Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastoma (GBM) has been known to have two distinct genetic pathways of tumorigenesis. Secondary GBM shows frequent TP53 mutation, but de novo (primary) GBM is usually independent of TP53 alteration. However, the subpopulation of TP53 altered cells in the latter tumor is obscure. In order to assess TP53 deleted cells in de novo GBM quantitatively, we performed dual color fluorescence in situ hybridization (FISH) for TP53 and centromere 17 in nine cases of de novo GBM with frozen surgical materials. Single TP53 signal cells indicating TP53 deletion were recognized in 8.7-35.6% (mean, 21.3%) among the nine cases. In addition, immunohistochemistry was performed for the Ki-67 antigen (MIB-1) and p53 protein in all nine cases. Labeling indices (LI) of MIB-1 ranged from 2.8 to 46.9% (mean, 20.8%). Between the group with the more dense subpopulation of TP53 deleted cells (15% or more) by FISH and the group with less subpopulation than the former, these LI of MIB-1 demonstrated statistically significant difference (respective means, 28.2% and 6.1%; P < 0.05). Conversely, LI of p53 protein shown to be 0-50.9% (mean, 24.9%) had no correlation with the subpopulation of TP53 deleted cells by FISH. Four cases who had higher LI of p53 protein (mean, 39.7%) than the subpopulation of TP53 deleted cells (mean, 12.7%), respectively, indicated the presence of many p53 protein immunoreactive cells without TP53 deletion. These results suggest that: (i) de novo GBM also has subpopulation of TP53 deleted cells; (ii) TP53 alteration, which may not be a major event, participates in cell proliferation of de novo GBM; and (iii) de novo GBM tends to have accumulation of wild-type p53 protein.
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PMID:TP53 deleted cells in de novo glioblastomas using fluorescence in situ hybridization. 1132 34

Angiogenesis is of vital importance for the growth of solid tumors and constitutes a target for anti-cancer therapy. Glioblastomas (GBMs) are histologically characterized by striking microvascular proliferation. The identification of the mechanism of angiogenesis is of major importance for the further development of anti-angiogenic therapy. Tumor angiogenesis might be the result of a combination of local tissue conditions (especially hypoxia) and specific genetic alterations acquired during oncogenesis. In order to investigate the relationship between genetic aberrations and tumor angiogenesis in GBM xenograft lines, the genetic alterations were examined by Comparative Genomic Hybridization (CGH). Two vascular phenotypes of GBM xenografts could be identified: a well vascularized and a poorly vascularized type. In this model, the poorly vascularized type had a larger number of genetic alterations. However, there was no unequivocal correlation between angiogenesis, growth rate and patterns of genetic alterations as detected by CGH.
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PMID:The relationship between genetic aberrations as detected by comparative genomic hybridization and vascularization in glioblastoma xenografts. 1138 8

Glioblastoma is a primary malignant astrocyte tumor of the central nervous system. Extraneural metastasis is uncommon. We report a case of spontaneous lung metastasis from a glioblastoma without prior surgery. Positive diagnosis was achieved from histology and immunohistochemistry
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PMID:[Pulmonary metastasis from a glioblastoma. A case report]. 1141 6

Glioblastoma multiform and astrocytoma are the most frequent primary cancer of the central nervous system of adult. Definitions of gross tumor volume (GTV) and clinical target volume (CTV) are based on the confrontation of clinical presentation (age, performance status, neurologic symptoms...), histological type and imaging aspects. For glioblastoma multiform, the GTV can be defined by the area of contrast enhancement observed on the CT scan or MRI. Definition of the CTV can be more difficult and have to take into account the risk of presence of isolated malignant cells in the oedema surrounding the tumor or in the adjacent brain structures. The classical concept of GTV plus a safety margin of 2 cm around is discussed with a CTV containing at least all the oedematous area and eventually adjacent brain structures (nuclei, corpus callosum or other long associative fibers...). For low grade astrocytoma, the definition of GTV can be difficult if the tumoral infiltration is diffuse without nodular visible tumor. CTV corresponds to at least T2 MRI hypersignal area when visible. For postoperative tumor, technical considerations are important for the detection of residual tumor. A safety margin around the resected area is designed according to the risk of presence of isolated cells or involvement of adjacent brain structures.
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PMID:[Gross tumor volume (GTV) and clinical target volume (CTV) in adult gliomas]. 1171 9

Tenascin-C is an adhesion-modulatory extracellular matrix molecule that is highly expressed in tumors. To investigate the effect of tenascin-C on tumor cells, we analyzed its antiadhesive nature and effect on tumor cell proliferation in a fibronectin context. Glioblastoma and breast carcinoma cell adhesion was compromised by a mixed fibronectin/tenascin-C substratum, which concomitantly caused increased tumor-cell proliferation. We identified the antiadhesive mechanism as a specific interference of tenascin-C with cell binding to the HepII/syndecan-4 site in fibronectin through direct binding of tenascin-C to the 13th fibronectin type III repeat (FNIII13). Cell adhesion and proliferation levels were restored by the addition of FNIII13. Overexpression of syndecan-4, but not syndecan-1 or -2, reverted the cell adhesion defect of tenascin-C. We characterized FNIII13 as the binding site for syndecan-4. Thus we describe a novel mechanism by which tenascin-C impairs the adhesive function of fibronectin through binding to FNIII13, thereby inhibiting the coreceptor function of syndecan-4 in fibronectin-induced integrin signaling.
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PMID:Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation. 1173 46

Pur(alpha) is a multifunctional DNA- and RNA-binding protein implicated in a variety of biological events including transcription and replication. Further, this protein has the ability to form a complex with several cellular proteins which are important for cell proliferation including the transcription factor, E2F-1. Pur(alpha) has a modular structure highlighted by alternating three basic aromatic class I and two acidic leucine-rich class II repeats in the central region of the protein. Here, we demonstrate that ectopic overexpression of Pur(alpha) suppresses proliferation of a variety of transformed and tumor cells including human glioblastoma. By utilizing various deletion mutants of Pur(alpha) in colony formation assay, we identified the region spanning the first class II repeat (residues 107-131) and the second class I repeat (residues 148-170) of Pur(alpha) which participate in growth inhibitory action of Pur(alpha). Results from protein transduction experiments using the synthetic peptides representing residues 109-131 and 123-154 of Pur(alpha) in fusion with the arginine rich domain of HIV-1 Tat revealed cellular internalization and nuclear appearance of the Tat-Pur(alpha) fusion peptide after 2 h and its detection in nuclei up to 24 h after treatment. Glioblastoma cells treated with Tat-Pur(alpha) (109-131) and Tat-Pur(alpha) (123-154) exhibited 41 and 47% decrease, respectively, in proliferation. Altogether these results illustrate the efficacy of Pur(alpha) in suppressing glioblastoma cell growth and provide evidence for the potential use of this protein and its derivative(s) in blocking proliferation of tumor cells.
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PMID:Growth inhibition of glioblastoma cells by human Pur(alpha). 1174 91

p21(Cip1/WAF1) (p21), a p53-inducible protein, is a critical regulator of cell cycle and cell survival. p21 binds to and inhibits both the DNA synthesis regulator proliferating cell nuclear antigen and cyclin A/E-CDK2 complexes. Recently, p21 has also been shown to be a positive regulator of cell cycle progression as p21 is necessary for the assembly and activation of cyclin D1-CDK4/6 complexes. Furthermore, elevated p21 protein levels have been observed in various aggressive tumors as well as linked to chemoresistance. Here we demonstrate that p21 is directly phosphorylated by AKT/PKB, a survival kinase that is hyperactivated in many late stage tumors. Two sites (Thr(145) and Ser(146)) in the carboxyl terminus of p21 are phosphorylated by AKT/PKB in vitro and in vivo. Phosphorylation of Thr(145) inhibits PCNA binding, whereas phosphorylation of Ser(146) significantly increases p21 protein stability. Glioblastoma cell lines with activated AKT/PKB show enhanced p21 stability, and they are more resistant to taxol-mediated toxicity. Finally, AKT/PKB controls the assembly of cyclin D1-CDK4 complexes through modulation of p21 and cyclin D1 levels. These data imply that enhanced levels of p21 in tumors are due, in part, to phosphorylation by activated AKT/PKB. Furthermore, they suggest that one mechanism of AKT/PKB regulation of tumor cell survival and/or proliferation is to stabilize p21 protein.
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PMID:AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival. 1175 12

HLA-G is a nonclassical MHC molecule with highly limited tissue distribution that has been attributed chiefly immune regulatory functions. Glioblastoma is paradigmatic for the capability of human cancers to paralyze the immune system. To delineate the potential role of HLA-G in glioblastoma immunobiology, expression patterns and functional relevance of this MHC class Ib molecule were investigated in glioma cells and brain tissues. HLA-G mRNA expression was detected in six of 12 glioma cell lines in the absence of IFN-gamma and in 10 of 12 cell lines in the presence of IFN-gamma. HLA-G protein was detected in four of 12 cell lines in the absence of IFN-gamma and in eight of 12 cell lines in the presence of IFN-gamma. Immunohistochemical analysis of human brain tumors revealed expression of HLA-G in four of five tissue samples. Functional studies on the role of HLA-G in glioma cells were conducted with alloreactive PBMCs, NK cells, and T cell subpopulations. Expression of membrane-bound HLA-G1 and soluble HLA-G5 inhibited alloreactive and Ag-specific immune responses. Gene transfer of HLA-G1 or HLA-G5 into HLA-G-negative glioma cells (U87MG) rendered cells highly resistant to direct alloreactive lysis, inhibited the alloproliferative response, and prevented efficient priming of cytotoxic T cells. The inhibitory effects of HLA-G were directed against CD8 and CD4 T cells, but appeared to be NK cell independent. Interestingly, few HLA-G-positive cells within a population of HLA-G-negative tumor cells exerted significant immune inhibitory effects. We conclude that the aberrant expression of HLA-G may contribute to immune escape in human glioblastoma.
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PMID:A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. 1197 Oct 28

Immature teratomas of the ovary represent less than 1% of all ovarian teratomas. They contain several tissues that derive from the three embryological layers: ectoderm, mesoderm and endoderm. They are rarely associated with peritoneal implants that are essentially composed of mature glial tissue, and of benign evolution. We report the case of a 37-year- old woman who presented an immature teratoma of the right ovary that recurred seven years later as a malignant neuroepithelial peritoneal tumor resembling a glioblastoma. Glioblastoma was diagnosed at a second recurrence six months later. We discuss the histopathogenesis of peritoneal implants secondary to immature teratomas.
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PMID:[Peritoneal glioblastoma: recurrence of ovarian immature teratoma (report of a case)]. 1212 96

Glioblastoma multiforme is the most undifferentiated type of brain tumor, and its prognosis is extremely poor. Glioblastoma cells exhibit highly migratory and invasive behavior, which makes surgical intervention unsuccessful. Here, we showed that glioblastoma cells express Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors assembled from the GluR1 and/or GluR4 subunits, and that their conversion to Ca(2+)-impermeable receptors by adenovirus-mediated transfer of the GluR2 cDNA inhibited cell locomotion and induced apoptosis. In contrast, overexpression of Ca(2+)-permeable AMPA receptors facilitated migration and proliferation of the tumor cells. These findings indicate that Ca(2+)-permeable AMPA receptors have crucial roles in growth of glioblastoma. Blockage of these Ca(2+)-permeable receptors may be a useful therapeutic strategy for the prevention of glioblastoma invasion.
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PMID:Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells. 1220 54


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