive tool that allows scientists to easily utilizing their available computing resources for high throughput and comprehensive sequence analyses. The install package for W.ND-BLAST is freely downloadable from . With registration the software is free, installation, networking, and usage instructions are provided as well as a support forum

THE IMPORTANCE OF REGENERATION IN ECHINODERMS (ECHINODERMATA)

Regeneracija je važan regulatorni proces obnove oštećenih i izgubljenih dijelova tijela životinje nakon ozljede, izlaganja stresu ili uslijed bijega od predatora. U ovome radu opisan je proces regeneracije pet razreda bodljikaša, njihov regeneracijski potencijal kao i pojava i razvoj regeneracije tijekom evolucije. Dosadašnja istraživanja i najnovija saznanja o regeneraciji kod bodljikaša uvelike će doprinijeti istraživanjima regeneracije na kralježnjacima točnije sisavcima s obzirom na njihovu blisku filogenetsku povezanost.Regeneration is an important regulatory process of recovering damaged and lost body parts in animals following an injury, exposure to stress, or escape from a predator. This paper describes the regeneration process in five classes of the phylum Echinodermata, their regenerative potential as well as the occurrence and development of regeneration during the evolution. The current research and the latest findings about regeneration in echinoderms, will greatly contribute to the research regeneration on vertebrates, more specifically mammals, due to their close phylogenetic relatedness