11 results on '"Mack, Brigitte"'
Search Results
2. CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma‐Initiating Cells and Predicts Metastasis
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Gassenmaier, Maximilian, Chen, Dong, Buchner, Alexander, Henkel, Lynette, Schiemann, Matthias, Mack, Brigitte, Schendel, Dolores J., Zimmermann, Wolfgang, and Pohla, Heike
- Abstract
In many solid tumors, cancer stem cells (CSC) represent a population with tumor‐initiating, self‐renewal, and differentiation potential, which can be identified by surface protein markers. No generally applicable markers are yet known for renal cell carcinoma (RCC). Two RCC cell lines (RCC‐26, RCC‐53) were found to differ widely in their capacity to form spheres in vitro and to establish tumors in mice, potentially reflecting differences in CSC content. A subpopulation expressing the CXC chemokine receptor 4 (CXCR4) was present only in the more tumorigenic cell line RCC‐53. When grown as spheres, most of the RCC‐53 cells were CXCR4‐positive, expressed stem cell‐associated transcription factor genes at elevated levels, and were more resistant toward the tyrosine kinase inhibitors sunitinib, sorafenib, and pazopanib. Sorted CXCR4‐positive cells exhibited greater capacity for sphere formation and tumor growth‐inducing potential in vivo than CXCR4‐negative cells. Significantly, higher CXCR4 mRNA levels in primary RCC tumors from patients with localized but not disseminated disease predicted shorter survival. Downregulation of CXCR4 expression by small interfering RNA (siRNA) or pharmacological inhibition by AMD3100 compromised tumor sphere formation, viability of CXCR4‐positive cells, and increased their responsiveness toward tyrosine kinase inhibitors. In conclusion, CXCR4 identifies a subpopulation of tumor‐initiating cells in RCC cell lines and plays a role in their maintenance. The relative insensitivity of such cells to tyrosine kinase inhibitors might contribute to the development of therapy resistance in RCC patients. Future therapies therefore could combine blockade of the CXCR4 signaling pathway with standard therapies for more effective treatments of metastatic RCC. STEMCells2013;31:1467–1476
- Published
- 2013
- Full Text
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3. CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
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Hampel, Franziska, Ehrenberg, Stefanie, Hojer, Caroline, Draeseke, Anne, Marschall-Schröter, Gabriele, Kühn, Ralf, Mack, Brigitte, Gires, Olivier, Vahl, Christoph J., Schmidt-Supprian, Marc, Strobl, Lothar J., and Zimber-Strobl, Ursula
- Abstract
B cell–specific gene ablation of Notch2 results in the loss of the marginal zone (MZ) B-cell lineage. To analyze the effects of constitutive Notch2 signaling in B cells, we have generated a transgenic mouse strain that allows the conditional expression of a constitutively active, intracellular form of Notch2 (Notch2IC). Expression of Notch2IC at the earliest developmental stages of the B-cell lineage completely abolished B-cell generation and led to the development of ectopic T cells in the bone marrow (BM), showing that Notch2IC is acting redundantly with Notch1IC in driving ectopic T-cell differentiation. In B cells clearly committed to the B-cell lineage induction of Notch2IC drove all cells toward the MZ B-cell compartment at the expense of follicular B cells. Notch2IC-expressing B cells reflected the phenotype of wild-type MZ B cells for their localization in the MZ, the expression of characteristic surface markers, their enhanced proliferation after stimulation, and increased basal activity of Akt, Erk, and Jnk. Notch2IC-driven MZ B-cell generation in the spleen was achieved even in the absence of CD19. Our results implicate that a constitutive Notch2 signal in transitional type 1 B cells is sufficient to drive MZ B-cell differentiation.
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- 2011
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4. CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
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Hampel, Franziska, Ehrenberg, Stefanie, Hojer, Caroline, Draeseke, Anne, Marschall-Schröter, Gabriele, Kühn, Ralf, Mack, Brigitte, Gires, Olivier, Vahl, Christoph J., Schmidt-Supprian, Marc, Strobl, Lothar J., and Zimber-Strobl, Ursula
- Abstract
B cell–specific gene ablation of Notch2 results in the loss of the marginal zone (MZ) B-cell lineage. To analyze the effects of constitutive Notch2 signaling in B cells, we have generated a transgenic mouse strain that allows the conditional expression of a constitutively active, intracellular form of Notch2 (Notch2IC). Expression of Notch2IC at the earliest developmental stages of the B-cell lineage completely abolished B-cell generation and led to the development of ectopic T cells in the bone marrow (BM), showing that Notch2IC is acting redundantly with Notch1IC in driving ectopic T-cell differentiation. In B cells clearly committed to the B-cell lineage induction of Notch2IC drove all cells toward the MZ B-cell compartment at the expense of follicular B cells. Notch2IC-expressing B cells reflected the phenotype of wild-type MZ B cells for their localization in the MZ, the expression of characteristic surface markers, their enhanced proliferation after stimulation, and increased basal activity of Akt, Erk, and Jnk. Notch2IC-driven MZ B-cell generation in the spleen was achieved even in the absence of CD19. Our results implicate that a constitutive Notch2 signal in transitional type 1 B cells is sufficient to drive MZ B-cell differentiation.
- Published
- 2011
- Full Text
- View/download PDF
5. B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice
- Author
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Chu, Yuanyuan, Vahl, J. Christoph, Kumar, Dilip, Heger, Klaus, Bertossi, Arianna, Wójtowicz, Edyta, Soberon, Valeria, Schenten, Dominik, Mack, Brigitte, Reutelshöfer, Miriam, Beyaert, Rudi, Amann, Kerstin, van Loo, Geert, and Schmidt-Supprian, Marc
- Abstract
The ubiquitin-editing enzyme A20/TNFAIP3 is essential for controlling signals inducing the activation of nuclear factor-κB transcription factors. Polymorphisms and mutations in the TNFAIP3 gene are linked to various human autoimmune conditions, and inactivation of A20 is a frequent event in human B-cell lymphomas characterized by constitutive nuclear factor-κB activity. Through B cell-specific ablation in the mouse, we show here that A20 is required for the normal differentiation of the marginal zone B and B1 cell subsets. However, loss of A20 in B cells lowers their activation threshold and enhances proliferation and survival in a gene-dose–dependent fashion. Through the expression of proinflammatory cytokines, most notably interleukin-6, A20-deficient B cells trigger a progressive inflammatory reaction in naive mice characterized by the expansion of myeloid cells, effector-type T cells, and regulatory T cells. This culminates in old mice in an autoimmune syndrome characterized by splenomegaly, plasma cell hyperplasia, and the presence of class-switched, tissue-specific autoantibodies.
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- 2011
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6. B cells lacking the tumor suppressor TNFAIP3/A20 display impaired differentiation and hyperactivation and cause inflammation and autoimmunity in aged mice
- Author
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Chu, Yuanyuan, Vahl, J. Christoph, Kumar, Dilip, Heger, Klaus, Bertossi, Arianna, Wójtowicz, Edyta, Soberon, Valeria, Schenten, Dominik, Mack, Brigitte, Reutelshöfer, Miriam, Beyaert, Rudi, Amann, Kerstin, van Loo, Geert, and Schmidt-Supprian, Marc
- Abstract
The ubiquitin-editing enzyme A20/TNFAIP3is essential for controlling signals inducing the activation of nuclear factor-κB transcription factors. Polymorphisms and mutations in the TNFAIP3gene are linked to various human autoimmune conditions, and inactivation of A20 is a frequent event in human B-cell lymphomas characterized by constitutive nuclear factor-κB activity. Through B cell-specific ablation in the mouse, we show here that A20 is required for the normal differentiation of the marginal zone B and B1 cell subsets. However, loss of A20 in B cells lowers their activation threshold and enhances proliferation and survival in a gene-dose–dependent fashion. Through the expression of proinflammatory cytokines, most notably interleukin-6, A20-deficient B cells trigger a progressive inflammatory reaction in naive mice characterized by the expansion of myeloid cells, effector-type T cells, and regulatory T cells. This culminates in old mice in an autoimmune syndrome characterized by splenomegaly, plasma cell hyperplasia, and the presence of class-switched, tissue-specific autoantibodies.
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- 2011
- Full Text
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7. Analysis of Plasmacytoid and Myeloid Dendritic Cells in Nasal Epithelium
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Hartmann, Evelyn, Graefe, Hendrik, Hopert, Anne, Pries, Ralph, Rothenfusser, Simon, Poeck, Hendrik, Mack, Brigitte, Endres, Stefan, Hartmann, Gunther, and Wollenberg, Barbara
- Abstract
ABSTRACTThe role of plasmacytoid dendritic cells (PDC), the major producers of alpha interferon upon viral infection, in the nasal mucosa is largely unknown. Here we examined the presence of PDC together with myeloid dendritic cells (MDC) in the nasal epithelia of healthy individuals, of asymptomatic patients with chronic nasal allergy, of patients undergoing steroid therapy, and of patients with infectious rhinitis or rhinosinusitis. Considerable numbers of PDC and MDC could be detected in the nasal epithelium. Furthermore, we demonstrate the expression of SDF-1, the major chemoattractant for PDC, in the nasal epithelium. PDC levels were significantly lower for patients with allergies than for healthy individuals. Interestingly, PDC and MDC were almost absent from patients who received treatment with glucocorticoids, while very high numbers of PDC were found for patients with recent upper respiratory tract infections. Our results demonstrate for the first time a quantitative analysis of PDC and MDC in the healthy nasal epithelium and in nasal epithelia from patients with different pathological conditions. With the identification of PDC, the major target cell for CpG DNA or immunostimulatory RNA, in the nasal epithelium, this study forms the basis for a local nasal application of such oligonucleotides for the treatment of viral infection and allergy.
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- 2006
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8. Localization of Transforming Growth Factor-β- Expressing Cells and Comparison with Major Extracellular Components in Aural Cholesteatoma
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Lang, Stephan, Schilling, Volker, Mack, Brigitte, Wollenberg, Barbara, and Nerlich, Andreas
- Abstract
Transforming growth factor-β (TGF-β) plays an important role in the regulation of extracellular matrix (ECM) deposition by stimulating the synthesis of individual matrix proteins like tenascin and fibronectin. Cholesteatoma shows significant changes in the ECM, supporting the view of adisturbed cell-matrix interaction. The purpose of our present study was to evaluate the distribution of TGF-β in comparison to the deposition of tenascin, fibronectin, and collagen as major components of the ECM in cholesteatoma (n = 12) by means of histochemistry and immunohistochemistry. We found TGF-P in lymphocytes and fibrohistiocytes in the stroma of 7 cholesteatomas. In corresponding sections, a marked expression of tenascin and fibronectin was seen manifesting as a continuous band along the epidermal-stromal junction, extending to the deeper stroma. In addition, in those cases of TGF-β expression, beginning collagen fibril formation was seen in adjacent deeper stroma layers, indicating beginning stromal fibrosis. These results suggest that TGF-β may be involved in the stimulation of the synthesis of tenascin, fibronectin, and collagen. Furthermore, the enhanced expression of tenascin and fibronectin provides evidence for a deregulated cell-matrix interaction in cholesteatoma associated with the enhanced proliferative process of cholesteatoma formation.
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- 1997
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9. Fluorescence microscopic and histologic analysis of photosensitizer uptake in human atherosclerotic lesions
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Gonschior, P., Erdemci, Aysel, Gerheuser, F., Mack, Brigitte, Gonschior, Gabi-M., Groh, J., Leunig, M., Goetz, A., and Höfling, B.
- Abstract
Abstract: Photodynamic therapy (PDT) using haematoporphyrin derivatives (HPD) activated by laser light is a well-established treatment modality for superficial tumours. PDT might therefore have a role in the prevention of restenosis in diseased human blood vessels following intraluminal therapy. This experiment addresses the possibility of using Photofrin in such a role and specifically addresses the preferential uptake of PHotofrin into atherosclerotic lesions. Normal (n=15) and atherosclerotic (n=52) human vessel segments were incubated with a medium containing 2.5 or 5 μg ml
−1 Photofrin. Quantitative fluorescence detection was used to measure the Photofrin content in the normal or diseased wall at intervals of 15, 30, and 60 min and 24 h of incubation. Fluorescence was concentration dependent and the maximum uptake was reached after 1 h incubation. Photofrin was preferentially taken up by diseased tissue and the quantified uptake in the ratio primary atherosclerosis: restenotic vessel: normal vessel was 4∶5∶1. Highly cellular plaque segments showed markedly increased fluorescence as compared to an acellular atherosclerotic matrix. Photofrin was quickly and selectively taken up by atherosclerotic lesions and this may form the basis for a selective photodynamic therapy for primary and restenotic atheroma.- Published
- 1993
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10. Overexpression of Tenascin in Cholesteatoma and External Auditory Meatal Skin Compared to Retroauricular Epidermis
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Schilling, Volker, Lang, Stephan, Rasp, Gerd, Mack, Brigitte, and Nerlich, Andreas
- Abstract
Schilling V, Lang S, Rasp G, Mack B, Nerlich A. Overexpression of tenascin in cholesteatoma and external auditory meatal skin compared to retroauricular epidermis. Acta Otolaryngol (Stockh) 1996; 116: 741-746.In the present study the distribution of tenascin in cholesteatoma was immunohistochemically investigated. the results were compared with those in external auditory meatal skin and in retroauricular skin of healthy controls. the staining pattern was additionally correlated to the degree of cell proliferation as detected by the monoclonal antibody MIB-I (Ki-67 antigen). Retroauricular skin showed a limited distribution of tenascin in the papillary dermis and a sparse reactivity of MIB-1 in only a few epithelial cells. External auditory meatal skin revealed a more pronounced reaction for tenascin and MIB-1. in contrast, cholesteatoma tissue exhibited an abundant and continuous expression of tenascin covering the whole stroma compartment. This coincided with a significant increase of MIB-1-positive cells in the basal and suprabasal epithelial layers. Doublestaining experiments revealed most prominent stromal tenascin-expression in areas with marked signs for epithelial proliferation. This suggests that tenascin is selectively increased in response to epidermal hyperproliferation. This matrix protein thus shows a quantitatively and qualitatively enhanced expression under pathological conditions. Moreover, the abundant reactivity for tenascin in the cholesteatoma provides evidence of a deregulated cell-matrix interaction involved in the hyperproliferative process of cholesteatoma formation.
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- 1996
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11. Probe-based confocal laser endomicroscopy in head and neck malignancies: early preclinical experience
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Betz, Christian, Wong, Brian J. F., Englhard, Anna, Girschick, Susanne, Mack, Brigitte, Volgger, Veronika, Gires, Oliver, Conderman, Christian, Stepp, Herbert, and Betz, Christian Stephan
- Published
- 2013
- Full Text
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