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Human Astrocytomas (human + astrocytoma)

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Life Sciences50%

Terms modified by Human Astrocytomas

  • human astrocytoma cell
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    Selected Abstracts

    Prognostic significance of integrin-linked kinase1 overexpression in astrocytoma

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
    Jun Li
    Abstract Integrin-linked kinase 1 (ILK1), a member of the serine/threonine kinases, has been demonstrated to be associated with numerous biological and pathological processes. However, the clinical and functional significance of ILK1 expression has not been characterized previously in human astrocytoma. In this study, we found that ILK1 was overexpressed, at both mRNA and protein levels, in astrocytoma cell lines as compared with normal human astrocytes. The ILK1 mRNA and protein were significantly increased up to 5.6-fold and 10.1-fold, respectively, in primary astrocytoma in comparison with the paired adjacent noncancerous brain tissues obtained from the same patient. Furthermore, immunohistochemical analysis revealed that ILK1 protein was positive in 208 of 228 (91.2%) paraffin-embedded archival astrocytoma specimens. Statistical analysis suggested that the upregulation of ILK1 was significantly correlated with the histological grading of astrocytoma (p = 0.000), and that patients with high ILK1 level exhibited shorter survival time (p < 0.001). Multivariate analysis revealed that ILK1 upregulation might be an independent prognostic indicator for the survival of patients with astrocytoma. Taken together, our results suggest that ILK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease. [source]

    Ceramide levels are inversely associated with malignant progression of human glial tumors

    GLIA, Issue 2 2002
    Laura Riboni
    Abstract Ceramide represents an important sphingoid mediator involved in the signaling pathways that control cell proliferation, differentiation, and death. To determine whether ceramide levels correlate with the malignant progression of human astrocytomas, we investigated these levels in surgical specimens of glial tumors of low-grade and high-grade malignancy. Tumor samples obtained from 52 patients who underwent therapeutic removal of primary brain tumors were used. The tumors were classified according to standard morphologic criteria and were grouped into tumors of low-grade and high-grade malignancy. Sections of normal brain tissue adjacent to the tumor were also analyzed in 11 of the 52 patients. After extraction and partial purification, ceramide was measured by quantitative derivatization to ceramide-1-phosphate using diacylglycerol kinase and [,- 32P]ATP. Ceramide levels were significantly lower in the combined high-grade tumors compared with low-grade tumors and in both tumor groups compared with peritumoral tissue. The results indicate an inverse correlation between the amount of ceramide and tumor malignancy as assessed by both the histological grading and ganglioside pattern. Moreover, overall survival analysis of 38 patients indicates that ceramide levels are significantly associated with patient survival. The present findings indicate that ceramide is inversely associated with malignant progression of human astrocytomas and poor prognosis. The downregulation of ceramide levels in human astrocytomas emerges as a novel alteration that may contribute to glial neoplastic transformation. The low ceramide levels in high-grade tumors may provide an advantage for their rapid growth and apoptotic resistant features. This study appears to support the rationale for the potential benefits of a ceramide-based chemotherapy. GLIA 39:105,113, 2002. © 2002 Wiley-Liss, Inc. [source]

    Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2008
    Suely K.N. Marie
    Abstract We have performed cDNA microarray analyses to identify gene expression differences between highly invasive glioblastoma multiforme (GBM) and typically benign pilocytic astrocytomas (PA). Despite the significant clinical and pathological differences between the 2 tumor types, only 63 genes were found to exhibit 2-fold or greater overexpression in GBM as compared to PA. Forty percent of these genes are related to the regulation of the cell cycle and mitosis. QT-PCR validation of 6 overexpressed genes: MELK, AUKB, ASPM, PRC1, IL13RA2 and KIAA0101 confirmed at least a 5-fold increase in the average expression levels in GBM. Maternal embryonic leucine zipper kinase (MELK) exhibited the most statistically significant difference. A more detailed investigation of MELK expression was undertaken to study its oncogenic relevance. In the examination of more than 100 tumors of the central nervous system, we found progressively higher expression of MELK with astrocytoma grade and a noteworthy uniformity of high level expression in GBM. Similar level of overexpression was also observed in medulloblastoma. We found neither gene promoter hypomethylation nor amplification to be a factor in MELK expression, but were able to demonstrate that MELK knockdown in malignant astrocytoma cell lines caused a reduction in proliferation and anchorage-independent growth in in vitro assays. Our results indicate that GBM and PA differ by the expression of surprisingly few genes. Among them, MELK correlated with malignancy grade in astrocytomas and represents a therapeutic target for the management of the most frequent brain tumors in adult and children. © 2007 Wiley-Liss, Inc. [source]

    Immunohistochemical appearance of HNE-protein conjugates in human astrocytomas

    BIOFACTORS, Issue 1-4 2005
    Kamelija Zarkovic
    Abstract Gliomas are tumors originating from astrocytes, oligodendrocytes or ependimal cells. Those of astrocytic origin are the most widespread of primary brain tumors and account for more then 60% of all CNS neoplasms. The current state of knowledge on the associations between tumor etiology and oxidative stress suggests that environmental factors that cause oxidative stress could also induce and promote cancer, especially in case of hereditary predisposition. Among mediators of oxidative stress, lipid peroxidation product 4-hydroxynonenal (HNE) is of particular relevance in oncology, as it is known to act as a growth-regulating factor and a signaling molecule. The aim of present study was to investigate by immunohistochemistry the presence of HNE-modified proteins in different types of astrocytoma. Our study comprised 45 astrocytic tumors. These tumors were graded in accordance with the WHO classification as diffuse astrocytomas (DA), anaplastic astrocytomas (AA) and glioblastomas (GB), while each group comprised 15 tumors. Slides of paraffin-embedded tumor tissue were stained with hematoxylin-eosin or were prepared for immunohistochemistry with monoclonal antibodies to HNE-histidine conjugate. Positive immunohistochemical reaction to HNE was analyzed semi-quantitatively. HNE positivity was proportional with malignancy of astrocytomas. The weakest presence of HNE-histidine adducts was found in DA, followed by AA and GB. Lowest intensity of HNE immunopositivity was present in tumor cells of almost all DA, predominantly around blood vessels. In malignant variants of astrocytoma, AA and GB, HNE positivity was moderate to strong, and diffusely distributed in all tumors. [source]