University of Erlangen-Nuremberg

About: University of Erlangen-Nuremberg is a education organization based out in Erlangen, Bayern, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 42405 authors who have published 85600 publications receiving 2663922 citations.

Human Y Chromosome Azoospermia Factors (AZF) Mapped to Different Subregions in Yq11

Abstract: In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia wereanalysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involvingseveral DNA loci, while an additional patient had an inherited deletion. They were mapped to three differentsubregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second andthird subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletionsobserved were not overlapping but the extension of the deleted Y DNA in each subregion was similar in eachpatient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phasewhen the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletionoccurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesisloci in Yq11 and that each locus is active during a different phase of male germ cell development. As the mostsevere phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc.Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed. INTRODUCTIONGenes for male germ cell development are present on the Ychromosome in different species groups (1–3). In men, theposition of a spermatogenesis locus was mapped in theeuchromatic part of the long Y arm (Yq11). It was called‘azoospermia factor’ (AZF), as the first six men observed withterminal deletions in Yq were azoospermic (4). Mature spermcells were not detectable in their seminal fluid. In all cases, the Ydeletions included the large heterochromatin block of the long Yarm (Yq12) and an undefined amount of the adjacent euchromatin(Yq11). Subsequently, the presence of AZF in Yq11 wasconfirmed by numerous studies at both cytogenetic (5) andmolecular level (6–8). However, the genetic complexity of AZFcould not be revealed by these analyses.This first became possible by the detection of sterile patientswith small interstitial deletions (i.e. microdeletions) in Yq11. Ina study with 13 sterile men suffering from idiopathic azoospermiatwo different microdeletions in Yq11 were observed (9). Theywere mapped to two non overlapping positions in Yq11 interval6 (10). However, further studies of Yq11 microdeletionsassociated to the phenotype of male sterility, only confirmed theposition of an AZF locus in distal Yq11 (11,12). The mostextensive study was performed by Reijo et al. (13) on 89 sterile

Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome.

Abstract: Objective Total mesorectal excision (TME) as proposed by R.J. Heald more than 20 years ago, is nowadays accepted worldwide for optimal rectal cancer surgery. This technique is focused on an intact package of the tumour and its main lymphatic drainage. This concept can be translated into colon cancer surgery, as the mesorectum is only part of the mesenteric planes which cover the colon and its lymphatic drainage like envelopes. According to the concept of TME for rectal cancer, we perform a concept of complete mesocolic excision (CME) for colonic cancer. This technique aims at the separation of the mesocolic from the parietal plane and true central ligation of the supplying arteries and draining veins right at their roots. Method Prospectively obtained data from 1329 consecutive patients of our department with RO-resection of colon cancer between 1978 and 2002 were analysed. Patient data of three subdivided time periods were compared. Results By consequent application of the procedure of CME, we were able to reduce local 5-year recurrence rates in colon cancer from 6.5% in the period from 1978 to 1984 to 3.6% in 1995 to 2002. In the same period, the cancer related 5-year survival rates in patients resected for cure increased from 82.1% to 89.1%. Conclusion The technique of CME in colon cancer surgery aims at a specimen with intact layers and a maximum of lymphnode harvest. This is translated into lower local recurrence rates and better overall survival.

TiO2 nanotubes: Self-organized electrochemical formation, properties and applications

Abstract: The present paper gives an overview and review on self-organized TiO2 nanotube layers and other transition metal oxide tubular structures grown by controlled anodic oxidation of a metal substrate We describe mechanistic aspects of the tube growth and discuss the electrochemical conditions that need to be fulfilled in order to synthesize these layers Key properties of these highly ordered, high aspect ratio tubular layers are discussed In the past few years, a wide range of functional applications of the layers have been explored ranging from photocatalysis, solar energy conversion, electrochromic effects over using the material as a template or catalyst support to applications in the biomedical field A comprehensive view on state of the art is provided

Migrating cancer stem cells: An integrated concept of malignant tumor progression.

Abstract: ED01-02 Most colorectal adenocarcinomas (CRC) have mutations in the APC gene leading to overexpression of the Wnt-pathway effector b-catenin. By acting as a transcriptional activator, nuclear b-catenin is decisively involved in two fundamental processes in embryonic development: epithelial to mesenchymal transition (EMT) and generation of stem cells (e.g. in intestine development). We have previously shown, that in particular tumor cells at the invasive front of CRCs accumulate nuclear b-catenin, undergo an EMT and aberrantly express EMT-associated transcriptional repressors, like ZEB1. The amount of these cells strongly correlates with clinical outcome and metastasis formation. We further showed that ZEB1 represses target genes involved in basement membrane formation and epithelial cell polarity. In contrast tumor cells in central tumor areas are differentiated and often show membranous, E-cadherin-bound b-catenin. Strikingly, also metastases show again a differentiated phenotype and lack nuclear b-catenin, indicating a regulatory role of the tumor environment for malignant progression. Based on the developmental functions of b-catenin and our data we propose, that the EMT-associated tumor cells at the invasive front act as "migrating cancer stem cells" which can re-differentiate and, depending on the range of dissemination, give raise to the primary carcinoma or metastases. In support of this hypothesis, we defined b-catenin target genes overexpressed in invading tumor cells: 1. A stem cell phenotype is supported by the b-catenin target genes hTERT and survivin. 2. Furthermore we identified target genes like uPA, MT1-MMP, and laminin5-g2 chain, which synergize to exert EMT and promigratory activity. We suggest that both primary tumors and metastases are derived from a pool of EMT-associated "migrating cancer stem cells" at the tumor host interface, which are defined by strong nuclear b-catenin accumulation and expression of its target genes. This gives these cells a feature, which drives malignant tumor progression including metastasis: the unusual combination of abilities allowing simultanously to migrate and behave as a cancer stem cell. Since ZEB1 might be the crucial mediator of EMT in tumor cells, it could be a promising therapeutic target to interfere with malignant tumor progression.

Migrating cancer stem cells — an integrated concept of malignant tumour progression

Abstract: The dissemination of tumour cells is the prerequisite of metastases and is correlated with a loss of epithelial differentiation and the acquisition of a migratory phenotype, a hallmark of malignant tumour progression. A stepwise, irreversible accumulation of genetic alterations is considered to be the responsible driving force. But strikingly, metastases of most carcinomas recapitulate the organization of their primary tumours. Although current models explain distinct and important aspects of carcinogenesis, each alone can not explain the sum of the cellular changes apparent in human cancer progression. We suggest an extended, integrated model that is consistent with all aspects of human tumour progression — the 'migrating cancer stem (MCS)-cell' concept.