Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemically assessed p53 expression was correlated with overall survival in 20 patients with glioblastoma multiforme. Various epitopes of p53 molecule were detected using DO-1, DO-7, CM-1 and BP-12-53 antibodies, proliferative activity was estimated using anti-PCNA and anti-Ki-67 antibodies and assessment of glycosylation changes using lectin histochemistry completed the study. The results show a statistically significant correlation between DO-1 binding and survival. However, we failed to find any similar statistically significant relationship using other antibodies used in this study. Nor the intensity of proliferative activity show any correlation with either p53 expression or overall survival. Glycosylation in glioblastoma multiforme cells reflected unspecific changes in tumor cells regardless of any relationship to p53 expression. The findings do not provide clear evidence for the predictive value of p53 expression. On the other hand, relatively larger numbers of p53 immunonegative cases may indicate that other mechanisms are involved in the development of this tumor.
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PMID:Expression of p53 in glioblastoma multiforme cells: relationship to survival, proliferation and glycosylation. 944 87

The aim of this study was to demonstrate that the induction of growth arrest in human glioblastoma multiforme (GBM) cell lines by retrovirus-mediated transduction of growth control genes was dependent upon the integrity of specific endogenous control pathways. We assessed the status of the endogenous p16INK4A, p21CIP1, pRb, or p53 genes in eight GBM lines. As expected, we found varied combinations of gene defects. The outcome of transducing five of these cell lines with p16INK4A, p21CIP1, pRb, or p53 genes was not entirely predictable. The growth-inhibitory effects mediated by the transfer of the gene encoding p16 was dependent on the presence of the pRb protein, but was independent of p53 status. p21, a broadly active CDK inhibitor and a strong inducer of growth arrest, was not a universal growth suppressor in the group of glioblastoma cell lines analyzed. The suppression of GBM cell proliferation by viruses encoding pRb or p53 was generally predictable and appeared to be independent of the status of either p16 or p21. Suppression of cell growth was assessed by a colony formation assay, by observance of alterations in morphology, and by cell viability staining for trypan blue exclusion. Our findings suggest that to accomplish the suppression of GBM cell proliferation by the transduction of these cell-cycle control genes, the status of endogenous cell-cycle control genes must be taken into account.
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PMID:Restoration of growth arrest by p16INK4, p21WAF1, pRB, and p53 is dependent on the integrity of the endogenous cell-cycle control pathways in human glioblastoma cell lines. 945 56

The immunohistochemically detected expression of p53, BCL-2, MDM-2 and PCNA proteins in samples of tumor tissues of 42 patients with astrocytomas or glioblastoma multiforme was statistically compared to degree of malignancy and overall survival. We found relation between p53 protein expression and survival in the high grade astrocytomas group (more cases of p53 immunonegative tumors with longer survival), and significantly higher BCL-2 protein expression as well as significantly higher MDM-2 protein expression in the group of low grade astrocytomas. PCNA protein expression showed any relation to tumor grade or survival. Despite the rather small number of samples these results support the hypothesis that MDM-2 protein may be a potent regulator of functional p53, expressed in low grade astrocytoma only.
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PMID:Prognostic factors in astrocytomas: relationship of p53, MDM-2, BCL-2 and PCNA immunohistochemical expression to tumor grade and overall patient survival. 947 89

A large number of oncogenes have been identified as aberrant in gliomas, but only the erbB oncogene (gene encoding the epidermal growth factor receptor [EGFR]) is amplified in an appreciable number. The loss or mutation of tumor-suppressor genes located on different autosomes may be associated with progression of malignant gliomas. The p53 tumor-suppressor gene (located on chromosome 17) is frequently associated with the loss of one allele in malignant gliomas, although a large number of malignant gliomas have no p53 mutations. Some of the latter tumors have an amplified murine double minute 2 (MDM2) gene, which suppresses p53 gene activity. Genetic material from chromosome 10 may also be lost, especially in glioblastoma multiforme. In addition to the aberrant expression of EGFR, another growth factor, platelet-derived growth factor, or PDGF (ligand and/or receptors) can be overexpressed, giving cells a selective growth advantage. The blood-brain barrier is substantially altered in malignant gliomas, resulting in cerebral edema. Therapy for malignant gliomas includes surgery, radiation therapy, and chemotherapy. Surgical resection that leaves little residual tumor produces longer survival than less vigorous surgery. Radiation therapy to a dose of at least 60 Gy is required to treat malignant gliomas. Increased survival beyond that produced by standard external radiotherapy requires much larger doses; interstitial radiotherapy permits such dosing. Radiosurgery is being tested. Chemotherapy with nitrosoureas is modestly useful but appears to benefit patients with anaplastic astrocytoma more so than those with glioblastoma.
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PMID:Biology and treatment of malignant glioma. 950 24

This review examines the apparently paradoxical conversion of transforming growth factor beta's (TGFbeta) regulatory role as a growth inhibitor among normal glial cells to that of a progression factor among glioblastomas (GM). In vitro, TGFbeta functions as an autocrine growth inhibitor of near-diploid gliomas of any grade. In contrast, hyperdiploid glioblastoma multiforme (HD-GM) cultures proliferate in response to TGFbeta, which is mediated by induction of platelet-derived growth factor B chain (PDGF-BB). The dominant hypothesis of TGFbeta's pathogenetic association with malignant transformation has been predicated upon acquisition of resistance to its growth inhibitory effects. However, the lack of obvious correlation with TGFbeta receptor (TbetaR) expression (or loss) between the HD-GM and the TGFbeta-inhibited GM cultures suggests the existence of intrinsically opposed regulatory mechanisms influenced by TGFbeta. The mechanism of conversion might be explained either by the loss of a putative tumor suppressor gene (TSG) which mediates TGFbeta's inhibition of growth or by enhancement of an active oncogenic pathway among the HD-GM. The frequency of mutations within glioma-associated TSG, such as TP53 and RB, suggests that defects in TGFbeta's inhibitory signaling pathway may have analogous effects in the progression to HD-GM, and TGFbeta's conversion to a mitogen. Alternative sites of inactivation which might explain the loss of TGFbeta's inhibitory effect include inactivating mutation/loss of the TbetaR type II, alterations in post-receptor signal transmission or the cyclin/cyclin dependent kinase system which regulates the phosphorylation of pRB. Loss or inactivation of a glial TSG with a consequent failure of inhibition appears to allow TGFbeta's other constitutive effects, such as induction of c-sis, to become functionally dominant. Mechanistically, TGFbeta's conversion from autocrine inhibitor to mitogen promotes 'clonal dominance' by conferring a Darwinian advantage to the hyperdiploid subpopulations through qualitative and quantitative differences in its modulation of PDGF-A and c-sis, with concomitant paracrine inhibition of competing, near-diploid elements.
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PMID:The role of transforming growth factor beta in glioma progression. 952 12

Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated material losses of 17p, the region that contains the TP53 gene, as the most frequent abnormality. Mutations in the TP53 gene are, however, very rare in these tumors. These findings strongly suggest that another, as yet unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by single-strand conformational polymorphism analysis on 41 pediatric brain tumor samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2 astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were limited to more distal markers. On the other hand, TP53 mutations were detected in 6 of 41 samples studied. Our results not only confirm the low penetrance of the TP53 gene on pediatric CNS tumors, but also provide further evidence of a putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926) and 17pter, specifically taking part in the development of PNET.
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PMID:Pediatric brain tumors: loss of heterozygosity at 17p and TP53 gene mutations. 954 59

Turcot's syndrome (TS) is a rare disorder associated with the development of both brain and colon neoplasms. Because of the very low incidence of the disease, its molecular basis remains unclear. Presented is a TS case of a 30-year-old Japanese male with a histopathologically confirmed diagnosis of both brain tumor (glioblastoma multiforme) and colon tumor (well-differentiated adenocarcinoma). Germline mutations of the p53 gene, somatic mutations of the Ki-ras, p53 and APC genes, and microsatellite instability (MSI) was examined using polymerase chain reaction (PCR)-single strand conformation polymorphism analysis, followed by PCR-direct sequencing, and sequencing after subcloning. No germline mutations of the p53 gene were found. Somatic mutations of Ki-ras and APC genes were found in the colon adenocarcinoma but not in the brain tumor. No somatic mutation of the p53 gene was present in either colon or brain tumors. Microsatellite instability of both colon and brain tumors was positive in two of four loci. These results indicate that the colon tumor of the TS patient carries the Ki-ras and APC gene mutations. The finding of MSI in both the brain and the colon tumors may support the hypothesis that alterations of DNA repair genes are involved in the tumor development of the TS patient.
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PMID:Genetic alterations in a patient with Turcot's syndrome. 958 76

Cell lines provide a useful system for further understanding the biology of glioblastoma multiforme. In this study, a new glioblastoma multiforme cell line, GATAGM-96 (Gulhane Askeri Tip Akademisi-Gliblastoma Multiforme-96), was established from a tumor specimen removed from an 80-year-old male patient who underwent surgery for intracranial tumor. Morphologic examination, immunocytochemical staining, growth kinetics, and karyotypic characteristics of this cell line were studied. The cytoskeleton was positive for neuron-specific enolase, vimentin, and neurofilament, and it was negative for glial fibrillary acidic protein, S-100 protein, p53 protein, epidermal growth factor, and transforming growth factor alpha. Growth kinetic studies demonstrated an approximate population doubling time of 38 to 42 h and a colony forming efficiency of 83.3%. The karyotype of the cells demonstrated it as hyperdiploid, with a large subpopulation of polyploid cells. There were numerous structural and numerical chromosome aberrations; most of them were present as clonal events. The phenotypic and chromosomal features detailed on the GATAGM-96 cell line should make it a useful addition to the cell lines currently available for in vitro and in vivo studies of glioblastoma multiforme.
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PMID:Establishment and characterization of a human glioblastoma multiforme cell line. 959 44

Although p53-gene mutations occur with significant frequency in diffuse low-grade and high-grade astrocytomas, and are postulated to play an important role in tumorigenesis in these cases, the role of the p53 gene in pilocytic astrocytomas remains unclear. Published data using DNA-based assays for p53-gene analysis in these tumors have shown contradictory results in mutation frequency (0-14%). It is not known whether these heterogeneous results stem from the biological diversity of this tumor group or from technical problems. To re-evaluate p53-gene status in pilocytic tumors, we analyzed 18 tumors chosen to represent the clinical and biological heterogeneity of this tumor type with respect to anatomical location, patient age, gender, ethnic origin (Caucasian or Japanese) and the concomitant occurrence of neurofibromatosis type 1 (NF1). All primary tumors were histologically diagnosed as pilocytic astrocytoma (WHO grade I), except for one anaplastic pilocytic astrocytoma (WHO grade III) which developed in an NF1 patient and recurred as glioblastoma multiforme (WHO grade IV). p53 mutations were detected using an assay in yeast which tests the transcriptional activity of p53 proteins synthesized from tumor mRNA-derived p53-cDNA templates. None of 18 tumors, including 3 NF1-related tumors, showed p53-gene mutations between and including exons 4 and 11. We conclude that p53-gene mutations are extremely rare findings in pilocytic astrocytomas, and are absent even in those exceptional cases in which malignant progression of such tumors has occurred.
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PMID:Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma diversity using a p53 functional assay. 962 43

Surgical resection followed by radiation therapy is the mainstay of treatment for glioblastoma multiforme (GBM), the most aggressive of the malignant gliomas. The poor clinical response of GBM and the intrinsic radiation resistance of this tumor type have prompted clinical investigations seeking to define the role of chemotherapy in the treatment of GBM. In this study, we examined the cytotoxic response of GBM-derived cell lines to treatment with both radiation and chemotherapy. We observed that the sensitivity of glioma cells to cisplatin- and FAS-induced apoptosis was diminished by prior treatment with ionizing radiation. Radiation conferred resistance to cisplatin and FAS cytotoxicity in a dose- and time-dependent manner. Radiation diminished the cisplatin-induced cytotoxicity of malignant glioma cells but failed to alter the cisplatin susceptibility of normal primary human astrocytes. Given the role of p53 in the response of cells to irradiation, we evaluated whether p53 function affects the observed radiation-induced resistance to cisplatin. By examining isogenic cell lines differing only in p53 function, we demonstrated that radiation conferred resistance to cisplatin independently of p53. Current clinical strategies in the treatment of astrocytic tumors, which include combined modality therapy, have been empirically derived from limited clinical experience. Further understanding of the molecular determinants of apoptosis associated with combined modality therapy may guide the design of more efficacious multimodality protocols.
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PMID:Ionizing radiation inhibits chemotherapy-induced apoptosis in cultured glioma cells: implications for combined modality therapy. 973 90


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