Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Keywords: ACTIVATION, ANTIGEN, assembly, CANCER, CANCER CELLS, CANCER-CELLS, CELL, CELLS, COLON-CANCER, colore
    Abstract: Most malignant features of cancer cells are triggered by activated oncogenes and the loss of tumor suppressors due to mutation or epigenetic inactivation. It is still unclear, to what extend the escape of emerging cancer cells from recognition and elimination by the immune system is determined by similar mechanisms. We compared the transcriptomes of HCT116 colorectal cancer cells deficient in DNA methyltransferases (DNMTs) and of cells, in which the RAS pathway as the major growth-promoting signaling system is blocked by inhibition of MAPK. We identified the MHC Class I genes HLA-A1/A2 and the ULBP2 gene encoding 1 of the 8 known ligands of the activating NK receptor NKG2D among a cluster of immune genes up-regulated under the conditions of both DNMT-deficiency and MEK-inhibition. Bisulphite sequencing analyses of HCT116 with DNMT deficiency or after MEK-inhibition showed that de-methylation of the ULPB2 promoter correlated with its enhanced surface expression. The HLA-A promoters were not methylated indicating that components of the HLA assembly machinery were also suppressed in DNMT-deficient and MEK-inhibited cells. Increased HLA-A2 surface expression was correlated with enhanced recognition and lysis by A2-specific CTL. On the contrary, elevated ULBP2 expression was not reflected by enhanced recognition and lysis by NK cells. Cosuppression of HLA Class I and NKG2D ligands and genes encoding peptide transporters or proteasomal genes mediates a strong functional link between RAS activation, DNMT activity and disruption of the antigen presenting system controlling immune recognition in colorectal cancer cells. (C) 2009 UICC
    Type of Publication: Journal article published
    PubMed ID: 19569244
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: EXPRESSION ; IN-VIVO ; GENES ; METABOLISM ; CELL-CYCLE ; TUMOR PROGRESSION ; COLORECTAL-CANCER ; REGULATORY ELEMENTS ; DNA-DAMAGE RESPONSE ; RHYTHMS
    Abstract: Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARgamma, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock.
    Type of Publication: Journal article published
    PubMed ID: 24875049
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-055X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die politische Schlagzeile „Die Zukunft heißt Europa” gilt nicht nur für den politischen Bereich, sondern auch für das Fach Anästhesie mit dem Ziel, einen europäischen Standard unter Berücksichtigung nationaler Interessen zu etablieren. Ein wichtiger Aspekt ist die Standardisierung der Ausbildung, die vom European Board of Anesthesiology, Reanimation and Intensive Care , bestehend aus jeweils zwei gewählten Repräsentanten jedes Mitgliedlandes, im Rahmen der Europäischen Union realisiert werden soll. Einen Beitrag zu diesem Ziel könnte der 10. Europäische und 45. Deutsche Anästhesiekongreß geleistet haben, an dem über 6000 Anästhesisten und Intensivmediziner aus knapp 90 Ländern teilgenommen haben. Den Kongreßteilnehmern wurde ein breites Spektrum anästhesiologischer, intensivmedizinischer, schmerztherapeutischer und notfallmedizinischer Beiträge angeboten, die Basiswissen, Ergebnisse experimenteller Studien und aktuelle Themen vorstellten.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...