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)

Molecular morphologic tools exist for simultaneously visualizing immunophenotype and genotype of tumors, but are frequently hampered by a delicate balance between removing sufficient amount of the protein blocking full access of the probe to hybridize to target nucleic acids while still preserving sufficient target antigen for immunophenotyping. The result is often suboptimal, with either insufficiently visualized gene deletions and amplifications due to masking protein, or overdigestion of the protein target. Our purpose was to design and validate a gated genotyping assay that enables optimal and concomitant detection of both gene and protein. Using the proliferating endothelial cell compartment within gliomas organized in a tissue microarray (TMA), we tested the hypothesis that tyramide signal amplification (TSA) with deposition of a fluorochrome could be used during immunophenotyping, permitting sufficient protein digestion while insuring probe accessibility to nucleic acid target. The method was successfully validated using a TMA containing 38 glioma cases previously genotyped for EGFR amplification. CD31 positive endothelial cells were segregated via TSA-based Alexa-Fluor 647 immunofluorescence for analysis of EGFR amplification of the gliomas organized in the TMA. Enhanced immunoFISH (TSA) successfully segregates immunophenotypically-defined cell populations for gated genotyping.
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PMID:Genotyping of phenotypically defined cells in neoplasia: enhanced immunoFISH via tyramide signal amplification (TSA) segregates immunophenotypically-defined cell populations for gated genotyping. 1720 77

In a previous report, the recombinant kringle domain (UK1) of the urokinase type plasminogen activator (uPA) showed antiangiogenic activity. Here, we investigated in vivo antitumor effects of the UK1 of human uPA employing a brain tumor model. The systemic administration of UK1 purified from pichia expression (10 and 50 mg/kg/day intraperitoneally for 25 days) led to suppress the growth of a U87 human glioma xenograft, implanted into the brains of male BALB/cSlc nude mice, by 35% and 80%, respectively. In the immunohistochemical analysis, the tumors treated with UK1 showed decreased vascularity and expression of angiogenesis-related factors including vascular endothelial growth factor (VEGF), angiogenin, alpha-smooth muscle actin, von Willebrand's factor, and CD31 (PECAM-1 [Platelet endothelial cell adhesion molecule-1]), and increased apoptosis. UKl inhibited the in vitro proliferation and tube formation of VEGF-stimulated endothelial cells but not the proliferation of glioma cells. These results suggest that UK1 inhibits the malignant glioma growth by suppression of angiogenesis.
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PMID:The recombinant kringle domain of urokinase plasminogen activator inhibits in vivo malignant glioma growth. 1723 42

The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-beta-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.
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PMID:Glioma-associated endothelial cells show evidence of replicative senescence. 1729 95

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

A critical event in tumor growth and progression is the upregulation of angiogenesis. Thus, targeting angiogenesis has become an attractive treatment modality in cancer medicine. Our study analyzed various solid tumor types for the expression of Dkk-3, a cystein-rich, N-glycosylated secreted member of the Dickkopf protein family that has been proposed as a tumor suppressor gene. Tissue microarrays of gliomas (n = 30), high-grade non-Hodgkin's lymphomas (NHL, n = 80), colorectal cancer (n = 35) and melanoma (n = 30) were immunohistochemically analyzed for Dkk-3 and CD31 expression. Moreover, the effects of Dkk-3 were studied in vitro in primary endothelial colony-forming cells (ECFC) and in vivo in a mouse melanoma model. In comparison to normal tissue, the number of blood vessels expressing Dkk-3 was increased in glioma, high-grade NHL, melanoma and colorectal carcinoma. Confocal laser scanning microscopy revealed that Dkk-3 vesicles localized also in Weibel Palade bodies. In vitro cell proliferation and migration of ECFC was not significantly affected by adenoviral overexpression or siRNA-mediated downregulation of Dkk-3. Interestingly, tube formation in matrigel decreased after downregulation of Dkk-3 and increased after adenoviral overexpression. Stable overexpression of murine Dkk-3 in B16F10 cells significantly increased microvessel density in the C57/BL6 melanoma model. Thus, we postulate a novel function of Dkk-3 in endothelial cells as a differentiation factor involved in remodeling the tumor vasculature.
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PMID:The Dickkopf-homolog 3 is expressed in tumor endothelial cells and supports capillary formation. 1803 87

Gambogic acid (GA) is the major active ingredient of gamboge, a brownish to orange resin exuded from Garcinia hanburryi tree in Southeast Asia. The present study aims to demonstrate that gambogic acid (GA) has potent anticancer activity for glioblastoma by in vitro and in vivo study. Rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). To reveal an involvement of the intrinsic mitochondrial pathway of apoptosis, the mitochondrial membrane potential and the western blot evaluation of Bax, Bcl-2, Caspase-3, caspase-9 and cytochrome c released from mitochondria were performed. Angiogenesis was detected by CD31 immunochemical study. The results showed that the uptake of GA by rBMEC was time-dependent, which indicated that it could pass BBB and represent a possible new target in glioma therapy. GA could cause apoptosis of rat C6 glioma cells in vitro in a concentration-dependent manner by triggering the intrinsic mitochondrial pathway of apoptosis. In vivo study also revealed that i.v. injection of GA once a day for two weeks could significantly reduce tumor volumes by antiangiogenesis and apoptotic induction of glioma cells. Collectively, the current data indicated that GA may be of potential use in treatment of glioblastoma by apoptotic induction and antiangiogenic effects.
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PMID:Inhibition of glioblastoma growth and angiogenesis by gambogic acid: an in vitro and in vivo study. 1807 Jun 17

Chordoid gliomas are rare, slow-growing neoplasms of the anterior third ventricle. We reported a case of chordoid glioma in a 41-year-old man with obstructive hydrocephalus. Histologically, the tumor consisted of polygonal epithelioid cells admixed with elongated cells in a myxoid stroma. A prominent lymphoplasmacytic infiltrate was present. The tumor cells expressed glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), vimentin, CD31, CD34, epidermal growth factor receptor (EGFR) and S100 but were negative for pankeratin and E-cadherin. The percentage of Ki67 positive cells was approximately 3%. Weak p53 immunoreactivity was seen in less than 10% of the cells. Array comparative genomic hybridization performed on this case, as well as on four other archived cases, showed losses at several loci. Fluorescence in situ hybridization (FISH) confirmed consistent genetic alterations at 9p21 and 11q13. These are the fifth through ninth reported cases of chordoid gliomas with molecular characterization suggesting a distinct genetic origin from other gliomas.
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PMID:Chordoid glioma: a case report and molecular characterization of five cases. 1865 91

Normalization of tumor vasculature by antiangiogenic agents may improve the delivery of cytotoxic drugs to the tumor, leading to more effective therapy. In this study, we used pharmacokinetic and pharmacodynamic approaches to investigate how sunitinib at different dose levels affects brain distribution of temozolomide (TMZ), and to ascertain the relationship between intratumoral TMZ concentrations and tumor vascularity in an orthotopic human glioma model. Three groups of intracerebral U87MG tumor-bearing mice were given either vehicle or sunitinib at 20 mg/kg or 60 mg/kg per day for 7 days before receiving a steady-state regimen of TMZ that consisted of an intravenous bolus and a 3-h intraarterial infusion. TMZ concentrations in plasma, normal brain, and brain tumor were determined, and several biomarkers related to the antiangiogenic activity of sunitinib were examined. TMZ distribution in the normal brain as indicated by the brain-to-plasma steady-state TMZ concentration ratios was analogous across the three treatment groups. The brain tumor-to-plasma steady-state TMZ concentration (ss C(t)/C(p)) ratio was significantly increased in the 20 mg/kg sunitinib group (0.98 +/- 0.17) compared with the control (0.76 +/- 0.17) and 60 mg/kg sunitinib (0.68 +/- 0.09) groups. The ss C(t)/C(p) ratios were significantly correlated with the vascular normalization index (VNI), derived from the expression of CD31, collagen IV, and alpha-smooth muscle actin, which represents the fraction of functioning vessels out of the total tumor vessels. In conclusion, the effect of sunitinib on the brain tumor distribution of TMZ was dose dependent and indicated that optimal tumor exposure was achieved at a lower dose and was associated with the VNI.
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PMID:Differential effect of sunitinib on the distribution of temozolomide in an orthotopic glioma model. 1897 16

Endothelial progenitor cells (EPCs) are important initiators of vasculogenesis in the process of tumor neovascularization. However, it is unclear how circulating EPCs contribute to the formation of tumor microvessels. In this study, we isolated CD34(+)/CD133(+) cells from human umbilical cord blood (HUCB) and obtained EPCs with the capacities of forming colonies, uptaking acetylated low-density lipoprotein (ac-LDL), binding lectins and expressing vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2, KDR), CD31 and von Willebrand factor (vWF). These EPCs were actively proliferative and migratory, and could formed capillary-like tubules in response to VEGF. When injected into mice bearing subcutaneously implanted human malignant glioma, EPCs specifically accumulated at the sites of tumors and differentiated into mature endothelial cells (ECs), which accounted for 18% ECs of the tumor microvessels. The incorporation of circulating EPCs into tumor vessel walls significantly affected the morphology and structure of the vasculature. Our results suggest that circulating EPCs constitute important components of tumor microvessel network and contribute to tumor microvascular architecture phenotype heterogeneity.
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PMID:Incorporation of endothelial progenitor cells into the neovasculature of malignant glioma xenograft. 1905 96

Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers, but its effects on gliomas are unknown. In this study, we investigated the effects of tetrandrine on the growth and angiogenesis of rat RT-2 gliomas. We treated RT-2 glioma cells with tetrandrine and then measured cytotoxicity, apoptosis and expression of vascular endothelial growth factor (VEGF). We also examined the cytotoxic effect of tetrandrine on the ECV304 human umbilical vein endothelial cells and the effects of tetrandrine on the in vivo angiogenesis. Tumor size and animal survival were followed in tetrandrine-treated rats with subcutaneous or intracerebral gliomas. Expression of CD31 in tetrandrine-treated gliomas was followed to study its effect on glioma-induced angiogenesis. Tetrandrine had cytotoxic effects and induced apoptosis of glioma cells in a concentration- and time-dependent manner. Tetrandrine also inhibited the expression of VEGF in glioma cells, induced cytotoxicity effect on the ECV304 cells and suppressed the in vivo angiogenesis. Tetrandrine (150 mg/kg/day) had significant antitumor effects on subcutaneous tumors and led to slower tumor growth rate, longer animal survival time and higher animal survival (p < 0.05). Tetrandrine also affected intracerebral tumors and prolonged animal survival (p < 0.05) without affecting survival rate. Immunohistochemical analyses showed that the subcutaneous gliomas from tetrandrine-treated rats had fewer microvessel densities than control rats (p = 0.01). The results demonstrate that tetrandrine is cytotoxic to RT-2 glioma cells, has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas. Tetrandrine has potential as a treatment for gliomas.
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PMID:Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats. 1916 64


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