1,720,965 research outputs found

    Effects of vitamin D and retinoic acid on human glioblastoma cell lines.

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    The biological significance of vitamin D receptors expressed by glioblastoma and other glial tumours is still unclear. In an effort to clarify this issue we studied the effects of increasing concentrations of 25-dihydroxyvitamin D3 and its metabolite 1 alpha,25-dihydroxyvitamin D3 on two human glioblastoma cell lines. Both substances were capable of inducing a significant (> 50%) reduction in growth of the two glioblastoma cell lines at dosages over 5 microM. When the HU 70 cell line was treated by increasing dilutions of 25-dihydroxyvitamin D3 combined with 1 microM all trans-retinoic acid, significant inhibition was apparent even after addition of 25-dihydroxyvitamin D3 in the nanomolar range. Reduction of growth index was mainly due to induced cell death. Our results provide in vitro evidence that vitamin D metabolites alone or in combination with retinoids may be potentially useful agents in the differentiation therapy of human malignant gliomas

    Vitamin D receptor expression in human brain tumors.

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    Vitamin D receptor (VDR) has important effects not only on physiological processes related to Ca2+ metabolism but also on cell growth and differentiation. VDR is a member of the Steroid-Thyroid Receptors Superfamily (STRS). Work in our and other laboratories has shown that several other members of the STRS (androgen, estrogen, glucocorticoid, and progesterone receptors) are present in astrocytomas and glioblastomas. We now report the finding of VDR-like mRNA in human anaplastic astrocytomas and glioblastomas. VDR mRNA levels, as determined by a method, developed in our laboratory, based on the polymerase chain reaction, are significantly higher in glioblastomas compared to both low and high grade astrocytomas. We discuss the biological and clinical implications of our result

    Basal ganglia precursors found in aggregates following embryonic transplantation adopt a striatal phenotype in heterotopic locations.

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    Transplantation of immature CNS-derived cells into the developing brain is a powerful approach to investigate the factors that regulate neuronal position and phenotype. CNS progenitor cells dissociated from the embryonic striatum and implanted into the brain of embryos of the same species generate cells that reaggregate to form easily recognizable structures that we previously called clusters and cells that disperse and integrate as single cells into the host brain. We sought to determine if the neurons in the clusters differentiate according to their final location or acquire a striatal phenotype in heterotopic positions. We transplanted dissociated cells from the E14 rat medial and lateral ganglionic eminences, either combined or in isolation, into the E16 embryonic rat brain. At all time points, we found clusters of BrdU- and DiI-labelled donor cells located in the forebrain and hindbrain, without any apparent preference for striatum. Immunocytochemical analyses revealed that cells in the clusters expressed DARPP-32 and ARPP-21, two antigens typically co-expressed in striatal medium-sized spiny neurons. In agreement with observations previously noted by several groups, isolated cells integrated into heterologous host areas do not express basal ganglia phenotypes. These data imply that immature striatal neuronal progenitors exert a community effect on each other that is permissive and/or instructive for development of a striatal phenotype in heterotopic locations

    Proliferative effect of dexamethasone on a human glioblastoma cell line (HU 197) is mediated by glucocorticoid receptors.

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    The relationship between Dexamethasone proliferative activity and the presence of glucocorticoid receptors was studied on a human glioblastoma cell line (HU 197). For this purpose, the 17 beta-Carboxamide steroid DXB, a glucocorticoid antagonist that competes with Dexamethasone for binding to the intracellular glucocorticoid receptor but does not trigger the glucocorticoid effect, was used. Concurrent treatments with Dexamethasone and DXB caused an inhibition of the proliferative effect obtained by Dexamethasone. The results obtained demonstrated that the Dexamethasone activity on cell proliferation is a specific receptor-mediated effect

    A short term analysis of the behaviour of conditionally immortalized neuronal progenitors and primary neuroepithelial cells implanted into the fetal rat brain.

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    Conditionally immortalized (temperature-sensitive) striatal-derived neuronal progenitor cell lines and primary neuroepithelial cells were transplanted into the CNS of gestational day 15-16 rat fetuses using an 'in utero' surgical procedure. Each fetus received 2.5-3 x 10(4) donor cells previously labelled in vitro by incubation with 5-bromo-2'-deoxyuridine (BrdU). At 5 days following transplantation, 69% of the fetuses were still alive. Engrafted cells were detected by BrdU immunohistochemistry, and the appearance of the engrafted cells and the time course of Nestin and PCNA expression were measured at 6, 24, 64 h and 5 days after transplantation. The evolution of Large T-Antigen immunoreactivity in engrafted temperature-sensitive (ts) cells was also evaluated at the above time intervals. The results indicate that the majority of the implanted cells were aggregated into clusters 24 h after transplantation. These clusters were not visible at 6 h, when most of the cells were isolated. The clusters were located in both the ventricles and parenchyma. These findings were common to both ts cells and striatal primary neuroepithelial cells. At 64 h and 5 days, isolated cells associated with the germinal layer and scattered throughout the parenchyma were also found. In the clusters, Nestin expression decreased proportionally with time following transplantation. Furthermore, Large T-Antigen immunoreactivity disappeared from ts cells between 6 and 24 h after transplantation. Finally, measurements of the temporal evolution of PCNA expression within the clusters indicate a progressive reduction in the mitotic activity of the transplanted cells. The results demonstrate that striatal primary neuroepithelial cells and conditionally immortalized neuronal progenitors can survive, migrate and/or compartimentalize into clusters whilst changing their antigenic properties and ability to proliferat

    The expression of genes of the steroid-thyroid hormone receptor superfamily in central nervous system tumors.

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    We studied the expression of ten genes (encoding the receptors for glucocorticoid, mineralocorticoid, progesterone, androgen, estrogen, thyroid, retinoid acid, vitamin D) belonging to the steroid-thyroid hormone receptor superfamily (STRS) in 12 neuroepithelial tumors, 12 meningiomas and 2 human glioblastoma cell lines. Our method, based on the polymerase chain reaction, allowed the simultaneous amplification of cDNAs of the STRS genes. On average, 7 STRS genes were simultaneously expressed in each sample. Our study indicates that many STRS gene are commonly co-expressed in human CNS tumors. The importance of our results for the ongoing and proposed hormonal treatment trials is discussed

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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