Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pleomorphic xanthoastrocytoma (PXA) is a low-grade glioma that may recur as a malignant diffuse astrocytoma such as glioblastoma (GBM). While the molecular genetic basis of diffuse astrocytomas has been studied extensively, PXAs have not been analyzed in detail. We, therefore analyzed DNA from archival primary and recurrent PXAs from eight patients (three grade II PXAs without recurrence, one grade II PXA with recurrence as grade II PXA, two grade II PXAs with progression to GBM, and two grade III anaplastic PXAs with recurrence as grade III anaplastic PXA or GBM) for genetic changes associated with diffuse astrocytomas. Single-strand conformation polymorphism analysis of p53 exons 5-8 revealed migration shifts in two cases, one primary PXA without recurrence and one recurrent grade II PXA in which the primary tumor did not show a shift. DNA sequencing showed two missense mutations in codons 220 (exon 6) and 292 (exon 8), respectively, mutations which have not been previously noted in astrocytomas. Differential polymerase chain reaction analysis demonstrated epidermal growth factor receptor gene amplification in only one tumor, a GBM without allelic loss of chromosome 10 that was the second GBM recurrence of an initial grade II PXA. Loss of heterozygosity studies on tumors from five patients, using three microsatellite polymorphisms on chromosome 10q and three on chromosome 19q, did not disclose allelic loss in any recurrent tumor. These findings suggest that the genetic events that underlie PXA formation and progression may differ significantly from those involved in diffuse astrocytoma tumorigenesis.
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PMID:Molecular genetic alterations in pleomorphic xanthoastrocytoma. 883 42

A total of 10 glioma cell lines were examined for alterations of the p16, p15, p53 and p21 genes, which are tumor suppressor genes or candidates with direct or indirect CDK-inhibitory functions. Genetic alterations (deletions or mutations) were frequently seen in the p16, p15 and p53 genes in these cell lines, but not in the p21 gene. When the states of the p16, p15 and p53 genes were compared among cell lines, all the cell lines showed abnormalities in at least 1 gene, often in 2 or 3 genes coincidentally, suggesting that dysfunction of these genes is closely related to glioma cell growth. Although alteration of all 3 genes was most frequent, there were cell lines having either p16/p15 or p53 or pl6 and p53 gene alterations, suggesting that the time order of these genetic alterations was variable depending on the cell line. Among cell lines examined, one with homozygous p53 gene deletion seemed of particular practical value, since such a cell line might be useful in various studies, including investigation of the functions of various mutant p53 genes in the absence of heteromeric protein formation. On examination of the primary tumor tissues, the same alterations of the p16/p15 and p53 genes as detected in the cell lines were demonstrated in all 6 cases examined: p16/p15 gene deletion in 1, p16 gene mutation in 1 and p53 gene mutations in 5 cases. This suggested that the p16/p15 and the p53 gene alterations and their combinations in at least some glioma cell lines reflected those in the primary glioma tissues.
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PMID:A comparative study of glioma cell lines for p16, p15, p53 and p21 gene alterations. 887 51

Excision repair cross-complementing rodent repair deficiency genes (ERCC) are human genes implicated in nucleotide excision repair. ERCC-2 has been implicated in the repair of DNA damaged by chemotherapeutic agents, and may thus play an important role in anticancer drug resistance. ERCC-2 gene expression is low in primary tumor samples rendering it difficult to quantitate. We have developed a semiquantitative method to measure ERCC-2 gene expression utilizing reverse transcription-polymerase chain reaction (RT-PCR). Total RNA extracted from established human tumor cell lines was reverse-transcribed to obtain cDNA. Serially diluted reference ERCC-2 DNA fragment was amplified by PCR to obtain a 617-bp fragment. A standard curve was then created using densitometry readings of the 617-bp bands on agarose gel. A fixed amount of sample cDNA from each cell line was amplified at the same time and the resultant PCR product was read by densitometer. Using the standard curve, ERCC-2 gene expression in a given amount of total RNA was quantitated and normalized to beta-actin expression. There was minimal variation in three repeated experiments with PCR amplification. ERCC-2 gene expression determined by this semiquantitative PCR was also correlated to ERCC-2 quantitation by Northern blot analysis, with a significant concordance (r = 0.912, P = 0.0002). We also successfully applied this sensitive method to quantify five clinical glioma samples.
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PMID:Quantitation of ERCC-2 gene expression in human tumor cell lines by reverse transcription-polymerase chain reaction in comparison to northern blot analysis. 902 7

Quantitative study of labeling index (expressed in per cent of positive cells to all tumor cells) of Ki-67 (Ki-67LI), a marker of tumor proliferation, was performed in a group of 37 primary glial tumors and their recurrences. Three cases were entirely negative (no positive cells were found). Mean Ki-67LI for all primary tumors was 19.2% and for their recurrences-20.1%. There was no significant difference between tumors with longer (exceeding 1 year) and shorter survival between first and second surgery. In 17 cases recurrent tumor was of the same grade and in 16 cases malignancy at second surgery was higher than in primary tumor. Among tumors whose malignancy increased between first and second surgery as well as among tumors with the same grade at first and second surgery there were cases with increased and decreased Ki-67LI comparing samples from primary and secondary (recidiving) tumors. It is however, noteworthy that there was no tumor with markedly (at least twofold) decreased Ki-67LI and increased malignancy. The present findings indicate that there is still no simple answer to the question of prognostic role of Ki-67 in gliomas.
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PMID:Ki-67 as a marker of proliferation activity in tumor progression of recurrent gliomas of supratentorial localization. Immunocytochemical quantitative studies. 920 Sep 58

A new cell line MGM-1 was established from a primary tumor of the left temporal lobe with histological diagnosis of glioblastoma multiforme, removed from a 64-year-old Japanese male. The patient died of recurrence and unusual extracranial metastases of the tumor 7 months after the surgery. The cultured MGM-1 cells are spindle or polygonal in shape. After serial passages, glial fibrillary acidic protein became negative immunocytochemically in vitro. The modal chromosome number was 61-64. Doubling time and soft agar colony forming efficiency were 42.9h and 0.4%, respectively (at 25th passage). MGM-1 is a highly motile cell line in vitro and its serum-free conditioned medium is chemotactic and chemokinetic for other glioma cells. Secretion of gelatinases (probably MMP-2/72-kDa type i.v. collagenase) and MMP-9/92-kDa type i.v. collagenase) and urokinase-type plasminogen activator were also investigated. MGM-1 would therefore be useful for studying the mechanisms regulating glioma-cell motility and invasion. The MGM-1 cell line has been propagated continuously by serial passages (more than 100 passages) during the past 4 years.
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PMID:Establishment and characterization of a new human glioblastoma cell line (MGM-1) with highly motile phenotype. 923 71

Malignant human gliomas are the most common forms of primary tumors in the central nerve system. Due to their location and invasive nature, treatment so far has been mainly palliative. Thus, understanding the molecular detail of tumor transformation and progression is crucial for developing effective therapeutic strategy for this fetal tumor. Among the genetic alternations found in these tumors, p53 inactivation and PDGF/PDGFR activation represent the early events, and the loss of chromosome 10 and gene amplification and rearrangement of EGFR represent the late events. Studies with both glioma cell lines and primary tumor tissues have strongly suggested that TGF-alpha and EGFR function as an important autocrine loop in supporting proliferation of human glioma, especially in high grade glioma, since elevated TGF-alpha expression is also found in these high grade tumors. Furthermore, down regulation of the expression of TGF-alpha by antisense constructs has been shown to inhibit several types of human tumor cell growth including glioma. Other means of therapeutic approaches using this autocrine loop as a target also include the use of monoclonal antibodies and their cytotoxic conjugated. Considerable understanding of the EGFR-mediated signal transduction pathways has become available recently, which including GRB2/mSOS1 mediated MAP kinase activation; JAK/STATs pathway; PLC-gamma pathway. However, much work still needs to be done before a specific component of these pathways can be applied for effective control of tumor growth in the clinic.
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PMID:The autocrine loop of TGF-alpha/EGFR and brain tumors. 944 27

We investigated chromosomal copy number changes in ethylnitrosourea-induced and serially transplanted gliomas of the rat by flow cytometry and Comparative Genomic in situ Hybridization (CGH). CGH analysis of a primary and four transplanted tumors revealed several genomic aberrations, including whole chromosome and subchromosomal gains and losses. Gains involved rat Chromosomes (RNO) 2, 3, 4, 5, 7, 9, 11, 12, 13, and Y, whereas losses affected RNO5, 13, 20, and Y. The primary tumor exhibited gain of RNO2q31qter and gain of RNO4. While gain of RNO2 was seen in nearly all investigated passages, gain of RNO4 was apparent in the primary tumor and in passage 2 and 5 tumors. Chromosomal alterations detected as single events were restricted to the transplanted tumors and included gain of RNO3q11, 3q41qter, 5q36, 7q34qter, 9q37, 11q, and Y, and loss of RNO5, 13, and 20q. Flow cytometry disclosed different aneuploid cell clones in the tumors investigated. The results are discussed in analogy to findings in human glial tumors.
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PMID:Comparative genomic in situ hybridization discloses chromosomal copy number changes in a transplanted brain tumor line of the rat (Rattus norvegicus). 950 1

We and others have reported that human malignant gliomas demonstrate intratumor heterogeneity in which many regions may be benign; however, the presence of regions of increased malignancy in these same tumors is generally indicative of poor patient prognosis. These data suggested that tumor progression may be a local phenomenon, resulting in regions that progress to a more malignant type prior to the progression of the entire tumor. Implicit in this premise is the idea that molecular markers of tumor progression may be detectable prior to histological evidence of progression. This report details analyses performed on a primary and recurrent tumor obtained from the same patient in which the primary tumor was of a higher histological grade than the recurrent tumor. Results of molecular, cytogenetic, flow cytometric, and histological analyses of the primary tumor were indicative of a grade 4 glioblastoma multiforme. Standard cytogenetic and flow cytometric analyses demonstrated that the cells were near-diploid with a stem line population of 46,XX normal G-banded karyotypes. In contrast, tissue resected from the recurrent tumor 5 months later was histologically less malignant; however, the molecular, cytogenetic, and flow cytometric analyses of this sample demonstrated the presence of specific genetic abnormalities typically found in more malignant tumors. These data demonstrate that specific molecular and/or genetic changes leading to tumor progression may become detectable in a glioma prior to the appearance of histological features of a higher grade tumor.
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PMID:Biological and molecular analysis of a low-grade recurrence of a glioblastoma multiforme. 981 6

A case of a primary yolk sac tumor of the spinal cord is reported. The patient was a 17-month-old Japanese girl, who was found to have an intramedullary mass at the upper thoracic level. The preoperative diagnosis was primary glioma, but histological examination of the surgical specimen revealed a yolk sac tumor. As there were no other lesions, the spinal cord lesion was considered to be the primary tumor. Based on our previous experience, we treated this patient with low-dose irradiation followed by combination chemotherapy with cisplatin, vinblastine and bleomycin. However, the effectiveness of this therapy was poor in this particular case, and the patient died of pyelonephritis with uncontrollable imbalance of serum electrolytes.
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PMID:Primary yolk sac tumor in the spinal cord. 984 Mar 66

We established two glioma cell lines from two surgical specimens obtained at different times from the same patient. One (No. 9R), which was derived from the recurrent tumor (glioblastoma, grade IV), proliferated more rapidly in vitro than the other (No. 9) from the primary tumor (slightly anaplastic astrocytoma, grade II-III). No. 9R showed heterotransplantability in nude mice, whereas No. 9 did not. These findings indicate that No. 9R has a more aggressive or malignant nature than No. 9. Both cell lines showed homozygous deletion of the representative tumor suppressor p16 and p15 genes, but no p53 gene alteration. However, examination of the overall mRNA expression profile using a commercially available cDNA-spotted membrane revealed much higher expression levels of several mRNAs, at least, in No. 9R than in No. 9, although the relationship between these mRNAs and the growth potentials remained unknown. These two cell lines, derived from the same individual, with different proliferating potentials may be useful for studies on the molecular bases of glioma malignancy and progression.
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PMID:Establishment of two glioma cell lines from two surgical specimens obtained at different times from the same individual. 1035 44


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