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)

To evaluate the NIH Image measured MIB-1 staining index (SI) as a useful tool for the determination of proliferative activity of gliomas, MIB-1 immunohistochemistry was performed on paraffin sections to estimate the proliferative activity of 50 gliomas. Five to eight RGB images at 200 magnifications were acquired per sample in a Macintosh computer using a RD-175 digital camera and Adope Photoshop program, followed by conversion of the RGB image to B (blue subtracted) and R (red subtracted) images and finally automatic cell counting of more than 1000 cells per sample by the NIH Image analysis program. The mean MIB-1 staining indices by both NIH count and visually assessed (manual) count respectively were 12.7% +/- 9.9% (mean +/- standard deviation) and 12.6% +/- 9.9% in all gliomas (n = 50), 2.9% +/- 0.6% and 2.3% +/- 0.6% in grade I and II astrocytomas (n = 9), 10.7% +/- 8.9% and 11.1% +/- 9.0% in grade III gliomas (n = 17), 16.1% +/- 9.1% and 16.3% +/- 9.1% in glioblastoma multiformes (n = 20), 26.0% +/- 4.9% and 24.5% +/- 2.6% in other glial tumors (n = 4). These paired values were assumed to be identical, since the p value obtained by paired t-test in all gliomas was 0.905. We conclude that the MIB-1 staining index measured by NIH Image is reliable and universal.
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PMID:A comparative study of MIB-1 staining indices of gliomas measured by NIH Image analysis program and conventional manual cell counting method. 1093 23

The actin-binding protein ezrin has been associated with motility and invasive behavior of malignant cells. To assess the presence of this protein in human glial cells of the brain and its potential role in benign and malignant glial tumors, we studied ezrin immunoreactivity (IR), proliferation (MIB-1-IR), and apoptosis (terminal dUTP nick-end labeling) in normal human brain tissues from 10 autopsies and tissues from 115 cases of human glial tumors including astro-cytomas, ependymomas, oligodendrogliomas, and glioblastomas. We found weak staining of peripheral processes in normal human brain astrocytes and in World Health Organization grade II benign astrocytomas. Staining was markedly increased in anaplastic astrocytomas (World Health Organization grade III) and clearly strongest in glioblastomas (World Health Organization grade IV). The increase of ezrin-IR correlated significantly with increasing malignancy of astrocytic tumors (P < 0.0001). Statistical analysis revealed a stronger association with increasing malignancy for ezrin-IR than for MIB-1-IR or terminal dUTP nick-end labeling staining. Ezrin-IR was absent in normal oligodendrocytes and in oligodendrogliomas, but pronounced in normal ependymal cells and ependymomas. Ezrin-IR seems to be specific for astrocytes and ependymal glia in the normal brain. Our results indicate that ezrin-IR may provide a useful tool for the distinction of oligodendrogliomas and astrocytomas and for the grading of astrocytic tumors.
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PMID:Ezrin immunoreactivity is associated with increasing malignancy of astrocytic tumors but is absent in oligodendrogliomas. 1110 50

This study sought to correlate quantitative presurgical proton magnetic resonance spectroscopic imaging (1H-MRSI) and diffusion imaging (DI) results with quantitative histopathological features of resected glioma tissue. The primary hypotheses were (1) glioma choline signal correlates with cell density, (2) glioma apparent diffusion coefficient (ADC) correlates inversely with cell density, (3) glioma choline signal correlates with cell proliferative index. Eighteen adult glioma patients were preoperatively imaged with 1H-MRSI and DI as part of clinically-indicated MRI evaluations. Cell density and proliferative index readings were made on surgical specimens obtained at surgery performed within 12 days of the radiologic scans. The resected tissue location was identified by comparing preoperative and postoperative MRI. The tumor to contralateral normalized choline signal ratio (nCho) and the ADC from resected tumor regions were measured from the preoperative imaging data. Counts of nuclei per high power field in 5-10 fields provided a quantitative measure of cell density. MIB-1 immunohistochemistry provided an index of the proportion of proliferating cells. There was a statistically significant inverse linear correlation between glioma ADC and cell density. There was also a statistically significant linear correlation between the glioma nCho and the cell density. The nCho measure did not significantly correlate with proliferative index. The results indicate that both ADC and spectroscopic choline measures are related to glioma cell density. Therefore they may prove useful for differentiating dense cellular neoplastic lesions from those that contain large proportions of acellular necrotic space.
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PMID:Relationships between choline magnetic resonance spectroscopy, apparent diffusion coefficient and quantitative histopathology in human glioma. 1126 1

The histopathological features, particularly hypervascularity, were examined in specimens resected from 21 patients, 15 with intractable epilepsy accompanying cortical dysplasia or dysembryoplastic neuroepithelial tumor (DNT), and 6 with benign brain tumors, such as ganglioglioma and low-grade glioma. Hypervascularity was found in resected specimens from 15 of the 21 patients (71.4%) and in 10 of the 12 patients (83.3%) who had double pathology. Counting of numbers of vessels by CD31 immunohistochemistry revealed that hypervascularity was prominent, especially in cases of vascular malformation or cortical dysplasia. However, almost all cases were negative for vascular endothelial growth factor (VEGF) staining, except for some cases of benign brain tumors. Moreover, all cases showed low or no proliferative potential in MIB-1 immunohistochemistry. These results suggest that the etiology of hypervascularity in the dysplastic lesions is one of a variety of cerebral malformations, as is the case with abnormal maturation and differentiation in neuroglial elements.
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PMID:Vascular abnormalities in surgical specimens obtained from the resected focus of intractable epilepsy. 1131 Sep 19

PLK-1 (polo-like kinase) belongs to the family of serine/threonine kinases and is involved in spindle formation, centrosome cycles and chromosome segregation. Hence, the kinase is tightly linked to cell proliferation. We could detect immunohistochemically highly expressed PLK protein in astrocytic tumours depending on the grade of anaplasia, in commercially available human glioma cell lines (U87MG, U118MG, U138MG), in one immortalized cell culture derived from a glioblastoma patient and in a primary culture derived from a glioblastoma patient. The highest labelling of PLK-1 was demonstrated in glioblastomas. There was a significant correlation between the PLK expression and the nuclear immunoreactivity of MIB-1. PLK-mRNA, found in all tumour specimens investigated emphasizes the close correlation to proliferation and growth. Furthermore, the relation of the PLK-1 expression to the Mitogen-activated Protein Kinase Cascades was studied by applying various highly specific inhibitors. While all inhibitors minimized the cell density, only the PLCy inhibitor clearly lead to a reduced PLK-1 expression in the three cell lines U87MG, U118MG, U138MG.
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PMID:Increased human polo-like kinase-1 expression in gliomas. 1167 24

Tumor cells often express phenotypic markers that are specific to the cells from which they originated. A neural RNA-binding protein, Musashil, is an evolutionarily well-conserved marker for neural stem cells/ progenitor cells. To examine the origin of gliomas, we examined the expression of the human Musashil homolog, MSI1, in human glioma tissues and in normal human adult and fetal brains. As we had seen previously in rodents, in the normal human brain, MSI1 was expressed in cells located in the ventricular and subventricular zones, in GFAP-negative glial cells, and in GFAP-positive astrocytes. In glioblastomas, MSI1 was expressed in GFAP-negative tumor cells forming foci that were clearly demarcated and surrounded by GFAP-positive cells. Tumor cells arranged in pseudopalisades were also strongly immunoreactive with MSI1 antibodies. The percentage of MSI1-labeled tumor cells increased in higher-grade astrocytomas and correlated with proliferative activity, as estimated by an MIB-1 staining index. Our results indicate that MSI1 is an excellent marker for neural progenitor cells including neural stem cells in normal human brains. Furthermore, the expression of MSI1 correlates well with the immature nature as well as the malignancy of tumor cells in human gliomas. Thus, we expect the analysis of MSI1 expression to contribute to the understanding of the cellular origin and biology of human gliomas.
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PMID:Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity. 1168 36

It has been reported that RCAS1 (receptor-binding cancer antigen expressed on SiSO cells) acts as a ligand for a receptor present on normal peripheral lymphocytes and induces apoptotic cell death. It is expressed in uterine and ovarian carcinomas, especially in invasive cancers. This immunohistochemical study is aimed to elucidate the expression of RCAS1 in human pituitary adenomas in order to clarify its role in their proliferative regulation and invasiveness. Five normal pituitary glands, 50 human pituitary adenomas, and one malignant glioma were subjected to immunohistochemical studies. In normal pituitary glands, immunostaining of RCAS1 and MIB-1 was not found. In malignant glioma, large numbers of cell nuclei were positive for MIB-1 (MIB-1 index: 28%), and RCAS1 was detected both in the cytoplasm and on the membrane of the tumor cells. Expression of RCAS1 was noted in 48% of pituitary adenomas immunohistochemically (60.0% of growth hormone-secreting adenomas, 60.0% of prolactin-secreting adenomas, 42.9% of adrenocorticotrophin-secreting adenomas, 40.0% of thyroid-stimulating hormone-secreting adenomas, 33.3% of nonfunctioning adenomas, and 44.4% of gonadotropin-subunit-positive adenomas). It showed no correlation with tumor type, size, and invasiveness. The statistically significant relationship between RCAS1 and MIB-1 positivity was identified in our study. These results suggest that expression of RCAS1 as well as MIB-1 positivity predict the growth potential of individual pituitary adenomas.
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PMID:Immunohistochemical analysis of RCAS1 in human pituitary adenomas. 1174 45

Technetium-99m methoxy-isobutylisonitrile (MIBI), like thallium-201 (201Tl), is a highly efficient agent for the diagnosis and monitoring of glioma tumors. Although 201Tl uptake is known to be partly associated with proliferative activity, little is known about the correlation between MIBI uptake and proliferation activity in gliomas. The current study was performed to assess the correlation between MIBI uptake and proliferative activities in gliomas, estimated by the monoclonal antibody to Ki-67 antigen (MIB-1) staining method. By comparing the results with those of 201Tl, we determined which tracer would be suitable for estimating proliferative activities. Twenty-four presurgical glioma patients (six with low-grade gliomas, five with anaplastic astrocytomas, and 13 with glioblastomas) were given MIBI and 201Tl SPECT. Early (10 min after injection) and delayed images (3 h after injection) were obtained for both MIBI and 201Tl scintigraphy. SPECT parameters, early ratio (ER), delayed ratio (DR), and retention index (RI) were obtained in both radiopharmaceuticals. All patients underwent subsequent surgical excision, and the specimens were immunostained for MIB-1. The proliferative activity was measured as a percentage positive nuclear area for MIB-1 (MI; MIB-1 index). To evaluate the relationship between the proliferative activity and SPECT parameters, we performed a correlation analysis. MI correlated with the MIBI uptake ratio (r = 0.75 for ER, and r = 0.7 for DR). Both DR and RI of 201Tl also correlated with MI, but weakly (r = 0.6 for DR, and. r = 0.59 for RI). There was no significant correlation between the MIB-1 index and the other parameters. MIBI-uptake parameters demonstrated a stronger positive correlation with the MIB-1 index than that of 201Tl. With the use of MIBI SPECT, we can estimate the proliferative activity of glioma noninvasively.
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PMID:The correlation between 99mTc-MIBI uptake and MIB-1 as a nuclear proliferation marker in glioma--a comparative study with 201Tl. 1179 39

DNA topoisomerase IIalpha (Topo IIalpha) is linked to tumour cell growth and chemoresistance. We examined immunohistochemically Topo IIalpha expression levels in a series of 36 consecutive paediatric optic pathway glioma (OPG) patients. Topo IIalpha labelling index (LI) ranged from 0.0 to 11.6 and was significantly associated with patient age, with higher levels of Topo IIalpha in children < or = 3 years (P=0.031). Topo IIalpha expression did not correlate with patient survival. Topo IIalpha LI was not significantly increased in specimens of repeat surgery. Topo IIalpha LI closely correlated with MIB-1 LI (R=0.781, P<0.001). We conclude that Topo IIalpha expression correlates with tumour cell proliferation in paediatric OPGs. Assessment of cell proliferation, however, does not assist in refining prognostic predictions. Enhanced Topo IIalpha expression in children < or = 3.0 years suggests that Topo IIalpha-interfering anticancer compounds for adjuvant treatment of OPGs may be of particular benefit to young children.
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PMID:DNA topoisomerase IIalpha expression in optic pathway gliomas of childhood. 1181 5

The recognition of molecular subsets among glioblastomas has raised the question whether distinct mutations in glioblastoma-associated genes may serve as prognostic markers. The present study on glioblastomas (GBM) from 97 consecutively sampled adult patients is based on a clinical, histopathological, immunohistochemical, and molecular genetic analysis. Parameters assessed were age at diagnosis, survival, cell type, proliferation, necrosis, microvascular proliferation, sarcomatous growth, lymphocytic infiltration, thromboses, calcifications, GFAP expression, MIB-1 index, loss of heterozygosity (LOH) of the chromosomal arms 1p, 10p, 10q, 17p, 19q and structural alterations in the TP53, EGFR and PTEN genes. As in previous studies, younger age was significantly associated with better survival. Among the molecular parameters, TP53 mutations and LOH10q emerged as favorable and poor prognostic factors, respectively. TP53 mutations were a favorable prognostic factor independent of whether glioblastomas were primary or secondary. LOH1p or 19q, lesions suspected to be over-represented in long term survivors with malignant glioma, were not associated with better survival. However, the combination of LOH1p and LOH19q defined GBM patients with a significantly better survival. Notably, these patients did not exhibit morphological features reminiscent of oligodendroglioma. These findings indicate that genotyping of glioblastoma may provide clinical information of prognostic importance.
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PMID:Impact of genotype and morphology on the prognosis of glioblastoma. 1193 87


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