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)

Diffuse type brainstem glioma is one of the most malignant types of brain tumors and the prognosis is extremely poor. The proliferative potential of these tumors is presumed to be very high, but there is little information about the cell kinetics of brainstem glioma because surgical resection is rarely performed. The histological grade, tumor spread, growth potential, and prognosis were evaluated in 40 autopsy cases of diffuse type brainstem glioma. To quantify the growth potentials of individual tumors, the proliferating cell indices of Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA) monoclonal antibodies were measured. Mean MIB-1 and PCNA proliferating cell indices were 20.4% (24 cases) and 37.0% (28 cases), respectively, in 34 glioblastomas. The median survival time was 40 weeks in 22 treated patients. The mean PCNA proliferating cell index was 10.8% in four of five anaplastic astrocytomas and the median survival time in four treated patients was 91 weeks. The MIB-1 and PCNA proliferating cell indices of one astrocytoma were 2.9% and 20.3%, respectively, and the survival time was 56 weeks. The overall median survival time was 32 weeks. There was a significant difference in PCNA proliferating cell indices between glioblastomas and anaplastic astrocytomas (p < 0.05) and there was a significant difference in survival time between glioblastomas (40 weeks) and anaplastic astrocytomas plus astrocytoma (74 weeks) among the treated patients (p < 0.05). Supratentorial extension was more frequent in glioblastomas than in anaplastic astrocytomas (p < 0.05). Our results suggest that the majority of diffuse type brainstem gliomas are glioblastoma and the proliferative potential is probably as high as that of adult supratentorial glioblastoma. Supratentorial extension and dissemination are relatively frequent in the advanced stage. Anaplastic astrocytoma or astrocytoma is rarer and less infiltrative and proliferative, and carries a slightly better prognosis than glioblastoma.
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PMID:Clinicopathological study of diffuse type brainstem gliomas: analysis of 40 autopsy cases. 1296 3

Thallium (Tl)-201 single-photon emission computed tomography (SPECT) is a useful tool for detecting brain tumors. In this study, we evaluated the utility of Tl-201 SPECT for determining the effect of maintenance chemotherapy with ACNU (nimustine hydrochloride)/VCR (vincristine sulfate) against malignant gliomas. The cases were comprised of 16 glioma cases; 6 astrocytomas, 2 anaplastic astrocytomas, and 8 glioblastomas. We first analyzed the correlation between Tl-201 uptake ratio and proliferative activity of the tumor, using Ki-67 immunohistochemistry in 13 cases of glioma. The uptake ratio of Tl-201 correlated with the Ki-67 staining indices (SI), and a closer correlation was obtained using Tl-201 delayed images than with the early images. We also analyzed the chronological changes of Tl-201 uptake ratio and volume of abnormal area evaluated by MRI T2-weighted imaging (MRI T2WI), in 10 cases of malignant glioma during maintenance chemotherapy. The Tl-201 uptake ratio gradually decreased with the effect of maintenance chemotherapy, and the sensitivity was superior to MRI findings. Together with MRI, Tl-201 SPECT is considered to be a useful indicator for evaluating the effect of maintenance chemotherapy against malignant gliomas.
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PMID:[Role of thallium SPECT for evaluating the effect of maintenance chemotherapy against malignant gliomas]. 1471 41

Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg(-1)) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.
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PMID:The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model. 1530 85

Chordoid glioma is an uncommon low-grade brain neoplasm arising in the third ventricular region, predominantly in middle-aged women. It characteristically shows chordoma-like histologic features and glial fibrillary acidic protein immunoreactivity. We present a case of chordoid glioma in a previously healthy 56-year-old woman admitted to our hospital because of a cranial trauma subsequent to an incidental fall. Radiologic examinations revealed a well-demarcated, partially cystic, enhancing mass at the level of the lamina terminalis. The lesion was surgically removed. The patient remained alive and well 8 months after the surgery. Histologically, the tumor consisted of clusters and cords of epithelioid cells embedded in a mucinous matrix. Lymphoplasmacytic infiltrates and Russell bodies were prominent. Immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein, neurofilaments, and neuron-specific enolase, suggesting a divergent neuronal and glial differentiation. The Ki-67 index was low. The clinicopathologic profile and the differential diagnosis of this tumor are discussed.
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PMID:Chordoid glioma: clinicopathologic profile and differential diagnosis of an uncommon tumor. 1550 76

Despite new approaches, treatment options for malignant gliomas are still limited, calling for further development of therapeutic strategies. The peroxisome proliferator-activated receptor (PPAR)gamma, a member of the nuclear hormone receptor family, represents a possible new target for neoplastic therapies. Synthetic PPARgamma agonists were developed and are already in clinical use for the treatment of type II diabetes, since PPARgamma plays a crucial role in lipid metabolism and regulation of insulin sensitivity. Beyond these metabolic effects, PPARgamma agonists exhibit antineoplastic effects in various malignant tumor cells. Here, we investigated the antineoplastic effects of the nonthiazolidinedione tyrosine-based PPARgamma ligand (S)-2-(1-carboxy-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}ethylamino)benzoic acid methyl ester (GW7845) in rat and human glioma cells. GW7845 reduced cellular viability of rat C6 glioma and human glioma cells in a time-dependent manner. Analysis of GW7845-treated tumor cells revealed induction of apoptotic cell death as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and cleaved caspase-3 activation. Furthermore, GW7845 reduced proliferation of C6 glioma cells as measured by Ki-67 immunore-activity. There was also a reduction of migration and invasion, assessed by Boyden chamber and spheroid experiments. Together, these data indicate that the PPARgamma agonist GW7845 may be of potential use in treatment of malignant gliomas.
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PMID:The nonthiazolidinedione tyrosine-based peroxisome proliferator-activated receptor gamma ligand GW7845 induces apoptosis and limits migration and invasion of rat and human glioma cells. 1566 44

The matrix metalloproteinase (MMP) family members catalyze extracellular proteolysis. Recent reports have suggested that expression of MMP-2 and -9 might play a critical role in neoplastic tissue invasion or metastasis. In this study, the relationship between the expression of MMP-2 and -9 and the histological features of tissues from 21 cases of human glioma were investigated. MMP-2 and -9 proteins were detected by immnohistochemical studies. Amplification of MMP-2 and -9 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) assay. MMP-2 and -9 mRNA was measured quantitatively by the real-time RT-PCR method. Immunohistochemically, 38% of the cases were positive for MMP-2. Amplification of MMP-2 mRNA by RT-PCR was detected in 62% of the cases. There was no significant relationship between the expression of MMP-2 protein or mRNA and the biological nature of the tumors, including aggressiveness and histologic classification. The quantity of MMP-2 mRNA was 0.035 +/- 0.113 (MMP-2/GAPDH %), which was significantly elevated in cases of neoplastic dissemination or recurrence (P < 0.05). Tumor cells were immunohistochemically positive for MMP-9 in 81% of the samples. A positive reaction was found not only in neoplastic cells but also in endothelial cells, suggesting that the expression of MMP-9 protein might be associated with tumoral angiogenesis. The expression of mRNA in MMP-9 was detected in 91% of the cases, suggesting a close relationship between expression of MMP-9 and malignancy. The quantity of MMP-9 was 0.097 +/- 0.113 (MMP-9/GAPDH %) in all samples, which was significantly elevated in cases of glioblastoma (P < 0.05). The average Ki-67 labeling index was 8.14 +/- 5.26 in samples from G2 glioma, 19.92 +/- 11.29 in samples from G3 glioma, and 23.52 +/- 10.14 in samples from glioblastoma. All of the cases with elevated indices had recurrence or dissemination. The results of our study suggest that quantity analyses of MMP-2 and -9 mRNA and Ki-67 labeling index should be useful for discerning tumoral behaviors such as invasion, dissemination, and recurrence.
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PMID:Expression and quantitative analysis of matrix metalloproteinase-2 and -9 in human gliomas. 1569 70

Monoclonal antibody (mAb) 806 is a novel epidermal growth factor receptor (EGFR) antibody with significant antitumor activity that recognizes a mutant EGFR commonly expressed in glioma known as delta2-7 EGFR (de2-7 EGFR or EGFRvIII) and a subset of the wild-type (wt) EGFR found in cells that overexpress the receptor. We have used two human xenograft mouse models to examine the efficacy of mAb 806 in combination with mAb 528, a prototypical anti-EGFR antibody with similar specificity to cetuximab. Treatment of nude mice, bearing s.c. or i.c. tumor human xenografts expressing the wt or de2-7 EGFR, with mAbs 806 and 528 in combination resulted in additive and in some cases synergistic, antitumor activity. Interestingly, mAb 528 was also effective against xenografts expressing the ligand independent de2-7 EGFR when used as a single agent, showing that its antitumor activity is not merely mediated through inhibition of ligand binding. When used as single agents, neither mAbs 806 or 528 induced down-regulation of the de2-7 EGFR either in vitro or in vivo. In contrast, the combination of antibodies produced a rapid and dramatic decrease in the total cell surface de2-7 EGFR both in vitro and in xenografts. Consistent with this decrease in total cell surface de2-7 EGFR, we observed up-regulation of the cell cycle inhibitor p27(KIP1) and a decrease in tumor cell proliferation as measured by Ki-67 immunostaining when the antibodies were used in combination in vivo. Thus, mAb 806 can synergize with other EGFR-specific antibodies thereby providing a rationale for its translation into the clinic.
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PMID:Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity. 1614 44

Many approaches to local tumor treatment have been reported and their efficacy demonstrated in patients with malignant glioma. We studied thermoreversible gelation polymer (TGP) as a novel drug delivery system (DDS) for treating this type of tumor. TGP exhibits sol-gel transition i.e., is water-soluble in the sol phase below the chosen sol-gel transiting temperature and water-insoluble in the gel phase above this temperature. We conjugated doxorubicin with TGP to prepare doxorubicin-TGP (DXR-TGP), then studied the kinetics of doxorubicin release from TGP and the antitumor activity of DXR-TGP in vitro and in vivo. The diffusive speed of doxorubicin from TGP was 9.4x10(-7) cm(2)/s and doxorubicin was reliably released from TGP. DXR-TGP showed antitumor activity against the human glioma cell lines T98G and U87MG and in a subcutaneous tumor model in nude mice. Pathologically, detection of the proliferation marker Ki-67 was considerably lower in the DXR-TGP group than in the control group (30-40% vs. 60-70%, respectively). This is to the best of our knowledge the first report of TGP as a novel drug delivery system, and further we provide evidence that TGP exhibits potential for use as a novel DDS for malignant glioma.
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PMID:Novel drug delivery system using thermoreversible gelation polymer for malignant glioma. 1629 93

Our previous work has shown that tolbutamide increases gap junctional permeability in poorly coupled C6 glioma cells and that this effect is similar and additive to that found with dbcAMP, a well-known activator of gap junctional communication. Furthermore, the increase in gap junctional communication promoted by tolbutamide or dbcAMP is concurrent with the inhibition of proliferation of C6 glioma cells. In the present work, we show that tolbutamide and dbcAMP increase the synthesis of the tumor suppressor protein Cx43 and that they decrease the level of Ki-67, a protein expressed when cells are proliferating. These effects were accompanied by a reduction in the phosphorylation of pRb, mainly on Ser-795, a residue critical for the control of cell proliferation. The decrease in the phosphorylation of pRb is not likely to be mediated by a reduction in the levels of D-type cyclins, since instead of decreasing the expression of cyclins, D1 and D3 increased slightly after treatment with tolbutamide or dbcAMP. However, the Cdk inhibitors p21 and p27 were up-regulated after treatment with tolbutamide and dbcAMP, suggesting that they would be involved in the decrease in pRb phosphorylation. When Cx43 was silenced by siRNA, neither tolbutamide nor dbcAMP were able to up-regulate p21 and consequently to reduce glioma cell proliferation, as judged by Ki-67 expression. In conclusion, tolbutamide and dbcAMP inhibit C6-glioma cell proliferation by increasing Cx43, which correlates with a reduction in pRb phosphorylation due to the up-regulation of the Cdk inhibitors p21 and p27.
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PMID:Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation. 1671 85

The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor family, represents a possible new target in glioma therapy. Because PPARgamma plays a crucial role in regulation of insulin sensitivity, synthetic agonists are already in clinical use for type II diabetes treatment. Beyond these metabolic effects, PPARgamma agonists exhibit antineoplastic effects. In this study, we investigated the antineoplastic effects of the PPARgamma agonist pioglitazone in glioma cells. Pioglitazone reduced cellular viability of rat, human, and PPARgamma-overexpressing glioma cells in vitro in a time- and concentration-dependent manner. No antineoplastic effects were induced by pioglitazone in glioma cells overexpressing a PPARgamma mutant. Furthermore, proliferation was reduced by pioglitazone, as measured by Ki-67 immunoreactivity, in vitro. Continuous intracerebral infusion of pioglitazone into gliomas induced by intrastriatal injection of C6 cells reduced tumor volumes by 83%. Oral administration of pioglitazone reduced tumor volumes by 76.9%. Subsequent brain tissue analysis revealed induction of apoptotic cell death. Ki-67 expression and BrdU incorporation revealed a reduction of proliferation in vivo. Reduced invasion of C6 cells and lower matrix metalloproteinase 9 levels in vivo indicate pioglitazone-mediated reduction of invasion. Together, these data indicate that pioglitazone may be of potential use in treatment of malignant gliomas.
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PMID:Inhibition of in vivo glioma growth and invasion by peroxisome proliferator-activated receptor gamma agonist treatment. 1688 36


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