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  1. Article ; Online: Cancer Stem Cells as Mediators of Treatment Resistance in Brain Tumors

    Per Ø. Sakariassen / Heike Immervoll / Martha Chekenya

    Neoplasia : An International Journal for Oncology Research, Vol 9, Iss 11, Pp 882-

    Status and Controversies

    2007  Volume 892

    Abstract: Malignant primary brain tumors are characterized by a short median survival and an almost 100% tumorrelated mortality. Despite the addition of new chemotherapy regimes, the overall survival has improved marginally, and radiotherapy is only transiently ... ...

    Abstract Malignant primary brain tumors are characterized by a short median survival and an almost 100% tumorrelated mortality. Despite the addition of new chemotherapy regimes, the overall survival has improved marginally, and radiotherapy is only transiently effective, illustrating the profound impact of treatment resistance on prognosis. Recent studies suggest that a small subpopulation of cancer stem cells (CSCs) has the capacity to repopulate tumors and drive malignant progression and mediate radio- and chemoresistance. This implies that future therapies should turn from the elimination of the rapidly dividing, but differentiated tumor cells, to specifically targeting the minority of tumor cells that repopulate the tumor. Although there exists some support for the CSC hypothesis, there remain many uncertainties regarding theoretical, technical, and interpretational aspects of the data supporting it. If correct, the CSC hypothesis could have profound implications for the way tumors are classified and treated. In this review of the literature, we provide original data and hypotheses supporting alternative explanations and outline some of the therapeutic implications that can be derived.
    Keywords Neural stem cell ; CD133 ; glioblastoma ; chemoresistance ; radioresistance ; Medicine ; R ; Internal medicine ; RC31-1245 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Publishing date 2007-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Correction

    Peter C Huszthy / Per Ø Sakariassen / Heidi Espedal / Karl A Brokstad / Rolf Bjerkvig / Hrvoje Miletic

    PLoS ONE, Vol 10, Iss 10, p e

    Engraftment of Human Glioblastoma Cells in Immunocompetent Rats through Acquired Immunosuppression.

    2015  Volume 0140303

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  3. Article ; Online: Engraftment of Human Glioblastoma Cells in Immunocompetent Rats through Acquired Immunosuppression.

    Peter C Huszthy / Per Ø Sakariassen / Heidi Espedal / Karl A Brokstad / Rolf Bjerkvig / Hrvoje Miletic

    PLoS ONE, Vol 10, Iss 8, p e

    2015  Volume 0136089

    Abstract: Transplantation of glioblastoma patient biopsy spheroids to the brain of T cell-compromised Rowett (nude) rats has been established as a representative animal model for human GBMs, with a tumor take rate close to 100%. In immunocompetent littermates ... ...

    Abstract Transplantation of glioblastoma patient biopsy spheroids to the brain of T cell-compromised Rowett (nude) rats has been established as a representative animal model for human GBMs, with a tumor take rate close to 100%. In immunocompetent littermates however, primary human GBM tissue is invariably rejected. Here we show that after repeated passaging cycles in nude rats, human GBM spheroids are enabled to grow in the brain of immunocompetent rats. In case of engraftment, xenografts in immunocompetent rats grow progressively and host leukocytes fail to enter the tumor bed, similar to what is seen in nude animals. In contrast, rejection is associated with massive infiltration of the tumor bed by leukocytes, predominantly ED1+ microglia/macrophages, CD4+ T helper cells and CD8+ effector cells, and correlates with elevated serum levels of pro-inflammatory cytokines IL-1α, IL-18 and TNF-α [corrected]. We observed that in nude rat brains, an adaptation to the host occurs after several in vivo passaging cycles, characterized by striking attenuation of microglial infiltration. Furthermore, tumor-derived chemokines that promote leukocyte migration and their entry into the CNS such as CXCL-10 and CXCL-12 are down-regulated, and the levels of TGF-β2 increase. We propose that through serial in vivo passaging in nude rats, human GBM cells learn to avoid and or/ suppress host immunity. Such adapted GBM cells are in turn able to engraft in immunocompetent rats without signs of an inflammatory response.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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