Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).
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PMID:Neoplasms involving the central nervous system in the older old. 1465 15

Investigation of the predictive value of a radiosurgery-relevant treatment of glioblastoma spheroids. Organotypic multicellular spheroids were cultured and irradiated (20 Gy). Morphology, apoptosis and immunohistochemical expression of p53, p21, MIB-1, TGF-beta and VEGF were examined 4 h, 24 h, 7 days, and 14 days following treatment. Cell proliferation decreased, while apoptosis was increased. No morphological damage was observed. p53 expression was significantly increased after 4 h. TGF-beta and VEGF expression were only slightly altered. Particularly early changes in proliferation and apoptosis can be observed in spheroids. Individual response differences suggest spheroids of human gliomas to be useful for monitoring radiosurgery effects.
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PMID:Effect of single dose irradiation on human glioblastoma spheroids in vitro. 1471 87

In this study, we investigated whether the expression of matrix metalloproteinase (MMP)-2 and MMP-9 correlated with invasiveness, proliferative potential, or prognosis in astrocytic tumors. Thirty-seven astrocytic tumors (8 diffuse astrocytomas, 15 anaplastic astrocytomas, and 14 glioblastomas) and three gliomatosis cerebri were investigated immunohistochemically. The invasive glioma group included three cases of gliomatosis cerebri and two of glioblastoma associated with cerebrospinal fluid dissemination. The expression of MMP-2 and MMP-9 was evaluated by assigning an immunohistochemical (IHC) score defined as the sum of expression frequency and intensity. mRNA expression patterns for the MMPs were also evaluated in a reverse transcription-polymerase chain reaction assay. Neither the MMP-2 nor MMP-9 IHC score was related to histological malignancy. The MMP-2 IHC score of the invasive glioma group was significantly higher than those of other kinds of astrocytic tumors. However, the MMP-9 IHC score did not correlate with dissemination among astrocytic tumors. An inverse correlation was observed between the MIB-1 labeling index and the IHC scores of MMP-2, but it was not significant. A Kaplan-Meyer survival analysis revealed no significant relationship between the survival rate and MMP-2 or MMP-9 expression. Our study showed that MMP-2 expression, but not MMP-9 expression, may be associated with invasion in astrocytic tumors.
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PMID:Matrix metalloproteinase-2 and -9 expression in astrocytic tumors. 1475 39

Brain specific angiogenesis inhibitor (BAI)-1 is a novel p53-inducible anti-angiogenic molecule. We examined the expression of BAI-1 in glial tumors and its association with patient survival. The expression of BAI-1 was evaluated in 20 brain tumors (meningiomas, pituitary adenomas, hemangiopericytomas, hemangioblastomas), 2 normal brain samples, 5 benign gliomas, and 26 glioblastomas. In the 26 glioblastoma tumors, we also evaluated the expression of VEGF, p53, p53 mutations, and MIB-1 to determine their association with survival. BAI-1 mRNA was expressed in all benign gliomas, normal brain, and 9 out of 26 glioblastomas, but not in the other tumors. Low VEGF and aberrant high expression of p53 were associated with a favorable outcome in univariate survival analysis, but they were not independent factors in multivariate analysis. For the treatment response, BAI-1 expression was associated with better response to radiation therapy (p=0.014). When we divided the patients into groups according to the expression patterns of BAI-1 and VEGF mRNA, the median survival of 9 patients with high VEGF expression and no expression of BAI-1 was just 6 months, while the median survival of the other 17 patients was 14 months (p=0.013). Glioblastomas with no BAI-1 and high VEGF mRNA expression are more often associated with poor clinical outcome. These findings suggest that the balance between the angiogenic and anti-angiogenic factors is important in the progression of glioblastoma and its response to treatment.
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PMID:Expression of VEGF and brain specific angiogenesis inhibitor-1 in glioblastoma: prognostic significance. 1501 Aug 86

We describe an unusual progression of astrocytoma into secondary glioblastoma exhibiting advanced neuronal immunophenotype. A tumor of the left frontal lobe of a 35-year-old man was diagnosed as astrocytoma. The tumor was treated by partial removal with postoperative chemoradiotherapy, followed by extensive removal of the residual regrowing tumor 5 month later. A secondary tumor was discovered and partially resected 8 years later, but the patient died 11 months following the operation due to extensive tumor progression showing subarachnoidal and intraventricular dissemination. The secondary tumor was small cell-predominant, highly proliferative tumor with an extremely high MIB-1 labeling index (80%). Unexpectedly, most of the tumor cells were positive for neuronal markers (synaptophysin and NeuN), but not for glial fibrillary acidic protein (GFAP). Retrospective examination of the original tumor revealed not only diffuse GFAP expression, but also neuronal marker expressions in small numbers of tumor cells that were hard to discriminate from the other cells on hematoxylin-eosin (HE) stain. This way of malignant progression of astrocytoma was quite unusual. Although the secondary tumor was classified as glioblastoma according to World Health Organization (WHO) classification (2000), it might be categorized into new variants of malignant glioneuronal tumors proposed recently.
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PMID:Secondary glioblastoma with advanced neuronal immunophenotype. 1596 44

Apolipoprotein D (apoD) expression has been shown to correlate both with cell cycle arrest and with prognosis in several types of malignancy, including central nervous system astrocytomas and medulloblastomas. ApoD expression was investigated by real-time quantitative RT-PCR using RNA extracted from 68 formalin-fixed, paraffin-embedded brain specimens. Glyceraldehyde phosphate dehydrogenase was used as an internal control. Quantitation was achieved on all specimens. Sixteen poorly infiltrating WHO grade I glial neoplasms (i.e., pilocytic astrocytomas and gangliogliomas) showed an average 20-fold higher apoD expression level compared with the 20 diffusely infiltrating glial neoplasms (i.e., glioblastoma, anaplastic astrocytoma, oligodendrogliomas; p=0.00004). A small number of exceptions (i.e., two high-expressing glioblastomas and three low-expressing gangliogliomas) were identified. Analyzed as individual tumor groups, poorly infiltrating grade I pilocytic astrocytomas and gangliogliomas differed significantly from each tumor type within the diffusely infiltrating higher-grade category (p<0.05 for each comparison) but not from each other (p>0.05). Conversely, each individual tumor type within the diffusely infiltrating category differed significantly from both pilocytic astrocytomas and gangliogliomas (p<0.05) but did not vary from other infiltrating tumors (p>0.05). Ependymomas, non-infiltrating grade II neoplasms, expressed levels of apoD similar to or lower than levels expressed by the diffusely infiltrating gliomas. Ten medulloblastomas with survival longer than 3 years averaged slightly higher apoD expression than four fatal medulloblastomas; however, this result was not statistically significant and individual exceptions were notable. In 17 of the medulloblastomas, MIB-1 proliferation rates quantitated by image cytometry did not correlate with apoD expression. In addition, apoD expression was 5-fold higher in the slowly proliferating grade I glial neoplasms compared with non-proliferating normal brain tissue (p=0.01), suggesting that apoD expression is not simply an inverse measure of proliferation. ApoD expression measured by quantitative RT-PCR may be useful in the differential diagnosis of primary brain tumors, particularly pilocytic astrocytomas and gangliogliomas.
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PMID:Apolipoprotein D expression in primary brain tumors: analysis by quantitative RT-PCR in formalin-fixed, paraffin-embedded tissue. 1605 49

The precise mechanisms governing the direct effect of IFN-beta, including apoptosis induction, are not yet fully understood. To gain a better insight into these mechanisms, we investigated the signaling pathways focusing particularly on interferon regulatory factor 1 (IRF-1) and IRF-2 in glioblastoma cell lines. Furthermore, we attempted to determine whether or not IRF-1 and IRF-2 act as additional prognostic indicators in diffusely infiltrating astrocytomas (DIA). We first assessed the cytotoxic effects of IFN-beta based on a cell growth study and modified MTT assay, and then quantified the apoptosis using a sandwich enzyme immunoassay following IFN-beta treatment in the cell lines, U-87MG, T98G, and A-172. Subsequently, we carried out an analysis of apoptosis-related molecules as evaluated by densitometric analysis of Western blots, focusing on IRF-1 and IRF-2, and two major initiator caspases, caspase-8 and caspase-9. Furthermore, we assessed the expression of type I IFN receptor, IRF-1, and IRF-2 using immunohistochemical techniques in 63 DIA (15 of WHO grade II, 18 of grade III, and 30 of grade IV), and analyzed their impact on prognosis. An increase in apoptosis was apparent after 48 h of IFN-beta treatment (1 x 10(4) IU/ml) in T98G but not in U-87MG or A-172. IFN-beta treatment for 6 h significantly enhanced the expression of IRF-1 in all three cell lines. However, an enhanced expression of IRF-2 was observed only in the not-most-sensitive, non-apoptosis-induced U-87MG and A-172. While minimal processing of caspase-8 was noted in the three cell lines throughout the experiment, caspase-9 activation was observed in the apoptosis-detected T98G after 48 h of treatment, as indicated by a 1.33-fold increase (P=0.037). On the other hand, the IRF-1 LI and IRF-1/IRF-2 LI ratio were greater in low-grade DAI, and were negatively correlated with the histopathological grade in DIA (P=0.017 and P=0.001, respectively). Furthermore, the IRF-1/IRF-2 LI ratio was negatively correlated with the MIB-1 LI in DIA (P=0.004), and represented an independent and most powerful determinant of overall survival compared to other conventional prognostic factors (P=0.018). However, the relation was not statistically significant when only patients with high-grade DIA were assessed. Our findings suggest that up-regulation of IRF-1 and IRF-2 might be an important determinant of susceptibility to IFN-beta mediated cytotoxicity including apoptosis. Furthermore, the IRF-1/IRF-2 LI ratio may reflect the proliferative state of DIA and constitute an important prognostic marker in DIA. Thus, IRF-1 and IRF-2 could represent one of the therapeutic target sites for the regulation of cell growth in DIA.
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PMID:Therapeutic implications of interferon regulatory factor (IRF)-1 and IRF-2 in diffusely infiltrating astrocytomas (DIA): response to interferon (IFN)-beta in glioblastoma cells and prognostic value for DIA. 1618 22

Multicellular tumor spheroids have been used to examine aspects of combined modality treatment since they often recreate the in vivo tumor environment much more closely than other models. The radioenhancement by gemcitabine (dFdC) on human glioma spheroids derived from cell lines (CLS) and biopsy tissue, grown as organotypic multicellular spheroids (OMS), was studied. CLS of GaMg and U87 and OMS of four glioblastoma patients were used. Radiochemosensitvity was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. Cell death (ethidium homodimer) was studied using a fluorescence cell viability assay. In CLS, combination treatment led to migration inhibition in GaMg and U87 of 85% and 62% (dFdC 46% and 52%, RT 21% and 43%) and proliferation inhibition of 83% and 85%, respectively. Following dFdC + RT in OMS (% of cases), apoptosis and p21 expression increased (50%), p53 expression increased (75%) and cell proliferation decreased (75%). Only minor morphological damage was observed. Confocal laser scanning microscopy identified an increased dead cell core after dFdC + RT (50%). In conclusion, dFdC can lead to an additively radioenhancement in CLS and individual OMS.
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PMID:Combined modality therapy of gemcitabine and irradiation on human glioma spheroids derived from cell lines and biopsy tissue. 1632 40

The fluorescence of protoporphyrin IX (PpIX) induced endogenously by 5-aminolevulinic acid (5-ALA) administration has recently been used for the intraoperative visualization of glioma tissues. To increase the sensitivity of photodetection, the emission spectra of 5-ALA-induced PpIX fluorescence was quantitatively measured in tissues taken from six cases of en bloc resected diffusely infiltrating astrocytomas (2 diffuse astrocytomas, 2 anaplastic astrocytomas, and 2 glioblastomas), and the correlation assessed between the fluorescence intensity and histological features. A total of 65 slices were analyzed by ex vivo spectroscopy. The ratio of the peak emission intensity to reflected excitation intensity or fluorescence intensity ratio was less than 0.001 for all 36 non-tumor tissues. The tissues with glioblastoma morphology had a fluorescence intensity ratio in excess of 0.090. The spectroscopic fluorescence intensity was positively correlated with the MIB-1 labeling index as an indicator of proliferation activity, the CD31-microvessel density as a pan-endothelial marker, and the vascular endothelial growth factor expression as an angiogenetic factor. The MIB-1 proliferation index was the most powerful determinant, suggesting that higher cell proliferation may govern preferential PpIX accumulation in glioma cells. This preliminary study suggests that spectroscopic analysis may be useful for optimizing the removal of diffuse gliomas.
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PMID:Quantitative spectroscopic analysis of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence intensity in diffusely infiltrating astrocytomas. 1731 41

Primary granulomatous angiitis of the central nervous system (CNS) is extremely rare. Its preoperative diagnosis is difficult as the condition displays nonspecific features on routine neuroimaging investigations. In this paper, the authors report findings of magnetic resonance (MR) spectroscopy and fractional anisotropy (FA) with diffusion tensor MR imaging in a case of granulomatous angiitis of the CNS. A 30-year-old man presented with morning headaches and grand mal seizures. An MR image revealed a mass resembling glioblastoma in the right temporal lobe. Magnetic resonance spectroscopy showed a high choline/creatine (Cho/Cr) ratio indicative of a malignant neoplasm, accompanied by a slight elevation of glutamate and glutamine. The FA value was very low, which is inconsistent with malignant glioma. The mass was totally removed surgically. Histologically, the peripheral lesion of the mass consisted of a rough accumulation of fat granule cells, infiltration of inflammatory cells, and distribution of capillary vessels. Some vessels within the lesion were replaced by granulomas. The histological diagnosis was granulomatous angiitis of the CNS. The MIB-1-positive rate of the granuloma was approximately 5%. Both MR spectroscopy and FA were unable to accurately diagnose granulomatous angiitis of the CNS prior to surgery; however, elevated Cho/Cr and glutamate and glutamine shown by MR spectroscopy may indicate the moderate proliferation potential of the granuloma and the inflammatory process, respectively, in this condition. Although the low FA value in the present case enabled the authors to rule out a diagnosis of glioblastoma, FA values in inflammatory lesions require careful interpretation.
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PMID:Primary granulomatous angiitis of the central nervous system: findings of magnetic resonance spectroscopy and fractional anisotropy in diffusion tensor imaging prior to surgery. Case report. 1793 38


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