Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: DISEASE ; Germany ; INTERFERON-ALPHA ; INTERFERON ; ALPHA ; BIOLOGY
    Type of Publication: Book chapter
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    facet.materialart.
    facet.materialart.
    Spektrum
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    facet.materialart.
    facet.materialart.
    Springer
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: EXPRESSION ; FACTOR RECEPTOR ; ACID SPHINGOMYELINASE ; DEATH DOMAIN ; ENDOTOXIN-SHOCK ; NF-KAPPA-B ; NITRIC-OXIDE SYNTHASE ; SIGNAL- TRANSDUCTION ; STRESS-INDUCED APOPTOSIS ; TNF-RECEPTOR ; TUMOR-NECROSIS-FACTOR
    Abstract: Stimulation of macrophages by lipopolysaccharide (LPS) leads to the synthesis of proinflammatory cytokines and nitric oxide (NO) and, as a consequence, to endotoxic shock. We provide evidence that LPS stimulates the activity of a membrane- associated neutral sphingomyelinase (nSMase) and that this activity is mandatory for the liberation of nuclear factor- kappaB (NFkappaB) and the induction of inducible NO-synthase (iNOS). With the aid of a newly developed, selective inhibitor of nSMase, C11AG, we could distinguish between nSMase-dependent and -independent LPS-induced signals. C11AG blocked LPS- stimulated sphingomyelin degradation and NFkappaB activation without interfering with p42 tyrosine phosphorylation. Concomitantly, the expression of iNOS was found to be reduced both in mononuclear cells and in murine endotoxemia. Therefore, specific Inhibitors of nSMase may define a new class of antiinflammatory substances
    Type of Publication: Journal article published
    PubMed ID: 12866359
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; tumor ; Germany ; COMPLEX ; COMPLEXES ; RE ; PH ; CRYSTAL ; PLATINUM
    Type of Publication: Journal article published
    PubMed ID: 16335917
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; Germany ; KINASE ; PROTEIN ; TISSUE ; TUMORS ; PATIENT ; ACTIVATION ; COMPLEX ; COMPLEXES ; prognosis ; RAT ; ASSOCIATION ; ALPHA ; DESIGN ; colorectal cancer ; COLORECTAL-CANCER ; COLON-CANCER ; BETA ; ADHESION ; MIGRATION ; INTEGRIN ; adenocarcinoma ; POOR-PROGNOSIS ; HUMAN EPIDERMAL-KERATINOCYTES ; HEALTHY ; CELL-MIGRATION ; ALPHA-6-BETA-4 INTEGRIN ; RE ; TUMOR INVASION ; cell migration ; INTERNALIZATION ; ALPHA-3-BETA-1 INTEGRIN ; BETA(1) INTEGRINS ; EXTRACELLULAR-MATRIX PROTEINS ; laminin ; METASTASIS SUPPRESSOR ; TRANSMEMBRANE 4 SUPERFAMILY
    Abstract: Purpose: Patients with pancreatic adenocarcinoma have a poor prognosis due to the extraordinary high invasive capacity of this tumor. Altered integrin and tetraspanin expression is suggested to be an important factor. We recently reported that after protein kinase C activation, colocalization of alpha 6 beta 4 with the tetraspanin CO-029 strongly supports migration of a rat pancreatic adenocarcinoma. The finding led us to explore whether and which integrin-tetraspanin complexes influence the motility of human pancreatic tumors. Experimental Design: Integrin and tetraspanin expression of pancreatic and colorectal adenocarcinoma was evaluated with emphasis on colocalization and the impact of integrin-tetraspanin associations on tumor cell motility. Results: The majority of pancreatic and colorectal tumors expressed the alpha 2, alpha 3, alpha 6, beta 1, and beta 4 integrins and the tetraspanins CD9, CD63, CD81, CD151, and CO-029. Expression of alpha 6 beta 4 and CO-029 was restricted to tumor cells, whereas alpha 1, alpha 2, a3, a6, 1, and CD9, CD81, CD151 were also expressed by the surrounding stroma. CD63, CD81, and beta 1 expression was observed at comparably high levels in healthy pancreatic tissue. alpha 3 beta 1 frequently colocalized and coimmunoprecipitated with CD9, CD81, and CD151, whereas alpha 6 beta 4 colocalized and coimmunoprecipitated mostly with CD151 and CO-029. Notably, protein kinase C activation strengthened only the colocalization of CD151 and CO-029 with beta 4 and was accompanied by internalization of the integrin-tetraspanin complex, decreased laminin 5 adhesion, and increased cell migration. Conclusion: alpha 6 beta 4 is selectively up-regulated in pancreatic and colorectal cancer. The association of alpha 6 beta 4 with CD151 and CO-029 correlates with increased tumor cell motility
    Type of Publication: Journal article published
    PubMed ID: 15837731
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: APOPTOSIS ; CELLS ; EXPRESSION ; proliferation ; tumor ; TUMOR-CELLS ; carcinoma ; Germany ; human ; PROTEIN ; DIFFERENTIATION ; MOLECULES ; TISSUE ; TUMORS ; LINES ; COMPLEX ; COMPLEXES ; RAT ; TISSUES ; CELL-LINES ; PHOSPHORYLATION ; ASSOCIATION ; MOLECULE ; resistance ; MEMBRANE ; LINE ; LOCALIZATION ; ADHESION ; POLYPEPTIDE ; EPITHELIAL-CELLS ; protein-protein interaction ; ADHESION MOLECULE ; cell lines ; pancreatic carcinoma ; COMPLEX-FORMATION ; RAT-TUMOR ; TIGHT JUNCTIONS ; RE ; PANCREATIC-CANCER ; TUMOR INVASION ; VARIANT ; COLORECTAL-CARCINOMA ; interaction ; claudin ; protein-protein ; CD9 ; D6.1A ; INTERACT ; ANTIGEN EP-CAM ; EpCAM ; glycolipid-enriched membrane microdomain ; HUMAN TUMORS ; protein complex
    Abstract: We recently described that in the metastasizing rat pancreatic carcinoma line BSp73ASML the cell-cell adhesion molecule EpCAM, CD44 variant isoforms and the tetraspanins D6.1A and CD9 form a complex that is located in glycolipid-enriched membrane microdomains. This complex contains, in addition, an undefined 20 kDa protein. As such complex formation influenced cell-cell adhesion and apoptosis resistance, it became of interest to identify the 20 kDa polypeptide. This 20 kDa protein, which co-precipitated with EpCAM in BSp73ASML lysates, was identified as the tight junction protein claudin-7. Correspondingly, an association between EpCAM and claudin-7 was noted in rat and human tumors and in non-transformed tissues of the gastrointestinal tract. Co-localization of the two molecules was most pronounced at basolateral membranes, but was also observed in tight junctions. Evidence for direct protein-protein interactions between EpCAM and claudin-7 was obtained by co-immunoprecipitation after treatment of tumor cells with a membrane-permeable chemical cross-linker. The complex, which is located in glycolipid-enriched membrane microdomains, is not disrupted by partial cholesterol depletion, but claudin-7 phosphorylation is restricted to the localization in glycolipid-enriched membrane microdomains. This is the first report on an association between EpCAM and claudins in both non-transformed tissues and metastasizing tumor cell lines. (c) 2005 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16054130
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: PEPTIDE ; CELLS ; IN-VITRO ; tumor ; carcinoma ; Germany ; GENERATION ; LINES ; TIME ; PATIENT ; DENDRITIC CELLS ; DOWN-REGULATION ; TRIAL ; NUMBER ; CLINICAL-TRIALS ; LINE ; B-CELLS ; PEPTIDES ; CARCINOMAS ; ANTIGEN-PRESENTING CELLS ; IMMUNOTHERAPY ; vaccination ; TARGETS ; INTERFERON-ALPHA ; RECOMBINANT INTERLEUKIN-2 ; QUANTITIES ; CTL ; renal cell carcinoma ; RE ; TUMOR-ANTIGENS ; PHASE-II TRIAL ; dendritic cell ; CELL-CARCINOMA ; human renal cell carcinoma ; RENAL-CELL-CARCINOMA ; APC ; ADOPTIVE TRANSFER ; antigen-presenting cell ; AUTOLOGOUS DENDRITIC CELLS ; B-LYMPHOCYTES ; peptide-specific cytotoxic T lymphocyte ; cytotoxic T lymphocyte
    Abstract: Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysate-pulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE-1 and MAGE-9 peptide-specific CTL lines. RAGE-1 and MAGE-9 are expressed in 56% and 38% of RCCs. Seven MAGE-9 and 13 RAGE-1-derived peptides were found to be immunogenic in the context of the HLA-A*0201 MHC. CTLs were generated by coculture with peptide-pulsed, activated B cells, which were easily generated in great quantities and displayed functional activity for a prolonged period of time. MAGE-9 and RAGE-1 peptide-specific CTL lines were strictly peptide-specific and displayed high cytotoxic activity not only against peptide-loaded T2 cells but also against HLA-A*0201-positive RCC lines, which naturally express MAGE-9, RAGE-1 or both. Thus, B cells are well suited as APCs for the generation of large numbers of tumor peptide-specific CTLs for adoptive transfer. MAGE-9 as well as RAGE-1 may well provide suitable targets for immunotherapy of RCC. (c) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15900605
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: APOPTOSIS ; CELLS ; EXPRESSION ; GROWTH ; INHIBITOR ; proliferation ; tumor ; Germany ; KINASE ; CDNA ; PROTEIN ; PROTEINS ; ADHESION MOLECULES ; NF-KAPPA-B ; ACTIVATION ; COMPLEX ; RESPONSES ; COMPLEXES ; MECHANISM ; ANTIGEN ; T-CELL ; T-CELLS ; C-JUN ; PHOSPHORYLATION ; signal transduction ; ALPHA ; IMMUNE-RESPONSES ; MOUSE ; LINE ; MONOCLONAL-ANTIBODIES ; RHO-ASSOCIATED KINASE ; KAPPA-B ; CROSS-LINKING ; MAP KINASES ; FAS-MEDIATED APOPTOSIS ; rodent ; T lymphocytes ; INDUCED CELL-DEATH ; STANDARD ; ABSENCE ; secretion ; HYALURONAN RECEPTOR ; DELAYED-TYPE HYPERSENSITIVITY ; JNK ; KINASES ; TRANSMEMBRANE DOMAIN ; PHOSPHOINOSITIDE 3-KINASE/AKT
    Abstract: CD44v6 is transiently expressed during T cell activation, and constitutively CD44v4-v7 expressing transgenic T cells show accelerated responses towards nominal antigens. The underlying mechanism is unknown. The mouse thymoma EL4 was transfected with CD44 standard isoform (CD44s) or CD44v6 cDNA (EL4-s, EL4-v6). Only EL4-v6 cells proliferated at an over 10-fold higher rate than untransfected cells, displayed up-regulated expression of CD69, CD25, and IL-2, and were protected from apoptosis by CD44v6 cross-linking. In the absence of any stimulus, ERK1/2 was partly phosphorylated, and phosphorylation was significantly increased by CD44v6 cross-linking. The same accounted for JNK, c-jun, and I kappa B alpha. Moreover, NF-kappa B was partly translocated into the nucleus. Instead, CD44s cross-linking induced ERK1/2, JNK, c-jun, and I kappa B alpha phosphorylation only in the context of TCR engagement. No selectively CD44v6 associated transmembrane proteins were uncovered in EL4 cells. However, CD44v6, as opposed to CD44s, did not colocalise with the TCR/CD3 complex after CD3 cross-linking. Furthermore, a CD44-associated 85-kDa protein became hypophosphorylated only after CD44v6 cross-linking. Threonine hypophosphorylation of this protein coincided with the activation of MAP and SAP kinases, which was prohibited in the presence of a phosphatase inhibitor. Thus, CD44v6, distinct to CD44s, stimulates autonomously growth and IL-2 secretion of a thymoma line and rescues cells from apoptosis. (c) 2004 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15894169
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: CELLS ; EXPRESSION ; Germany ; DISEASE ; SITE ; DISTINCT ; GENE ; MOLECULES ; MICE ; ACTIVATION ; COMPLEX ; ARTHRITIS ; COMPLEXES ; IFN-GAMMA ; MARKER ; INDUCTION ; SKIN ; T cell activation ; T cells ; T-CELLS ; FLOW ; cytokines ; DELETION ; immunohistochemistry ; NUMBER ; PATHOGENESIS ; MOUSE MODEL ; INTERFERON ; INTERFERON-GAMMA ; human hair follicle ; T lymphocytes ; C3H/HEJ MICE ; FOLLICLE ; MAJOR HISTOCOMPATIBILITY COMPLEX ; AUTOIMMUNITY ; CYTOKINE ; HAIR FOLLICLE ; REQUIREMENT ; IMMUNE PRIVILEGE ; alopecia areata ; CD8(+) CELLS ; HAIR LOSS ; LOSSES ; lymph node ; LYMPH-NODE ; ONSET ; RESISTANT ; AA ; autoimmune disease ; regulatory T cells ; experimental animal models
    Abstract: Background: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4+ T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined. Methods: To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA. Results: AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFN gamma(-/-)) and on to wild-type mice (IFN gamma(+/+)). Results: While 90% of wild-type mice developed AA, none of the IFN gamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4+ and CD8+ T cells in controls, while in IFN gamma(-/-) mice skin-infiltrating CD8+ T cells were absent and the number of CD4+ cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFN gamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFN gamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFN gamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFN gamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFN gamma(-/-) mice. Conclusions: IFN gamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA
    Type of Publication: Journal article published
    PubMed ID: 16911275
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...