Apr. Das Sakrileg: Im Mai wechselt Andreas Möller vom BVB zu Sie nannten ihn Heulsuse, Weichei oder ganz erbarmungslos: Heintje. Aug. Der Entertainer Harald Schmidt hat ihn mal zur Fussballerin des Jahres gekürt, weil der Spieler Andreas Möller als Heulsuse gilt. Schlimm ist. Febr. Andreas Möller war in den 90ern einer der talentiertesten Zweikämpfe, viele nannten ihn aus diesem Grund auch „Heulsuse Möller“, waren.
Andreas Möller Heulsuse VideoStefan Effenberg vs. Andreas Möller
Andreas möller heulsuse -Im November behauptete er in einem Fernsehinterview, er könne sich nicht erinnern, diese Aussage getätigt zu haben. Mehmet Scholl und Hasan Salihamidzic gelangen beim 6: Doch der Fünfmeterraum ist Sperrgebiet, Kahn-Land. April gegen den Hamburger SV. Sein Hauptaugenmerk lag dabei darauf, vom dortigen Trainer Didier Deschamps Arbeitsweisen und Trainingsmethoden zu erlernen. Spiele zwischen Dortmund und Bayern sind nichts für Weicheier. Als Heulsuse geht er wegen dieser Bilder aber mit Sicherheit nicht in die Geschichte ein — sondern eher als einer der umstrittensten Spieler der Geschichte des Revier-Derbys.
Extracellular vesicles represent a rich source of novel biomarkers in the diagnosis and prognosis of disease.
However, there is currently limited information elucidating the most efficient methods for obtaining high yields of pure exosomes, a subset of extracellular vesicles, from cell culture supernatant and complex biological fluids such as plasma.
To this end, we comprehensively characterize a variety of exosome isolation protocols for their efficiency, yield and purity of isolated exosomes.
Repeated ultracentrifugation steps can reduce the quality of exosome preparations leading to lower exosome yield. We show that concentration of cell culture conditioned media using ultrafiltration devices results in increased vesicle isolation when compared to traditional ultracentrifugation protocols.
We find that centrifuge-based concentrating methods are more appropriate than pressure-driven concentrating devices and allow the rapid isolation of exosomes from both NSCLC cell culture conditioned media and complex biological fluids.
In fact to date, no protocol detailing exosome isolation utilizing current commercial methods from both cells and patient samples has been described.
Utilizing tunable resistive pulse sensing and protein analysis, we provide a comparative analysis of 4 exosome isolation techniques, indicating their efficacy and preparation purity.
Our results demonstrate that current precipitation protocols for the isolation of exosomes from cell culture conditioned media and plasma provide the least pure preparations of exosomes, whereas size exclusion isolation is comparable to density gradient purification of exosomes.
We have identified current shortcomings in common extracellular vesicle isolation methods and provide a potential standardized method that is effective, reproducible and can be utilized for various starting materials.
We believe this method will have extensive application in the growing field of extracellular vesicle research.
Loss of Siah2 does not impact angiogenic potential of murine endothelial cells. Angiogenesis is triggered in response to hypoxia under many circumstances, from healthy cells and tissues during embryogenesis to pathological conditions like the formation of new blood vessels to supply the tumours and promote invasive cancer.
Siah2 has been shown to regulate the hypoxia pathway upstream of hypoxia-induced transcription factor subunit Hif-1alpha, and therefore may play an important role in angiogenesis in response to hypoxic stress in endothelial cells.
This study aims to investigate the basic function of Siah2 in endothelial cells under hypoxia and to test the ability of Siah2 deficient cells to mount an angiogenic response when deprived of oxygen.
We and others have previously shown that Siah2 is crucial for mediating the hypoxic response in many different cell types studied.
Thus, we conclude that Siah2 is not essential for the hypoxic response of endothelial cells. Published by Elsevier Inc.
Metastatic progression is the major cause of breast cancer related mortality. Further exploration of these results revealed that endogenous type-I IFN signaling to the host haematopoietic system is a key determinant of metastasis-free survival and critical to the responsiveness of the circulating NK cell population.
Together, this study indicates that the dysregulated immunity resulting from a loss of host type-I IFN signaling is sufficient to drive metastasis, and provides a rationale for targeting the endogenous type-I IFN pathway as an anti-metastatic strategy.
Toll-Like Receptor 3 regulates NK cell responses to cytokines and controls experimental metastasis.
C is a promising adjuvant for cancer vaccines because it induces strong anti-tumor responses, mainly through the activation of dendritic cells DCs and natural killer NK cells.
However, little is known about the role of TLR3 sensing of endogenous ligands in tumor immunosurveillance.
Here, we investigated whether TLR3 could modulate immune responses and facilitate tumor control without administration of an agonist.
We observed only limited impact of TLR3 deficiency on spontaneous carcinogenesis and primary growth of B16F10, E or MC38 tumors when injected subcutaneously to mice; but importantly, TLR3 limited experimental B16F10 lung metastasis.
Bone-marrow chimera experiments established that competent NK cell responses required TLR3 sensing on radio-sensitive immune cells. Altogether, our data demonstrate a pivotal role of endogenous TLR3 stimulation for the acquisition of full NK cell functions and protection against experimental metastasis.
The effects of hypoxia on tumour progression in breast cancer. The mobilization of bone marrow-derived cells BMDCs to distant tissues prior to the arrival of disseminated tumor cells has been shown preclinically to facilitate metastasis through the establishment of metastatic niches.
Primary tumor hypoxia has been demonstrated to play a pivotal role in the production of chemokines and cytokines responsible for the mobilization of these BMDCs, especially in breast cancer.
Preclinical evidence has demonstrated that CAIX is required for breast tumor growth and metastasis, however, the mechanism by which CAIX exerts its prometastatic function is not well understood.
AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; February 26 — March 1, ; San Diego, CA The recruitment of bone marrow-derived cells BMDCs to distant tissue sites prior to the arrival of disseminated tumor cells has been shown to facilitate metastasis in a preclinical setting through the establishment of the pre-metastatic niche.
Primary tumor hypoxia has been shown to play a pivotal role in the production of chemokines and cytokines responsible for the mobilization of these BMDCs, especially in breast cancer.
Carbonic anhydrase IX CAIX expression is highly upregulated by breast cancer cells in hypoxia where its activity contributes to cell survival through the buffering of intracellular pH.
Preclinically, CAIX has been demonstrated to be required for breast tumor growth and metastasis, whereas clinically, CAIX is an established indicator of poor prognosis and distant metastasis in breast cancer patients.
However, the mechanism by which CAIX exerts its pro-metastatic function is incompletely understood. We investigated whether CAIX function in the hypoxic niche of the primary tumor was involved in establishment of the pre-metastatic niche through the production of soluble mediators of this process.
The ubiquitin ligase Siah is a novel regulator of Zeb1 in breast cancer. Elucidating the mechanisms that underlie metastasis is of paramount importance to understanding tumor progression and to the development of novel therapeutics.
Epithelial to Mesenchymal Transition EMT plays a vital role in tumor cell dissemination and is regulated by a core cassette of transcription factors.
Despite recent advances, the molecular pathways that regulate the EMT program have not yet been fully delineated. The induction of EMT in breast cancer cells leads to the down-regulation of Siah, while the loss of Siah induces a mesenchymal phenotype, concurrent with an up-regulation of Zeb1.
Overexpression of Siah in vitro mediates Zeb1 degradation, which can be blocked with a Siah peptide inhibitor. Thus, this work demonstrates that Siah is a novel regulator of EMT.
This work is the first to identify a mechanism of post-translational regulation of the key Epithelial to Mesenchymal Transition transcription factor Zeb1.
Extracellular vesicles are spherical bilayered proteolipids, harboring various bioactive molecules.
Due to the complexity of the vesicular nomenclatures and components, online searches for extracellular vesicle-related publications and vesicular components are currently challenging.
We present an improved version of EVpedia, a public database for extracellular vesicles research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools, and a personalized function.
In addition, about members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of extracellular vesicle research.
The NLRP3 inflammasome plays a crucial role in the innate immune response to pathogens and exogenous or endogenous danger signals.
Its activity must be precisely and tightly regulated to generate tailored immune responses. However, the immune cell subsets and cytokines controlling NLRP3 inflammasome activity are still poorly understood.
Historically, it has been difficult to monitor the acute impact of anticancer therapies on hematopoietic organs on a whole-body scale. Deeper understanding of the effect of treatments on bone marrow would be of great potential value in the rational design of intensive treatment regimens.
It is trapped in cells in proportion to thymidine-kinase 1 enzyme expression, which is upregulated during DNA synthesis. This study investigates the potential of 18 F-FLT to monitor acute effects of chemotherapy on cellular proliferation and its recovery in bone marrow, spleen, and liver during treatment with 2 different chemotherapy regimens.
Visual and semiquantitative standardized uptake value SUV measurements were performed in bone marrow outside the radiotherapy field, liver, spleen, and small bowel.
These were correlated to blood counts and smears in a subset of patients. Liver uptake changed little. This technology may support novel treatment planning and monitoring approaches in oncology patients.
Beta-blockade of breast cancer metastasis: Receptor regulation and downstream signaling pathways. Chronic stress accelerates breast cancer metastasis through beta-adrenergic signaling and recent clinical studies found that beta-blockade reduced metastasis in women with breast cancer.
However, the specific beta-adrenergic receptor subtype s through which stress-responsive neurotransmitters mediates effects on cancer remain unknown.
To identify the receptor that transmits beta-adrenergic signaling to primary mammary tumors, we used bioluminescence imaging to longitudinally quantify the effect on metastasis of beta-blockers that selectively inhibit beta1 vs.
Treatment with the beta2-selective antagonist ICI similarly reduced stress-enhanced metastasis to control levels. In contrast, beta-1 selective blockade failed to protect against metastasis.
Pharmacological intervention studies and gene expression analyses have started to define the downstream signaling pathways of beta-adrenergic regulation of metastasis.
These studies may provide mechanistic explanation for recent clinical findings that not all beta-blockers protect against metastasis and provide a framework for selection of cancer patients who may optimally benefit from beta-blockade.
Ming Gene Chai, Caroline P. Robert Lane, Erica K. Bob1 Obf-1 or OCA-B is a kDa transcriptional coactivator encoded by the Pou2af1 gene that is essential for normal B-cell development and immune responses in mice.
During lymphocyte activation, Bob1 protein levels dramatically increase independently of mRNA levels, suggesting that the stability of Bob1 is regulated.
We used a fluorescent protein-based reporter system to analyze protein stability in response to genetic and physiological perturbations and show that, while Bob1 degradation is proteasome mediated, it does not require ubiquitination of Bob1.
Furthermore, degradation of Bob1 in B cells appears to be largely independent of the E3 ubiquitin ligase Siah.
We propose a novel mechanism of Bob1 turnover in B cells, whereby an acidic region in the C terminus of Bob1 regulates the activity of degron signals elsewhere in the protein.
Changes that make the C terminus more acidic, including tyrosine phosphorylation-mimetic mutations, stabilize the instable murine Bob1 protein, indicating that B cells may regulate Bob1 stability and activity via signaling pathways.
Finally, we show that expressing a stable Bob1 mutant in B cells suppresses cell proliferation and induces changes in surface marker expression commonly seen during B-cell differentiation.
Intratumoral hypoxia is a poor prognostic factor associated with reduced disease-free survival in many cancer types, including breast cancer.
Hypoxia encourages tumor cell proliferation, stimulates angiogenesis and lymphangiogenesis, and promotes epithelial-mesenchymal transition and metastasis.
In addition, NAC treatment actually increased metastatic burden in an experimental metastasis model. This work raises questions regarding the validity of NAC as an anti-tumorigenic agent in breast cancer, and highlights the need to further investigate its properties in vivo in different cancer models.
The region of interest tool was used to define the metastatic tumor area and avoid the inclusion of normal lung tissue, giving a percentage of DAB Ki67 positive cells in each tumor.
Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability. Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity.
Here we demonstrate that under hypoxic conditions, the ubiquitin ligase Siah seven in absentia homolog 2 controls ASPP2 availability, with concomitant effect on epithelial cell polarity.
Biochemical analysis confirmed this interaction and mapped degron motifs within ASPP2, which are required for Siah2-mediated ubiquitination and proteasomal-dependent degradation.
Conversely, increase of Siah2 expression under hypoxia decreases ASPP2 levels and the formation of apical polarity in 3D culture.
In all, our studies demonstrate the role of Siah2 in regulation of TJ integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability.
Oncogene advance online publication, 6 May ; doi: It is rapidly becoming evident that the formation of tumor-promoting pre-metastatic niches in secondary organs adds a previously unrecognized degree of complexity to the challenge of curing metastatic disease.
Primary tumor cells orchestrate pre-metastatic niche formation through secretion of a variety of cytokines and growth factors that promote mobilization and recruitment of bone marrow-derived cells to future metastatic sites.
Hypoxia within the primary tumor, and secretion of specific microvesicles termed exosomes, are emerging as important processes and vehicles for tumor-derived factors to modulate pre-metastatic sites.
It has also come to light that reduced immune surveillance is a novel mechanism through which primary tumors create favorable niches in secondary organs.
This review provides an overview of our current understanding of underlying mechanisms of pre-metastatic niche formation and highlights the common links as well as discrepancies between independent studies.
Furthermore, the possible clinical implications, links to metastatic persistence and dormancy, and novel approaches for treatment of metastatic disease through reversal of pre-metastatic niche formation are identified and explored.
Siah2-deficient mice show impaired skin wound repair. Hypoxia is associated with the dermal wound healing process and hypoxia signaling is presumed to be crucial for normal wound repair.
The Siah2 ubiquitin ligase controls the abundance of hypoxia-inducible factor-1 alpha, and loss of Siah2 results in destabilization of hypoxia-inducible factor-1 alpha under hypoxia.
Together, our data show, for the first time, that Siah2 is involved as a positive regulator in the wound healing response.
Understanding the role of hypoxia signaling in tissue repair and fibrosis and interference with the hypoxia signaling pathway via regulation of Siah2 may provide new targets for clinical regulation of fibrosis and scarring.
The role of Type I interferons in immunoregulation of breast cancer metastasis to the bone. Breast cancer spread to distant sites is often incurable.
Our recent findings demonstrate that Type I interferons secreted by tumor cells induce anti-metastatic immune responses that prevent breast cancer metastasis to the bone.
This provides novel insights into the importance of the crosstalk between neoplastic and immune cells in the metastatic process.
Hypoxia-driven immunosuppression contributes to the pre-metastatic niche. Primary tumor cells create favorable microenvironments in secondary organs, termed pre-metastatic niches, that promote the formation of metastases.
A Promising Anticancer Target. Siah ubiquitin ligases play important roles in a number of signaling pathways involved in the progression and spread of cancer in cell-based models but their role in tumor progression remains controversial.
Siah proteins have been described to be both oncogenic as well as tumor-suppressive in a variety of patient cohort studies and animal cancer models. This review collates the current knowledge of Siah in cancer progression and identifies potential methods of translation of these findings into the clinic.
Furthermore, key experiments needed to close the gaps in our understanding of the role Siah proteins play in tumor progression are suggested.
The interaction between murine melanoma and the immune system reveals that prolonged responses predispose for autoimmunity.
We have used the poorly immunogenic B16F10 melanoma model to characterize a very heterogeneous antitumor effect of the immune response induced by Treg depletion.
Strikingly, the duration of the tumor-immune system interaction provoked in individual Treg-depleted mice positively correlated with their propensity to develop vitiligo.
A rapid complete tumor rejection was not associated with the development of autoimmunity, however, a proportion of mice that suppressed, but did not effectively clear, B16F10 melanoma did develop vitiligo.
The significant implication is that approaches that combine with Treg depletion to rapidly reject tumors may also diminish autoimmune toxicities.
Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs.
To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber TEC and characterized the gene and protein expression of cytokines in the newly developing tissues.
Macrophage derived factors, such as MCP-1, appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of non-bone marrow-derived progenitors.
This study provides new information about key elements that are involved in early development of new adipose tissue.
NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma. Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma.
The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers.
Ein Stichwort, das Möller auch in Offenbach zu hören bekommen wird. Etwa die seines Vorgängers Michael Dämgen.
Erst vor wenigen Wochen folgte der Feststellung die Ergänzung: Die Lizenz dafür hat er, aber auch das Format?
Hier können Sie die Rechte an diesem Artikel erwerben. Dzsenifer Marozsan musste drei Monate pausieren wegen einer Lungenembolie.
Auslöser war die Anti-Baby-Pille. Nun will sie wieder zu alter Form finden — ganz ohne Hormone. Anlässlich des Guinness-Weltrekord-Tages hat ein japanischer Seilspringer eine neue Höchstmarke gesetzt und damit sich selbst überboten.
Als er dabei zur misslichen Lage des FC Bayern gefragt wird, reagiert er erstaunlich. Ein Sieg würde das Achtelfinale näherrücken lassen.
Fortschritte in der Neurologie. Suche Suche Login Logout. Kurz bevor die Waffen an der Front schweigen, überschlagen sich in Deutschland die Ereignisse.
Precambrian Research , , Zircon geochronology of the Koraput alkaline complex: Insights from combined geochemical and U-Pb-Hf isotope analyses, and implications for the timing of alkaline magmatism in the Eastern Ghats Belt, India.
Gondwana Research , 34 , Paleoproterozoic continental crust generation events at 2. Earth and Planetary Science Letters , , Indo-Antarctic derived detritus on the northern margin of Gondwana: Terra Nova , 26 1 , Graduate Apply Now Application Information.
Skip to main content. Post-doctoral research and teaching fellow positions in Sydney, Mainz and Potsdam.