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Sample records for c6 rat glioma

  1. Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection.

    NARCIS (Netherlands)

    Zoula, S.; Rijken, P.F.J.W.; Peters, J.P.W.; Farion, R.; Sanden, B.P.J. van den; Kogel, A.J. van der; Decorps, M.; Remy, C.

    2003-01-01

    In C6 rat brain glioma, we have investigated the relation between hypoxia and the presence of lipid droplets in the cytoplasm of viable cells adjacent to necrosis. For this purpose, rats were stereotaxically implanted with C6 cells. Experiments were carried out by the end of the tumour development.

  2. MRI and morphological observation in C6 glioma model rats and significance

    International Nuclear Information System (INIS)

    Objective: To establish stable and reliable rat C6 glioma model, and to perform MRI dynamic observation and pathomorphological observation in model animal brain, and to provide experimental basis for pharmaceutical research on anti-glioma drugs. Methods: The C6 glioma cells were cultured and 20 μL cultural fluid containing 1×106 C6 cells was sterotactically implanted into the left caudate nuclei in 10 male Wistar rats, respectively. The changes in the behavior of the rats after implantation were observed and recorded. MRI dynamic scanning was performed in 10 rats 2, 3 and 4 weeks after implantation and the brain tissues were taken for general and pathological examination when the 10 rats were naturally dead. The survival period of tumor-bearing rats was calculated. Results: 2 weeks after implantation the rats showed decreased activities and food intake, fur lackluster, and conjunctival congestion and so on; 3 weeks later, some rats appeared nerve symptoms such as body twitch, body hemiplegy, body distortion, rotation and so on. All the 10 rats died in 8-30 d. The median survival period of the tumor-bearing rats was 18 d, the average survival period was (18.3±7.3) d. The pathological examination showed that the tumor cells were arranged irregularly closely and karyokinesis was easy to see; tumor vascular tissue proliferation and tumor invasive growth into surrounding normal tissues were found. The expression of glial fibrillary acidic protein (GFAP) was positive in the tumors. Conclusion: A stable animal model of intracranial glioma is successfully established by stereotactic implantation of C6 cells into the rat caudate nucleus. The results of MRI dynamic observation and pathohistological observation on the model animal brain tissue. Can provide experimental basis for selecting the appropriate time window to perform the pharmaceutical research on anti-glioma drugs. (authors)

  3. The Effects of Venlafaxine and Dexamethasone on the Expression of HSP70 in Rat C6 Glioma Cells

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    Yu, Jaehak; Roh, Sungwon; Lee, Jun-Seok; Yang, Byung-Hwan; Choi, Mi Ran; Chai, Young Gyu; Kim, Seok Hyeon

    2010-01-01

    Objective The present study aimed to determine the intracellular action of the antidepressant, venlafaxine, in C6 glioma cells using heat shock protein 70 (HSP70) immunocytochemistry and HSP70 Western blots; HSP70 is known to be associated with stress and depression. Methods The extent of HSP70 expression was measured after rat C6 glioma cells were treated with 1) dexamethasone only, 2) venlafaxine only, 3) simultaneous venlafaxine and dexamethasone, or 4) dexamethasone after venlafaxine pret...

  4. Effects of lead on viability and intracellular metal content of C6 rat glioma cells

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    Tiffany-Castiglioni, E.; Garcia, D.M.; Wu, J.N.; Zmudzki, J.; Bratton, G.R.

    1988-01-01

    Cultured C6 rat glioma cells were exposed to lead (Pb) acetate (0, 1, 10, or 100 ..mu..M) for 3-4 d. Cells were analyzed for changes in viability and intracellular lead, iron, and copper concentrations after Pb treatment was discontinued. The results were compared with previous findings on astroglia and oligodendroglia in culture in order to evaluate C6 cultures as a model for Pb toxicity in glia. Viability was measured by three methods on the day Pb was removed from the cells (designated d 0), and 2 and 9 d after Pb treatment was discontinued (designated d 2 and 9). The methods used were trypan blue dye exclusion, total cell counts, and incorporation of (/sup 3/H)-L-leucine into proteins. With respect to Pb and Fe uptake, C6 cells closely resembled immature astroglia in culture. Unlike C6 cells, however, astroglia showed elevations of intracellular Fe and Cu after treatment. Thus, Pb effects on C6 cells resembled those on cultured oligodendroglia and astroglia in some respects but not in others. C6 cells appear to be an adequate model for selected events in glial toxicosis, such as PB-stimulated protein synthesis in oligodendroglia and Pb uptake in astroglia, but not Pb-induced alterations of intracellular Cu and Fe in astroglia. Their use as a model for glial progenitor cells in Pb toxicity studies remains to be determined.

  5. In vitro effects of ellagic acid in C6 rat glioma cell cultures in terms of cytotoxicity and proliferation

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    Cenap Ekinci

    2012-09-01

    Full Text Available Objectives: Ellagic acid is a plant-derived polyphenoliccompound. The aim of this study is to investigate in vitroeffects of ellagic acid on the proliferation and viability ofrat C6 glioma cell lineage depending on dose and timeand also is to evaluate ultrastructural changes in C6 gliomaspheroids.Materials and methods: Effects of ellagic acid on rat C6glioma cell line were investigated by using two-dimensionalmodels of tumor cell culture depending on doseand time. The effects of Ellagic acid was evaluated ascell proliferation, cell viability, and synthesis phase of cellcycle, and cell structure at 24th, 48th, 72nd hours. Cell structurewas evaluated at 24th and 72nd hours in three dimensionalcell culture spheroid models.Results: Reducing effect of ellagic acid on cell proliferationand cell viability was seen in two dimensional cultures(p0. 05. Electronmicrographs in which three dimensional cell culturespheroid models was investigated, structural changeswas found to be different from the control group.Conclusions: In the evaluation of effects of ellagic acidon rat C6 glioma cells using two-dimensional culture models,it was observed that ellagic acid caused reduced cellviability, deterioration in cell structure and prevented cellproliferation. J Clin Exp Invest 2012; 3 (3: 350-356Key words: Ellagic acid, C6 glioma cells, cell culture,brain tumor, glioma

  6. Construction of rat glioma cell line C6-Luc for reproducing an animal model with stable expression of luciferase

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    Wei HUANG

    2011-01-01

    Full Text Available Objective To construct the rat glioma cell line C6-Luc to stably express the firefly luciferase.Methods The optimal concentration of hygromycin for screening C6 rat glioma cells was determined by concentration gradient method.The eukaryotic plasmid pGL4.50 expressing luciferase was transfected into C6 cells by using FuGENE HD transfection reagent,followed by screening the polyclonal cell lines with hygromycin,subsequently screening the monoclonal cell line by limited dilution.The positive monoclonal cell lines were identified with reporter gene assay,thereafter the expression stability of luciferase was investigated in the positive cell lines.The bioluminescence detection in vitro in the positive monoclonal cell line was performed to determine the minimum detection amount of cells,and the correlation between bioluminescence intensity and cell amount was analyzed by linear regression analysis.The positive monoclonal cells were implanted into the brain of Wistar rats,and the tumor growth in rats’ brain was detected in vivo using the bioluminescence imaging detection system.Results The optimal concentration of hygromycin used in screening C6 cells was 250 μg/ml.The eukaryotic plasmids pGL4.50 was successfully transfected into C6 cells,and 12 monoclonal cell lines were obtained by anti-hygromycin screening.A positive clone with the highest activity of luciferase,designated as C6-Luc,was successfully identified by using luciferase reporter gene assay,which showed a stable activity of expressing luciferase after 3 continuous passages of cultivation.The bioluminescence detection in vitro showed that the minimum detection amount of C6-Luc cells was 78.A good linear correlation existed between bioluminescence intensity and the amount of C6-Luc cells,with an equation of y=81.348x-2143.1 and correlation coefficient(r of 0.997.The in vivo bioluminescence imaging detection showed tumorigenesis could be detected after implantation of C6-Luc cells into

  7. Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

    International Nuclear Information System (INIS)

    Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

  8. Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

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    Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-07-15

    Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

  9. Anticancer and antiangiogenic effects of methanol extracts of Lonicera caprifolium L. on C6 rat glioma cells

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    Nergiz Hacer Turgut

    2016-03-01

    Full Text Available Objective: Gliomas are brain tumors with high morbidity and mortality. For the treatment of gliomas, it is important to develop new and powerful treatments that could complement existing clinical treatment. Lonicera caprifolium L. (L. caprifolium has various uses in herbal traditional medicine. This study was conducted to determine the phenolic acid levels and DNA damage protection potential of L. caprifolium extract, and to explore the antitumor effect of the extract by investigating its toxicity on C6 rat glioma cell lines and normal L929 mouse fibroblast cell lines. We also aimed to investigate the antiangiogenic potential of the extract. Method: Phenolic acid content was determined by HPLC analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. The effect of extracts on the proliferation of cancer cells was evaluated by XTT assay. Antiangiogenic effect was determined with Chorioallantoic membrane model. Results: The extract was found rich in vanillic acid (273.003 µg/g; while the amount of chlorogenic acid was almost at negligible level (0.028 µg/g. 0.005-0.05 mg / ml extract protected against the hazardous effects of UV and H2O2 in all DNA bands. The presence of the extract significantly reduced C6 cell proliferation compared to control (p<0.05. The extract had antiproliferative effect with a half maximum inhibition of concentration (IC50 value of 0.45 mg/ml. L. caprifolium extract in 10-6, 10-5 and 10-4 M concentrations caused antiangiogenic effect. Antiangiogenic scores of L. caprifolium were 0.6, 0.73 and 1.6, respectively. Conclusions: These results show that L. caprifolium has potential cytotoxic and antiangiogenic effect on C6 rat glioma cells and that the phenolic acid content of the plant may partially influence these activities.

  10. Paramagnetic Gd2O3 Nanoparticle-Based Targeting Theranostic Agent for C6 Rat Glioma Cell

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    Seong-Pyo Hong

    2016-01-01

    Full Text Available This study aimed to synthesize theranostic agent targeting C6 rat glioma cell, which was based on the dextran coated paramagnetic gadolinium oxide nanoparticles (D-PGONs conjugated with folic acid (FA or paclitaxel (PTX. The D-PGONs were synthesized by the in situ coprecipitation method, and the average value of the size distribution was 2.9 nm. FTIR spectroscopy was fulfilled to confirm the conjugations of FA or PTX with D-PGONs. The bioprotective effects of dextran coating and chemotherapeutic effect of PTX in the C6 glioma cell were evaluated by the MTT assay. The differences in uptakes between the synthesized theranostic agents into C6 cells were observed by confocal laser scanning microscopy. In addition, the magnetic contrast enhancement with different concentration of the synthesized agent was compared by the T1-weighted MRI imaging. It was experimentally shown that the synthesized theranostic agent targets C6 cells due to the ligand-receptor-mediated endocytosis and provides enhancement in MR contrast depending on the concentration due to the paramagnetic property of gadolinium nanoparticle. In addition, it was shown by the results of MTT assay that the synthesized nanocomposites were more effective in reducing cell viability than bare gadolinium nanoparticles. In conclusion, it was shown that FA and PTX conjugated D-PGONs could be used as the theranostic agent with paramagnetism and chemotherapeutic property.

  11. Combination hyperbaric oxygen and temozolomide therapy in c6 rat glioma model Terapia combinada de oxigênio hiperbárico e temozomida no modelo C6 de glioma em ratos

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    Yaşar Dagıstan

    2012-06-01

    Full Text Available PURPOSE: Temozolomide (TMZ has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (% was decreased significantly in tumor tissue of the group 3 rats compared to group1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.OBJETIVO: A temozolomida (TMZ tem atividade anti-tumoral em pacientes com glioma maligno. Oxigênio hiperbárico (HBO pode aumentar a eficácia de terapias que são limitadas devido a um microambiente do tumor hipóxico. Foram examinados os efeitos combinados de TMZ-HBO em um modelo de glioma em rato. MÉTODOS: Após a injeção estereotáxica de células de glioma de rato C6/LacZ no cérebro de ratos Wistar, os ratos foram distribuídos aleatoriamente em três grupos de tratamento: Grupo 1: tratamento de controle. Grupo 2: TMZ sozinho. Grupo 3: uma combinação de TMZ e HBO. Os ratos foram sacrificados 18 dias após o tratamento. Foram avaliados o número de vasos intra

  12. Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs)

    International Nuclear Information System (INIS)

    The aim of this work was to compare the effects of 24-h exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side-effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by nanotechnology, like nanomaterials (NMs) such as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes, the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO3) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination, whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses to AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells

  13. Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs)

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    Salazar-García, Samuel; Silva-Ramírez, Ana Sonia; Ramirez-Lee, Manuel A.; Rosas-Hernandez, Hector [Universidad Autonoma de San Luis Potosi, Facultad de Ciencias Quimicas (Mexico); Rangel-López, Edgar [Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suárez, Laboratorio de Aminoacidos Excitadores (Mexico); Castillo, Claudia G. [Facultad de Medicina, Universidad Autonoma de San Luis Potosi (Mexico); Santamaría, Abel [Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suárez, Laboratorio de Aminoacidos Excitadores (Mexico); Martinez-Castañon, Gabriel A. [Universidad Autonoma de San Luis Potosi, Facultad de Estomatologia (Mexico); Gonzalez, Carmen, E-mail: cgonzalez.uaslp@gmail.com, E-mail: gonzalez.castillocarmen@fcq.uaslp.mx [Universidad Autonoma de San Luis Potosi, Facultad de Ciencias Quimicas (Mexico)

    2015-11-15

    The aim of this work was to compare the effects of 24-h exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side-effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by nanotechnology, like nanomaterials (NMs) such as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes, the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO{sub 3}) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination, whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses to AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells.

  14. CT perfusion imaging as an early biomarker of differential response to stereotactic radiosurgery in C6 rat gliomas.

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    Timothy Pok Chi Yeung

    Full Text Available BACKGROUND: The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model. METHODS: Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8 or stereotactic radiosurgery (N = 25, 12 Gy in one fraction delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival >15 days were designated as responders while those with survival ≤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline. RESULTS: Early signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P<0.04. Responders to stereotactic radiosurgery showed lower relative blood volume (rBV, and permeability-surface area (PS product on day 7 post-stereotactic radiosurgery when compared to controls and non-responders (P<0.05. rBV and PS on day 7 showed correlations with overall survival (P<0.05, and were predictive of survival with 92% accuracy. CONCLUSIONS: Response to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation.

  15. Heat shock induction of a 65 kDa ATP—binding proteinase in rat C6 glioma cells

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    XUCUNSHUAN; MARCOMEYER; 等

    1999-01-01

    The 45,55,65 and 100kDa ATP-binding proteinases(ATP-BPases) of the heat-shocked (44℃ for 30 min,recovery for 12h) rat C6 glioma cells were purified by DEAE-ionexchange and ATP-affinity chromatography.Their molecular masses,isoelectric points (pI),pH-optima and other properties were analyzed by native proteinase gels.It was shown that the 65 kDa ATP-BPase is specifically induced by heat shock and not detectable in control cells.Its N-terminal 1-9amino acid sequence was determined by Edman degradation,but no homologies to other proteins in the protein data bases were found.30 and 31kDa proteinases can be cleaved from the 45,55 and 65 kDa proteinases to which they are linked.A possible relationship of the heat-induced 65 kDa ATP-BPase with the ATP-dependent proteinases (ATP-DPases) in prokaryotes and eukaryotes is discussed.

  16. 槲皮素血浆代谢物抗大鼠C6脑胶质瘤细胞的作用%Effects of the plasma metabolites of quercetin on rat C6 glioma cells

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    王刚; 杜士明; 杨光义; 常明泉; 曾南; 叶方

    2012-01-01

    OBJECTIVE To investigate the effects of the plasma metabolites of quercetin on rat C6 glioma cells. METHODS C6 glioma cells were incubated with the serum metabolic product of QUE-NL containing quercetin, quercitin and isorhamnetin separately for 24 h,then the cytotoxicity of the serum metabolic product of QUE-NL was assessed by assay for the activity of lactate dehydrogenase(LDH) ,the apoptosis and mitochondrial membrane potential was detected by flow cytometry. RESULTS Quercetin and isorhamnetin had cyto-toxici effect on cultured rat C6 glioma cells in vitro , and could inhibit proliferation and induce apoptosis(P<0. 05). Quercetin decreased the mitochondrial membrane potential obviously(P<0. 05). CONCLUSION The methylation of quercetin existence forms of QUE-NL in rats' plasma were the major anti-tumor activity constituents. The antitumor activities of metabolic products of quercetin glycosides were weak. The results provide experimental foundation for application and its target preparation in the therapy of glioma cell.%目的:考察槲皮素大鼠血浆中的代谢物对大鼠C6脑胶质瘤细胞增殖与凋亡的作用.方法:将槲皮素血浆代谢产物槲皮素、槲皮苷和异鼠李素分别与C6胶质瘤细胞共培养24 h后,LDH活性法检测代谢产物对C6脑胶质瘤细胞的毒性作用,流式细胞仪检测C6胶质瘤细胞凋亡与线粒体膜电位变化.结果:槲皮素和异鼠李素对大鼠C6胶质瘤细胞有显著的细胞毒性作用,均能显著诱导C6胶质瘤凋亡(P<0.05),槲皮素显著降低线粒体膜电位(P<0.05).结论:槲皮素血浆中的槲皮素甲基化代谢产物是主要的抗肿瘤活性成分,而槲皮素苷类代谢产物抗肿瘤活性较弱,为槲皮素及其靶向制剂进一步应用于脑胶质瘤的治疗提供参考依据.

  17. Investigating effect of fusion gene therapy by MR diffusion-weighted imaging in a rat C6 glioma model

    International Nuclear Information System (INIS)

    Objective: To evaluate the use of diffusion-weighted imaging (DWI) for early detection of tumor response to Angiostatin-Endostatin (Statin-AE) fusion gene therapy in a rat C6 glioma model. Methods: Fifty male wistar rats with C6 tumor cells implanted into the striatum were examined by a 3.0T MR scanner, then the rats bearing tumors were divided into two groups, treatment group and control group. Rats in the treatment group received 107 plaque forming unit (pfu) recombinant herps simplex viral (R-HSV) mediated Statin-AE fusion gene therapy on day 7, and then the tumors were conformed on MRI. Conventional MR and DWI examination were acquired on 1, 2, 3 weeks after implantation with a 5-inch surface coil. Two (1 w), eight (2 w) and all the residual rats (3 w) of each group were sacrificed to perform the histopathological examination after each MRI examination. Pretreatment and post treatment tumor volumes and apparent diffusion coefficient (ADC) values were calculated. Bank sum test and t test were employed for statistical analysis. Results: On MRI, 43 rats demonstrated tumors on day 7 with a successful rate of 86%. On week 2, the tumor volumes of the controls and treatment group were 90. 6 and 91.64 mm3 , with no significant difference (Z=-0.14, P>0.05). On week 3, the tumor volumes of the controls and treatment group were 156.64 and 29.64 mm3, and a significant difference was observed (Z=-3.45, P-3 and (0.99 ± 0.08) x 10-3mm2/s, and the values of the tumor peripheral parts of the two groups were (1.00 ± 0.25) x 10-3 and (0.83 ± 0.12) x 10-3 mm2/s, the ADC values of both tumor centers and peripheral parts of the treatment group were significantly higher than those of the control group (t=-0.82 and -0.46, P-3 and (0.99 ± 0.09) x 10-3mm2/s, and the values of the tumor peripheral parts of the two groups were (0.81±0.19) x 10-3 and (0.78±0.11) x 10-3 mm2/s, there were no statistical difference between the two groups (t=0.82, and -0.46, P<0.05). HE stained slices

  18. Characterization of Ca(2+)-activated 86Rb+ fluxes in rat C6 glioma cells: a system for identifying novel IKCa-channel toxins.

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    de-Allie, F. A.; Bolsover, S. R.; Nowicky, A. V.; Strong, P N

    1996-01-01

    1. The pharmacological characteristics of a putative Ca2+ activated K+ channel (IKCa channel) in rat glioma C6 cells were studied in the presence of the Ca2+ ionophore, ionomycin and various K+ channel blockers, 86Rb+ being used as a radioisotopic tracer for K+. 2. The resting 86Rb+ influx into C6 cells was 318 +/- 20 pmol s-1. The threshold for ionomycin activation of 86Rb+ influx was approx. 100 nM. At ionomycin concentrations above the activation threshold, the initial rate of 86Rb+ influx...

  19. Synthesis of dihydropyrimidin-2-one/thione library and cytotoxic activity against the human U138-MG and Rat C6 glioma cell lines

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    Canto, Romulo F.S.; Eifler-Lima, Vera Lucia [Universidade Federal do Rio Grande do Sul (LaSOM/PPGCF/UFRGS), Porto Alegre, RS (Brazil). Programa de Pos Graduacao em Ciencias Farmaceuticas. Lab. de Sintese Organica; Bernardi, Andressa; Battastini, Ana Maria O. [Universidade Federal do Rio Grande do Sul (ICBS/UFRGS), Porto Alegre, RS (Brazil). Inst. de Ciencias Basicas da Saude; Russowsky, Dennis [Universidade Federal do Rio Grande do Sul (IQ/UFRGS), Porto Alegre, RS (Brazil). Inst. de Quimica

    2011-07-01

    Two series of 4-aryl-3,4-dihydropyrimidin-2(1H)-(thio)ones including monastrol (1a), have been synthesized by an environment-friendly methodology based on the combined use of citric acid or oxalic acid and TEOF (triethylorthoformate). The library was evaluated as inhibitor of cell proliferation on two glioma cell lines (human-U138-MG and Rat-C6). The compounds derived from thiourea 1f and 1d were more cytotoxic than monastrol. The compound derived from urea 2d showed the highest cytotoxic activity among the analyzed compounds. (author)

  20. Establishment of C6 brain glioma models through stereotactic technique for laser interstitial thermotherapy research

    Directory of Open Access Journals (Sweden)

    Jian Shi

    2015-01-01

    Conclusion: The rat C6 brain glioma model established in the study was a perfect model to study LITT of glioma. Infrared thermograph technique measured temperature conveniently and effectively. The technique is noninvasive, and the obtained data could be further processed using software used in LITT research. To measure deep-tissue temperature, combining thermocouple with infrared thermograph technique would present better results.

  1. Wild Type p53 gene sensitizes rat C6 glioma cells to HSV-TK/ACV treatment in vitro and in vivo.

    Science.gov (United States)

    Huang, Qiang; Xia, Zhibo; You, Yongping; Pu, Peiyu

    2010-12-01

    Suicide gene therapy using herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV), has been extensively tested for the treatment of glioma. Our previous study showed that exogenous wild type p53 (wt-p53) enhanced the anti-tumor effect of HSV-TK/GCV therapy. However, the use of GCV is hindered by its low penetration to the brain and its toxicity when used at higher dose. In the present study, we used another pro-drug, acyclovir (ACV), and examined the therapeutic efficacy of HSV-TK/ACV combining with wt-p53 in C6 glioma cells. We observed that wt-p53 combined with HSV-TK/ACV resulted in the super-additive anti-tumor effect in vitro. Exogenous wt-p53 significantly enhanced the sensitivity of TK positive C6 cells to ACV in vitro. Our in vivo experiment demonstrated that the effect of wt-p53 and HSV-TK/ACV combination therapy was better than that of HSV-TK/ACV alone. The survival time of tumor-bearing rats treated with wt-p53 in combination with HSV-TK/ACV was also significantly prolonged than those treated with HSV-TK/ACV alone. These results suggest that wt-p53 can enhance the therapeutic efficacy of HSV-TK/ACV both in vitro and in vivo. These findings are considerably valuable with the respect of using less toxic ACV as prodrug. This novel strategy could provide benefit to HSV-TK/prodrug gene therapy.

  2. Effects of endostatin on C6 glioma-induced edema

    Institute of Scientific and Technical Information of China (English)

    YANG Li-juan; LIN Zhi-xiong; KANG De-zhi; WENG Shen-mei; LIN Jian-hua; HUANG Qiang; ZHANG Peng-fei

    2011-01-01

    Background Glioma-induced edema is considered as one of the most pathological characteristics of glioma and a significant source of morbidity and mortality.New strategies are needed for the treatment of peritumoral edema in glioma.Endostatin has been proven to be beneficial as an anti-angiogenic agent in experimental gliomas,but the effects are unclear.This study aimed to investigate the effects of endostatin on C6 glioma-induced edema.Methods Tumorigenic mice were established by subcutaneous injection of three glioma cell lines,C6-null cells and stable transfected-C6 cells overexpressing mock vector (C6-mock cells) and endostatin (C6-endo cells).Endostatin expression in xenograft C6 glioma was determined by immunostaining and Western blotting.Glioma-induced edema and tumor vessel permeability were assayed.The effect of endostatin on vascular enodothelial growth factor (VEGF) expression in vivo was analyzed by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA).The number of vesiculo-vascuolar organelles (VVOs) formed in tumor endothelia was calculated using electron microscopy.Data were analyzed by using one-way analysis of variance (ANOVA) followed by Dunnett's post hoc test for multiple comparisons to the control groups.Results Overexpression of endostatin (C6-endo cells) significantly suppressed tumor growth and reduced tumor edema and vessel permeability.ELISA analysis showed that the level of VEGF protein was markedly decreased in tumor from C6-endo cells compared with tumor from C6-null cells and C6-mock cells.Similar results were obtained by Q-PCR.Furthermore,the number of VVOs observed in tumor from C6-endo mice was significantly reduced compared with tumor from C6-null cells or C6-mock cells.Conclusions Our data provide primary evidence that endostatin reduces glioma-induced edema and vascular permeability.Using endostatin may be an effective strategy for treating glioma edema.

  3. Nitric oxide inhibits uptake of dopamine and N-methyl-4-phenylpyridinium (MPP+) but not release of MPP+ in rat C6 glioma cells expressing human dopamine transporter

    Science.gov (United States)

    Cao, Bo-Jin; Reith, Maarten E A

    2002-01-01

    Conflicting results have been reported regarding the influence of nitric oxide (NO) and peroxynitrite on dopamine (DA) uptake and release. In the present study, effects of NO donors were studied in rat C6 glioma cells expressing human DA transporter. [3H]-DA uptake was inhibited by S-nitroso-thiol S-nitroso-N-acetylpenicillamine, spermine/NO, diethylamine/NO (DEA/NO), (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)-amino]/NO (PAPA/NO), and 3-morphosynodiomine (SIN-1) in a rank order correlating with their half lives as NO donors, whereas no effect was observed for diethylenetriamine/NO and dipropylenetriamine/NO, which release NO very slowly. Hydroxycobalamin, a NO scavenger, but not superoxide dismutase and catalase, enzymes that metabolize superoxide and hydrogen peroxide, respectively, abolished the inhibitory effect of DEA/NO and SIN-1, indicating that they inhibit DA uptake through a mechanism related to the production of NO but unrelated to the formation of peroxynitrite. In consonance, peroxynitrite did not alter DA uptake in the present system. DEA/NO and PAPA/NO reduced [3H]-MPP+ uptake, whereas the release of [3H]-MPP+ was not modified, demonstrating that NO can inhibit uptake of DA transporter substrate without accelerating DA transporter-mediated reverse transport of substrate under the same conditions. PMID:12466224

  4. 西兰花多肽对大鼠C6胶质瘤细胞生长的影响%The effect of broccoli polypeptide on C6 glioma cells of rat

    Institute of Scientific and Technical Information of China (English)

    徐俊杰; 于洪泉; 国巍; 赵伟; 金宏; 温娜; 齐玲

    2012-01-01

    目的 研究西兰花多肽对大鼠C6胶质瘤细胞生长的影响.方法 培养C6胶质瘤细胞,用西兰花多肽(0、0.01、0.1、1、10μ/ml)作用细胞72h,MTT法检测胶质瘤细胞的生长情况.结果 西兰花多肽作用C6胶质瘤细胞72h时,各药物浓度组都表现为对细胞的抑制作用,1μl/ml组(0.58 ±0.08 vs 0.75 ±0.02)和10μl/ml组(0.07 ±0.01 vs 0.75 ±0.02)表现出显著的抑制生长作用(P<0.01).结论 西兰花多肽可抑制C6胶质瘤细胞的生长,并且随着药物浓度升高药物作用增强,说明西兰花多肽具有抑制肿瘤细胞生长的作用.%Objective To study the effects of broccoli polypeptide on the proliferation of C6 glioma cells. Method Cultured C6 glioma cells were treated with different dose of broccoli polypeptide(0,0. 01 ,0. 1 ,1 , 10μl/ml)for 72h. The level of cell growth was detected by MTT assay. Results After 72h,all dosed of polypeptide inhibited the growth of cells, especially in 1(0,1/μml group(0. 58 ±0.08 vs 0.75 ±0.02) and 10(1,1/μml group(0.07 ±0.01 vs 0.75 ±0.02) when compared with respective control group(P <0. 01). Conclusion Broccoli polypeptide may inhibit the proliferation of C6 glioma cells, and the effect is increased with dose, which suggests that broccoli polypeptide can inhibit the growth of tumor cells.

  5. Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

    Directory of Open Access Journals (Sweden)

    Zahra Moinfar

    Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

  6. Intracellular labeling and quantification process by magnetic resonance imaging using iron oxide magnetic nanoparticles in rat C6 glioma cell line; Marcacao intracelular e processo de quantificacao por imagem por ressonancia magnetica utilizando nanoparticulas magneticas de oxido de ferro em celulas da linhagem C6 de glioma de rato

    Energy Technology Data Exchange (ETDEWEB)

    Mamani, Javier Bustamante; Pavon, Lorena Favaro; Sibov, Tatiana Tais; Rossan, Fabiana; Silveira, Paulo Henrique; Cardenas, Walter Humberto; Gamarra, Lionel Fernel, E-mail: javierbm@einstein.br [Instituto do Cerebro - InCe, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Miyaki, Liza Aya Mabuchi [Faculdade de Enfermagem, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Amaro Junior, Edson [Departamento de Diagnostico por Imagem e Instituto do Cerebro - InCe, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil)

    2012-04-15

    Objective: To assess intracellular labeling and quantification by magnetic resonance imaging using iron oxide magnetic nanoparticles coated with biocompatible materials in rat C6 glioma cells in vitro. These methods will provide direction for future trials of tumor induction in vivo as well as possible magnetic hyperthermia applications. Methods: Aminosilane, dextran, polyvinyl alcohol, and starch-coated magnetic nanoparticles were used in the qualitative assessment of C6 cell labeling via light microscopy. The influence of the transfection agent poly-L-lysine on cellular uptake was examined. The quantification process was performed by relaxometry analysis in T{sub 1} and T{sub 2} weighted phantom images. Results: Light microscopy revealed that the aminosilane-coated magnetic nanoparticles alone or complexed with poly-L-lysine showed higher cellular uptake than did the uncoated magnetic particles. The relaxactivities of the aminosilane-coated magnetic nanoparticles with a hydrodynamic diameter of 50nm to a 3-T field were r{sub 1}=(6.1 +- 0.3) x10{sup -5} ms{sup -1}mL/{mu}g, r{sub 2}=(5.3 +- 0.1) x 10{sup -4} ms{sup -1}mL/{mu}g, with a ratio of r{sub 2} / r{sub 1}{approx_equal} 9. The iron uptake in the cells was calculated by analyzing the relaxation rates (R{sub 1}and R{sub 2}) using a mathematical relationship. Conclusions: C6 glioma cells have a high uptake efficiency for aminosilane-coated magnetic nanoparticles complexed with the transfection agent poly-L-lysine. The large ratio r{sub 2} / r{sub 1}{approx_equal} 9 indicates that these magnetic nanoparticles are ideal for quantification by magnetic resonance imaging with T{sub 2}-weighted imaging techniques. (author)

  7. Baicalin interferes with iron accumulation in C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Chunyan Guo; Xin Chen

    2011-01-01

    Baicalin reacts with ferric ammonium citrate and acts as an-iron chelator. The maximal reaction time for baicalin to interact with irons was approximately 3 hours. C6 glioma cell survival decreased following iron-loading, with a large number of cells accumulating iron. In addition, lipid peroxidation increased. Iron accumulation and lipid peroxidation were the major cause of cellular death. Baicalin and ferric ammonium citrate alleviated iron accumulation in C6 cells and lowered the mortality of nerve cells. In addition, malondialdehyde and lactate dehydrogenase levels reduced. These results indicate that baicalin strongly inhibits lipid peroxidation via chelation, reduces the content of iron in C6 cells, lowers lipid peroxidation, and thus plays a protective role against iron-induced nerve cell death.

  8. Induction of apoptosis and inhibition of proliferation of C6 glioma cells in vitro by tamoxifen

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the anti-tumor effect and mechanism of tamoxifen on rat C6 glioma cells. Methods C6 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with 3% fetal calf serum (FCS), and treated with tamoxifen of different concentrations, i.e. group A (1.25μmol/L), group B (2.50 μmol/L), group C (5.00 μmol/L), group D (10.00 μmol/L), group E (20.00 μmol/L) and control group (0.00 μmol/L). Morphological changes, MTT assay and 5-bromo-2'-deoxyuriding labeling ratio were assessed. Apoptosis was observed by flow cytometry. Results C6 cells treated with different doses of tamoxifen for 24, 48, and 72 hours became irregular in shape, while cells treated with vehicle grew normally. MTT assay showed that tamoxifen did not suppress C6 cell growth until 72 hours after treatment. Seventy-two hours after treatment, there were significant differences in cell viable rate between group A versus groups C, D and E; so did group B versus group D as well as group E (P<0.05). BrdU incorporation assay indicated significant difference of BrdU labbled index (BrdU LI) among groups A, C, E and control group 48 hours after treatment (P<0.05). And the BrdU LI decreased with the increased concentration of tamoxifen. Flow cytometry (FCM) showed significant difference between treated group and control group at 24, 48, and 72 hours after treatment (P<0.05). Conclusion Tamoxifen significantly suppresses the growth of C6 glioma cells in a time- and dose-dependent manner. The mechanism of tamoxifen suppressing C6 glioma cells may be inhibiting proliferation and inducing apoptosis. Therefore, tamoxifen can be a candidate as a chemotherapy agent for glioma.

  9. Construction of rat glioma cell line C6-Luc for reproducing an animal model with stable expression of luciferase%大鼠脑胶质瘤荧光素酶动物模型建模细胞株C6-Luc的构建

    Institute of Scientific and Technical Information of China (English)

    黄伟; 吕明; 李保卫; 王玉丽; 邵荣光; 高钟镐

    2011-01-01

    Objective To construct the rat glioma cell line C6-Luc to stably express the firefly luciferase.Methods The optimal concentration of hygromycin for screening C6 rat glioma cells was determined by concentration gradient method.The eukaryotic plasmid pGL4.50 expressing luciferase was transfected into C6 cells by using FuGENE* HD transfection reagent, followed by screening the polyclonal cell lines with hygromycin, subsequently screening the monoclonal cell line by limited dilution.The positive monoclonal cell lines were identified with reporter gene assay, thereafter the expression stability of luciferase was investigated in the positive cell lines.The bioluminescence detection in vitro in the positive monoclonal cell line was performed to determine the minimum detection amount of cells,and the correlation between bioluminescence intensity and ce11 amount was analyzed by linear regression analysis.The positive monoclonal cells were implanted into the brain of Wistar rats, and the tumor growth in rats brain was detected in vivo using the bioluminescence imaging detection system.Results The optimal concentration of hygromycin used in screening C6 cells was 250 μg/mL The eukaryotic plasmids pGL4.50 was successfully transfected into C6 cells, and 12 monoclonal cell lines were obtained by anti-hygromycin screening.A positive clone with the highest activity of luciferase, designated as C6-Luc, was successfully identified by using luciferase reporter gene assay, which showed a stable activity of expressing luciferase after 3 continuous passages of cultivation.The bioluminescence detection in vitro showed that the minimum detection amount of C6-Luc cells was 78.A good linear correlation existed between bioluminescence intensity and the amount of C6-Luc cells, with an equation of y=81.348x-2143.1 and correlation coefficient(r) of 0.997.The in vivo bioluminescence imaging detection showed tumorigenesis could be detected after implantation of C6-Luc cells into the brain of

  10. 苦参碱对胶质瘤大鼠模型中Fas表达的调节作用的实验研究%Effect of mtrine on Fas expression in C6 glioma in rats

    Institute of Scientific and Technical Information of China (English)

    戚基萍; 刘微; 张淑君; 昝丽坤; 孙玉兰; 宋月佳

    2009-01-01

    目的 探讨苦参碱应用前后C6脑胶质瘤大鼠模型中Fas因子的表达变化及意义.方法采用脑立体定向技术,将体外培养的C6胶质瘤细胞注入大鼠尾状核区制备胶质瘤大鼠模型,并根据是否用药及用药量的多少分为空白对照组、冰片组、苦参碱低剂量组、苦参碱高剂量组、苦参碱低剂量+冰片组、苦参碱高剂量+冰片组.通过大鼠生存状态、标本的大体所见、MRI、HE染色观察苦参碱对胶质瘤大鼠模型生存质量及胶质瘤体积的影响,用免疫组织化学方法检测苦参碱对胶质瘤大鼠模型肿瘤细胞中Fas表达的影响.结果 大鼠生存状态、标本的大体所见、MRI及HE染色显示苦参碱可显著提高胶质瘤大鼠模型的生存质量,抑制胶质瘤细胞增殖.免疫组化结果显示,苦参碱低剂量+冰片组(98.16±11.82)、苦参碱高剂量+冰片组(1 12.80±12.12)Fas表达高于空白对照组(39.09±7.79)、冰片组(46.87±7.43)、苦参碱低剂量组(42.41±7.83)、苦参碱高剂量组(44.20±7.47),苦参碱高剂量+冰片组Fas表达高于苦参碱低剂量+冰片组,差异均有统计学意义(P<0.05).结论 苦参碱能增加胶质瘤细胞中Fas的表达,抑制胶质瘤细胞增殖.%Objective To investigate the effect of matrine on Fas expression in C6 glima in a tumor-bearing rat model. Methods Cultured cerebral glioma C6 cells wgre injected stereotactically into the lef tcaudate nucleus of the rats.The ratswere randomized into untreated group,bomeol-treated group,low-dose matrine group,high-dose maaine group,low-dose matrine+bomeol group,and high-dose matrine+borneol group.The effect of matrine on the quality of life of the rats and the glioma volume was evaluated according to the survival state of the rats and by gross observation,magnetic resonance imaging(MRJ)and HE smining of the brain tissue.Immunohistochemistry was performed to detect Fas expression in the glioma cells. Results The survival state

  11. FLIP inhibits induction of apoptosis by cisplatin in rat C6 glioma cells%FLIP蛋白抑制顺铂诱导大鼠C6胶质瘤细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    贺亚龙; 贺晓生; 章翔; 屈朔瑶; 王江

    2009-01-01

    目的 探讨自杀相关因子(Fas)相关死亡结构域样白介素1(IL-1)β转化酶抑制蛋白(FLIP) 对于顺铂(CDDP)诱导大鼠脑胶质瘤细胞(C6细胞株)凋亡的抑制作用,为进一步研究胶质瘤的耐药性奠定分子生物学基础.方法 利用由Ad-Max腺病毒包装系统成功构建的携载大鼠FLIP基因的腺病毒表达载体Ad-FLIP感染大鼠C6胶质瘤细胞,24 h后经逆转录酶-多聚酶链反应(RT-PCR)及Western blot检测感染组及对照组细胞中FLIP基因的mRNA及蛋白表达水平;分别给予Ad-FLIP感染组及对照组细胞不同浓度的CDDP(0,1,2,4,8 mg/ml),药物处理48 h后,经流式细胞仪(FCM)分析细胞凋亡状况;四唑蓝显色法(MTT)测定并比较两组细胞活力.结果 Ad-FLIP感染组细胞与对照组细胞相比,FLIP mRNA和蛋白表达水平明显增高;流式细胞仪检测结果显示Ad-FLIP感染组细胞凋亡率明显低于对照组.MTT法结果提示经CDDP处理后,Ad-FLIP感染组与对照组细胞活力均有下降,但FLIP蛋白具有明显的抑制作用.结论 FLIP蛋白在大鼠C6胶质瘤细胞中具有抵抗化疗药物的作用.

  12. 牛蒡子苷元对大鼠脑胶质瘤的作用及初步作用机制探讨%Effects and primary mechanism of arctigenin in C6 rat glioma

    Institute of Scientific and Technical Information of China (English)

    苏勤勇; 李晓梅; 姚景春; 王平平; 张贵民

    2015-01-01

    Aim To observe the effect and primary mechanism of arctigenin ( ARG) in C6 rat glioma. At the same time, to investigate the effect of ARG com-bined with temozolomide. Methods C6 glioma rat model was established, and 90 rats were divided into six groups, which were subcutaneously administered with model, low and high ARG (0. 05 and 0. 1 mg· kg-1 , sc) , temozolomide (20 mg·kg-1 , p. o. ) , low ARG combined with temozolomide(TMZ / ARG 0. 05) and high ARG combined with temozolomide ( TMZ /ARG 0. 1 ) . The tumor specimens of brain were col-lected after tumor graft. Proliferating cell nuclear anti-gen ( PCNA ) , glial fibrillary acidic protein ( GFAP ) and CD40 in tumor specimens were determined by im-munohistochemistry. Results ① Compared with the model group, the tumor sizes of rats in the arctigenin treatment groups were decreased ( P significantly decreased PCNA and CD40 expression ( P<0. 05 ) and increased GFAP expression ( P<0. 05 ) .③ Compared with model group, arctigenin combined with temozolomide decreased the tumor sizes ( P <0. 01 ) , and the tumor inhibition rate was higher than that of the arctigenin and temozolomide. At the same time, arctigenin combined with temozolomide de-creased PCNA and CD40 expression ( P <0. 01 ) and increased GFAP expression ( P <0. 05 ) , which was better than arctigenin and temozolomide. Conclusion Arctigenin inhibits rat glioma growth, and synergizes with temozolomide, which may be associated with in-hibiting PCNA and CD40 expression and strengthening GFAP expression.%目的:观察牛蒡子苷元对大鼠C6胶质瘤的作用及作用机制的研究。同时探讨牛蒡子苷元与替莫唑胺合用对脑胶质瘤是否有协同作用。方法采用脑内注射C6胶质瘤细胞建立大鼠C6胶质瘤模型;牛蒡子苷元连续皮下给药15 d,替莫唑胺从d5开始给药,连续灌胃给药5 d;测量肿瘤的长短径,计算肿瘤体积;采用免疫组化方法检测脑瘤组织中GFAP、PCNA和CD40的表达。结

  13. Induction of apoptosis and inhibition of proliferation of C6 glioma cells in vitro by tamoxifen

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the anti-tumor effect and mechanism of tamoxifen on rat C6 glioma cells. Methods C6 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with 3% fetal calf serum (FCS), and treated with tamoxifen of different concentrations, i.e. group A (1.25μmol/L), group B (2.50 μmol/L), group C (5.00 μmol/L), group D (10.00 μmol/L), group E (20.00 μmol/L) and control group (0.00 μmol/L). Morphological changes, MTT assay and 5-bromo-2'-deoxyuriding labeling ratio were assessed. Apopto...

  14. 腺相关病毒介导重组血管抑素联合雷公藤红素对大鼠颅内C6胶质瘤的抗血管生成作用%Anti-angiogenesis effect of adeno-associated virus-mediated recombinant angiostatin combined with celastrol on intracranial C6 glioma in rats

    Institute of Scientific and Technical Information of China (English)

    王冠; 周洁; 冯珂珂; 田麒

    2011-01-01

    目的:腺相关病毒(adeno-associated virus,AAV)介导的重组血管抑素(angiostatin,AS)联合应用雷公藤红素( celastrol)治疗大鼠颅内C6胶质瘤,观察其对肿瘤体积、新生血管密度及肿瘤细胞凋亡的影响,探讨抗血管生成重组基因联合雷公藤红素对胶质瘤治疗的前景.方法:建立颅内原位荷C6脑胶质瘤大鼠模型,7d后随机分为4组,分别给予0.9%氯化钠溶液(作为对照)、AAV-AS、雷公藤红素及两者联合用药.每隔7d行头部强化MRI检查,计算肿瘤体积.于22 d后处死动物,检测AS蛋白表达、血管密度及肿瘤细胞凋亡情况.结果:联合治疗组及AAV-AS治疗组均检测到AS蛋白表达,证实基因转导成功.联合治疗组第22天时肿瘤体积、血管密度和凋亡指数均与对照组、雷公藤红素组及AAV-AS治疗组相比差异有统计学意义(P<0.05),联合治疗可以抑制肿瘤生长,降低新生血管密度,促进肿瘤细胞凋亡.结论:基因治疗联合雷公藤红素可通过抑制胶质瘤血管生成而抑制肿瘤生长;两者联合应用具有协同作用,可弥补两者单独应用的不足之处.%Objective: To examine the effects of therapeutic alliance of adeno-associated virus-mediated recombinant angiostatin (AAV-AS) combined with celastrol on tumor growth, microvessel density and apoptosis of intracranial glioma in rats, and to give a prospective of this therapeutic alliance. Methods: A rat intracranial C6 glioma model was established, and then the rats (n=40) were randomly assigned into four groups after 7 days, which were saline control group, AAV-AS group, celastrol group and therapeutic alliance group. The tumor growth was examined by magnetic resonance imaging (MRI) every 7 days, and the volume of tumor was calculated. The rats were killed after 22 days, and the expression of AS protein, the microvessel density and the apoptosis of tumor cells were detected. Results: The expression of AS protein was detectable in AAV

  15. 蒿甲醚对C6胶质瘤细胞的抑制作用%Inhibitory effect of artemether on C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    邓兴力; 颜小荣; 李宣鹏; 王波; 魏小兵; 李杨; 李玉

    2011-01-01

    目的 研究蒿甲醚对大鼠C6胶质瘤细胞的抑制作用.方法 C6胶质瘤细胞经培养后,按是否加入蒿甲醚分为实验组和对照组,均采用四甲基偶氮唑盐(MTT)法、流式细胞技术(FCM)及Hoechst33258荧光染色法检测细胞凋亡情况.结果 MTT法检测显示:24、48、72h3个时间组蒿甲醚对C6胶质瘤细胞的半数抑制浓度(IC50)分别为(195.08±3.27) μmol/L、(119.64±4.06) μmol/L、(87.84±0.93) μmol/L.FCM法检测显示:24、48、72 h3个时间组C6胶质瘤细胞凋亡率分别为:7.95%、22.01%、31.22%;且G0-G1期细胞比例增加,S期和G2-M期细胞比例降低.荧光染色显示:实验组细胞内出现凋亡小体;而对照组细胞呈弥散均匀荧光.结论 蒿甲醚能抑制C6胶质瘤细胞生长,且其抑制作用呈现时间依赖性和浓度依赖性;蒿甲醚能干扰C6胶质瘤细胞的细胞周期,可将其阻滞在G0-G1期并诱导其凋亡.%Objective To research inhibitory effect of artemether on C6 glioma cells in rats. Methods According to whether adding the artemether, C6 glioma cells were divided into the experimental group and control group after cultivation. Cell apoptosis was detected by MTT method, flow cytometry (FCM) and Hoechst33258 fluorescence staining. Results 50% inhibit concentrations (IC50) of artemether to C6 glioma cells in the time group of 24,48, 72h were 195.08±3.27 μmol/L, 119.64±4.06 μmol/L, 87.84±0.93 μmol/L respectively by MTT method. Cell apoptosis rates of C6 glioma cells in the time group of 24, 48, 72h were 7.95%, 22.01%, 31.22% respectively, and the cells percentage at Go-G, phase increased and the cells percentage at S phase and GrM phase decreased by FCM. Apoptotic body was seen in the cells of the experimental group, while diffuse and uniform fluorescence was observed in the control group by fluorescence staining. Conclusions Artemether can inhibit the growth of C6 glioma cells, and the inhibitory effect shows time dependence and

  16. Orphan nuclear receptor Nur77 is required for the differentiation of C6 glioma cells induced by cholera toxin

    Institute of Scientific and Technical Information of China (English)

    Dong XU; Yi-jun HUANG; Yan LI; Wei YIN; Guang-mei YAN

    2009-01-01

    Aim: To investigate a possible regulator gene involved in the cholera toxin-induced differentiation of rat C6 glioma cells. Methods: The global changes in the mRNA expression pattern induced by cholera toxin were analyzed using gene chip microarray. The selected gene was then silenced by RNA interference or overexpressed with an ORF plasmid to determine its necessity in this process. Results: Nur77, a member of the orphan nuclear receptor family (NR4A), was markedly up-regulated during the process of differentiation. Furthermore, RNAi of nur77 attenuated the induction effect of cholera toxin on C6 cells, whereas overexpression of nur77 led to similarly differentiated behavior, including morphologic and biomarker changes, as well as cell cycle arrest. Conclusion: Nur77 participated actively and essentially as an important regulator in the cholera toxin-induced differentiation of C6 cells.

  17. Modulation of p75 neurotrophin receptor under hypoxic conditions induces migration and invasion of C6 glioma cells.

    Science.gov (United States)

    Wang, Ting-Chung; Luo, Sheng-Jie; Lin, Chun-Liang; Chang, Pey-Jium; Chen, Miao-Fen

    2015-01-01

    p75 neurotrophin receptor (p75NTR) has been reported to play important roles in various cancer types. However, the exact mechanism of tumorigenesis involving p75NTR is unknown. In this study, we investigated the relationship between the expression of p75NTR in malignant glioma and the impact on tumor cell migration and invasion. p75NTR and hypoxia-inducible factor-1α (HIF-1α) expression was down-regulated by short-hairpin RNA and up-regulated with expression vectors. By immunohistochemical staining and Western blot analysis, we found that p75NTR was expressed in both human and rat malignant gliomas. Knockdown of p75NTR increased the expression of vimentin, vascular endothelial growth factor, Matrix metalloproteinase 9, and TWIST, and enhanced the invasion and migration abilities assessed by transwell assay in the C6 tumor cells. Inverse expressions of p75NTR and HIF-1α were detected in glioma cell lines under hypoxic conditions, while increased HIF-1α significantly downregulated the expression of p75NTR, suggesting a HIF-1α-p75NTR-EMT pathway that may regulate glioma cells invasion and migration. Downregulation of p75NTR increased phosphorylation of Src, focal adhesion kinase (FAK) and paxillin. Knockdown of p75NTR also dysregulated β-catenin-mediated cell junctions, and up-regulated the expressions of fibronectin and L1CAM in the cell-cell junctions, thus suggesting that p75NTR knockdown contributed to a more aggressive migration phenotype via FAK signaling pathway. Our studies suggested that modulation of p75NTR under hypoxic condition could enhance C6 cells migration and invasion by induction of EMT, and activation of the FAK pathway. The HIF-1α-p75NTR-EMT axis may play a central role in glioma tumorigenesis. PMID:25527128

  18. Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Wen-hai FAN; Yi HOU; Fan-kai MENG; Xiao-fei WANG; Yi-nan LUO; Peng-fei GE

    2011-01-01

    Aim: Proteasome inhibitors have been found to suppress gtioma cell proliferation and induce apoptosis, but the mechanisms are not fully elucidated. In this study we investigated the mechanisms underlying the apoptosis induced by the proteasome inhibitor MG-132 in glioma cells.Methods: C6 glioma cells were used. MTF assay was used to analyze cell proliferation. Proteasome activity was assayed using Succi-nyI-LLVY-AMC, and intracellular ROS level was evaluated with the redox-sensitive dye DCFH-DA. Apoptosis was detected using fluores-cence and transmission electron microscopy as well as flow cytometry. The expression of apoptosis-related proteins was investigated using Western blot analysis.Results: MG-132 inhibited C6 glioma cell proliferation in a time- and dose-dependent manner (the IC value at 24 h was 18.5 μmol/L). MG-132 (18.5 μmol/L) suppressed the proteasome activity by about 70% at 3 h. It induced apoptosis via down-regulation of antiapop-totic proteins Bcl-2 and XlAP0 up-regulation of pro-apoptotic protein Bax and caspase-3, and production of cleaved C-terminal 85 kDa PARP). It also caused a more than 5-fold increase of reactive oxygen species. Tiron (1 mmol/L) effectively blocked oxidative stress induced by MG-132 (18.5 pmol/L), attenuated proliferation inhibition and apoptosis in C6 glioma cells, and reversed the expression pattern of apoptosis-related proteins.Conclusion: MG-132 induced apoptosis of C6 glioma cells via the oxidative stress.

  19. Investigating effect of fusion gene therapy by MR diffusion-weighted imaging in a rat C6 glioma model%融合基因治疗大鼠C6胶质瘤的MR扩散加权成像研究

    Institute of Scientific and Technical Information of China (English)

    沈慧聪; 赵炜疆; 高培毅; 戴建平; 魏新华; 王建交; 李少武; 马军; 艾林; 刘福生; 柴奇

    2008-01-01

    Objective To evaluate the use of diffusion-weighted imaging(DWI)for early detection of tumor response to Angiostatin-Endostatin(Statin-AE)fusion gene therapy in a rat C6 glioma model.Methods Fifty male wistar rats with C6 tumor cells implanted into the striatum were examined by a 3.0T MR scanner,then the rats beating tmors were divided into two groups,treatment group and control group.Rats in the treatment group received 107 plaque forming unit(pfu)recombinant herps simplex viral (R-HSV)mediated Statin-AE fusion gene therapy on day 7,and then the tumors were conformed on MRI.Conventional MR and DWI examination were acquired on 1,2,3 weeks after implantation with a 5-inch surface coil.Two(1 w),eight(2 w)and all the residual rats(3 w)of each group were sacrificed to perform the histopathological examination after each MBI examination.Pretreatment and post treatment tumor volulnes and apparent diffusion coefficient(ADC)values were calculated.Rank sum test and t test were employed for statistical analysis.Results On MRI,43 rats demonstrated tumors on day 7 with a successful rate of 86%,On week 2,the tumor volumes of the controh and treatment group were 90.6 and 91.64 mm3,with no significant difference(Z=-0.14,P>0.05).On week 3,the tumor volumes of the controls and treatment group were 156.64 and 29.64 mm3,and a significant difference was observed(Z=-3.45,P<0.01).On week 2.the ADC values of the tumor centers of the treatment group and the control group were (1.20±0.25)×10-3 and(0.99±0.08)×10-3 mm2/s,and the values of the tumor peripheral parts of the two groups were(1.00±0.25)×10-3 and(0.83±0.12)×10-3mm2/s,the ADC values of both tumor centers and peripheral parts of the treatment group were significantly higher than those of the control group (t=-0.82 and-0.46,P<0.05).On week 3,the ADC values of the tumor centers of the treatment group and the control group were(0.92±0.21)× 10-3 and(0.99±0.09)×10-3mm2/s,and the values of the tumor peripheral parts of

  20. Evaluation of radiation effects against C6 glioma in combination with vaccinia virus-p53 gene therapy

    Science.gov (United States)

    Gridley, D. S.; Andres, M. L.; Li, J.; Timiryasova, T.; Chen, B.; Fodor, I.; Nelson, G. A. (Principal Investigator)

    1998-01-01

    The primary objective of this study was to evaluate the antitumor effects of recombinant vaccinia virus-p53 (rVV-p53) in combination with radiation therapy against the C6 rat glioma, a p53 deficient tumor that is relatively radioresistant. VV-LIVP, the parental virus (Lister strain), was used as a control. Localized treatment of subcutaneous C6 tumors in athymic mice with either rVV-p53 or VV-LIVP together with tumor irradiation resulted in low tumor incidence and significantly slower tumor progression compared to the agents given as single modalities. Assays of blood and spleen indicated that immune system activation may account, at least partly, for the enhance tumor inhibition seen with combined treatment. No overt signs of treatment-related toxicity were noted.

  1. Wuweizisu C from Schisandra chinensis decreases membrane potential in C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Young-whan CHOI; Kyeok KIM; Ji-yeong JO; Hyo-lim KIM; You-jin LEE; Woo-jung SHIN; Santosh J SACKET; Mijin HAN; Dong-soon IM

    2008-01-01

    Aim:To study the effects of dibenzocyclooctadiene lignans isolated from Schi-sandra chinensis, such as wuweizisu C, gomisin N, gomisin A, and schisandrin, on the membrane potential in C6 glioma cells. Methods: The membrane po-tential was estimated by measuring the fluorescence change in DiBAC-loaded glioma cells. Results: Wuweizisu C decreased the membrane potential in a concentration-dependent manner. Gomisin N and gomisin A, however, showed differential modulation and no change was induced by schisandrin or dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate, a syn-thetic drug derived from dibenzocyclooctadiene lignans. We found no involve-ment of Gi/o proteins, phospholipase C, and extracellular Na+ on the wuweizisu C-indueed decrease of the membrane potential. Wuweizisu C by itself did not change the intracellular Ca2+ [Ca2+]I concentration, but decreased the ATP-indu-ted Ca2+ increase in C6 glioma cells. The 4 lignans at all concentrations used in this study did not induce any effect on cell viability. Furthermore, we found a similar decrease of the membrane potential by wuweizisu C in PC12 neuronal cells. Conclusion: Our results suggest that the decrease in the membrane poten-tial and the modulation of [Ca2+]I concentration by wuweizisu C could be impor-tant action mechanisms ofwuweizisu C.

  2. Cas Ilgly Induces Apoptosis in Glioma C6 Cells In Vitro and In Vivo through Caspase-Dependent and Caspase-Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2005-06-01

    Full Text Available In this work, we investigated the effects of Casiopeina Il-gly (Cas ILgly—a new copper compound exhibiting antineoplastic activity—on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas Ilgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas Ilgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-l-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas Ilgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas Ilgly. ROS formation induced by Cas Ilgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas Ilgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas Ilgly for the treatment of malignant gliomas.

  3. In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model

    Directory of Open Access Journals (Sweden)

    Meurer Luise

    2006-09-01

    Full Text Available Abstract Background ATP is an important signalling molecule in the peripheral and central nervous system. Both glioma growth and tumor resection induces cell death, thus liberating nucleotides to the extracellular medium. Nucleotides are hydrolyzed very slowly by gliomas when compared with astrocytes and induce neuronal cell death and glioma proliferation. The objective of the present study was to test the involvement of extracellular ATP in glioblastoma growth in a rat glioma model. Methods To deplete the extracellular ATP, the enzyme apyrase was tested on the treatment of gliomas implanted in the rats CNS. One million glioma C6 cells in 3 microliters of DMEM/FCS were injected in the right striata of male Wistar rats, 250–270 g. After 20 days, the rats were decapitated and the brain sectioning and stained with hematoxylin and eosine. We performed immunohistochemical experiments with Ki67, CD31 and VEGF. Total RNA was isolated from cultured glioma C6 cells and the cDNA was analyzed by Real Time-PCR with primers for the NTPDase family. Results C6 glioma cells effectively have a low expression of all NTPDases investigated, in comparison with normal astrocytes. The implanted glioma co-injected with apyrase had a significant reduction in the tumor size (p Conclusion These results indicate that the participation of extracellular ATP and the ecto-nucleotidases may be associated with the development of this type of brain tumor in an in vivo glioma model.

  4. Curcumin delivery by methoxy polyethylene glycol-poly(caprolactone) nanoparticles inhibits the growth of C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Junfei Shao; Donghui Zheng; Zhifeng Jiang; Huae Xu; Yong Hu; Xiaolin Li; Xiaowei Lu

    2011-01-01

    As a potential anticancer agent, curcumin (Cum) has been reported for its chemopreventive and chemotherapeutic activity in a series of cancers through influencing cell cycle arrest, differentiation, apoptosis, etc. Therefore, the potential activity against various cancers of Cure raises the possibility of its application as a novel model drug in nanopartiele-based delivery systems. The current study reported a spherical core-shell structure curcumin-loaded nanoparticle (Cum-np) formed by amphllic methoxy polyethylene glycolpoly(caprolactone) (mPEG-PCL) block copolymers. Characterization tests indicated that Cum was incorporated into mPEG-PCL-based nanoparticles with high encapsulation efficiency due to its lipophilicity. The incorporated Cum could be released from Cum-np in a sustained manner. Cum was effectively transported into the cells by nanoparticles through endocytosis and localized around the nuclei in the cytoplasms. In vitro studies proved that the cytotoxicity of Cum-np would be pro-apoptosis effect against rat C6 glioma cell line in a dose-dependent manner. The present results suggest that Cum-np could be a potential useful chemotherapeutic formulation for malignant glioma therapy. Moreover, the development of traditional Chinese medicine with nanoscale drug formation warrants more intensive research for its clinical applications.

  5. Topographical control of cell-cell interaction in C6 glioma by nanodot arrays

    Science.gov (United States)

    Lee, Chia-Hui; Cheng, Ya-Wen; Huang, G. Steven

    2014-05-01

    Nanotopography modulates the physiological behavior of cells and cell-cell interactions, but the manner of communication remains unclear. Cell networking (syncytium) of astroglia provides the optimal microenvironment for communication of the nervous system. C6 glioma cells were seeded on nanodot arrays with dot diameters ranging from 10 to 200 nm. Cell viability, morphology, cytoskeleton, and adhesion showed optimal cell growth on 50-nm nanodots if sufficient incubation was allowed. In particular, the astrocytic syncytium level maximized at 50 nm. The gap junction protein Cx43 showed size-dependent and time-dependent transport from the nucleus to the cell membrane. The transport efficiency was greatly enhanced by incubation on 50-nm nanodots. In summary, nanotopography is capable of modulating cell behavior and influencing the cell-cell interactions of astrocytes. By fine-tuning the nanoenvironment, it may be possible to regulate cell-cell communications and optimize the biocompatibility of neural implants.

  6. Effects of antigliomatin from the scorpion venom of Buthus martensii Karsch on chloride channels on C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Zan Wang; Mingxian Li; Hongmei Meng; Min Huang; Weihong Lin; Li Cui; Shao Wang

    2011-01-01

    Using whole-cell patch-clamp recordings, the effects of antigliomatin were observed on chloride channels on C6 glioma cells cultured in vitro. Antigliomatin was extracted from the venom of the scorpion Buthus martensii Karsch. Chloride channels are closed under normal osmotic pressure. When osmotic pressure was reduced to 120, 110 and 100 mV, the cell volume enlarged, chloride channels opened, and the chloride channel current increased. Three minutes after antigliomatin treatment, the chloride channel current decreased in a dose-dependent manner. These results show that antigliomatin extracted from the venom of the scorpion Buthus martensii Karsch diminishes chloride channel currents on C6 glioma cells.

  7. Stable EGFP Gene Expression in C6 Glioma Cell Line after Transduction with HIV-1-based Lentiviral Vector

    Institute of Scientific and Technical Information of China (English)

    JIN Gui-shan; LIU Fu-sheng; CHAI Qi; WANG Jian-jao; LI Jun-hua

    2008-01-01

    Objective:To establish a stable C6/EGFP glioma cell line for studies on glioma. Methods:The C6 glioma cell line was transfected with the human immunodeficiency virus type Ⅰ(HIV-1)based lentivirus vector containing two enhancer-promoters CMV and EF1α.Enhanced green fluorescent protein(EGFP)-positive C6 cells were sorted out by fluorescence-activated cell sort.Expression of EGFP was observed by fluorescent microscopy.EGFP gene in C6 genome was assessed by Polymerase chain reaction(PCR)and DNA sequencing.Original and transfected cells were compared biologically and cytomorphologically. Results:Lentivirus vector transfection produced up to 40% EGFP-positive cells.After fluorescence-activated cell sort selection,a pure cell line C6/EGFP was established.PCR and DNA sequencing revealed integration of EGFP gene in C6 cell genome.Analysis of cell characteristics revealed no difference between transfected and original cells. Conclusion:A C6/EGFP cell line expressing EGFP as a marker is established,in which the EGFP gene is integrated into the genome.This cell line can be served as a promising tool for further basic research and gene therapy studies.

  8. Hydrophobic fractal surface from glycerol tripalmitate and the effects on C6 glioma cell growth.

    Science.gov (United States)

    Zhang, Shanshan; Chen, Xuerui; Yu, Jing; Hong, Biyuan; Lei, Qunfang; Fang, Wenjun

    2016-06-01

    To provide a biomimic environment for glial cell culture, glycerol tripalmitate (PPP) has been used as a raw material to prepare fractal surfaces with different degrees of hydrophobicity. The spontaneous formation of the hydrophobic fractal surfaces was monitored by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The surface morphologies were observed by a scanning electron microscope (SEM), and then the fractal dimension (FD) values of the surfaces were determined with the box-counting method. C6 glioma cells were cultured and compared on different hydrophobic PPP surfaces and poly-L-lysine (PLL)-coated surface. The cell numbers as a function of incubation time on different surfaces during the cell proliferation process were measured, and the cell morphologies were observed under a fluorescence microscope. Influences of hydrophobic fractal surfaces on the cell number and morphology were analyzed. The experimental results show that the cell proliferation rates decrease while the cell morphology complexities increase with the growth of the fractal dimensions of the PPP surfaces. PMID:26970826

  9. GDNF剪接体α-pro-GDNF在大鼠C6胶质瘤细胞中的表达及其意义%The expression and significaceof GDNF splice variant α-pro-GDNF in rat C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    魏赫; 李亨; 雷宇; 于如同; 虞正权; 高殿帅

    2016-01-01

    目的:探讨大鼠C6胶质瘤细胞中GDNF选择性剪接体的表达情况及意义.方法:通过检测C6胶质瘤细胞中GDNF基因△78位点剪接体α-pro-GDNF mRNA和β-pro-GDNF mRNA及其受体蛋白GFRα1、GFRα2、Ret和NCAM表达,结合介导肿瘤迁移相关蛋白RhoA、Cdc42、Rac1的表达情况,分析其相关关系.结果:(1)C6胶质瘤细胞中,可以检测到α-pro-GDNF和β-pro-GDNF的mRNA表达,且α-pro-GDNF mRNA表达水平比β-pro-GDNF高;与星形胶质细胞相比,α-pro-GDNF mRNA表达水平的增高趋势较β-pro-GDNF明显;(2)C6胶质瘤细胞中RhoA mRNA表达水平与α-pro-GDNF mRNA表达水平成显著正相关(R2=0.699,P<0.05),Cdc 42 mRNA表达水平与α-pro-GDNF mRNA表达水平呈显著正相关(R2=0.803,P<0.05),与β-pro-GDNF mRNA表达相关性不显著.结论:C6胶质瘤中α-pro-GDNF具有优先表达,可能与胶质瘤细胞的迁移具有相关性.

  10. Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma

    OpenAIRE

    Varadharajan Thiyagarajan; May-Jywan Tsai; Ching-Feng Weng

    2015-01-01

    Focal adhesion kinase (FAK) is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma ce...

  11. Theraputic Effect of Lipid-Coated Microbubble Carrying Taxol on Rat with Intracranial C6 Glioma%脂膜微囊承载紫杉醇靶向性治疗大鼠颅内C6胶质瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    宫崧峰; 李新钢

    2009-01-01

    目的:研究脂膜微囊承载紫杉醇靶向性治疗大鼠颅内C6胶质瘤的机制.方法:建立大鼠C6胶质瘤动物模型12只,成瘤大鼠分为四组;注射LCM-Taxol组,注射LCM组.注射Taxol组及载瘤动物组,每组取一只在最后一次尾静脉注射相应药物后处死,获取大鼠脑组织标本,进行常规HE染色,油红O染色.观察LCM在肿瘤位点分布的特点;同时观察不同处理组大鼠的生存期.结果:油红O染色显示注射LCM-Taxol组,肿瘤区域有LCM聚集,胶质瘤明显坏死;而注射LCM组,肿瘤区域有LCM出现,但肿瘤区域无明显坏死;注射TAXOL组及载瘤动物组肿瘤区域无明显坏死;生存期结果示Taxol-LCM组生存期明显长于注射LCM组和注射Taxol组及载瘤动物组,而注射LCM组、注射Taxol组、单纯载瘤动物组生存期差异不明显.结论:LCM-Taxol可以承载药物靶向性聚集于颅内胶质瘤区域,并起到杀伤肿瘤的作用,明显延长了大鼠的生存期;而注射LCM组、注射Taxol组未能明显延长载瘤大鼠的生存期.

  12. Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma.

    Science.gov (United States)

    Thiyagarajan, Varadharajan; Tsai, May-Jywan; Weng, Ching-Feng

    2015-01-01

    Focal adhesion kinase (FAK) is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma cell lines, which exhibits sub G1 phase cell cycle, and further induction of apoptosis is confirmed by a TUNEL assay. Antroquinonol decreases anti-apoptotic proteins, whereas it increases p53 and pro-apoptotic proteins. Alterations of cell morphology are observed after treatment by atomic force microscopy. Molecular docking results reveal that antroquinonol has an H-bond with the Arg 86 residue of FAK. The protein levels of Src, pSrc, FAK, pFAK, Rac1, and cdc42 are decreased after antroquinonol treatment. Additionally, antroquinonol also regulates the expression of epithelial to mesenchymal transition (EMT) proteins. Furthermore, antroquinonol suppresses the C6 glioma growth in xenograft studies. Together, these results suggest that antroquinonol is a potential anti-tumorigenesis and anti-metastasis inhibitor of FAK. PMID:26517117

  13. Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma.

    Directory of Open Access Journals (Sweden)

    Varadharajan Thiyagarajan

    Full Text Available Focal adhesion kinase (FAK is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma cell lines, which exhibits sub G1 phase cell cycle, and further induction of apoptosis is confirmed by a TUNEL assay. Antroquinonol decreases anti-apoptotic proteins, whereas it increases p53 and pro-apoptotic proteins. Alterations of cell morphology are observed after treatment by atomic force microscopy. Molecular docking results reveal that antroquinonol has an H-bond with the Arg 86 residue of FAK. The protein levels of Src, pSrc, FAK, pFAK, Rac1, and cdc42 are decreased after antroquinonol treatment. Additionally, antroquinonol also regulates the expression of epithelial to mesenchymal transition (EMT proteins. Furthermore, antroquinonol suppresses the C6 glioma growth in xenograft studies. Together, these results suggest that antroquinonol is a potential anti-tumorigenesis and anti-metastasis inhibitor of FAK.

  14. The effect of yacon (Samallanthus sonchifolius) ethanol extract on cell proliferation and migration of C6 glioma cells stimulated with fetal bovine serum

    OpenAIRE

    Lee, Kang Pa; Choi, Nan Hee; Kim, Jin Teak; Park, In-Sik

    2015-01-01

    BACKGROUND/OBJECTIVES Yacon (Samallanthus sonchifolius), a common edible plant grown throughout the world, is well known for its antidiabetic properties. It is also known to have several other pharmacological properties including anti-inflammatory, anti-oxidant, anti-allergic, and anti-cancer effects. To date, the effect of yacon on gliomas has not been studied. In this study, we investigated the effects of yacon on the migration and proliferation of C6 glioma cells stimulated by fetal bovine...

  15. Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex virus thymidine kinase suicide gene

    International Nuclear Information System (INIS)

    The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase (HSVtk) gene was constructed. The vector was transfected into the packaging cell line PG13. It was shown that individual transfected cells differ in the production of recombinant retrovirus and in their susceptibility to be killed by ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduced the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to influence subcutaneous and intracerebral tumors developed after injection of C6 rat glioma cells with subsequent injection of HSVtk retrovirus producing cells. (author)

  16. 三苯氧胺对胶质瘤C6细胞垂体瘤转化基因表达及肿瘤生长影响的体内研究%Effect of tamoxifen on pituitary tumor transforming gene expression in C6 cell and tumor growth of glioma in vivo

    Institute of Scientific and Technical Information of China (English)

    滕达; 王婷; 戴如飞

    2008-01-01

    目的 探讨体内三苯氧胺对胶质瘤C6细胞垂体瘤转化基因(PTTG)表达及细胞生长的影响.方法 建立SD大鼠C6胶质瘤移植动物模型,将32只荷瘤裸鼠随机分为4组:空白对照组、高(2 mg·kg-1·d-1)、中(0.2 mg·kg-1·d-1)、低(0.02 mg·kg-1·d-1)剂量三苯氧胺作用组,共给药20 d.空白对照组给等量的生理盐水.定期观察肿瘤生长情况,测量肿瘤体积,计算抑瘤率.处死全部动物模型,剔出肿瘤,逆转录-聚合酶链反应(RT-PCR)检测FITG mRNA表达.结果 与空白对照组相比,各组三苯氧胺均能抑制肿瘤生长,其体积抑瘤率分别为47.6%、35.5%、21.2%,各组间差异均有统计学意义(P<0.05);FITG mRNA的表达在低、中、高剂量组均降低,各组间差异均有统计学意义(P<0.05).结论 三苯氧胺能以量效的方式抑制胶质瘤PTTG的表达和肿瘤生长,本研究为临床应用三苯氧胺治疗胶质瘤提供了理论基础.%Objective To investigate the effect of tamoxifen on pituitary tumor transforming gene ex-pression in C6 cell and tumor growth of glioma in vivo. Methods Animal models were established on 32 SD rats with C6 cells of glioma. The rats bearing with C6 glioma were divided into 4 groups randomly, which were treated without tamoxifen or with different doses of tamoxifen(0. 02 mg · kg-1 · d-1, 0. 2 mg · kg-1 · d-1, 2mg · kg-1 · d-1) once a day for 20 days. The dimension of tumors were measured, the tumor inhibition rates were caculated, and living state of the rats were observed. The expression of PTTG mRNA was detected by RTPCR. Results All kinds of doses of tamoxifen could inhibit the tumors growth in rats with C6 glioma, and the tumor volume were reduced by 47.6%, 35.5% and 21.2% in the high-, middle-and low-dose groups respec-tively, there were significantly differences among the 4 groups ( P < 0. 05 ). Low-, middle- and high- dose of tamoxifen all could inhibit the expression of PTTG mRNA, and there were significantly

  17. Induction of cell cycle arrest at G1 and S phases and cAMP-dependent differentiation in C6 glioma by low concentration of cycloheximide

    Directory of Open Access Journals (Sweden)

    Zhang Samuel S

    2010-12-01

    Full Text Available Abstract Background Differentiation therapy has been shown effective in treatment of several types of cancer cells and may prove to be effective in treatment of glioblastoma multiforme, the most common and most aggressive primary brain tumor. Although extensively used as a reagent to inhibit protein synthesis in mammalian cells, whether cycloheximide treatment leads to glioma cell differentiation has not been reported. Methods C6 glioma cell was treated with or without cycloheximide at low concentrations (0.5-1 μg/ml for 1, 2 and 3 days. Cell proliferation rate was assessed by direct cell counting and colony formation assays. Apoptosis was assessed by Hoechst 33258 staining and FACS analysis. Changes in several cell cycle regulators such as Cyclins D1 and E, PCNA and Ki67, and several apoptosis-related regulators such as p53, p-JNK, p-AKT, and PARP were determined by Western blot analysis. C6 glioma differentiation was determined by morphological characterization, immunostaining and Western blot analysis on upregulation of GFAP and o p-STAT3 expression, and upregulation of intracellular cAMP. Results Treatment of C6 cell with low concentration of cycloheximide inhibited cell proliferation and depleted cells at both G2 and M phases, suggesting blockade at G1 and S phases. While no cell death was observed, cells underwent profound morphological transformation that indicated cell differentiation. Western blotting and immunostaining analyses further indicated that changes in expression of several cell cycle regulators and the differentiation marker GFAP were accompanied with cycloheximide-induced cell cycle arrest and cell differentiation. Increase in intracellular cAMP, a known promoter for C6 cell differentiation, was found to be elevated and required for cycloheximide-promoted C6 cell differentiation. Conclusion Our results suggest that partial inhibition of protein synthesis in C6 glioma by low concentration of cycloheximide induces cell cycle

  18. Experimental Study on Treatment of Glioma by Embyonic Neural Stem Cell Transplnation in Rats

    Institute of Scientific and Technical Information of China (English)

    LUO Jie; ZHANG Li; TU Hanjun; HU Juntao; LI Xinjian; LI Dongsheng; LEI Ting

    2007-01-01

    The neural stem cells in Wistar rats were cultured in vitro, purified, and transplanted into C6 glioma model in order to observe their biological characters and provide a basic foundation for treatment of neurological diseases by neural stem cell transplantation. The cells at hippocampal area from gestation 15-day rats were cultured in vitro, and frozen and preserved in liquid nitrogen. C6 tu-mor-bearing models (n=25) and neural stem cells transplantation models (n=35) were established.When the tumor grew to 3 to 4 weeks,5 rats in each group were randomly selected for MRI examina-tion. At different intervals, the rats were perfused and sampled for HE staining, GFAP and BrdU im-munohistochemical staining. The results showed that after resuscitation of neural stem cells at 1-4 passages, the cell viability was 40%-63% with the difference being not significant. The cells could proliferate, passage, and most cells transplanted into glioma model survived. The mean survival time in neural stem cell transplantation group and control was 4.28 and 3.88 weeks respectively, and the average tumor size in the former was smaller than in the latter. It was concluded that embryonic neu- ral stem cells in rats could proliferate and differentiate, and after resuscitation the biological charac- teristic and viability of the cells were not influenced. Neural stem cells had inhibitory effects on the growth of glioma cells and could prolong the survival of rat model.

  19. Particulate Matter Facilitates C6 Glioma Cells Activation and the Release of Inflammatory Factors Through MAPK and JAK2/STAT3 Pathways.

    Science.gov (United States)

    Li, Ting; Zhao, Jianya; Ge, Jianbin; Yang, Jianbin; Song, Xinjian; Wang, Cheng; Mao, Jiamin; Zhang, Yan; Zou, Ye; Liu, Yanmei; Chen, Gang

    2016-08-01

    It has been widely accepted that astrocytes, play a role in regulating almost every physiological system. In the present study, we investigated the role of particulate matter (PM) in regulating activation of astrocytes. The glial cell strain C6 was cloned from a rat glioma which was induced by N-nitrosomethylurea. The C6 cells were plated at a density of 5 × 10(6) cells/10 cm diameter dish and incubated with different concentrations (0, 12, 25, 50, 100, 200, and 400 μg/mL) of PM for 24 h and different time (0, 1, 3, 6, 8,12, and 24 h) with 100 μg/mL at 37 °C. The study revealed that PM stimulated the expression of inducible nitric oxide synthase (iNOS) as well as the production of IL-1β in a dose- and time-dependent manner. Furthermore, activation of JAK2/STAT3 and p38/JNK/ERK MAPKs was found in astrocytes following PM treatment. Blockage of JAK and p38/JNK/ERK MAPKs with their specific inhibitors, AG490, SB202190, SP600125 and U0126 significantly reduced PM-induced iNOS expression and IL-1β production. In addition, it was demonstrated that inhibition of p38, JNK and JAK prevented STAT3 tyrosine phosphorylation induced by PM, while blocking ERK did not. MAPKs (p38 and JNK) could regulate tyrosine STAT3 phosphorylation, which suggested that the JAK2/STAT3 pathway might be the downstream of p38/JNK MAPK pathways. PMID:27068033

  20. Fibroblast growth factor-2 up-regulates the expression of nestin through the Ras–Raf–ERK–Sp1 signaling axis in C6 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kai-Wei [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China); Huang, Yuan-Li [Department of Biotechnology, College of Health Science, Asia University, Taichung 413, Taiwan (China); Wong, Zong-Ruei; Su, Peng-Han [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China); Huang, Bu-Miin [Department of Cell Biology and Anatomy, National Cheng-Kung University, Tainan 701, Taiwan (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei 106, Taiwan (China); Technology Commons, College of Life Science, National Taiwan University, Taipei 106, Taiwan (China); Yang, Hsi-Yuan, E-mail: hyhy@ntu.edu.tw [Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)

    2013-05-17

    Highlights: •Nestin expression in C6 glioma cells is induced by FGF-2. •Nestin expression is induced by FGF-2 via de novo RNA and protein synthesis. •The FGFR inhibitor SU5402 blocks the FGF-2-induced nestin expression. •The mRNA of FGFR1 and 3 are detected in C6 glioma cells. •Ras–Raf–ERK–Sp1 signaling pathway is responsibe for FGF-2-induced nestin expression. -- Abstract: Nestin is a 240-kDa intermediate filament protein expressed mainly in neural and myogenic stem cells. Although a substantial number of studies have focused on the expression of nestin during development of the central nervous system, little is known about the factors that induce and regulate its expression. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and stimulates the proliferation and differentiation of a subset of nestin-expressing cells, including neural progenitor cells, glial precursor cells, and smooth muscle cells. To assess whether FGF-2 is a potent factor that induces the expression of nestin, C6 glioma cells were used. The results showed that nestin expression was up-regulated by FGF-2 via de novo RNA and protein synthesis. Our RT-PCR results showed that C6 glioma cells express FGFR1/3, and FGFRs is required for FGF-2-induced nestin expression. Further signaling analysis also revealed that FGF-2-induced nestin expression is mediated through FGFR–MAPK–ERK signaling axis and the transcriptional factor Sp1. These findings provide new insight into the regulation of nestin in glial system and enable the further studies on the function of nestin in glial cells.

  1. DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum (ER) stress.

    Science.gov (United States)

    Zhang, Lan; Tong, Xupeng; Zhang, Jin; Huang, Jian; Wang, Jinhui

    2015-06-01

    2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin (named DAW22), a sesquiterpene coumarin isolated from the roots of Ferula ferulaeoides (Steud.) Korov., has been reported to bear anti-proliferative activities toward different types of cancer cells. In this study, we demonstrated that DAW22 induced apoptosis in C6 glioma cells. Subsequently, we found that DAW22-induced apoptosis in C6 glioma cells occurred via the mitochondria-mediated and death-receptor pathways. Moreover, we found a massive cytoplasmic vacuolization, a dramatic change of endoplasmic reticulum (ER), up-regulation of CHOP and cleavage of caspase-12, suggesting that DAW22-induced apoptosis is involved in ER stress. In addition, we revealed that DAW22 treatment induced the activation of PERK, ATF6α and IRE1α. We further found that knockdown of CHOP affected DAW22-induced apoptosis, and DAW22-stimulated down-regulation of Bcl-2, caspase-8 activation and PARP cleavage were inhibited. Taken together, these results demonstrate that DAW22 induces apoptosis by ER stress and mitochondrial/death-receptor pathways, which may provide a new clue for exploiting this compound as a potential anti-neoplastic drug in future glioma cancer therapy. PMID:25776007

  2. Suppression of intracranial glioma tumorigenesis with vascular endothelial growth factor antisense oligonucleotide in rats

    Institute of Scientific and Technical Information of China (English)

    李维方; 张光霁; 朱诚; 金由辛; 卢亦成

    2003-01-01

    Objective: To observe the inhibition of intracranial glioma tumorigenesis by vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotide (ODN) in rats. Methods: Totally 20 μl Hank's liquid containing 1×106 C6 glioma cells was seeded into rat right caudate putamen in high-flow microinfusion with stereotactic technique. VEGF antisense ODN was simultaneously used with glioma cell. Each rat of the treated groupⅠ and the treated group Ⅱ was treated with 1 000 μmol/L VEGF antisense ODN. Each rat of the treated group Ⅲ and the treated group Ⅳ was treated with 2 000 μmol/L VEGF antisense ODN. The experimental periods of the treated group Ⅰ, the treated group Ⅲ and the control group Ⅰ were 2 weeks, those of the treated group Ⅱ, the treated group Ⅳ and the control group Ⅱ were 3 weeks. Before sacrifice, MRI was performed on each rat. Tumor magnitude and pathologic examination were detected after samples were dissected. Results: The survival state of all treated rats was better, and that of the control rats was in severe danger. The tumor volumes of the treated group Ⅰ and the treated group Ⅱ were remarkably lessened. Tumor tissue could not be found macroscopically in the brain samples of the treated group Ⅲ and the treated group Ⅳ, but tumor nest could be found with microscopy. Tumors of the treated groupⅠand the treated group Ⅱ had weak expressions of VEGF mRNA and VEGF, while normal brains and the samples of the treated group Ⅲ and the treated group Ⅳ had negative expressions, but tumors of the control groups had strong expressions. Conclusion: VEGF antisense ODN used early in situ can suppress angiogenesis and growth of rat intracranial glioma to retard tumorigenesis.

  3. Concurrent Chemotherapy of Malignant Glioma in Rats by Using Multidrug-Loaded Biodegradable Nanofibrous Membranes

    Science.gov (United States)

    Tseng, Yuan-Yun; Huang, Yin-Chen; Yang, Tao-Chieh; Yang, Shun-Tai; Liu, Shou-Cheng; Chang, Tzu-Min; Kau, Yi-Chuan; Liu, Shih-Jung

    2016-07-01

    Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma.

  4. Applying stereotactic technique to establish C6 brain glioma models for laser interstitial thermotherapy research%立体定向技术建立大鼠脑胶质瘤激光间质热疗模型

    Institute of Scientific and Technical Information of China (English)

    石键; 张宏; 卜文良; 陈鹏; 赵洪洋; 傅伟明

    2010-01-01

    Objective C6 brain glioma models were established with stereotactic technique to study laser interstitial thermotherapy (LITT) in SD rats C6 intracranial glioma models. Methods The C6 cells cultured in vitro were stereotaxically implanted into the right caudate nucleus of SD rat brain (20 μl free serum DMEM for one rat which concentration was 1×10~(11)/L). The following step was to judge MRI scan. Tumor was confirmed with staining of ⅧR, GFAP and S - 100 immunohistochemistry. After MRI scanning and correction of tumor location, the models were divided into groups according treating time and laser power from 2 to 10 W. Semiconductor laser optical fibers were inserted in tumors for LITT, simultaneously cortex's temperature conducted from center target was measured by ThermaCAM S65 type infrared thermograph, and (or) deep tissue's temperature around target was measured by thermocouple. Results Inoculated with optimized stereotactic technique, rat C6 gliomas resembled histopathological features of human glioma. This kind of model was a more reliant and reproducible one, with 96. 67% yield of intracranial tumor as well as no extracranial growth extension. The difference between cortex temperature conducted from center target and deep tissue temperature around target had no statistical significance (P>0.05). Conclusion A rat C6 brain glioma model resembles histopathological features of human glioma, as a perfect model to study LITT of glioma. Infrared thermograph technique to measure temperature conveniently, effectually, non invasive and the data could be treated by software in LITT research. Combining thermocouple to measure deep tissue temperature, it would have a better effect.%目的 利用立体定向技术接种SD大鼠C6脑胶质瘤,并建立脑胶质瘤激光间质热疗(LITT)模型.方法 采用立体定向技术,将体外培养并调制的C6胶质瘤细胞悬液20μl(浓度1×10~(11)/L)接种于SD大鼠右侧尾状核区.分时段MRI检查;做组织病理

  5. Concurrent Chemotherapy of Malignant Glioma in Rats by Using Multidrug-Loaded Biodegradable Nanofibrous Membranes

    Science.gov (United States)

    Tseng, Yuan-Yun; Huang, Yin-Chen; Yang, Tao-Chieh; Yang, Shun-Tai; Liu, Shou-Cheng; Chang, Tzu-Min; Kau, Yi-Chuan; Liu, Shih-Jung

    2016-07-01

    Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P < 0.001). Furthermore, the results suggested that the BIC/PLGA nanofibers reduced the malignancy of C6 glioma. The experimental findings indicate that the multianticancer drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma.

  6. Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

    OpenAIRE

    Shih-Hung Yang; Seu-Mei Wang; Jhih-Pu Syu; Ying Chen; Sheng-De Wang; Yu-Sen Peng; Meng-Fai Kuo; Hsiu-Ni Kung

    2014-01-01

    Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was a...

  7. Gamma knife treatment of rat glioma Influences of irradiation dose on apoptosis and necrosis

    Institute of Scientific and Technical Information of China (English)

    Peng Wang; Mianshun Pan; Xinggen Fang

    2008-01-01

    BACKGROUND: Apoptosis and necrosis are cellular death mechanisms that are induced in glioma cells following gamma knife irradiation. Increased apoptosis is essential for maintaining and enhancing treatment efficacy.OBJECTIVE: To observe apoptotic and necrotic mechanisms of rat glioma models induced by gamma knife treatment and to analyze the influences of irradiation doses on apoptosis and necrosis. DESIGN: Controlled animal experiment. SETTING: Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital.MATERIALS: Eighteen female specific pathogen free Sprague Dawley rats, weighing 180-210 g and 5-6 weeks old, were purchased from the Experimental Animal Center, Medical College of Suzhou University. Rat C6 glioma cells were purchased from the cell bank of Chinese Academy of Sciences. Annexin V-FITC Reagent Kit (Bender Med System. Company, USA) and a flow cytometer (Becton Dickinson FACSCalibur) were provided.METHODS: The experiment was conducted at the Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital from December 2006 to May 2007. All rats were inoculated with C6 glioma cells, i.e., 4 μL of a C6 glioma cell suspension was injected 5 mm deep in the cortex. All rats were divided randomly into a model group, 9-Gy treatment group, and 12-Gy treatment group. There were six rats in each group.MAIN OUTCOME MEASURES: Apoptosis and necrosis of normal brain tissue and glioma were observed by Flow Cytometry one week after irradiation, and pathological changes to tumor tissue were identified by HE staining.RESULTS: Eighteen rats were initially selected for the study: two rats from the model and 12-Gy treatment groups died from accidental anesthesia. The remaining 16 rats were included in the final result analysis. Cellular apoptosis and necrosis: apoptosis and necrosis were significantly increased in the treatment groups after gamma knife irradiation, compared to the model group (P < 0

  8. Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

    Directory of Open Access Journals (Sweden)

    Shih-Hung Yang

    2014-01-01

    Full Text Available Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND, a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

  9. Exposure of C6 glioma cells to Pb(II) increases the phosphorylation of p38{sup MAPK} and JNK1/2 but not of ERK1/2

    Energy Technology Data Exchange (ETDEWEB)

    Posser, Thais; Rossi, Francesco M.; Oliveira, Camila S.; Leal, Rodrigo B. [Universidade Federal de Santa Catarina, Departamento de Bioquimica, Centro de Ciencias Biologicas, Florianopolis, SC (Brazil); Mendes de Aguiar, Claudia B.N.; Garcez, Ricardo C.; Trentin, Andrea G. [Universidade Federal de Santa Catarina, Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Florianopolis, SC (Brazil); Moura Neto, Vivaldo [Universidade Federal do Rio de Janeiro, Departamento de Anatomia, Centro de Ciencias da Saude, Rio de Janeiro, RJ (Brazil)

    2007-06-15

    Pb(II) is a neurotoxic pollutant that produces permanent cognitive deficits in children. Pb(II) can modulate cell signaling pathways and cell viability in a variety of cell types. However, these actions are not well demonstrated on glial cells, which represent an important target for metals into the central nervous system. The present work was undertaken to determine the ability of Pb(II) in modulating the activity of mitogen activated protein kinases (MAPKs) in cultures of C6 rat glioma cells, a useful functional model for the study of astrocytes. Additionally, cell viability was analyzed by measurement of MTT reduction. Cells were exposed to lead acetate 0.1, 1, 10 {mu}M for 24 and 48 h. MAPKs activation - in particular ERK1/2, p38{sup MAPK} and JNK1/2 - were analyzed by western blotting. Results showed that 10 {mu}M Pb(II) treatment for 24 h caused a discrete stimulation of p38{sup MAPK} phosphorylation. However, 1 and 10 {mu}M Pb(II) treatment for 48 h provoked a significant stimulation in the phosphorylation state of p38{sup MAPK} and JNK1/2. The phosphorylation state of ERK1/2 was not modified by any Pb(II) treatment. Moreover, data indicate that at 48 h treatment even 1 {mu}M Pb(II) can be cytotoxic, causing impairment on cell viability. Therefore, depending on a long incubation period, a significant concomitant activation of p38{sup MAPK} and JNK1/2 by Pb(II) took place in parallel with the impairment of C6 glioma cells viability. (orig.)

  10. THE EXPERIMENTAL ON EFFECT OF BRUCEA JAVANICA OIL EMULSION COMBINED WITH CON-VENTIONAL RADIOTHERAPY ON C6 GLIOMA CELLS%鸦胆子油乳注射液联合普通放疗对C6胶质瘤细胞作用实验研究

    Institute of Scientific and Technical Information of China (English)

    尹绍成; 董德宏; 王艳军; 王建宁; 冯娜; 石文建

    2014-01-01

    目的:探讨鸦胆子油乳注射液联合常规放疗对C6胶质瘤细胞增殖的影响。方法体外培养大鼠C6胶质瘤细胞,用MTT比色法检测抑制作用。实验分成对照组,单纯放疗组,单纯用药组,用药联合放疗组。药物与放疗联合组分先放疗后给药和先用药后放疗二种。单纯用药组及药物与放疗联合组设药物浓度设为1.25、2.5、5、10g/L四个亚组。结果MTT比色法显示常规放疗联合鸦胆子油乳注射液与单纯常规放疗相比,早期(24h)药物浓度≥2.5g/L时药物联合放疗抑制率高于单纯放疗;随作用时间延长(48h)药物联合放疗抑制率均大于普通放疗。常规放疗联合鸦胆子油乳注射液与单纯应用鸦胆子油乳注射液相比,早期(24h)药物浓度≥2.5g/L时联合放疗对C6胶质瘤细胞抑制率高于单纯用药,但随作用时间延长(48h)抑制率差异不明显。结论体外鸦胆子油乳注射液能抑制C6胶质瘤细胞增殖,并呈时间-剂量依赖性。随时间延长(48h)放疗联合鸦胆子油乳抑制作用高于常规放疗;放疗联合药物与单独用药对C6胶质瘤细胞作用无明显差异。放疗后用药好于放疗前用药。%Objective To explore the effect of brucea javanica oil emulsion combined with conventional ra-diotherapy on proliferation of C6 glioma cells .Methods Rat C6 glioma cells were cultured in vitro .MTT colorimetric assay was used to measure the inhibitory effect .All cells were divided into control group ,sin-gle radiotherapy group ,single drug group and combination group ,while combination group classified drugs before radiotherapy subgroup and drugs after radiotherapy subgroup .Drugs concentration was set at 1 .25 g/L ,2 .5g/L ,5g/L and 10g/L respectively .Results MTT demonstrated that the inhibition rates of com-bination group on C6 glioma cells were higher than them of once radiotherapy alone when drug concentra-tion was equal or

  11. Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

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    Sonja Stojković

    2016-06-01

    Full Text Available Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl-1-nitrosourea (BCNU and temozolomide (TMZ. Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.

  12. Combination Adenovirus-Mediated HSV-tk/GCV and Antisense IGF-1 Gene Therapy for Rat Glioma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate the effects of combination adenovirus-mediated HSV-tk/GCV system and antisense IGF-1 gene therapy for rat glioma and analyze the mechanism.Methods Using the recombinant adenovirus vector,GCV killing effeciency after combined gene transfer of HSV-tk and antisense IGF-1 was observed in vitro.Rat glioma was treated with HSV-tk/GCV and antisense IGF-1 and the survival rate of rats was observed.Results C6 cells transfected with tk and antisense IGF-1 gene were more sensitive to GCV than that transfected with tk gene alone.The survival of the combination gene therapy group was prolonged significantly and large amounts of CD+4,CD+8 lymphocytes were detected in the tumor tissues.Conclusion Antisense IGF-1 gene may enhance the tumor-killing effects of HSV-tk/GCV.

  13. SURFACE MULTI-FUNCTIONALIZATION OF POLY(LACTIC ACID)NANOPARTICLES AND C6 GLIOMA CELL TARGETING in vivo

    Institute of Scientific and Technical Information of China (English)

    Xu-bo Yuan; Chun-sheng Kang; Yun-hui Zhao; Ming-qi Gu; Pei-yu Pu

    2009-01-01

    Polysaccharide coated PLA nanopartieles bearing aldehyde groups were prepared by dialysis of DMSO solution of cholesterol hydrophobic-modified dextran polyaldehyde and PLA against water.The average diameter of the nanoparticles was about 160 nm,and the size distribution was nearly homogenous.The nanoparticles were functionalized simultaneously with CD71 and EGFR antibody through the Schiff's base reaction,and then radiolabeled with 99mTc.After perfused the radiolabeled nanoparticles into tumor-bearing rats through left common carotid artery,the radioactivity in liver,spleen,kidney and brain was measured by scintillation counter.The results showed that less than 2% of nanoparticles were uptaken by the brain due to the uptake of the nanoparticles by the RES system.However,the coupling of transferrin antibody on the nanoparticles facilitated the penetration of nanoparticles across the blood brain barrier,and more specially,compared with monofuctionalized and native nanoparticles,the multifunctionalization enhanced the tumor accumulation of the nanoparticles in vivo.

  14. A Truncated form of CD200 (CD200S) Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages12

    Science.gov (United States)

    Kobayashi, Kana; Yano, Hajime; Umakoshi, Akihiro; Matsumoto, Shirabe; Mise, Ayano; Funahashi, Yu; Ueno, Yoshitomo; Kamei, Yoshiaki; Takada, Yasutsugu; Kumon, Yoshiaki; Ohnishi, Takanori; Tanaka, Junya

    2016-01-01

    CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L) but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs) in C6-CD200S tumors displayed dendritic cell (DC)-like morphology with multiple processes and CD86 expression. Furthermore, CD3+, CD4+ or CD8+ cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8+ cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas. PMID:27108386

  15. A Truncated form of CD200 (CD200S Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Kana Kobayashi

    2016-04-01

    Full Text Available CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs in C6-CD200S tumors displayed dendritic cell (DC-like morphology with multiple processes and CD86 expression. Furthermore, CD3+, CD4+ or CD8+ cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8+ cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas.

  16. Cinnamon polyphenols regulate S100ß, sirtuins, and neuroactive proteins in rat C6 glioma cells

    Science.gov (United States)

    Dietary polyphenols exert neuroprotective effects in a variety of brain disorders, including Alzheimer’s disease, ischemia/stroke, and Parkinson’s disease. The protective effects of polyphenols in the brain and in neural cell cultures have been established. The role of glial cells in providing prote...

  17. Involvement of MEK-ERK1-2 pathway in the anti-oxidant response in C6 glioma cells after diesel exhaust particles exposure.

    Science.gov (United States)

    Farina, Francesca; Milani, Chiara; Botto, Laura; Lonati, Elena; Bulbarelli, Alessandra; Palestini, Paola

    2016-05-27

    Ultrafine particles translocate to the central nervous system and activate oxidative stress-related pathways. The transcription factor Nrf2 activation by ERK1-2 has been suggested as a key regulator of cellular response to oxidative stress. C6 glioma cells have been treated with different doses of diesel exhaust particles (25μg/ml, DEP25, and 50μg/ml, DEP50), for different times. Cells have been screened for oxidative stress and inflammatory markers, and for the activation of the MEK-ERK1-2 pathway. The same markers have been examined after inhibition of MEK, the kinase upstream to ERK1-2. 3h and 24h of DEP25 and DEP50 induced a significant increase in HO-1 levels. After 24h, DEP25 and DEP50 induced an increase in HO-1 and Cyp1b1 levels, while increase in OGG1 level was observed only with DEP25. After 5h of treatment with DEP25, ERK1-2 resulted phosphorylated, concomitantly with a significant increase in HO-1 levels, no changes in iNOS levels, and decreased levels of anti-oxidant enzymes. After treatment with MEK inhibitor U0126, ERK1-2 showed no activation, with a consequent decrease in Nrf2, no increase in HO-1 and a significant increase of iNOS. MEK inhibitor is able to deplete anti-oxidant enzymes. In conclusion, the MEK-ERK1-2 pathway is involved in regulating the anti-oxidant strategies to compensate the oxidative status induced by DEP treatment. PMID:27091075

  18. Effective transvascular drug delivery to glioma in rats by using a pulsed laser-induced photomechanical wave (Conference Presentation)

    Science.gov (United States)

    Akutsu, Yusuke; Sato, Shunichi; Tomiyama, Arata; Tsunoi, Yasuyuki; Kawauchi, Satoko; Mori, Kentaro; Terakawa, Mitsuhiro

    2016-03-01

    Glioma is one of the most aggressive cancers, for which efficacy of conventional chemotherapy is often limited due to the blood-tumor barrier (BTB). Thus, the development of a method for enhancing the BTB permeability is strongly desired. In this study, we applied a photomechanical wave (PMW), which was generated by the irradiation of a light-absorbing material with a nanosecond laser pulse, to transiently open the BTB in a rat intracranial glioma model using C6 cells. A tumor was grown in the both hemispheres, and a solution of Evans blue (EB), as a test drug, was injected into the tail vein. Thereafter, we applied a PMW generated at a laser fluence of 0.2 J/cm2 (averaged peak pressure, ~27 MPa), 0.4 J/cm2 (~54 MPa) or 0.6 J/cm2 (~78MPa), to one hemisphere through the cranial window, while the other hemisphere served as a control. Four hours later, the rat was perfused, and we compared intensity distributions of EB fluorescence between the both hemispheres. Intensities of EB fluorescence both in the peritumoral and tumor core regions were increased with increasing the laser fluence, but hemorrhage was observed at the highest fluence. Thus, 0.4 J/cm2 would be optimum for efficient and safe BTB opening. On the basis of fluorescence microscopy with the use of enhanced green fluorescent protein-expressing C6 cells, we confirmed that a drug was delivered into targeted glioma cells in the peritumoral region. These results show the validity of the present transvascular drug delivery method to glioma.

  19. The 9LLUC/Wistar rat glioma model is not suitable for immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Liping Yang; Jingxiang Zhao; Guihong Zhou; Yunfang Wang; Lusi Li; Hongfeng Yuan; Xue Nan; Lidong Guan; Xuetao Pei

    2012-01-01

    The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9LLUC glioma cells syngenic to Fischer 344 (F344) rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9LLUC/F344 rats, and tumor regression was found in some 9LLUC/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9LLUC/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9LLUC/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.

  20. 混合脐血间充质干细胞体外抑制C6胶质瘤细胞增殖%Study on the mechanisms of the mixed umbilical cord blood-derived mesenchymal stem cells in inhibiting proliferation of C6 glioma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    焦红亮; 王晓宁; 孙剑瑞; 李建斌; 关方霞; 杨波

    2014-01-01

    Objective Study on the mechanisms of the mixed umbilical cord blood-derived mesenchymal stem cells in inhibiting proliferation of C6 glioma cells.It provided experimental and theoretical basis for the mixed umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) treatment of C6 glioma in vivo.Methods B cell lymphoma/leukemia-2 (bcl-2) and Cysteinyl aspartate-specific protease-3 (Caspase-3) protein expression of C6 cells were analyzed by immunohistochemistry.Results The mixed UCB-MSCs inhibited the proliferation of enhanced green fluorescent protein (EGFP)-C6 glioma cells in vitro.When the E/T ratio is same,Expression of Caspase-3 in the mixed group [E/T =(5 + 5)∶1,(56 ± 5)%],but the single group is [E/T =10∶ 1,(33 ± 6) %] ; Expression of bcl-2 in mixed group is [E/T =(5 + 5) ∶ 1,(27 ± 3) %],but a single group is [E/T =10∶ 1,(46 ± 7) %].Caspase-3 protein expression tended to increase,however,bcl-2 protein expression decreased.Conclusion Compared with the single group,the mixed UCB-MSCs could inhibit proliferation of C6 cells in vitro.%目的 探讨混合脐血间充质干细胞(UCB-MSCs)体外抑制C6胶质瘤细胞增殖机制.方法 采用免疫组织化学检测C6细胞B细胞淋巴瘤/白血病-2(bcl-2)和半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3蛋白的表达,E/T(E:效应细胞即UCB-MSCs,T:靶细胞即C6细胞)=0∶1、10∶1、(5+5)∶1时,采用免疫组织化学检测C6细胞的bcl-2和Caspase-3蛋白的表达.结果 混合UCB-MSCs对C6细胞在蛋白表达上有使凋亡蛋白Caspase-3表达增高的趋势,抑凋亡蛋白bcl-2表达降低的趋势;促凋亡蛋白表达量和凋亡细胞数随E/T的比例增高而增高,呈现比例依赖关系;当E/T比例相同时,混合组[E/T=(5+5)∶1,(56±5)%]UCB-MSCs促凋亡蛋白表达量比单份组[E/T=10∶1,(33±6)%]高;抑凋亡蛋白表达量混合组[E/T=(5+5)∶1,(27±3)%],单份组[E/T=10∶1,(46±7)%].结论 与单份组比较,混合UCB-MSCs对体外C6细胞更具有抑制增殖作用.

  1. Effects of Photodynamic Therapy on the Ultrastructure of Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To study the change in ultrastructure of C6 glioma cells after photodynamic therapy (PDT), to compare morphological differences in necrosis and apoptosis before and after PDT treatment, and to evaluate the effect of photodynamic therapy on the blood brain tumor barrier (BTB) of C6 glioma. Methods The model was produced by transplanting C6 glioma cells cultured in vitro using Peterson method into the caudate nuclei of Wister rats. The experiment group received PDT for two weeks after the operation. The sub-cellular structure, blood-brain-barrier (BBB) and BTB in both groups were observed under electron microscope. Results Apoptosis in different phases and necrosis could be observed in some C6 glioma cells.Swelling occurred on the ultrastructure of cellular organs such as mitochondria and endoplasmic reticulum in most of the cells.Damage to the BTB, reduction of the number of cellular organs in endothelial cells of the capillary blood vessels, stretch of the tight junction, and enlargement of the gaps between endothelial cells were also seen in the experiment group. Meanwhile,limited impact on the normal sub-cellular structures and BBB was observed. Conclusion PDT could induce apoptosis and necrosis of C6 glioma cells due to the damage to the ultrastructure of mitochondria and endoplasmic reticulum. The weakened function of C6 glioma BTB initiated by PDT makes it possible to perform a combined therapy of PDT and chemotherapy for glioma.

  2. Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression

    Directory of Open Access Journals (Sweden)

    Colquhoun Alison

    2009-03-01

    Full Text Available Abstract Background Gamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo. Methods Established C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR. Results GLA caused a significant decrease in tumour size (75 ± 8.8% and reduced MVD by 44 ± 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF (71 ± 16% and the VEGF receptor Flt1 (57 ± 5.8% but not Flk1. Expression of ERK1/2 was also reduced by 27 ± 7.7% and 31 ± 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2 was reduced by 35 ± 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 ± 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 ± 18% while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 ± 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 ± 7.3% while p21 remained unchanged. The expression of p53 was increased (44 ± 16% by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 ± 11% of BrdU incorporation into the tumour in vivo. Conclusion Overall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein

  3. 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure influence the expression of glutamate transporter GLT-1 in C6 glioma cells via the Ca(2+) /protein kinase C pathway.

    Science.gov (United States)

    Zhao, Jianya; Zhang, Yan; Zhao, Jianmei; Wang, Cheng; Mao, Jiamin; Li, Ting; Wang, Xiaoke; Nie, Xiaoke; Jiang, Shengyang; Wu, Qiyun

    2016-11-01

    The widespread environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is considered one of the most toxic dioxin-like compounds. Although epidemiological studies have shown that TCDD exposure is linked to some neurological and neurophysiological disorders, the underlying mechanism of TCDD-mediated neurotoxicity has remained unclear. Astrocytes are the most abundant cells in the nervous systems, and are recognized as the important mediators of normal brain functions as well as neurological, neurodevelopmental and neurodegenerative brain diseases. In this study, we investigated the role of TCDD in regulating the expression of glutamate transporter GLT-1 in astrocytes. TCDD, at concentrations of 0.1-100 nm, had no significantly harmful effect on the viability of C6 glioma cells. However, the expression of GLT-1 in C6 glioma cells was downregulated in a dose- and time-dependent manner. TCDD also caused activation of protein kinase C (PKC), as TCDD induced translocation of the PKC from the cytoplasm or perinuclear to the membrane. The translocation of PKC was inhibited by one Ca(2+) blocker, nifedipine, suggesting that the effects are triggered by the initial elevated intracellular concentration of free Ca(2+) . Finally, we showed that inhibition of the PKC activity reverses the TCDD-triggered reduction of GLT-1. In summary, our results suggested that TCDD exposure could downregulate the expression of GLT-1 in C6 via Ca(2+) /PKC pathway. The downregulation of GLT-1 might participate in TCDD-mediated neurotoxicity. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Braf Mutations Initiate the Development of Rat Gliomas Induced by Postnatal Exposure to N-Ethyl-N-Nitrosourea.

    Science.gov (United States)

    Wang, Qi; Satomi, Kaishi; Oh, Ji Eun; Hutter, Barbara; Brors, Benedikt; Diessl, Nicolle; Liu, Hai-Kun; Wolf, Stephan; Wiestler, Otmar; Kleihues, Paul; Koelsch, Bernd; Kindler-Röhrborn, Andrea; Ohgaki, Hiroko

    2016-10-01

    A single dose of N-ethyl-N-nitrosourea (ENU) during late prenatal or early postnatal development induces a high incidence of malignant schwannomas and gliomas in rats. Although T->A mutations in the transmembrane domain of the Neu (c-ErbB-2) gene are the driver mutations in ENU-induced malignant schwannomas, the molecular basis of ENU-induced gliomas remains enigmatic. We performed whole-genome sequencing of gliomas that developed in three BDIV and two BDIX rats exposed to a single dose of 80 mg ENU/kg body weight on postnatal day one. T:A->A:T and T:A->C:G mutations, which are typical for ENU-induced mutagenesis, were predominant (41% to 55% of all somatic single nucleotide mutations). T->A mutations were identified in all five rat gliomas at Braf codon 545 (V545E), which corresponds to the human BRAF V600E. Additional screening revealed that 33 gliomas in BDIV rats and 12 gliomas in BDIX rats all carried a Braf V545E mutation, whereas peritumoral brain tissue of either strain had the wild-type sequence. The gliomas were immunoreactive to BRAF V600E antibody. These results indicate that Braf mutation is a frequent early event in the development of rat gliomas caused by a single dose of ENU. PMID:27658714

  5. Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats.

    Science.gov (United States)

    Shevtsov, M A; Parr, M A; Ryzhov, V A; Zemtsova, E G; Arbenin, A Yu; Ponomareva, A N; Smirnov, V M; Multhoff, G

    2016-01-01

    Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues. PMID:27386761

  6. Synergy of enediyne antibiotic lidamycin and temozolomide in suppressing glioma growth with potentiated apoptosis induction.

    Science.gov (United States)

    Li, Xing-Qi; Ouyang, Zhi-Gang; Zhang, Sheng-Hua; Liu, Hong; Shang, Yue; Li, Yi; Zhen, Yong-Su

    2014-08-01

    The present work evaluated the synergistic efficacy of an enediyne antibiotic lidamycin (LDM) plus temozolomide (TMZ) against glioma in vitro and in vivo. LDM plus TMZ inhibited the proliferations of rat glioma C6 cells and human glioma U87 cells more efficiently than the single usage of LDM or TMZ. In addition, LDM also potentiated the apoptosis inductions by TMZ in rat C6 cells and human U87 cells. Meanwhile, the results of TdT-mediated dUTP Nick End Labeling assay for subcutaneous U87 tumor sections indicated an enhanced apoptosis induction in vivo by LDM plus TMZ, which confirmed the high potency of the combination for glioma therapy. As determined by Western blot, apoptosis signal pathways in C6 cells and U87 cells were markedly affected by the synergistic alteration of P53, bax, procaspase 3, and bcd-2 expression. In both subcutaneous U87 xenograft and C6 intracerebral orthotopic implant model, TMZ-induced glioma growth suppression was dramatically potentiated by LDM. As shown, the combination therapy efficiently reduced the tumor volumes and tumor weights of the human glioma U87 xenograft. Kaplan-Meier assay revealed that LDM plus TMZ dramatically prolonged the life span of C6 intracerebral tumor-bearing rats with decreased tumor size. This study indicates that the combination of LDM with TMZ might be a promising strategy for glioma therapy. PMID:24842385

  7. Enhanced survival of glioma bearing rats using a combination of boronated epidermal growth factor and boronophenylalanine

    International Nuclear Information System (INIS)

    Following intratumoral (i.t.) injection, boronated epidermal growth factor (BSD-EGF) selectively targeted F98EGFR gliomas. Using BSD-EGF as the capture agent survival times were significantly increased over those observed in rats bearing F98 wildtype tumors following BNCT. These were further increased by the combination BSD-EGF with i.v. BPA. (author)

  8. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  9. Differential inhibitory effects of 2-azafluorenones on PI-PLC activation but not on PC-PLC- or PC-PLD-activation induced by histamine, PAF, PMA or A23187 in C6 glioma cells.

    Science.gov (United States)

    Wang, Hai-Long; Wang, Li-Chuan; Wei, Jiann-Wu

    2013-02-28

    In this study, C6 glioma cells were used to test the effects of 2-azafluorenone and its related compounds on membrane phosphatidylinositol (PI) and phosphatidylcholine (PC) turnover. An increase of [³H]-labeled inositol phosphate (IP1) formation by histamine (100 μM) or A23187 (100 nM) via the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) to breakdown labeled substrate was observed, and this effect could be partially blocked by about half at 100 μM of 2-azafluorenones. Histamine induced the increase of IP1 formation, but failed to cause an increase in extracellularly releasing of [3H]choline metabolites, or intracellular accumulation of [³H]phosphscholine. However, platelet activation factor (PAF) from 0.2 to 1 μM, and phorbol 12-myristate-13-acetate (PMA) at 1 μM caused an increase in extracellularly releasing of [³H]choline metabolites, and intracellular accumulation of [³H]phosphocholine via the activation on phosphatidylcholine (PC)-PLC. These responses of PAF and PMA were not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at high concentration (10⁻⁴ M). A23187 induced an increase of intracellular [³H]choline release via the activation of PCphospholipase D (PLD). This increasing effect of 100 nM A23187 was not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at a high concentration of 10⁻⁴ M. In summary, the inhibitory effect of 2-azafluorenone and its related compound 4-methyl-2-azafluorenone was observed selectively on PIPLC, but not on PC-PLC or PC-PLD based on changes of products after the activation of these enzymes.

  10. Optic glioma

    Science.gov (United States)

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  11. Feasibility of synchrotron radiation computed tomography on rats bearing glioma after iodine or gadolinium injection. Jeune Equipe RSRM-UJF.

    Science.gov (United States)

    Le Duc, G; Corde, S; Elleaume, H; Estève, F; Charvet, A M; Brochard, T; Fiedler, S; Collomb, A; Le Bas, J F

    2000-01-01

    The purpose of this work was to demonstrate the feasibility of a new imaging technique called synchrotron radiation computed tomography (SRCT). This technique leads to a direct assessment of the in vivo concentration of an iodine- or gadolinium-labeled compound. Rats bearing C6 glioma were imaged by MRI prior to the SRCT experiment. The SRCT experiments were performed after a 1.3 g I/kg (n = 5) or a 0.4 g Gd/kg (n = 5) injection. Finally, brains were sampled for histology. The SRCT images exhibited contrast enhancement at the tumor location. Ten minutes after injection, iodine and gadolinium tissular concentrations were equal to 0.80 ( +/- 0.40) mg/cm3 and 0.50 ( +/- 0.10) mg/cm3, respectively in the peripheral area of the tumor (respective background value: 0.20 +/- 0.02 to 0.10 +/- 0.01). Correlation to MRI and histology revealed that the contrast uptake occurred in the most vascularized area of the tumor. The present study summarizes the feasibility of in vivo SRCT to obtain quantitative information about iodine and gadolinium-labeled compounds. Beyond brain tumor pathology, the SRCT appears as a complementary approach to MRI and CT, for studying iodine- and gadolinium-labeled compounds by the direct achievement of the tissular concentration value in the tissue.

  12. Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

    DEFF Research Database (Denmark)

    Edvardsen, K; Brünner, N; Spang-Thomsen, M;

    1993-01-01

    A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared...... to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those...

  13. Endothelial progenitor cells (EPCs as gene carrier system for rat model of human glioma.

    Directory of Open Access Journals (Sweden)

    Nadimpalli Ravi S Varma

    Full Text Available BACKGROUND: Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1 intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2 whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities. METHODS AND RESULTS: Collected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS. Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors. CONCLUSION: EPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for

  14. ALA-mediated photodynamic therapy of experimental malignant glioma in the BD-IX rat model

    Science.gov (United States)

    Hirschberg, Henry; Angell-Petersen, Even; Peng, Qian; Sun, Chung-Ho; Sorensen, Dag R.; Carper, Steven W.; Madsen, Steen J.

    2005-04-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resec-tion indicating that a more aggressive form of local therapy could be of benefit. Photodynamic therapy (PDT) is a local form of treatment involving the administration of a tumor-localizing photosensitizing drug that is activated by light of a specific wavelength The results of in vitro experiments indicated that PDT, given at low fluence rates was substantially more effective at inhibiting glioma spheroid growth than short term high fluence rate regimes. This prompted the initia-tion of in vivo studies of low fluence rate 5-aminolevulinic acid (ALA) PDT in a rat glioma model. Methods:BT4C cell line tumors were established in the brains of inbred BD- IX rats. Eighteen days following tumor induction the animals were injected with 125 mg/kg ALA ip. and four hours later light treatment at various fluences and fluence rates were given after the introduction of an optical fiber. Tumor histology and animal survival were examined. Results: In vitro experiments verified that the cell line was sensitive to ALA PDT. Microfluorometry of frozen tissue sections showed that PpIX is produced with a greater than 20:1 tumor to normal tissue selectivity ratio four hours after ALA injection. Histological examination demonstrated neutrophil infiltration and tumor central necrosis in low fluence rate treated tumors. Conclusions: Low fluence rate long term ALA mediated PDT had a more pronounced effect on tumor histology than single shot short duration treatments at similar total fluence levels.

  15. Prolonged survival of Fischer rats bearing F98 glioma after iodine-enhanced synchrotron stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Purpose: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumors followed by stereotactic irradiation with X-rays from a synchrotron source. The purpose of this study was to determine whether the efficacy of iodine-enhanced SSR could be further improved in the F98 rodent glioma model, by using a concomitant injection of an iodinated contrast agent and a transient blood-brain barrier opener (mannitol) during irradiation. Methods and Materials: Fourteen days after intracerebral inoculations of F98 cells, the rats were irradiated with 50-keV X-rays while receiving an infusion of hyperosmotic mannitol with iodine, either intravenously or via the carotid (9 to 15 rats per group, 117 rats total). Results: For doses ≤15 Gy, the intracarotid infusion of mannitol and iodine improved the rats' survival compared with intravenous injection or irradiation alone. The percentage-increased life spans (ILS) were 91%, 116%, and 169% without iodine, after infusion of iodine and mannitol intravenously, and intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without iodine had the longest survival (ILS = 607%), but no additional benefit was obtained with iodine and mannitol. Conclusions: Iodine-enhanced SSR is significantly improved with concomitant intracarotid infusion of iodine and mannitol for radiation doses ≤15 Gy

  16. RETROVIRAL-MEDIATED SUICIDE GENE THERAPY OF EXPERIMENTAL GLIOMA

    Institute of Scientific and Technical Information of China (English)

    Xu Lingfei; Ge Kai; Zheng Zhongcheng; Sun Lanying; Liu Xinyuan

    1998-01-01

    Objective: To establish a retroviral-mediated suicide gene therapy system for experimental glioma and test its efficacy. Methods: C6 rat glioma cells were infected with recombinant retrovirus containing HSV-tk gene. The C6/tk cell line which stably expressed tk was selected and cloned. The sensitivities of C6/tk cells to several nucleoside analogues, such as GCV, BVdU, ACV were compared by the growth inhibition studies. Antitumor effects were also observed after GCV treatment in nude mice bearing tumors derived from C6/tk cells. Results:The growth inhibition studies showed that GCV was the most efficient prodrug in this system. C6/tk cells were highly sensitive to GCV, with an IC50<0.2 μmol/L, being 500-fold less than that in tk-negative C6 cells. In vivo studies showed significant tumor inhibition in the treatment group. Conclusion: Glioma cells can be eradicated by using retroviral-mediated suicide gene system in vitro as well as in vivo.

  17. Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors

    DEFF Research Database (Denmark)

    Persson, Bertil R R; Koch, Catrin Bauréus; Grafström, Gustav;

    2010-01-01

    Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors......, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time...... significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect...

  18. PDGF-B链基因三链形成寡核苷酸对C6胶质瘤细胞增殖和凋亡的影响%Effects of proliferation and apoptosis of C6 glioma cells with triplex forming oligonucleotides (TFO)

    Institute of Scientific and Technical Information of China (English)

    李维方; 周定标; 余新光; 金由辛

    2005-01-01

    目的观察PDGF-B链基因三链形成寡核苷酸(triplex-forming oligonucleotide,TFO)对C6胶质瘤细胞增殖和凋亡的影响.方法应用流式细胞技术观察TFO对C6胶质瘤细胞PDGF-B、PCNA表达的影响,应用流式细胞技术观察TFO对C6胶质瘤细胞凋亡的影响.结果TFO对C6胶质瘤细胞PDGF-B、PCNA的表达有明显抑制作用,而且抑制作用存在浓度依赖性.TFO有明显诱导C6胶质瘤细胞细胞凋亡作用,而且诱导作用存在浓度依赖性.结论TFO抑制C6胶质瘤细胞细胞增殖,同时诱导C6胶质瘤细胞细胞凋亡.

  19. Characterization of microglia/macrophages in gliomas developed in S-100β-v-erbB transgenic rats.

    Science.gov (United States)

    Sasaki, Atsushi; Yokoo, Hideaki; Tanaka, Yuko; Homma, Taku; Nakazato, Yoichi; Ohgaki, Hiroko

    2013-10-01

    Glioma-infiltrating microglia/macrophages are referred to as tumor-associated macrophages (TAMs). Transgenic (TG) rats expressing v-erbB, which is a viral form of the epidermal growth factor receptor, under transcriptional regulation by the S100-β promoter, develop brain tumors. This study was designed to clarify the pathological characteristics of TAMs in these experimental tumors. We carried out immunohistochemical and morphometrical analyses of microglia/macrophages in brain tumors (5 malignant glioma, 4 anaplastic oligodendroglioma, 4 astrocytoma) that developed in TG rats. TAMs with ionized calcium-binding adaptor molecule 1 (Iba1) positivity and morphology of activated, non-phagocytic microglia increased within and around the tumors in malignant gliomas and anaplastic astrocytomas. The Iba1-positive TAMs of the tumor core were significantly more activated than Iba1-positive microglia of non-neoplastic brain tissue in intraparenchymal anaplastic oligodendrogliomas. Iba1 expression showed a significant positive correlation to Ki-67 expression in all the gliomas. Most TAMs showed no or little expression against CD68, CD163 or CD204, although CD204-positive TAMs were observed in necrosis as well as in the proliferating vascular wall. In conclusion, S-100β-v-erbB TG rats may serve as a useful animal model for further analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs toward the M2 phenotype remains unclear. PMID:23331472

  20. The effects of triplex forming oligonucleotide (TFO) on the proliferation and cell cycle with C6 glioma cells%PDGF-B链基因三链形成寡核苷酸对C6胶质瘤细胞增殖和细胞周期的影响

    Institute of Scientific and Technical Information of China (English)

    李维方; 周定标; 余新光; 金由辛

    2004-01-01

    目的观察PDGF-B链基因三链形成寡核苷酸(triplex-forming oligonucleotide,TFO)对C6胶质瘤细胞增殖和细胞周期的影响.方法应用免疫荧光流式细胞技术观察PDGF-B链基因TFO对C6胶质瘤细胞PDGF-B、PCNA表达的影响.应用流式细胞技术观察PDGF-B链基因TFO对C6胶质瘤细胞细胞周期的影响.结果 PDGF-B链基因TFO对C6胶质瘤细胞PDGF-B链基因、PCNA的表达有明显抑制作用,而且抑制作用存在浓度依赖性.PDGF-B链基因TFO能使C6胶质瘤细胞S期的百分率明显降低,阻止细胞由静止期(G0-G1期)进入(S期).结论 PDGF-B链基因TFO能够抑制C6胶质瘤细胞PDGF-B链基因的表达,阻碍细胞进入S期,降低细胞增殖能力.

  1. Impact of Focused Ultrasound-enhanced Drug Delivery on Survival in Rats with Glioma

    Science.gov (United States)

    Treat, Lisa Hsu; Zhang, Yongzhi; McDannold, Nathan; Hynynen, Kullervo

    2009-04-01

    Malignancies of the brain remain difficult to treat with chemotherapy because the selective permeability of the blood-brain barrier (BBB) blocks many potent agents from reaching their target. Previous studies have illustrated the feasibility of drug and antibody delivery across the BBB using MRI-guided focused ultrasound. In this study, we investigated the impact of focused ultrasound-enhanced delivery of doxorubicin on survival in rats with aggressive glioma. Sprague-Dawley rats were implanted with 9 L gliosarcoma cells in the brain. Eight days after implantation, each rat received one of the following: (1) no treatment (control), (2) a single treatment with microbubble-enhanced MRI-guided focused ultrasound (FUS only), (3) a single treatment with i.v. liposomal doxorubicin (DOX only), or (4) a single treatment with microbubble-enhanced MRI-guided focused ultrasound and concurrent i.v. injections of liposomal doxorubicin (FUS+DOX). The survival time from implantation to death or euthanasia was recorded. We observed a modest but significant increase in median survival time in rats treated with combined MRI-guided focused ultrasound chemotherapy, compared to chemotherapy alone (psurvival between those who received stand-alone chemotherapy and those who did not receive any treatment (p>0.10). Our study demonstrates for the first time a therapeutic benefit achieved with ultrasound-enhanced drug delivery across the blood-brain barrier. This confirmation of efficacy in an in vivo tumor model indicates that targeted drug delivery using MRI-guided focused ultrasound has the potential to have a major impact on the treatment of patients with brain tumors and other neurological disorders.

  2. PDGF-B链基因TFO抑制C6胶质瘤细胞PDGF-B链基因表达及细胞生长%Inhibiting the expression of PDGF-B chain and the proliferation of C6 glioma cells with triplex-forming oligonucleotide

    Institute of Scientific and Technical Information of China (English)

    李维方; 周定标; 余新光; 金由辛

    2004-01-01

    目的:观察 PDGF-B 链基因三链形成寡核苷酸(triplex-forming oligonucleotide,TFO)对 C6 胶质瘤细胞 PDGF-B 链基因表达和细胞生长的作用.探索 PDGF-B 链基因 TFO 作为抗肿瘤治疗新药的可能性.方法:应用MTT法观察 PDGF-B 链基因 TFO对 C6 胶质瘤细胞生长的抑制作用;应用流式细胞技术观察 PDGF-B 链基因 TFO 对 C6 胶质瘤细胞 PDGF-B 链基因表达的影响.结果:PDGF-B 链基因 TFO 对 C6 胶质瘤细胞 PDGF-B 链基因的表达和细胞生长有明显抑制作用,而且抑制作用存在浓度依赖性.结论:PDGF-B 链基因 TFO 能够抑制 C6 胶质瘤细胞 PDGF-B 链基因的表达和细胞生长,有望成为抑制 PDGF-B 原癌基因表达的一种全新药物.

  3. Specific targeting of gliomas with multifunctional superparamagnetic iron oxide nanoparticle optical and magnetic resonance imaging contrast agents

    Institute of Scientific and Technical Information of China (English)

    Xiang-xi MENG; Jia-qi WAN; Meng JING; Shi-guang ZHAO; Wei CAI; En-zhong LIU

    2007-01-01

    Aim: To determine whether glioma cells can be specifically and efficiently tar- geted by superparamagnetic iron oxide nanoparticle (SPIO)-fluorescein isothiocyanate (FITC)-chlorotoxin (SPIOFC) that is detectable by magnetic reso- nance imaging (MRI) and optical imaging. Methods: SPIOFC was synthesized by conjugating SPIO with FITC and chlorotoxin. Glioma cells (human U251-MG and rat C6) were cultured with SPIOFC and SPIOF (SPIO-FITC), respectively. Neural cells were treated with SPIOFC as the control for SPIOFC-targeted glioma cells. The internalization of SPIOFC by glioma cells was assessed by MRI and was quantified using inductively-coupled plasma emission spectroscopy. The optical imaging ability of SPIOFC was evaluated by confocal laser scanning microscopy. Results: Iron per cell of U251 (72.5±1.8 pg) and C6 (74.9±2.2 pg) cells cultured with SPIOFC were significantly more than those of U251 (6.6±1.0 pg) and C6 (7.1±0.8 pg) cells incubated with SPIOF. The T2 signal intensity of U251 and C6 cells cultured with SPIOFC (233.6±25.9 and 211.4±17.2, respectively) were substantially lower than those of U251 and C6 cells incubated with SPIOF (2275.3±268.6 and 2342.7±222.4, respectively). Moreover, there were significant differences in iron per cell and T2 signal intensity between SPIOFC-treated neural cells (1.3±0.3; 2533.6±199.2) and SPIOFC-treated glioma cells. SPIOFC internalized by glioma cells exhibited green fluorescence by confocal laser scanning microscopy. Conclusion: SPIOFC is suitable for the specific and efficient targeting of glioma cells. MRI and optical imaging in conjunction with SPIOFC can differentiate glioma cells from normal brain tissue cells.

  4. Utilization of {sup 13}C-enriched substrates for the NMR study of the channelling of Krebs cycle intermediates in glioma C6; Utilisation de substrats enrichis en {sup 13}C pour l`etude par RMN de la canalisation des intermediaires du cycle de Krebs dans le gliome C6

    Energy Technology Data Exchange (ETDEWEB)

    Merle, M.; Peron, M.; Valeins, H.; Canioni, P. [Bordeaux-2 Univ., 33 (France)

    1994-12-31

    Unequal enrichments are observed for the C2 and C3 carbons of glutamate (C2>C3) and of aspartate (C3>C2) during incubation of C6 cells with (1-{sup 13} C) glucose. In order to study if this result is the result of an entry of {sup 13}C at the oxalo-acetate level or of another phenomenon, the enrichment distribution on asparte C1 and C4 carbons of C6 cells incubated with (1-{sup 13} C) glucose and the enrichment of C2 and C3 carbons of glutamate during cell incubation with (2-{sup 13} C) acetate, i.e. cases where the entry of {sup 13}C in the cycle, via the activity of the pyruvate carboxylase, is very unlikely, are examined. 4 figs., 1 tab., 1 ref.

  5. Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas

    Directory of Open Access Journals (Sweden)

    Matsutani Tomoo

    2012-10-01

    Full Text Available Abstract Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. Methods In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines. Results We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1 was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. Conclusion SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.

  6. Dynamic-contrast-enhanced-MRI with extravasating contrast reagent: Rat cerebral glioma blood volume determination

    Science.gov (United States)

    Li, Xin; Rooney, William D.; Várallyay, Csanád G.; Gahramanov, Seymur; Muldoon, Leslie L.; Goodman, James A.; Tagge, Ian J.; Selzer, Audrey H.; Pike, Martin M.; Neuwelt, Edward A.; Springer, Charles S.

    2010-10-01

    The accurate mapping of the tumor blood volume (TBV) fraction ( vb) is a highly desired imaging biometric goal. It is commonly thought that achieving this is difficult, if not impossible, when small molecule contrast reagents (CRs) are used for the T1-weighted (Dynamic-Contrast-Enhanced) DCE-MRI technique. This is because angiogenic malignant tumor vessels allow facile CR extravasation. Here, a three-site equilibrium water exchange model is applied to DCE-MRI data from the cerebrally-implanted rat brain U87 glioma, a tumor exhibiting rapid CR extravasation. Analyses of segments of the (and the entire) DCE data time-course with this "shutter-speed" pharmacokinetic model, which admits finite water exchange kinetics, allow TBV estimation from the first-pass segment. Pairwise parameter determinances were tested with grid searches of 2D parametric error surfaces. Tumor blood volume ( vb), as well as ve (the extracellular, extravascular space volume fraction), and Ktrans (a CR extravasation rate measure) parametric maps are presented. The role of the Patlak Plot in DCE-MRI is also considered.

  7. 脂膜微囊承载紫杉醇靶向性治疗C6胶质瘤的体内外实验研究%The targeted therapeutic effect of a lipid-coated microbubble carrying Taxol on C6 glioma in vivo and vitro

    Institute of Scientific and Technical Information of China (English)

    宫崧峰; 李新钢; 李刚; 王东海; 徐淑军; 周旭东

    2007-01-01

    目的:在体内外研究脂膜微囊(LCM)承载紫杉醇(Taxol)治疗大鼠颅内C6质瘤的机制.方法:体外实验应用紫杉醇-脂膜微囊(Taxol-LCM)或单用LCM处理C6细胞系,采用免疫荧光显微镜或激光共聚焦显微镜下观察LCM在肿瘤细胞内的分布特点,用药前后肿瘤细胞形态的改变和细胞内超微结构的变化,动态观察LCM进入细胞的全过程;体内实验建立大鼠C6胶质瘤动物模型12只,成瘤大鼠分为4组:注射LCM-Taxol组、注射LCM组、注射Taxol组及载瘤动物组,每组取一只在最后一次尾静脉注射相应药物后处死,获取大鼠脑组织标本,进行油红O染色,观察LCM在肿瘤位点分布的特点;同时观察不同处理组大鼠的生存期.结果:体外实验表明,Taxol可结合于LCM并被胶质瘤细胞内吞,起到很强的的杀伤肿瘤细胞作用.其内吞过程为LCM先结合于细胞膜表面,后在细胞内重新分布,最终被细胞浆内的酸性成分所降解.体内油红O染色显示,注射LCM-Taxol组肿瘤区域有LCM聚集,胶质瘤明显坏死;而注射LCM组,肿瘤区域有LCM出现,但肿瘤区域无明显坏死;注射Taxol组及载瘤动物组肿瘤区域无明显坏死;生存期结果示,Taxol-LCM组生存期明显长于其他3组,而与其他3组生存期比较差异不明显.结论:LCM可承载Taxol在体内外起到杀伤胶质瘤细胞的作用.

  8. Preparation, biodistribution and neurotoxicity of liposomal cisplatin following convection enhanced delivery in normal and F98 glioma bearing rats.

    Directory of Open Access Journals (Sweden)

    Tianyao Huo

    Full Text Available The purpose of this study was to evaluate two novel liposomal formulations of cisplatin as potential therapeutic agents for treatment of the F98 rat glioma. The first was a commercially produced agent, Lipoplatin™, which currently is in a Phase III clinical trial for treatment of non-small cell lung cancer (NSCLC. The second, produced in our laboratory, was based on the ability of cisplatin to form coordination complexes with lipid cholesteryl hemisuccinate (CHEMS. The in vitro tumoricidal activity of the former previously has been described in detail by other investigators. The CHEMS liposomal formulation had a Pt loading efficiency of 25% and showed more potent in vitro cytotoxicity against F98 glioma cells than free cisplatin at 24 h. In vivo CHEMS liposomes showed high retention at 24 h after intracerebral (i.c. convection enhanced delivery (CED to F98 glioma bearing rats. Neurotoxicologic studies were carried out in non-tumor bearing Fischer rats following i.c. CED of Lipoplatin™ or CHEMS liposomes or their "hollow" counterparts. Unexpectedly, Lipoplatin™ was highly neurotoxic when given i.c. by CED and resulted in death immediately following or within a few days after administration. Similarly "hollow" Lipoplatin™ liposomes showed similar neurotoxicity indicating that this was due to the liposomes themselves rather than the cisplatin. This was particularly surprising since Lipoplatin™ has been well tolerated when administered intravenously. In contrast, CHEMS liposomes and their "hollow" counterparts were clinically well tolerated. However, a variety of dose dependent neuropathologic changes from none to severe were seen at either 10 or 14 d following their administration. These findings suggest that further refinements in the design and formulation of cisplatin containing liposomes will be required before they can be administered i.c. by CED for the treatment of brain tumors and that a formulation that may be safe when given

  9. Temporal dynamic changes of connexin 43 expression in C6 cells following lipopolysaccharide stimulation

    Institute of Scientific and Technical Information of China (English)

    Ling Liu; Haiyan Liu; Zhenping Gao; Linbo Zhang; Lue Su; Guojun Dong; Haiyang Yu; Jiayi Tian; Hang Zhao; Yanyan Xu

    2012-01-01

    Connexin 43, a gap junction protein, is expressed mainly in glia in the central nervous system.Neuroinflammation plays an important role in central nervous system injury. Changes to glial connexin 43 levels and neuroinflammation may trigger brain injury and neurodegenerative diseases.To illustrate the relationship between connexin 43 and neuroinflammation, this study investigated how connexin 43 expression levels change in lipopolysaccharide-stimulated rat C6 glioma cells. C6 cells were treated with 0.05, 0.25, 0.5, 1, 2.5 and 5 μg/mL lipopolysaccharide for 24 hours. The nitrite estimation-detected nitric oxide release level was elevated substantially after lipopolysaccharide stimulation. To test the transcriptional level changes of inducible nitric oxide synthase, tumor necrosis factor-α and connexin 43 mRNA, C6 cells were treated with 5 μg/mL lipopolysaccharide for 3-48 hours. Reverse transcription-PCR showed that the expression of inducible nitric oxide synthase and tumor necrosis factor-α mRNA increased over time, but connexin 43 mRNA levels increased in lipopolysaccharide-stimulated C6 cells at 3 and 6 hours, and then decreased from 12 to 48 hours. Connexin 43 protein expression was detected by immunofluorescence staining, and the protein levels matched the mRNA expression levels. These results suggest that connexin 43 expression is biphasic in lipopolysaccharide-inducedneuroinflammation in C6 cells, which may be correlated with the connexin 43 compensatorymechanism.

  10. Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma.

    Science.gov (United States)

    Wang, Ting-Chung; Cheng, Chun-Yu; Yang, Wei-Hsun; Chen, Wen-Cheng; Chang, Pey-Jium

    2015-11-01

    The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life‑threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague‑Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma.

  11. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm3 volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm3 volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  12. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Deman, Pierre [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Vautrin, Mathias [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); DOSIsoft, Cachan (France); Edouard, Magali [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Stupar, Vasile [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Bobyk, Laure; Farion, Regine [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Elleaume, Helene [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Remy, Chantal; Barbier, Emmanuel L. [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Esteve, Francois [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Adam, Jean-Francois, E-mail: adam@esrf.fr [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France)

    2012-03-15

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  13. Experimental study on BPA uptake of C6, BT-325 and SHG-44 glioma cell lines%胶质瘤细胞系摄取BPA实验研究

    Institute of Scientific and Technical Information of China (English)

    曹锐峰; 章翔; 陈伟; 江新标; 姬西团; 王西玲; 梁景文

    2003-01-01

    目的探讨孵育时间和细胞周期对胶质瘤细胞摄取BPA(p-boronophenylalanine)的影响,进一步阐明BPA的胶质瘤细胞选择性作用机制.方法将C6,BT-325,SHG-44胶质瘤细胞和原代大鼠星形胶质细胞培养在含BPA的培养液中,分别培养4 h、8 h、12 h、16 h、20 h和24 h后,采用感应耦合等离子体原子发射光谱(ICP-AES)法测定细胞内硼的含量.培养24 h后,流式细胞仪分选Go/G1和G2/M期的细胞,ICP-AES法分别测定细胞内硼的水平.结果三种胶质瘤细胞在每个检测时间点的细胞内硼含量均显著高于对照组胶质细胞(P<0.01).三种胶质瘤细胞G2/M期与Go/G1期相比硼含量均明显增高(P<0.05),而星形胶质细胞两期差异不明显.C6、SHG-44和BT-325与星形胶质细胞Go/G1期的硼浓度比分别为1.46、1.51和1.40,G2/M期的硼浓度比分别为3.65、3.96和3.76.结论有丝分裂的过程可以加强胶质瘤对BPA的吸收,这一过程可能与胶质瘤细胞对BPA的主动运输有关.主动运输可能是BPA对胶质瘤选择性作用的基础.

  14. Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats.

    Science.gov (United States)

    Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

    2016-12-01

    The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate (r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM(-1) s(-1). In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian

  15. Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats

    Science.gov (United States)

    Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

    2016-04-01

    The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate ( r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM-1 s-1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly

  16. The impact of hypoxia and oxygenation modification on the radiation response of an intracranial rat glioma

    International Nuclear Information System (INIS)

    Purpose: The median survival for a patient treated for GBM is 1 year. Reasons for the poor long term benefit of conventional therapy, which includes radiation therapy, are poorly understood. Gliomas have areas of hypoxia which may predict for radioresistance. The purpose of this project was to test the hypothesis that hyperbaric oxygen was superior to nicotinamide plus carbogen in decreasing the extent of hypoxia and in increasing survival following fractionated irradiation in an intracranial glioma tumor model. Materials and Methods: RG-2 tumor cells were transplanted intracranially into female Fischer 344 rats. Hypoxia was studied using immunohistochemical staining of drug-protein adducts in tumor following removal of the brain after i.p. injection of pimonidazole hydrochloride under conditions of room air, 3 atmospheres oxygen (HBO), or nicotinamide (200 mg/kg i.p.) with carbogen. Serum nicotinamide and metabolites were measured by HPLC on samples taken 20 minutes after giving nicotinamide (200 mg/kg, i.p.). In a survival study animals were randomized on day 14 post-transplant to 1 of 4 treatment groups: 1) sham - anesthesia only; 2) XRT - 4 Gy x 5; 3) HBO - XRT after breathing for 5 minutes once 3 atmospheres of 100% oxygen was obtained; and 4) Carbogen/Nicotinamide - XRT with i.p. nicotinamide 20 minutes prior to irradiation and carbogen breathing for 5 minutes after saturation of the chamber. Following treatment, animals were followed until death. Results: Immunohistochemical evaluation of the tumors from animals breathing room air revealed pimonidazole adducts indicating the presence of hypoxia. Those tumors evaluated from animals treated with HBO did not show evidence of hypoxia marker binding. The median serum nicotinamide level obtained was 258.2 μg/ml. Median survivals post-transplant were: 1) Sham - 22 days; 2) XRT - 28 days; 3) HBO - 28 days; and 4) Carbogen/Nicotinamide - 26 days. Only XRT and HBO were statistically better than Sham (p = 0.002 and p

  17. Effect of Hyperbaric Oxygen on the Growth of Intracranial Glioma in Rats

    Directory of Open Access Journals (Sweden)

    Jian-Bo Ding

    2015-01-01

    Conclusions: The current results demonstrate that HBO alone may promote tumor growth, and is therefore not suitable to treat patients with gliomas with neurological deficits or disorders with HBO alone. If HBO must be used as a mean of rehabilitation, it is recommended that HBO should be combined with radiotherapy or chemotherapy.

  18. 1H MR spectroscopic imaging of phospholipase-mediated membrane lipid release in apoptotic rat glioma in vivo.

    Science.gov (United States)

    Liimatainen, Timo J; Erkkilä, Arja T; Valonen, Piia; Vidgren, Helvi; Lakso, Merja; Wong, Garry; Gröhn, Olli H J; Ylä-Herttuala, Seppo; Hakumäki, Juhana M

    2008-06-01

    The purpose of the current study was to determine regional spatiotemporal differences and to gain insight on the mechanisms responsible for lipid accumulation during apoptotic cell death using in vivo MR spectroscopic imaging in combination with histology and biochemical membrane lipid analyses. Rats bearing BT4C gliomas were treated with ganciclovir (GCV) for 14 days, and combined in vivo quantitative MR spectroscopic imaging (MRSI) of gliomas with histology and a biochemical analysis of major cell membrane constituents. By using 1H MRSI in vivo in combination with histology, we were able to demonstrate previously unattainable regional lipid concentration differences in tumors during GCV-induced apoptosis, with 5-microL tissue volume resolution. Our results also show that, during treatment, phospholipase A2 (PLA2) expression is significantly elevated by 37+/-13% (P<0.05) and tumor cell membranes loose a significant proportion of unsaturated fatty acyl moieties (56+/-6 mmol/kg, P<0.05). These changes are reflected in both histology and significant MR-visible lipid accumulation, demonstrating that phospholipid hydrolysis in tissue undergoing apoptosis can be imaged with MRSI. Our work demonstrates the versatility of 1H MRSI in studying apoptosis in vivo, which is likely to pave way for the use of MRSI in both experimental and clinical anticancer trials. PMID:18506792

  19. Effect of plasma exchange in combination with deoxyspergualin on the survival of guinea-pig hearts in macrophage-depleted C6-deficient rats.

    NARCIS (Netherlands)

    Wu, G; Korsgren, O; Sun, S; Rooijen, van N.; Tibell, A

    2003-01-01

    0.01 vs. controls). In untreated control rats, xenoreactive antibody (IgM, IgG) levels decreased immediately after PE, but their levels rapidly returned to normal. In rats treated with DSG or DSG + Lip-Cl2MDP, the IgM levels remained low during the observation period. Immunohistochemistry showed tha

  20. Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma

    International Nuclear Information System (INIS)

    A major challenge in the development of cell based therapies for glioma is to deliver optimal number of cells (therapeutic dose) to the tumor. Imaging tools such as magnetic resonance imaging (MRI), optical imaging, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has been used in cell tracking and/or biodistribution studies. In this study, we evaluate the dynamic biodistribution of systemic injected labeled cells [human cord blood derived endothelial progenitor cells (EPCs) and cytotoxic T-cells (CTLs)] in rat glioma model with in vivo SPECT imaging. Human cord blood EPCs, T-cells and CD14+ cells (monocytes/dendritic cells) were isolated using the MidiMACS system. CD14+ cells were converted to dendritic cells (DC) and also primed with U251 tumor cell line lysate. T-cells were co-cultured with irradiated primed DCs at 10:1 ratio to make CTLs. Both EPCs and CTLs were labeled with In-111-oxine at 37°C in serum free DMEM media. Glioma bearing animals were randomly assigned into three groups. In-111 labeled cells or In-111 oxine alone were injected through tail vein and SPECT imaging was performed on day 0, 1, and 3. In-111 oxine activity in various organs and tumor area was determined. Histochemical analysis was performed to further confirm the migration and homing of injected cells at the tumor site. EPCs and CTLs showed an In-111 labeling efficiency of 87.06 ± 7.75% and 70.8 ± 12.9% respectively. Initially cell migration was observed in lung following inravenous administration of In-111 labeled cells and decreased on day 1 and 3, which indicate re-distribution of labeled cells from lung to other organs. Relatively higher In-111 oxine activity was observed in tumor areas at 24 hours in animals received In-111 labeled cells (EPCs or CTLs). Histiological analysis revealed iron positive cells in and around the tumor area in animals that received labeled cells (CTLs and EPCs). We observed differential biodistribution of In-111

  1. 巢蛋白基因沉默通过激活细胞周期依赖性激酶(cdk5)促进大鼠神经胶质瘤细胞C6的迁移和增殖%Silencing of Nestin Promotes Glioma Cell Migration and Proliferation through Activation of Cyclin-dependent Kinase 5

    Institute of Scientific and Technical Information of China (English)

    兰宝金; 马晓雯; 沈丽; 鲁文静; 兰峰; 曹翠丽; 葛瑞民; 陈玲珑; 张小燕; 陆爱丽; 吴碧莲

    2011-01-01

    中间纤维蛋白巢蛋白(nestin)在各种胚胎前体细胞及成熟组织中均有表达.近年一些研究显示,巢蛋白的表达上调和一些恶性肿瘤的病理特征有相关性.但是,巢蛋白在干细胞分化及肿瘤发生中的作用还不为人知.在本研宄中,我们运用短发卡状的RNA为工具,以大鼠神经胶质瘤细胞系C6为模型,对巢蛋白的功能进行了研究.划痕实验和迁移实验的结果均显示,巢蛋白基因沉默可以促进C6细胞的迁移.同时,BrdU渗入实验显示,此过程伴随着细胞增殖的增加.进一步研究显示,细胞周期依赖性激酶cdk5的活性在此过程中有显著的增加.此外,巢蛋白基因沉默所引起的迁移改变可以被cdk5特异性抑制剂roscovitine所回复,而对细胞增殖则没有显著影响.综上所述,本研究揭示了巢蛋白基因沉默与神经胶质瘤细胞的迁移和增殖相关,而cdk5是此过程的重要调节因子.%Nestin is an intermediate filament protein expressed in the progenitor cells of various embryonic and adult tissues. Recently, studies have indicated that overexpression of nestin associated with clinical pathology of several malignant tumors. However, little is known about the function of nestin in both stem cell differentiation and cancer carcinogenesis. In the study, we used short hairpin RNA transfection to investigate the function of nestin in C6 glioma cells. The results indicated that nestin silencing increased cell motility from both wound healing and transwell assays and moderately elevated cell proliferation from the BrdU incorporation assay. The nestin knockdown induced increase of Cdk5 kinase activity could be reversed by the CdkS specific inhibitor roscovitine. This study showed that Cdk5 was an important regulator to mediated the function of nestin in cell mortality and proliferation in glioma cells.

  2. Multiple Gliomas

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Multiple gliomas are well-recognized but uncommon tumors. The incidence of multiple gliomas according to some reports ranges from 0.5% to 20% of all gliomas diagnosed. Multiple gliomas can be divided into two categories. One is by location of the lesions (multifocal and multicentric). The second type is by the time of the lesions occur (synchronous and metachronous). The lesions generally show hypo, or isodensity on CT; a hypo- or isointense signal on T1-weighted images, and a hyperintense signal on T2-weighted images. Glioblastoma is the most frequent histotype. The prognosis of multiple gliomas remains unfavorable. The treatment of multiple gliomas includes surgery, radiotherapy and chemotherapy. Distinction between multicentric and multifocal gliomas is difficult. This report reviews in detail the aspects of multiple gliomas mentioned above.

  3. Nuclear microprobe determination of platinum quantitative distribution in rat brain tumors after cisplatin or carboplatin injection for PAT treatment of glioma

    Science.gov (United States)

    Ortega, R.; Biston, M.-C.; Devès, G.; Bohic, S.; Carmona, A.

    2005-04-01

    Conventional radiotherapy of high-grade glioma is unsuccessful since less than 50% of patients survive at 6 months, therefore glioma treatment is still challenging. A new radiotherapy procedure has been recently proposed, the photoactivation therapy (PAT), associating synchrotron radiation with a chemotherapy agent, such as cisplatin. PAT aims at using the monochromaticity and the very high brilliance of the synchrotron radiation for selective excitation of a high-Z compound introduced in tumor cell DNA to maximize the photoelectric effect probability, thus increasing local toxicity. Synchrotron irradiation of cisplatin at the platinum absorption K-edge resulted in a dramatic increase in life span relative to median survival time in the F98 glioma model in Fisher rat. In the purpose to optimize the platinum concentration into the tumor, the platinum content of irradiated target needs to be quantified. These results will enable to correlate injected dose to cellular platinum content in the tumor at the time of irradiation, and to study the spatial diffusion and distribution of the platinum into the tumor and the surrounding healthy tissues from the point of injection. Male Fisher 344 rats were inoculated with 103 F98 glioma cells. Thirteen days after stereotactic inoculation, intracerebral injection at the tumor site of 40 μg of carboplatin and 3 or 5 μg of cisplatin was performed. Platinum quantitative distribution in tumors and adjacent brain tissues was determined using μ-PIXE and μ-RBS analysis.

  4. Nuclear microprobe determination of platinum quantitative distribution in rat brain tumors after cisplatin or carboplatin injection for PAT treatment of glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, R. [Chimie Nucleaire Analytique Bioenvironnementale, UMR 5084 CNRS/Universite de Bordeaux 1, Gradignan 33175 (France)]. E-mail: ortega@cenbg.in2p3.fr; Biston, M.-C. [Institut National de la Sante et de la Recherche Medicale ' Rayonnement Synchrotron et Recherche Medicale' and ID17 Medical Beamline, ESRF, Grenoble (France); Deves, G. [Chimie Nucleaire Analytique Bioenvironnementale, UMR 5084 CNRS/Universite de Bordeaux 1, Gradignan 33175 (France); Bohic, S. [ID22 Beamline, European Synchrotron Radiation Facility, Grenoble (France); Carmona, A. [Chimie Nucleaire Analytique Bioenvironnementale, UMR 5084 CNRS/Universite de Bordeaux 1, Gradignan 33175 (France); Centro Nacional de Aceleradores, Universidad de Sevilla, Sevilla (Spain)

    2005-04-01

    Conventional radiotherapy of high-grade glioma is unsuccessful since less than 50% of patients survive at 6 months, therefore glioma treatment is still challenging. A new radiotherapy procedure has been recently proposed, the photoactivation therapy (PAT), associating synchrotron radiation with a chemotherapy agent, such as cisplatin. PAT aims at using the monochromaticity and the very high brilliance of the synchrotron radiation for selective excitation of a high-Z compound introduced in tumor cell DNA to maximize the photoelectric effect probability, thus increasing local toxicity. Synchrotron irradiation of cisplatin at the platinum absorption K-edge resulted in a dramatic increase in life span relative to median survival time in the F98 glioma model in Fisher rat. In the purpose to optimize the platinum concentration into the tumor, the platinum content of irradiated target needs to be quantified. These results will enable to correlate injected dose to cellular platinum content in the tumor at the time of irradiation, and to study the spatial diffusion and distribution of the platinum into the tumor and the surrounding healthy tissues from the point of injection. Male Fisher 344 rats were inoculated with 10{sup 3} F98 glioma cells. Thirteen days after stereotactic inoculation, intracerebral injection at the tumor site of 40 {mu}g of carboplatin and 3 or 5 {mu}g of cisplatin was performed. Platinum quantitative distribution in tumors and adjacent brain tissues was determined using {mu}-PIXE and {mu}-RBS analysis.

  5. The engineered Salmonella typhimurium inhibits tumorigenesis in advanced glioma

    Directory of Open Access Journals (Sweden)

    Chen JQ

    2015-09-01

    Full Text Available Jian-qiang Chen,1 Yue-fu Zhan,2 Wei Wang,1 Sheng-nan Jiang,2,3 Xiang-ying Li21Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Radiology, Affiliated to Haikou Hospital Xiangya School of Medicine, Central South University, Haikou, People’s Republic of China; 3Department of Nuclear Medicine, Central South University Xiangya School of Medicine Affiliated HaiKou Hospital, Haikou, Hainan, People’s Republic of ChinaObjective: To explore the antitumor role of the attenuated Salmonella typhimurium ΔppGpp with inducible cytolysin A (ClyA in advanced stage of glioma.Materials and methods: The C6 rat glioma cells were orthotopically implanted by surgery into the caudate nucleus of rat brains. The rats were then randomly divided into the treatment group (SL + ClyA (n=12, negative control group (SL (n=12, and control group (phosphate-buffered saline [PBS] (n=12. In the treatment group, the attenuated S. typhimurium were transformed with the plasmid-encoded antitumor gene ClyA. The expression of ClyA was controlled by the TetR-regulated promoter in response to extracellular doxycycline. The plasmid also contained an imaging gene lux to allow illumination of the tumor infected by the bacteria. The rat glioma C6 cells were implanted into the caudate nucleus of all rats. The engineered S. typhimurium and respective controls were injected intravenously into the rats 21 days after initial tumor implantation. The pathological analysis of the glioma tumor was performed at 21 days and 28 days (7 days after doxycycline treatment postimplantation. All rats underwent MRI (magnetic resonance imaging and bioluminescence study at 21 days and 28 days postimplantation to detect tumor volume. The differences between the three groups in tumor volume and survival time were analyzed.Results: Advanced stage glioma  was detected at 21 days postimplantation. Bioluminescence showed that the

  6. D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate.

    Science.gov (United States)

    El Sayed, S M; Abou El-Magd, R M; Shishido, Y; Chung, S P; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-01-01

    Glioma tumors are refractory to conventional treatment. Glioblastoma multiforme is the most aggressive type of primary brain tumors in humans. In this study, we introduce oxidative stress-energy depletion (OSED) therapy as a new suggested treatment for glioblastoma. OSED utilizes D-amino acid oxidase (DAO), which is a promising therapeutic protein that induces oxidative stress and apoptosis through generating hydrogen peroxide (H2O2). OSED combines DAO with 3-bromopyruvate (3BP), a hexokinase II (HK II) inhibitor that interferes with Warburg effect, a metabolic alteration of most tumor cells that is characterized by enhanced aerobic glycolysis. Our data revealed that 3BP induced depletion of energetic capabilities of glioma cells. 3BP induced H2O2 production as a novel mechanism of its action. C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation, clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes. DAO gene therapy using atelocollagen as an in vivo transfection agent proved effective in a glioma tumor model in Sprague-Dawley (SD) rats, especially after combination with 3BP. OSED treatment was safe and tolerable in SD rats. OSED therapy may be a promising therapeutic modality for glioma. PMID:21921941

  7. Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells.

    Science.gov (United States)

    Ma, Jian; Yang, Yan-Ru; Chen, Wei; Chen, Mei-Hua; Wang, Hao; Wang, Xiao-Dan; Sun, Li-Li; Wang, Feng-Ze; Wang, De-Cai

    2016-08-01

    Although temozolomide (TMZ) is the most effective chemotherapy agent for glioma, chemotherapy resistance has limited its clinical use. Fluoxetine (FLT), which is widely used in cancer-related depression, has exhibited potent anticancer properties in different cancer cell types. The aim of this study was i) to evaluate the antitumor mechanism of FLT, and ii) to further evaluate the effects of a combination of FLT and TMZ on glioma cells. Glioma cell lines were exposed to FLT and/or TMZ. Cell viability and apoptosis were examined by CCK-8 assay, flow cytometry and caspase-3 activity assay, respectively. The expression of endoplasmic reticulum-stress (ERS) apoptosis-related proteins was measured using real-time PCR and western blotting. Synergism between the two drugs was evaluated by the combination index (CI) through CompuSyn software. FLT significantly and dose-dependently inhibited the proliferation of various glioma cell lines, and rat glioma C6 cells had a highly sensitive response to the addition of FLT. FLT treatment increased the early apoptosis rate, induced typical apoptotic morphology in the C6 cells and activated caspase-3 with no change in the mitochondrial membrane potential. Further study showed that FLT activated the ERS marker, CHOP. This induction was associated with activation of the PERK-eIF2α-ATF4 and ATF6 cascade. Concomitantly, GADD34, a downstream molecule of CHOP, was also increased. Combined FLT and TMZ treatment showed a synergistic cytotoxic effect in the C6 glioma cells. Knockdown of CHOP expression abolished the synergistic effect of FLT and TMZ in the C6 cells, which suggests that FLT may sensitize glioma cells to TMZ through activation of the CHOP-dependent apoptosis pathway. These results revealed that FLT induced glioma cell apoptosis and sensitized glioma cells to TMZ through activation of the CHOP‑dependent apoptosis pathway. The present study provides a primary basis for using the combination of these drugs in patients with

  8. Presence of insulin receptors in cultured glial C6 cells. Regulation by butyrate.

    Science.gov (United States)

    Montiel, F; Ortiz-Caro, J; Villa, A; Pascual, A; Aranda, A

    1989-01-01

    The presence of insulin receptor and its regulation by butyrate and other short-chain fatty acids was studied in C6 cells, a rat glioma cell line. Intact C6 cells bind 125I-insulin in a rapid, reversible and specific manner. Scatchard analysis of the binding data gives typical curvilinear plots with apparent affinities of approx. 6 nM and 70 nM for the low-affinity (approx. 90% of total) and high-affinity (approx. 10% of total) sites respectively. Incubation with butyrate results in a time- and dose-dependent decrease of insulin binding to C6 cells. A maximal effect was found with 2 mM-butyrate that decreased the receptor by 40-70% after 48 h. Butyrate decreased numbers of receptors of both classes, but did not significantly alter receptor affinity. Other short-chain fatty acids, as well as keto acids, had a similar effect, but with a lower potency. Cycloheximide caused an accumulation of insulin receptors at the cell surface, since insulin binding increased and receptor affinity did not change after incubation with the inhibitor. Simultaneous addition of butyrate and cycloheximide abolished the loss of receptors produced by the fatty acid. In cells preincubated with butyrate, cycloheximide also produced a large increase in receptor numbers, showing that in the absence of new receptor synthesis a large pool of receptors re-appears at the surface of butyrate-treated cells. PMID:2930502

  9. Significance of the expression of green fluorescent protein on detection of glioma invasion in vivo

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the invasion and metastasis of gliomain vivo by xenotransplanted tumor established by implanting C6 glioma cells transfected with green fluorescent protein (GFP) gene in vitro into the brain of SD rats. Methods: C6 cells were transfected with a plasmid vector (pEGEP-N3) containing the GFP gene. Stable GFP-expressing clones were isolated and performed examination by flow cytometry and electron microscope. GFP-expressing cells were stereotactically injected into the brain parenchyma of SD rats to establish xenotransplanted tumor. Four weeks later rats were killed and continuous brain sections respectively were examined by HE staining, immunohistochemistry method and fluorescence microscopy for detection of tumor cell invasion. Xenotransplanted tumor was primarily cultured to determine the storage of exotic GFP gene in vivo. Results: There were not obvious changes in cell cycle and ultrastructure for the cells transfected with GFP gene. C6 cells transfected with GFP gene maintained stable high-level GFP expression in the central nervous system during their growth in vivo. GFP fluorescence clearly demarcated the primary tumor margin and readily allowed for the detection of distant invasion on the single-cell level, which was evidently superior to HE and immunohistochemistry staining. There was not GFP gene loss of transfected cells in vivo. Conclusions: It is suggested that C6 cells transfected with GFP gene can be visualized by fluorescent microscopy after intracranial implantation. This model is an excellent experimental animal model in research on invasion of glioma.

  10. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  11. Comparative study on the stem cell phenotypes of C6 cells under different culture conditions

    Institute of Scientific and Technical Information of China (English)

    ZHANG Suo-jun; YE Fei; XIE Rui-fan; HU Feng; WANG Bao-feng; WAN Feng; GUO Dong-sheng; LEI Ting

    2011-01-01

    Background Glioma stem cell (GSC) hypothesis posits that a subpopulation of cells within gliomas have true clonogenic and tumorigenic potential. Significantly, a more controversial correlate to GSC is that cells in different culture conditions might display distinct stem cell properties. Considering these possibilities, we applied an approach comparing stem cell characteristics of C6 glioma cells under different culture conditions.Methods C6 cells were cultured under three different growth conditions, i.e., adherent growth in conventional 10% serum medium, non-adherent spheres growth in serum-free medium, as well as adherent growth on laminin-coated flask in serum-free medium. Growth characteristics were detected contrastively through neurosphere formation assay and cell cycle analysis. Markers were determined by immunofluorescence, relative-quantitative reverse transcription (RT)-PCR,Western blotting and flow cytometry. Side population cells were analyzed via flow cytometry. Tumor models were detected by magnetic resonance imaging and hematoxylin & eosin staining. Data analyses were performed with SPSS software (17.0).Results C6 cells (C6-Adh, C6-SC-Sph and C6-SC-Adh) showed distinctive growth patterns and proliferation capacity.Compared to suspending C6-SC-Sph, adherent C6-Adh and C6-SC-Adh displayed higher growth ratio. C6-SC-Sph and C6-SC-Adh showed enhanced capability of neurosphere formation and self-renewal. High side population ratio was detected in C6-SC-Sph and C6-SC-Adh. CD133 was not detected in all three kinds of cells. Conversely, Nestin and β-Ⅲ-tubulin were demonstrated positive, nonetheless with no statistical significance (P >0.05). Interestingly, lower expression of glial fibrillary acidic protein was demonstrated in C6-SC-Sph and C6-SC-Adh. C6-Adh, C6-SC-Sph and C6-SC-Adh were all displayed in situ oncogenicity, while statistical difference of survival time was not confirmed.Conclusions C6 glioma cell line is endowed with some GSC

  12. Effect of combined treatment with x-irradiation and 5-fluorouracil in multicellular spheroids of rat glioma

    Energy Technology Data Exchange (ETDEWEB)

    Kuwahara, Kenji; Katakura, Ryuichi; Suzuki, Jiro; Sasaki, Takehito; Mori, Teruaki

    1987-12-01

    The effect of combined treatment with X-irradiation and 5-fluorouracil (5-Fu) on the spheroids of rat glioma clone-6 cells was compared with that on exponentially grown monolayer cells. Isobolographic analysis showed the effect of the combined treatment to be supra-additive in both multicellular spheroids and monolayer cells when irradiation followed 24 hours of treatment with 5-Fu. X-irradiation prior to 5-Fu treatment showed an additive effect. The effect of X-irradiation on spheroids was enhanced after 3 hours of 5-Fu treatment, whereas its effect on monolayer cells was augmented only when prior 5-Fu treatment exceeded 12 hours. Potentiation of the effect of X-irradiation on spheroids by prior treatment with 5-Fu is thought to be due to reoxygenation of previously hypoxic cells and partial synchronization of proliferating cells. These results suggest that when X-irradiation is applied shortly after 5-Fu treatment the effect on solid tumors is selectively enhanced, while the effect on actively proliferating normal tissues is reduced.

  13. Glioma cell density in a rat gene therapy model gauged by water relaxation rate along a fictitious magnetic field.

    Science.gov (United States)

    Liimatainen, Timo; Sierra, Alejandra; Hanson, Timothy; Sorce, Dennis J; Ylä-Herttuala, Seppo; Garwood, Michael; Michaeli, Shalom; Gröhn, Olli

    2012-01-01

    Longitudinal and transverse rotating-frame relaxation time constants, T(1) (ρ) and T(2) (ρ) , have previously been successfully applied to detect gene therapy responses and acute stroke in animal models. Those experiments were performed with continuous-wave irradiation or with frequency-modulated pulses operating in an adiabatic regime. The technique called Relaxation Along a Fictitious Field (RAFF) is a recent extension of frequency-modulated rotating-frame relaxation methods. In RAFF, spin locking takes place along a fictitious magnetic field, and the decay rate is a function of both T(1ρ) and T(2ρ) processes. In this work, the time constant characterizing water relaxation with RAFF (T(RAFF) ) was evaluated for its utility as a marker of response to gene therapy in a rat glioma model. To investigate the sensitivity to early treatment response, we measured several rotating-frame and free-precession relaxation time constants and the water apparent diffusion coefficients, and these were compared with histological cell counts in 8 days of treated and control groups of animals. T(RAFF) was the only parameter exhibiting significant association with cell density in three different tumor regions (border, intermediate, and core tissues). These results indicate that T(RAFF) may provide a marker to identify tumors responding to treatment. PMID:21721037

  14. Macrophages loaded with gold nanoshells for photothermal ablation of glioma: An in vitro model

    Science.gov (United States)

    Makkouk, Amani Riad

    The current median survival of patients with glioblastoma multiforme (GBM), the most common type of glioma, remains at 14.6 months despite multimodal treatments (surgery, radiotherapy and chemotherapy). This research aims to study the feasibility of photothermal ablation of glioma using gold nanoshells that are heated upon laser irradiation at their resonance wavelength. The novelty of our approach lies in improving nanoshell tumor delivery by loading them in macrophages, which are known to be recruited to gliomas via tumor-released chemoattractive agents. Ferumoxides, superparamagnetic iron oxide (SPIO) nanoparticles, are needed as an additional macrophage load in order to visualize macrophage accumulation in the tumor with magnetic resonance imaging (MRI) prior to laser irradiation. The feasibility of this approach was studied in an in vitro model of glioma spheroids with the use of continuous wave (CW) laser light for ablation. The optimal loading of both murine and rat macrophages with Ferumoxides was determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES). Higher concentrations of SPIO were observed in rat macrophages, and the optimal concentration was chosen at 100 microg Fe/ml. Macrophages were found to be very sensitive to near infra-red (NIR) laser irradiation, and their use as vehicles was thus not expected to hinder the function of loaded nanoshells as tumor-ablating tools. The intracellular presence of gold nanoshells in macrophages was confirmed with TEM imaging. Next, the loading of both murine and rat macrophages with gold nanoshells was studied using UV/Vis spectrophotometry, where higher nanoshell uptake was found in rat macrophages. Incubation of loaded murine and rat macrophages with rat C-6 and human ACBT spheroids, respectively, resulted in their infiltration of the spheroids. Subsequent laser irradiation at 55 W/cm2 for 10 min and follow-up of spheroid average diameter size over 14 days post-irradiation showed that

  15. 蒿甲醚对大鼠原位脑胶质瘤抑瘤及抗血管生成的实验研究%Study on Inhibitory Effects of Artemether on Brain Glioma Growth and Angiogenesis in SD Rats

    Institute of Scientific and Technical Information of China (English)

    伍治平; 朱启顺; 魏万里; 黄洁; 沈红梅; 童书云

    2012-01-01

    Objective To explore the inhibitory effect of artemether (Artrn) on glioma growth and angiogenesis in brain tumor bearing SD rats. Methods MTT (Methy thiazolyl tetrazolium) assay was used to evaluate the inhibitory effect of Artemether treatment on C6 glioma cells. 48 (24 male and 24 female) SD rats which were subcutaneous planted with SD rat C6 glioma cell (1× 1 06/ΜL) in cerebral cortex were divided randomly into 3 groups, each group had 8 rats. Blank control group:rats were orally given normal saline. Positive control group: rats were orally given Lomustine. Different artemether therapy groups: rats were given different doses of artemether. Treatment started on day 3 and continued until day 10 and SD rats were killed on day 20. Whole brain was fixed with 4% paraformaldehyde through alive left ventricle perfusion. The length- path and short- path of tumor each rat was measured by staff gauge in vertical and horizontal. Volume of tumor was calculated following formula: V (mm3) = a2bTT 6 (a:short- path, b:length- path) . Micro- vascular dense (MVD) was observed and countered under the microscopy by immunohistory chemistry. Results Inhibitory rates of Artemether at different dosages were 54.5%, 61.0%, 64.5% and 69.8%, respectively, and compared with blank control group, different experiment groups had significant difference (P = 0.000 respectively) . Micro-vascular dense in different therapy groups was significant lower than that in blank control group (P<0.05, P<0.01 respectively) and volume of brain glioma in different therapy groups was significant smaller than that in blank control group. Conclusions Artemether has inhibitory effect on brain glioma growth in SD rats. The mechanism of Artemether inhibiting brain glioma growth may be penetrating the blood- brain barrier by inhibiting angiogenesis.%目的 探讨蒿甲醚是否在选择性地杀伤SD大鼠原位脑胶质瘤的同时还具有抑制血管生成的作用.方法 采用四甲基偶氮唑蓝(MTT)法测

  16. 仙台病毒 Tianjin 株缺陷干扰颗粒体内外诱导大鼠脑胶质瘤细胞凋亡的研究%Study on the apoptosis of rat glioma cells induced by defective interfering particles of Sendai virus strain Tianjin

    Institute of Scientific and Technical Information of China (English)

    韩哲; 周洪经; 赵杰; 贾浩波; 陈曦腾; 石立莹

    2013-01-01

    Objective To investigate the apoptosis of rat glioma C 6 cells induced by defective in-terfering( DI) particles of Sendai virus strain Tianjin .Methods Rat glioma C6 cells were treated with dif-ferent titers of DI particles of Sendai virus strain Tianjin in vitro with culture media as negative control and intact virus as positive control .At different time point , cells were collected and their apoptosis was detected by DNA gel electrophorsis , TUNEL assay and AnnexinⅤ/PI double-labeled flow cytometry .The C6 glioma-bearing rat model was established and then treated with three intratumoral injections of DI particles , intact virus or saline three times at interval of two days .The antitumor effects of ID particles were evaluated through daily measuring of the tumor size .Hematoxylin-eosin( HE) staining was used to observe the patho-logical changes in tumor tissues .TUNEL assay was performed to detect the apoptosis of tumor tissues .Re-sults Rat glioma C6 cells treated with DI particles or intact virus in vitro showed typical DNA ladder pattern in agarose gel electrophoresis in a time-and dose-dependent manner .With the intervention of DI particles , the apoptosis rate of C6 cells showed a time-and dose-dependent manner and was significantly higher than that of the control group (P0.05).Conclusion The DI particles of Sendai virus strain Tianjin could induce apoptosis of rat glioma C 6 cells in a time-and dose-dependent manner both in vitro and in vivo, suggesting that the DI particles might be applicable for the treatment of neurogliocytoma in the future.%目的探讨仙台病毒Tianjin株缺损干扰颗粒( defective interfering particles ,DI颗粒)体内外诱导大鼠脑胶质瘤细胞C6凋亡的作用。方法将不同滴度仙台病毒Tianjin株DI颗粒分别与大鼠脑胶质瘤细胞C6作用不同时间,以培养基作为阴性对照、完整病毒作为阳性对照,通过DNA片段琼脂糖凝胶电泳、TUNEL染色、AnnexinⅤ-FITC/PI标记流

  17. Prodrug-activating Gene Therapy with Rabbit Cytochrome P450 4B1/4-Ipomeanol or 2-Aminoanthracene System in Glioma Cells

    International Nuclear Information System (INIS)

    We determined the cytotoxic properties of cytochrome P450 4B1 (CYP4B1) activated 4-ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) in rat glioma to verify the CYP4B1/4-ipo or 2-AA system for prodrug-activating gene therapy. The cyp4B1 cDNA was cloned into pcDNA3.1/ Hygro from rabbit lung total RNA (pcDAN-cyp4B1). Lentiviral vector encoding firefly luciferase (fLuc) was infected into C6 (rat glioma), and the fLuc-expressing cell was selected (C6-L). After transfection with pcDNA-cyp4B1 vector into C6-L, the single clone expressing cyp4B1 gene was selected (C6-CL). Prodrug for various concentrations of 4-ipo or 2-AA was treated for 72 h and 96 h. The cell survival rate of C6-CL was determined using MTT assay and trypan-blue dye exclusion methods. By RT-PCR analysis, fLuc and CYP4B1 expression was detected in C6-CL, but not in C6. MTT assay and trypan-blue dye exclusion showed that IC'5'0 of C6-CL was 0.3 mM and <0.01 mM after 4-ipo or 2-AA treatment at 96 h or 72 h exposure, respectively. Cell survivals of C6-CL were more rapidly reduced after treatment with 4-ipo or 2-AA than those of C6-L cells. The cell survival rate with MTT and trypan-blue dye exclusion assay was well correlated with fLuc activity in C6-CL cells. Conclusions CYP4B1-based prodrug-activating gene therapy may have the potential to treat glioma and the cytotoxic effects of CYP4B1 enzyme activated 4-ipo or 2-AA in C6, and could be clearly determined by bioluminescent activity in C6-CL.

  18. Picosecond fluorescence lifetime imaging microscope for imaging of living glioma cells

    Science.gov (United States)

    Fang, Qiyin; Wang, Jingjing; Sun, Yinghua; Vernier, Thomas; Papaioannou, Thanassis; Jo, Javier; Thu, Mya M.; Gundersen, Martin A.; Marcu, Laura

    2005-03-01

    In this communication, we report the imaging of living glioma cells using fluorescence lifetime imaging (FLIM) technique. The growing interests in developing novel techniques for diagnosis and minimally invasive therapy of brain tumor have led to microscopic studies of subcellular structures and intracellular processes in glioma cells. Fluorescence microscopy has been used with a number of exogenous molecular probes specific for certain intracellular structures such as mitochondria, peripheral benzodiazepine receptor (PBR), and calcium concentration. When probes with overlapping emission spectra being used, separate samples are required to image each probe individually under conventional fluorescence microscopy. We have developed a wide-field FLIM microscope that uses fluorescence lifetime as an additional contrast for resolving multiple markers in the same essay. The FLIM microscope consists of a violet diode laser and a nitrogen-pumped dye laser to provide tunable sub-nanosecond excitation from UV to NIR. The detection system is based on a time-gated ICCD camera with minimum 80 ps gate width. The performance of the system was evaluated using fluorescence dyes with reported lifetime values. Living rat glioma C6 cells were stained with JC-1 and Rhodamine 123. FLIM images were acquired and their lifetimes in living cells were found in good agreements with values measured in solutions by a time-domain fluorescence spectrometer. These results indicate that imaging of glioma cells using FLIM can resolve multiple spectrally-overlapping probes and provide quantitative functional information about the intracellular environment.

  19. Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling

    Institute of Scientific and Technical Information of China (English)

    DONG Jun; LAN Qing; HUANG Qiang; DAI Xing-liang; LU Zhao-hui; FEI Xi-feng; CHEN Hua; ZHANG Quan-bin; ZHAO Yao-dong; WANG Zhi-min; WANG Ai-dong

    2012-01-01

    Background The primary reasons for local recurrence and therapeutic failure in the treatment of malignant gliomas are the invasion and interactions of tumor cells with surrounding normal brain cells.However,these tumor cells are hard to be visualized directly in histopathological preparations,or in experimental glioma models.Therefore,we developed an experimental human dual-color in vivo glioma model,which made tracking solitary invasive glioma cells possible,for the purpose of visualizing the interactions between red fluorescence labeled human glioma cells and host brain cells.This may offer references for further studying the roles of tumor microenvironment during glioma tissue remodeling.Methods Transgenic female C57BL/6 mice expressing enhanced green fluorescent protein (EGFP) were crossed with male Balb/c nude mice.Then sib mating was allowed to occur continuously in order to establish an inbred nude mice strain with 50% of their offspring that are EGFP positive.Human glioma cell lines U87-MG and SU3 were transfected with red fluorescent protein (RFP) gene,and a rat C6 glioma cell line was stained directly with CM-Dil,to establish three glioma cell lines emitting red fluorescence (SU3-RFP,U87-RFP,and C6-CM-Dil).Red fluorescence tumor cells were inoculated via intra-cerebral injection into caudate nucleus of the EGFP nude mice.Tumor-bearing mice were sacrificed when their clinical symptoms appeared,and the whole brain was harvested and snap frozen for further analysis.Confocal laser scanning microscopy was performed to monitor the mutual interactions between tumor cells and host brain cells.Results Almost all the essential tissues of the established EGFP athymic Balb/c nude mice,except hair and erythrocytes,fluoresced green under excitation using a blue light-emitting flashlight with a central peak of 470 nm,approximately 50% of the offsprings were nu/nu EGFP+.SU3-RFP,U87-RFP,and C6-CM-Dil almost 100% expressed red fluorescence under the fluorescence

  20. Evaluation of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid accumulation in low-grade glioma in chemically induced rat models: PET and autoradiography compared with morphological images and histopathological findings

    International Nuclear Information System (INIS)

    Introduction: Magnetic resonance imaging (MRI) can have a problem to delineate diffuse gliomas with an intact blood–brain barrier (BBB) especially when a marked peritumoral edema is present. We evaluated the potential of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid (anti-18F-FACBC) positron emission tomography (PET) to delineate the extent of diffuse gliomas by comparing PET findings with autoradiography, in vivo and ex vivo MRI, and histopathology findings. Methods: Dynamic PET was performed in rats with N-ethyl-N-nitrosourea-induced glioma for 60 min after anti-18F-FACBC injection. Contrast-enhanced MRI was performed before or after PET. The PET images were fused with in vivo and ex vivo MR images, and histopathological images for direct comparisons. Autoradiograms were compared with the results of Evans Blue (EB) extravasation (to assess BBB integrity) and hematoxylin-eosin staining. Results: Histopathological examination, including EB extravasation assessment, and enhanced T1-weighted MRI identified several diffuse gliomas with slight BBB disruption, similar to low-grade human gliomas. Anti-18F-FACBC uptake was specific and high in the gliomas, irrespective of BBB integrity. Higher anti-18F-FACBC uptake corresponded to areas of T2 hyperintensity, independent of gadolinium enhancement. Ex vivo autoradiography also showed high anti-18F-FACBC accumulation in tumors lacking EB extravasation and a correlation between anti-18F-FACBC accumulation and tumor cell density, but not EB extravasation. Conclusions: Anti-18F-FACBC-PET allowed visualization of gliomas irrespective of BBB integrity. The tumor-to-normal uptake ratio of anti-18F-FACBC generally correlated with the relative cell density. Anti-18F-FACBC PET combined with MRI shows promise for preoperative glioma delineation. Advances in knowledge: Radiopharmaceuticals that cross the BBB, such as anti-18F-FACBC, are taken up by low-grade gliomas with equivocal MRI findings due to an intact BBB

  1. Comparative evaluation of gadoteridol versus gadopentetate dimeglumine for contrast-enhanced MRI in a rat brain glioma model at 1.5 and 3.0 T

    International Nuclear Information System (INIS)

    Objective: To compare gadoteridol and gadopentetate dimeglumine (Gd-DTPA) with respect to lesion enhancement in a rat brain glioma model at 1. 5 and 3.0 T. Methods: Glioma cells were injected into the brains of 42 male CDF (Fisher 344) rats through implanted cannula to create Glioma animal model. One week after implantation, all rats were randomly divided in to four groups which included 12, 10, 10, 10 rats. The comparisons included the contrast effect of gadoteridol versus gadopentetate dimeglumine at both 1.5 and 3.0 T. In addition, gadoteridol alone was evaluated by comparing the standard dose at both two field strengths and half dose at 3.0 T to a standard full dose at 1.5 T. Two MRI scans for different contrast agent injections were performed in each animal model with an interval of 24 hours. T1-weighted images were analyzed pre-contrast and at five time points (1, 3, 5, 7 and 9 min) post-contrast with respect to lesion signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast enhancement (CE). Student t test was used for statistics. Results: The mean SNR, CNR, and CE were respectively 54.4±3.2, 17.0±3.3 and 20.8±3.4 with gadopentetate dimeglumine versus 53.2±3.2, 17.2±3.1 and 20.8±3.2 with gadoteridol at 1.5 T at every postconuast time point (t=2.247, 0.403, 0.076, P>0.05). The mean SNR, CNR, and CE were respectively 94.8±7.1, 38.0±6.0 and 45.0±6.3 with gadopentetate dimeglumine versus 95.5±2.9, 37.2±2.7 and 45.6±2.8 with gadoteridol at 3.0 T (t= 0.303, 0.573, 0.357, P>0.05). No statistically significant differences were found in these parameters between the two agents at any time point at either field strength. Standard dose gadoteridol demonstrated significant improvements in SNR (51.9±3.0 at 1.5 T vs 86.1±4.9 at 3.0 T), CNR (15.6±3.0 at 1.5 T vs 27.4±5.0 at 3.0 T) and CE (18.6±3.0 at 1.5 T vs 37.3±5.3 at 3.0 T) at 3.0 T as compared to 1.5 T at every time post-contrast (t=36.227, 11.977, 17.106, P0.05). Conclusions

  2. MAGI3 Suppresses Glioma Cell Proliferation via Upregulation of PTEN Expression

    Institute of Scientific and Technical Information of China (English)

    MA Qian; ZHAO Ji Zong; HE Jun Qi; ZHANG Yan; MENG Ran; XIE Kun Ming; XIONG Ying; LIN Song; HE Zong Lin K; TAO Tao; YANG Ying

    2015-01-01

    Objective To investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation. Methods The expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA). Results Expression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples. Conclusion The loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

  3. Enhancement of Raman Light Scattering in Dye-Labeled Rat Glioma Cells by Langmuir-Blodgett CNT-Bundles Arranged on Metal-Containing Conducting Polymer Film

    CERN Document Server

    Egorov, A S; Grushevskaya, H V; Krot, V I; Krylova, N G; Lipnevich, I V; Orekhovskaya, T I; Shulitsky, B G

    2015-01-01

    We have fabricated layered nanocomposite consisting of a nanoporous anodic alumina sublayer (AOA), an ultrathin metal-containing polymer Langmuir-Blodgett (LB) film coating AOA, and multi-walled carbon nanotube (MCNT) - bundles which are arranged on the LB-film. MCNTs were preliminarily chemically modified by carboxyl groups and functionalized by stearic acid. We have experimentally observed an enhancement of Raman light scattering on surface plasmons in the LB-monolayers. This enhancement is due to charge and energy transfer. We demonstrate that propidium iodide (PI) fluorescence is quenched by the MCNT-bundles. A method of two-dimensional system imaging based on the MCNT-enhanced Raman spectroscopy has been proposed. This method has been applied to visualize focal adhesion sites on membranes of living PI-labeled rat glioma cells.

  4. Reproducibility of O-(2-{sup 18}F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Stegmayr, Carina; Schoeneck, Michael; Oliveira, Dennis; Willuweit, Antje [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); Filss, Christian; Coenen, Heinz H.; Langen, Karl-Josef [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Galldiks, Norbert [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine, Research Center Juelich, Juelich (Germany); University of Aachen, Department of Nuclear Medicine and Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Juelich (Germany)

    2016-06-15

    Positron emission tomography (PET) using O-(2-{sup 18}F-fluoroethyl)-L-tyrosine ({sup 18}F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of {sup 18}F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy. F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of {sup 18}F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of {sup 18}F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC). The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC. TBR of {sup 18}F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation. (orig.)

  5. Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles.

    Science.gov (United States)

    Kanazawa, Takanori; Morisaki, Kazuki; Suzuki, Shohei; Takashima, Yuuki

    2014-05-01

    New therapeutic strategies are required to develop candidate drugs and ensure efficient delivery of these drugs to the brain and the central nervous system (CNS). Small interfering RNA (siRNA)-based therapies have been investigated as potential novel approaches for the treatment of brain disorders. Previously, we showed that Tat, a cell-penetrating peptide derived from HIV-Tat, and the modified block copolymers (MPEG-PCL-Tat) can form stable complexes with siRNA or can be loaded with an anticancer drug and efficiently deliver the drugs to the brain tissue via intranasal delivery. In this study, to develop a novel, efficient, and safe therapeutic strategy for managing brain disorders, we used MPEG-PCL-Tat micelles with a nose-to-brain delivery system to investigate its therapeutic effects on a rat model of malignant glioma using siRNA with a Raf-1 (siRaf-1)/camptothecin (CPT) codelivery system. MPEG-PCL-Tat and CPT-loaded MPEG-PCL-Tat can form a stable complex with siRNA with a particle size from 60 to 200 nm and a positive charge at N/P ratios up to 5. Additionally, MPEG-PCL-Tat/siRaf-1 and CPT-loaded MPEG-PCL-Tat/siRaf-1 have fostered cell death in rat glioma cells after the high cellular uptake of siRaf-1/drug by the MPEG-PCL-Tat carrier. Furthermore, compared to the unloaded MPEG-PCL-Tat/siRaf-1 complex, a CPT-loaded MPEG-PCL-Tat/siRaf-1 complex achieved the high therapeutic effect because of the additive effects of CPT and siRaf-1. These results indicate that drug/siRNA codelivery using MPEG-PCL-Tat nanomicelles with nose-to-brain delivery is an excellent therapeutic approach for brain and CNS diseases.

  6. Reproducibility of O-(2-18F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of 18F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy. F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of 18F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of 18F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC). The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC. TBR of 18F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation. (orig.)

  7. Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats.

    Science.gov (United States)

    Tyler, Betty; Wadsworth, Scott; Recinos, Violette; Mehta, Vivek; Vellimana, Ananth; Li, Khan; Rosenblatt, Joel; Do, Hiep; Gallia, Gary L; Siu, I-Mei; Wicks, Robert T; Rudek, Michelle A; Zhao, Ming; Brem, Henry

    2011-07-01

    Rapamycin, an anti-proliferative agent, is effective in the treatment of renal cell carcinoma and recurrent breast cancers. We proposed that this potent mammalian target of rapamycin inhibitor may be useful for the treatment of gliomas as well. We examined the cytotoxicity of rapamycin against a rodent glioma cell line, determined the toxicity of rapamycin when delivered intracranially, and investigated the efficacy of local delivery of rapamycin for the treatment of experimental malignant glioma in vivo. We also examined the dose-dependent efficacy of rapamycin and the effect when locally delivered rapamycin was combined with radiation therapy. Rapamycin was cytotoxic to 9L cells, causing 34% growth inhibition at a concentration of 0.01 µg/mL. No in vivo toxicity was observed when rapamycin was incorporated into biodegradable caprolactone-glycolide (35:65) polymer beads at 0.3%, 3%, and 30% loading doses and implanted intracranially. Three separate efficacy studies were performed to test the reproducibility of the effect of the rapamycin beads as well as the validity of this treatment approach. Animals treated with the highest dose of rapamycin beads tested (30%) consistently demonstrated significantly longer survival durations than the control and placebo groups. All dose-escalating rapamycin bead treatment groups (0.3%, 3% and 30%), treated both concurrently with tumor and in a delayed manner after tumor placement, experienced a significant increase in survival, compared with controls. Radiation therapy in addition to the simultaneous treatment with 30% rapamycin beads led to significantly longer survival duration than either therapy alone. These results suggest that the local delivery of rapamycin for the treatment of gliomas should be further investigated.

  8. Synergistic inhibition of angiogenesis and glioma cell-induced angiogenesis by the combination of temozolomide and enediyne antibiotic lidamycin.

    Science.gov (United States)

    Li, Xing-Qi; Ouyang, Zhi-Gang; Zhang, Sheng-Hua; Liu, Hong; Shang, Yue; Li, Yi; Zhen, Yong-Su

    2014-04-01

    Present work mainly evaluated the inhibitory effects of lidamycin (LDM), an enediyne antibiotic, on angiogenesis or glioma-induced angiogenesis in vitro and in vivo, especially its synergistic anti-angiogenesis with temozolomide (TMZ). LDM alone efficiently inhibited proliferations and induced apoptosis of rat brain microvessel endothelial cells (rBMEC). LDM also interrupted the tube formation of rat brain microvessel endothelial cells (rBMEC) and rat aortic ring spreading. The blockade of rBMEC invasion and C6 cell-induced rBMEC migration by LDM was associated with decrease of VEGF secretion in a co-culture system. TMZ dramatically potentiated the effects of LDM on anti-proliferation, apoptosis induction, and synergistically inhibited angiogenesis events. As determined by western blot and ELISA, the interaction of tumor cells and the rBMEC was markedly interrupted by LDM plus TMZ with synergistic regulations of VEGF induced angiogenesis signal pathway, tumor cell invasion/migration, and apoptosis signal pathway. Immunofluorohistochemistry of CD31 and VEGF showed that LDM plus TMZ resulted in synergistic decrease of microvessel density (MVD) and VEGF expression in human glioma U87 cell subcutaneous xenograft. This study indicates that the high efficacy of LDM and the synergistic effects of LDM plus TMZ against glioma are mediated, at least in part, by the potentiated anti-angiogenesis. PMID:24424202

  9. Enhanced invasion in vitro and the distribution patterns in vivo of CD133+ glioma stem cells

    Institute of Scientific and Technical Information of China (English)

    YU Sheng-ping; YANG Xue-jun; ZHANG Bin; MING Hao-lang; CHEN Cong; REN Bing-cheng; LIU Zhi-feng; LIU Bin

    2011-01-01

    Background Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy.Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies,it is not clear whether cancer stem cells are involved in invasiveness.This study aimed to assess invasive ability of glioma stem cells (GSCs) derived from C6 glioma cell line and the distribution patterns of GSCs in Sprague-Dawley (SD) rat brain tumor.Methods Serum-free medium culture and magnetic isolation were used to gain purely CD133+ GSCs.The invasive stem cell markers and luxol fast blue staining for white matter tracts were performed to show the distribution patterns of GSCs in brain tumor of rats and the relationship among GSCs,vessels,and white matter tracts.The results of matrigel invasion assay were estimated using the Student's t test and the analysis of Western blotting was performed using the one-way analysis of variance (ANOVA) test.Results CD133+GSCs(number:85.3±4.1)were significantly more invasive in vitro than matched CD133- cells(number:25.9±3.1) (t=14.5,P <0.005).GSCs invaded into the brain diffusely and located in perivascular niche of tumor-brain interface or resided within perivascular niche next to white fiber tracts.The polarity of glioma cells containing GSCs was parallel to the white matter tracts.Conclusions Our data suggest that CD133+ GSCs exhibit more aggressive invasion in vitro and GSCs in vivo probably disseminate along the long axis of blood vessels and transit through the white matter tracts.The therapies targeting GSCs invasion combined with traditional glioblastoma multiforme therapeutic paradigms might be a new approach for avoiding malignant glioma recurrence.

  10. A Spectroscopic Survey of Electronic Transitions of C$_6$H, $^{13}$C$_6$H, and C$_6$D

    CERN Document Server

    Bacalla, Xavier; Linnartz, Harold; Ubachs, Wim; Zhao, Dongfeng

    2016-01-01

    Electronic spectra of C$_6$H are measured in the $18\\,950-21\\,100$ cm$^{-1}$ domain using cavity ring-down spectroscopy of a supersonically expanding hydrocarbon plasma. In total, 19 (sub)bands of C$_6$H are presented, all probing the vibrational manifold of the B$^2\\Pi$ electronically excited state. The assignments are guided by electronic spectra available from matrix isolation work, isotopic substitution experiments (yielding also spectra for $^{13}$C$_6$H and C$_6$D), predictions from ab initio calculations as well as rotational fitting and vibrational contour simulations using the available ground state parameters as obtained from microwave experiments. Besides the $0_0^0$ origin band, three non-degenerate stretching vibrations along the linear backbone of the C$_6$H molecule are assigned: the $\

  11. Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model

    Science.gov (United States)

    Aryal, Muna; Park, Juyoung; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan

    2015-03-01

    Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood-brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg-1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823  ±  600, 1817  ±  732 and 2432  ±  448 ng g-1) in the control tumors at 9, 14 and 17 d. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P drug delivery are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found to be variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da; hydrodynamic diameter: ≃2 nm). It may be necessary

  12. Photochemical internalization of bleomycin for glioma treatment

    Science.gov (United States)

    Mathews, Marlon S.; Blickenstaff, Joseph W.; Shih, En-Chung; Zamora, Genesis; Vo, Van; Sun, Chung-Ho; Hirschberg, Henry; Madsen, Steen J.

    2012-05-01

    We study the use of photochemical internalization (PCI) for enhancing chemotherapeutic response to malignant glioma cells in vitro. Two models are studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared to AlPcS2a-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS2a (PDT effect), bleomycin (chemotherapy effect), or AlPcS2a+bleomycin (PCI effect) and were illuminated (670 nm). Toxicity was evaluated using colony formation assays or spheroid growth kinetics. F98 cells in monolayer/spheroids were not particularly sensitive to the effects of low radiant exposure (1.5 J/cm2 @ 5 mW/cm2) AlPcS2a-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations-incubation of F98 cells in 0.1 μg/ml for 4 h resulted in 80% survival, but less toxic in human glioma spheroids respectively. In both in vitro systems investigated, a significant PCI effect is seen. PCI using 1.5 J/cm2 together with 0.25 μg/ml bleomycin resulted in approximately 20% and 18% survival of F98 rat glioma cells and human glioma spheroids, respectively. These results show that AlPcS2a-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.

  13. Improved survival in rats with glioma using MRI-guided focused ultrasound and microbubbles to disrupt the blood-brain barrier and deliver Doxil

    Science.gov (United States)

    Aryal, Muna; Zhi Zhang, Yong; Vykhodtseva, Natalia; Park, Juyoung; Power, Chanikarn; McDannold, Nathan

    2012-02-01

    Blood-brain-barrier (BBB) limits the transportation of most neuropeptides, proteins (enzymes, antibodies), chemotherapeutic agents, and genes that have therapeutic potential for the treatment of brain diseases. Different methods have been used to overcome this limitation, but they are invasive, non-targeted, or require the development of new drugs. We have developed a method that uses MRI-guided focused ultrasound (FUS) combined with circulating microbubbles to temporarily open BBB in and around brain tumors to deliver chemotherapy agents. Here, we tested whether this noninvasive technique could enhance the effectiveness of a chemotherapy agent (Doxil). Using 690 kHz FUS transducer and microbubble (Definity), we induced BBB disruption in intracranially-implanted 9L glioma tumors in rat's brain in three weekly sessions. Animals who received BBB disruption and Doxil had a median survival time of 34.5 days, which was significantly longer than that found in control animals which is 16, 18.5, 21 days who received no treatment, BBB disruption only and Doxil only respectively This work demonstrates that FUS technique has promise in overcoming barriers to drug delivery, which are particularly stark in the brain due to the BBB.

  14. Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

    Energy Technology Data Exchange (ETDEWEB)

    Barth, Rolf F., E-mail: rolf.barth@osumc.edu [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Yang Weilian; Huo Tianyao [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Riley, Kent J.; Binns, Peter J. [Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Grecula, John C., E-mail: john.grecula@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Gupta, Nilendu, E-mail: nilendu.gupta@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Rousseau, Julia, E-mail: julia.rousseau@yahoo.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France); Elleaume, Helene, E-mail: h.elleaume@esrf.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France)

    2011-12-15

    In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood-brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.

  15. Predicting in vivo glioma growth with the reaction diffusion equation constrained by quantitative magnetic resonance imaging data

    Science.gov (United States)

    Hormuth, David A., II; Weis, Jared A.; Barnes, Stephanie L.; Miga, Michael I.; Rericha, Erin C.; Quaranta, Vito; Yankeelov, Thomas E.

    2015-07-01

    Reaction-diffusion models have been widely used to model glioma growth. However, it has not been shown how accurately this model can predict future tumor status using model parameters (i.e., tumor cell diffusion and proliferation) estimated from quantitative in vivo imaging data. To this end, we used in silico studies to develop the methods needed to accurately estimate tumor specific reaction-diffusion model parameters, and then tested the accuracy with which these parameters can predict future growth. The analogous study was then performed in a murine model of glioma growth. The parameter estimation approach was tested using an in silico tumor ‘grown’ for ten days as dictated by the reaction-diffusion equation. Parameters were estimated from early time points and used to predict subsequent growth. Prediction accuracy was assessed at global (total volume and Dice value) and local (concordance correlation coefficient, CCC) levels. Guided by the in silico study, rats (n = 9) with C6 gliomas, imaged with diffusion weighted magnetic resonance imaging, were used to evaluate the model’s accuracy for predicting in vivo tumor growth. The in silico study resulted in low global (tumor volume error 0.92) and local (CCC values >0.80) level errors for predictions up to six days into the future. The in vivo study showed higher global (tumor volume error >11.7%, Dice silico study shows that model parameters can be accurately estimated and used to accurately predict future tumor growth at both the global and local scale. However, the poor predictive accuracy in the experimental study suggests the reaction-diffusion equation is an incomplete description of in vivo C6 glioma biology and may require further modeling of intra-tumor interactions including segmentation of (for example) proliferative and necrotic regions.

  16. Therapeutic effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and radiation on the rat glioma

    International Nuclear Information System (INIS)

    The effect of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(chloroethyl)-3-nitrosourea hydrochloride (ACNU) or x radiation on the rat glioma clone-6 cells (RG cells) was analyzed by colony formation assay in vitro. The surviving fraction after administration of ACNU 100 μg/ml showed a biphasic curve with a break point about 90 min and 50% survival at 15 min. The dose-survival curve for ACNU (120 min. exposure) showed the existence of a shoulder, at 0 - 25 μg/ml, with Do of 13 μg/ml. The dose-survival curve for x-rays showed Dq-490 rad, Do = 220 rad, and an extrapolation number (n) = 3.1. It was found that when x-rays were given more than 3 hours after ACNU administration, the surviving fraction was smaller than when ACNU and x-rays were given in quick succession, but the effectiveness of the combination was revealed to be additive of ACNU and radiation alone. The lethal effects of ACNU and radiation on normal glia like cells of new born rats were examined Do was 4 μg/ml for ACNU and 180 rad for x-rays, and Dq was 150 rad for x-rays, but not detected for ACNU. In vivo measurements using subcutaneous RG cell tumors showed synergistic increase in doubling time when the tumors were irradiated with x-rays (1000 rad) at 3 to 12 hours after ACNU administration (10 mg/kg), while no synergistic increase of survival was observed. These findings not only indicated that combinations of ACNU and radiation showed synergistic cell-killing effects on tumor growth but also suggested that the effects may have occurred in normal tissues. (Kondo, M.)

  17. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  18. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    International Nuclear Information System (INIS)

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of 3H-labeled PK 11195 [1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] or [3H]flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes

  19. Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells

    Science.gov (United States)

    YU, ZHIYUN; ZHAO, GANG; LI, PENGLIANG; LI, YUNQIAN; ZHOU, GUANGTONG; CHEN, YONG; XIE, GUIFANG

    2016-01-01

    Glioblastoma is the most common and most aggressive brain tumor in adults. The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas, but it is not curative. The difficulties in treating glioblastoma may be as a result of the presence of glioma stem cells (GSCs), which are a source of relapse and chemoresistance. Another reason may be that endogenous Akt kinase activity may be activated in response to clinically relevant concentrations of TMZ. Akt activation is correlated with the increased tumorigenicity, invasiveness and stemness of cancer cells and overexpression of an active form of Akt increases glioma cell resistance to TMZ. Mounting evidence has demonstrated that cancer stem cells are preferentially sensitive to an inhibitor of Akt and down-regulation of the PI3K/Akt pathway may enhance the cytotoxicity of TMZ. Metformin (MET), the first-line drug for treating diabetes, it has been proved that it reduces AKT activation and selectively kills cancer stem cells, but whether it can potentiate the cytotoxicity of TMZ for GSCs remains unknown. In the present study, the GSCs isolated from human glioma cell line U87 and Rat glioma cell line C6, in vitro treatment with TMZ either alone or with MET. The present study demonstrates that MET acts synergistically with TMZ in inhibiting GSCs proliferation and generating the highest apoptotic rates when compared to either drug alone. These findings implicate that GSCs cytotoxicity mediated by TMZ may be stimulated by MET, have a synergistic effect, but the definite mechanisms remain elusive. PMID:27073554

  20. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects.

    Science.gov (United States)

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Chung, S P; Diem, T H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-02-01

    Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner. PMID:22318356

  1. Overexpression of high molecular weight FGF-2 forms inhibits glioma growth by acting on cell-cycle progression and protein translation

    International Nuclear Information System (INIS)

    In order to clarify the role of HMW FGF-2 in glioma development and angiogenesis, we over-expressed different human FGF-2 isoforms in C6 rat glioma cell line using a tetracycline-regulated expression system. Phenotypic modifications were analyzed in vitro and compared to untransfected cells or to cells over-expressing 18 kDa FGF-2 or all FGF-2 isoforms. In particular, we demonstrate that HMW FGF-2 has unique features in inhibiting glioma cell proliferation. HMW FGF-2 expressing cells showed a cell-cycle arrest at the G2M, demonstrating a role of HMW FGF-2 in controlling the entry in mitosis. Moreover, hydroxyurea was ineffective in blocking cells at the G1S boundary when HMW FGF-2 was expressed. We also show that the HMW FGF-2 isoforms inhibit 4E-BP1 phosphorylation at critical sites restoring the translation inhibitory activity of 4E-BP1. In vivo, inhibition of tumor growth was observed when cells expressed HMW FGF-2. This indicates that HMW FGF-2 inhibits tumor growth in glioma cells by acting on cell-cycle progression and protein translation

  2. P16.31THERANOSTIC APPLICATION OF WATER-SOLUBLE GADOLINIUM FULLERENE (GD@FUL) IN EXPERIMENTAL GLIOMA MODEL

    Science.gov (United States)

    Shevtsov, M.; Nikolaev, B.; Marchenko, Y.; Yakovleva, L.; Dobrodumov, A.; Török, G.; Pitkin, E.; Lebedev, V.

    2014-01-01

    Glioblastoma multiforme (GMB) is a highly invasive brain tumour with poor prognosis. Alternative treatments offering a better outcome are needed. Novel approach could be based on gadofullerenes that can be used as diagnostic MR imaging contrast agent and as a therapeutic drug. Water soluble gadofullerene Gd@Ful with composition Gd@C82(OH)x x ≥20 was synthesized for theranostic study. Nanosuspensions of Gd@Ful were used for magnetic relaxation measurements in vitro and for MR imaging of a rat with intracranially implanted C6 glioma. Gd@Ful was shown to reduce proton relaxation times in vitro, and provide dual contrast of T1- and T2-weighted images in a rat brain tumour model after paramagnetic intravenous delivery. Magnetic relaxation times and relaxivity of water protons under action of Gd@Ful were strongly shortened due to cluster formation and increase of motional correlation times of protons in the vicinity of the fulleren cage. The Gd@Ful administration promoted the improvement of glioma contrast enhancement at T2-weighted images due to accumulation of paramagnetic substance at the tumour site. The contrast efficiency of Gd@Ful corresponds to the characteristics of negative contrast agent. Retention of the Gd@Ful in the C6 glioma provides not only the tumor contrast enhancement but also has a high therapeutic relevance. We observed the increased survival rates in animals that were intravenously administered with Gd@Ful. Thus, in experimental group the survival was 75% higher then in the control group, constituting 34.2 ± 9.94 and 19.5 ± 3.02 days respectively (P < 0.001). The Gd@Ful solution is shown to be a contrast enhancer with high anti-tumour therapeutic potency.

  3. Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Hardeep Kataria

    Full Text Available Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha, also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6 and human neuroblastoma (IMR-32 cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.

  4. Using of the surface plasmon resonance cytosensor for real-time and non-invasive monitoring of cellular effects in living C6 cells induced by PMA

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Developing novel instruments and technologies for spatio-temporal and dynamic measurements of the intricate cellular effects involving molecular translocation, signal transduction, and molecular interactions inside living cells is essential for the cell and molecular biology science. For the purpose of monitoring and investigating molecular events in living cells at real-time, the surface plasmon resonance based cytosensor (SBCS) for cell culturing and signal monitoring was established, and on the basis of it, the corresponding technology was also established by monitoring and analyzing SPR responses induced in rat C6 glioma cells by phorbol 12-myristate 13-acetate (PMA). The SPR signals induced by PMA in living C6 cells were significantly different from those groups without cells. These responses were strongly dependent on and saturable to the concentrations of PMA, and could be suppressed by the specific and potent PKC inhibitors, which indicated that the measured signal could be the reflection of the redistribution of intracellular components near the cell membrane triggered by the activation of PKC. This research provides a quantitative and non-invasive technique to study the spatio-temporal characteristics of the cellular effects in living cells at real-time. Furthermore, this technology could also be widely used in the basic research as well as applied realms, such as space effects evaluation, environmental safety assessment, biological weapon detection, cellular and molecular research, and drug screening.

  5. Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer

    Directory of Open Access Journals (Sweden)

    Gao S

    2015-12-01

    Full Text Available Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,* 1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf-modified polyamidoamine dendrimer (PAMAM was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL-encoding plasmid open reading frame (pORF-hTRAIL, Trail, was condensed by Tf-modified PAMAM to form nanoparticles (NPs. PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days, temozolomide (24.5 days, PAMAM-PEG-Tf/pEGFP (19 days, or saline (17 days. The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the

  6. Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION-cmHsp70.1)

    Science.gov (United States)

    Shevtsov, Maxim A.; Nikolaev, Boris P.; Ryzhov, Vyacheslav A.; Yakovleva, Ludmila Y.; Marchenko, Yaroslav Y.; Parr, Marina A.; Rolich, Valerij I.; Mikhrina, Anastasiya L.; Dobrodumov, Anatolii V.; Pitkin, Emil; Multhoff, Gabriele

    2015-12-01

    The stress-inducible 72 kDa heat shock protein Hsp70 is known to be expressed on the membrane of highly aggressive tumor cells including high-grade gliomas, but not on the corresponding normal cells. Membrane Hsp70 (mHsp70) is rapidly internalized into tumor cells and thus targeting of mHsp70 might provide a promising strategy for theranostics. Superparamagnetic iron oxide nanoparticles (SPIONs) are contrast negative agents that are used for the detection of tumors with MRI. Herein, we conjugated the Hsp70-specific antibody (cmHsp70.1) which is known to recognize mHsp70 to superparamagnetic iron nanoparticles to assess tumor-specific targeting before and after ionizing irradiation. In vitro experiments demonstrated the selectivity of SPION-cmHsp70.1 conjugates to free and mHsp70 in different tumor cell types (C6 glioblastoma, K562 leukemia, HeLa cervix carcinoma) in a dose-dependent manner. High-resolution MRI (11 T) on T2-weighted images showed the retention of the conjugates in the C6 glioma model. Accumulation of SPION-cmHsp70.1 nanoparticles in the glioma resulted in a nearly 2-fold drop of values in comparison to non-conjugated SPIONs. Biodistribution analysis using NLR-M2 measurements showed a 7-fold increase in the tumor-to-background (normal brain) uptake ratio of SPION-cmHsp70.1 conjugates in glioma-bearing rats in comparison to SPIONs. This accumulation within Hsp70-positive glioma was further enhanced after a single dose (10 Gy) of ionizing radiation. Elevated accumulation of the magnetic conjugates in the tumor due to radiosensitization proves the combination of radiotherapy and application of Hsp70-targeted agents in brain tumors.The stress-inducible 72 kDa heat shock protein Hsp70 is known to be expressed on the membrane of highly aggressive tumor cells including high-grade gliomas, but not on the corresponding normal cells. Membrane Hsp70 (mHsp70) is rapidly internalized into tumor cells and thus targeting of mHsp70 might provide a promising strategy

  7. Transcriptional regulation of 2',3'-cyclic nucleotide 3'-phosphodiesterase gene expression by cyclic AMP in C6 cells.

    Science.gov (United States)

    Gravel, M; Gao, E; Hervouet-Zeiber, C; Parsons, V; Braun, P E

    2000-11-01

    It was recently shown that the two transcripts encoding the isoforms of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP1 and CNP2) are differentially regulated during the process of oligodendrocyte maturation. In oligodendrocyte precursors, only CNP2 mRNA is present, whereas in differentiating oligodendrocytes, both CNP1 and CNP2 mRNAs are expressed. This pattern of CNP expression is likely due to stage-specific transcriptional regulation of the two CNP promoters during the process of oligodendrocyte differentiation. Here, we report the influence of increased intracellular cyclic AMP (cAMP) levels on the transcription of both CNP1 and CNP2 mRNAs in rat C6 glioma cells. We found that the transcription of CNP1 mRNA was significantly increased in comparison with that of CNP2 mRNA in cells treated with cAMP analogues to elevate intracellular cAMP levels. This up-regulation of CNP1 expression (a) is due to an increase of transcription, (b) requires de novo protein synthesis, and (c) requires the activity of protein kinase A. These results are physiologically significant and support the idea that a cAMP-mediated pathway is part of the molecular mechanisms regulating the expression of CNP1 in oligodendrocytes. The regulation of CNP1 promoter activity by cAMP was then investigated in stably transfected C6 cell lines containing various deletions of the CNP promoter directing the bacterial chloramphenicol acetyltransferase gene. We showed that the sequence between nucleotides -126 and -102 was essential for the cAMP-dependent induction of CNP1 expression. Gel retardation analysis showed that two protein-DNA complexes are formed between this sequence and nuclear factors from C6 cells treated or not treated with cAMP. This suggests that the induction of CNP1 mRNA transcription is not mediated by changes in binding of nuclear factors that interact directly with the -126/-102 sequence. Sequence analysis of this region revealed the presence of a putative activator protein-2 (AP

  8. 氧自由基与脑胶质瘤瘤周水肿关系的实验研究%Relationship Between Oxygen Free Radical and Peritumor Edema in Glioma

    Institute of Scientific and Technical Information of China (English)

    赵心同; 赵洪洋; 姚东晓; 王海均

    2011-01-01

    目的:探讨自由基和脑胶质瘤瘤周水肿的关系.方法:体外培养大鼠C6脑胶质瘤细胞株,采用立体定向技术将细胞株接种在右侧尾状核,建立大鼠脑胶质瘤模型,共60只,术后5天将荷瘤大鼠随机分为3组(EDA高剂量组,EDA低剂量组和对照组),每组各20只,每组10只用来测定荷瘤大鼠瘤周脑组织含水量、SOD活性及MDA含量,剩余10只用来观察荷瘤大鼠生存时间.结果:EDA干预组荷瘤大鼠瘤周脑组织含水量下降,SOD活性增高,MDA含量下降,以EDA高剂量组更为显著.各组荷瘤大鼠瘤周脑组织含水量与SOD活性呈负相关,而与MDA含量呈正相关.且EDA组荷瘤大鼠生存时间延长.结论:由基参与大鼠脑胶质瘤瘤周水肿的形成,自由基清除剂能够减轻大鼠脑胶质瘤瘤周脑组织水肿.%Objective: To investigate the relationship between oxygen free radical and peritumor edema in glioma. Methods: The rat C6 glioma cells were cultivated in vitro. The suspention of C6 glioma cells was stereotaxically injected into right caudate to establish rat C6 glioma model. After surgery, all rat glioma models were randomly classified into 3 groups (edaravone-trteated group in high dose,edaravone-trteated group in low dose and control group). Each group had twenty rats. Ten rats from each group were used to determine the moisture content in peritumor brain tissues, SOD activity and the content of MDA. The other 10 rats were used to detect the survival time after surgery. Results: The decreased moisture and MDA contents in peritumor brain tissues and increased SOD activity were found in edaravune-treated group, especially in high dose. The survival time was longer in edaravone-treated group than that of control group.Conclusion: Oxygen free radical is involved in the formation of peritumor edema in glioma, and the free radical scavenger may reduce the peritumor edema in glioma.

  9. Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation

    Directory of Open Access Journals (Sweden)

    Trejo-Solís Cristina

    2012-04-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate. Methods The in vitro antineoplastic effect and mechanism of action of Casiopeina III-ia (Cas III-ia, a copper compound, on rat malignant glioma C6 cells was investigated. Results Cas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS and increased activity of c-jun NH2-terminal kinase (JNK. The presence of 3-methyladenine (as selective autophagy inhibitor increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants (N-acetylcysteine decreased apoptosis, autophagy and JNK activity. Moreover, the JNK –specific inhibitor SP600125 prevented Cas III-ia-induced cell death. Conclusions Our data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS –dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma.

  10. Histologic classification of gliomas.

    Science.gov (United States)

    Perry, Arie; Wesseling, Pieter

    2016-01-01

    Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation. PMID:26948349

  11. 29 CFR 2560.502c-6 - Civil penalties under section 502(c)(6).

    Science.gov (United States)

    2010-07-01

    ... Section 2560.502c-6 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY... administrator (within the meaning of section 3(16)(A) of the Act) of an employee benefit plan (within the... to the Federal Civil Penalties Inflation Adjustment Act of 1990, as amended), computed from the...

  12. Genetic Alterations in Glioma

    International Nuclear Information System (INIS)

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

  13. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    International Nuclear Information System (INIS)

    Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19

  14. Superconductivity at elevated temperatures in C6Yb and C6Ca

    International Nuclear Information System (INIS)

    In this paper we discuss our discovery [T.E. Weller, et al., Nat. Phys., submitted for publication] of superconductivity in C6Yb and C6Ca at 6.5 and 11.5K, respectively. In addition, we present evidence based on an H-T phase diagram demonstrating that these compounds are significantly more isotropic than pure graphite. This is unexpected as the effect of introducing the intercalant is to move the graphite layers further apart. These new compounds are placed in context with previous reports on superconducting graphite intercalation compounds. This comparison raises the question of whether a simple charge transfer model, utilized to understand earlier studies, is adequate and highlights the need to revisit the theoretical model

  15. Expression and function of DMT1 without IRE in C6 cells mediated by recombinant adenovirus

    Institute of Scientific and Technical Information of China (English)

    Xixun DU; Huamin XU; Hong JIANG; Jun WANG; Lei WANG; Junxia XIE

    2009-01-01

    Divalent metal transporter 1 (DMT1) is a ferrous iron import protein. The improper expression of DMT1 is involved in neurodegenerative diseases. In the present study, we constructed a recombinant adenovirus containing the gene of DMT1 without the iron response element (DMT1-IRE) and investigated its expression and function in the C6 glioma cell line. The DMTI-IRE gene, obtained by RT-PCR, was cloned into the shuttle plasmid-ing pAdTrack-CMV containing green fluorescent protein (GFP) reporter gene. Linearized plasmid pAdTrack-CMV-DMTI-IRE was subsequently co-transformed into Escher-iehia coli (E. coli) BJ5183 cells along with an adenoviral backbone plasmid pAdEasy-1 after digestion with Pme I. Pac I-digested pAdEasy 1-DMT 1-IRE was then transfected into El-transformed human embryonic kidney cells (HEK293 cells), in which recombinant adenoviruses were generated within 7 to 10 days. The results demon-strated that we obtained the DMTI-IRE gene. pAdEasyl-DMT1-IRE yielded a large fragment, plus a smaller fragment of 4.5kb after digestion with Pac I. PCR confirmed pAdEasy1-DMT1-IRE contained gene DMT1-IRE, indicating the successful construction of recombi-nant adenovirus plasmid containing DMT1-IRE. GFP fluorescence further confirmed the generation of recombi-nant AdDMTI-IRE adenovirus. AdDMTI-IRE could efficiently infect C6 glioma cells. And cell viability decreased in AdDMT1-IRE infected cells after iron overload compared to the control. These results suggest that the over expressed DMT1-IRE can aggravate the iron induced cell death due to its iron influx function.

  16. 42 CFR 52c.6 - Expenditure of grant funds.

    Science.gov (United States)

    2010-10-01

    ... the applicable cost principles prescribed by subpart Q of 45 CFR part 74. (b) The Secretary may permit... 42 Public Health 1 2010-10-01 2010-10-01 false Expenditure of grant funds. 52c.6 Section 52c.6... RESEARCH SUPPORT PROGRAM § 52c.6 Expenditure of grant funds. (a) Any funds granted pursuant to this...

  17. A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

    Science.gov (United States)

    2016-07-08

    Pilomyxoid Astrocytoma; Pilocytic Astrocytoma; Glioma, Astrocytic; Optic Nerve Glioma; Pleomorphic Xanthoastrocytoma; Glioblastoma Multiforme; Anaplastic Astrocytoma; Gliosarcoma; Diffuse Intrinsic Pontine Glioma; DIPG; Low-grade Glioma; Brainstem Glioma

  18. The classical photoactivated drug 8-methoxypsoralen and related compounds are effective without UV light irradiation against glioma cells.

    Science.gov (United States)

    de Oliveira, Diêgo Madureira; Ferreira Lima, Rute Maria; Clarencio, Jorge; Velozo, Eudes da Silva; de Amorim, Ilza Alves; Andrade da Mota, Tales Henrique; Costa, Silvia Lima; Silva, Fábio Pittella; El-Bachá, Ramon Dos Santos

    2016-10-01

    Currently, there is no effective therapy for high grade gliomas. 8-Methoxypsoralen (8-MOP) is a compound used in the treatment of skin diseases combined with UV light irradiation. In this work, rat glioma C6 cells, normal astrocytes and human glioblastoma GL-15 cells comprised an in vitro model to evaluate the antitumor activity of 8-MOP. We found that 8-MOP promoted a time- and concentration-dependent reduction of cell viability in tumor, but not in normal cells. This effect was more evident in log-phase growing culture, indicating antiproliferative activity, which was confirmed by colony formation assay. Long-term effect of 8-MOP at low concentration was also attested. The concentrations used in the tests (0.02-0.4 mM) were lower than plasmatic concentration found in patients. Despite the treatment leads to considerable morphological changes and apoptosis when used at high concentrations, 8-MOP did not promote cell cycle arrest, change in migration pattern neither necrosis. In addition, we evaluated the effect of 8-MOP in MDA-MB-231, CT-26 and SCC-3 cell lines, derived from other kind of primary tumors, and found that CT-26 cells did not respond to 8-MOP treatment, indicating that this compound does not act through a generic mechanism. Coumarin derivatives structurally related to 8-MOP were screened for its antitumor potential and presented different patterns of biological activity, and then it was possible to suggest the relevance of 8-MOP molecular structure for antiproliferative action. Therefore, 8-MOP, a drug with an outstanding record of safety, and related coumarins are good prototypes for development of a new class of anti-glioma drugs. PMID:27292695

  19. RNAi沉默AQP-4技术治疗胶质瘤性脑水肿的实验研究%An experimental study of the treatment of glioma brain edema by RNAi silencing AQP-4

    Institute of Scientific and Technical Information of China (English)

    梁冰; 刘晓智; 张赛; 苏治国; 陈镭; 姜忠敏; 于士柱; 刘振林

    2012-01-01

    目的 应用RNA干扰(RNAi)技术靶向沉默胶质瘤内水通道蛋白4(AQP -4)的表达,观察其对胶质瘤源性脑水肿的治疗效果.方法 构建靶向AQP-4的siRNA质粒,免疫荧光化学方法检测其对C6细胞AQP-4的沉默效果;建立SD大鼠颅内C6胶质瘤模型,分对照组、空载组、无义序列组和siRNA组;聚合酶链式反应和蛋白印迹方法分别检测第3、6、9、12天AQP-4的mRNA和蛋白水平;干/湿比重法和Evans蓝测定法检测不同时相脑组织含水量和血脑屏障通透性改变;比较动物生存期.结果 siRNA可沉默AQP-4表达;siRNA组脑组织水含量和血脑屏障通透性均明显低于对照组、空载组和无义序列组,动物生存期最长.结论 靶向AQP-4的RNAi技术可在一定程度上减轻胶质瘤性脑水肿的发生和发展,为胶质瘤脑水肿提供了一种新的治疗策略选择.%Objective To observe the treatment effect on glioma cerebral edema by RNA interference ( RNAi ) technology silencing aquaporin 4 ( AQP-4 ) expression.Methods The siRNA plasmid targeting AQP-4 was constructed,and transfected into C6 glioma cells by liposome.Immunofluorescence assay was used to verify the silencing effect of AQP-4.The intracal C6 glioma model was established in SD rats,and four sub-groups,control group,empty vector transfected group,nonsense group and AQP-4 siRNA treated group,were divided.The AQP-4 mRNA and protein levels,in rats model brain tissue on 3,6,9,and 12 day,were detected by RT-PCR and Western Blot.Moreover,dry/wet weight method and evans blue assay were used to detect the brain water content and blood-brain barrier permeability changes.Then the animal survival was compared.Results siRNA can effectively reduce AQP -4 expression in C6 glioma cells.Compared with the control and empty vector transfected group in vivo,AQP-4 siRNA treatment group can effectively reduce AQP-4 mRNA and protein level,decrease brain water content,and reduce blood-brain barrier

  20. Nuclear motility in glioma cells reveals a cell-line dependent role of various cytoskeletal components.

    Directory of Open Access Journals (Sweden)

    Alexa Kiss

    Full Text Available Nuclear migration is a general term for the movement of the nucleus towards a specific site in the cell. These movements are involved in a number of fundamental biological processes, such as fertilization, cell division, and embryonic development. Despite of its importance, the mechanism of nuclear migration is still poorly understood in mammalian cells. In order to shed light on the mechanical processes underlying nuclear movements, we adapted a micro-patterning based assay. C6 rat and U87 human glioma cells seeded on fibronectin patterns--thereby forced into a bipolar morphology--displayed oscillatory movements of the nucleus or the whole cell, respectively. We found that both the actomyosin system and microtubules are involved in the nuclear/cellular movements of both cell lines, but their contributions are cell-/migration-type specific. Dynein activity was necessary for nuclear migration of C6 cells but active myosin-II was dispensable. On the other hand, coupled nuclear and cellular movements of U87 cells were driven by actomyosin contraction. We explain these cell-line dependent effects by the intrinsic differences in the overall mechanical tension due to the various cytoskeletal elements inside the cell. Our observations showed that the movements of the nucleus and the centrosome are strongly correlated and display large variation, indicating a tight but flexible coupling between them. The data also indicate that the forces responsible for nuclear movements are not acting directly via the centrosome. Based on our observations, we propose a new model for nuclear oscillations in C6 cells in which dynein and microtubule dynamics are the main drivers of nuclear movements. This mechanism is similar to the meiotic nuclear oscillations of Schizosaccharomyces pombe and may be evolutionary conserved.

  1. Gene Therapy for Gliomas

    OpenAIRE

    Nanda, Dharminderkoemar

    2008-01-01

    textabstractThe overall median survival in glioblastoma multiforme (GBM) patients is less than one year and fewer than 5% of patients survive more than 5 years. The current standard of care for GBM patients involves neurosurgical resection of the tumor followed by radiotherapy with concomitant and adjuvant temozolomide chemotherapy. After initial treatment, all malignant gliomas eventually recur, mostly within a 2-3 cm margin of the original tumor on CT/MRI. The poor prognosis warrants resear...

  2. Molecular hallmarks of gliomas

    OpenAIRE

    Pojo, Marta; Costa, Bruno Marques

    2011-01-01

    Gliomas are a heterogeneous group of neoplasias that account for the majority of primary tumors of the central nervous system, of which glioblastoma multiforme is by far the most common and malignant subtype. These are particularly dramatic diseases, as they rank first among all human tumor types for the tumor‐related average years of life lost, and for which curative therapies are not yet available. Their etiology remains mostly undetermined: so far, only exposure to high‐dose therapeutic ra...

  3. Exogenous Hydrogen Sulfide Stimulates the Angiogenesis of Rat Glioblastoma%外源性H2S促进大鼠恶性胶质瘤的血管新生*

    Institute of Scientific and Technical Information of China (English)

    李战永; 孔德强; 杨卓; 张涛

    2013-01-01

    Objective To investigate the stimulating effect of exogenous hydrogen sulfide (H2S) on angiogenesis in glioblastoma (GBM). Methods Twenty adult Sprague-Dawley (SD) rats were randomly divided into two groups, glioma group (C6 glioma cell intracerebral implantation, n=10) and glioma-H2S group (C6 glioma cell intracerebral implantation and sodium hydrosulfide (NaHS) intraperitoneal injection, n=10). The tumor-bearing rat model was established by intracerebral injection of rat C6 glioma cells. After one week, normal saline was injected in glioma group and NaHS was injected in glio-ma-H2S group. Food and water were freely available during all phases of the experiment. After three weeks, rats were decapi-tated and brains were removed. HE staining was performed to show tumor structure and intratumoral angiogenesis. The immu-nohistochemical analysis was used to detect the expressions of CD34 and MMP-2, respectively. The microvessel density (MVD) in GBM was also measured. Results HE staining showed that the implanted tumors were predominantly spheroid with clear border and no capsule could be detected. The neovascular proliferations were observed in tumors. There were high-er expressions of CD34 and MMP-2 in glioma-H2S group. The value of MVD was significantly higher in glioma-H2S group than that of glioma group (P<0.01). Conclusion Exogenous H2S serves as a stimulator of angiogenesis in the development of rat GBM, which may be related with the increased MMP-2 expression promoted by H2S.%  目的探讨外源性硫化氢(H2S)对大鼠恶性胶质瘤内血管新生的影响。方法成年雄性SD大鼠20只,随机分成肿瘤组和肿瘤-H2S组,每组10只。2组大鼠均脑内注射C6细胞,1周后,肿瘤组腹腔注射生理盐水,肿瘤-H2S组腹腔注射外源性H2S,即硫氢化钠(NaHS)溶液。均正常饲养,3周后断头取脑。组织病理学观察瘤体结构以及瘤内微血管生成情况,免疫组化评估瘤体内CD34

  4. Microwave losses of bulk CaC 6

    Science.gov (United States)

    Cifariello, G.; Di Gennaro, E.; Lamura, G.; Andreone, A.; Emery, N.; Hérold, C.; Marêché, J. F.; Lagrange, P.

    2007-09-01

    We report a study of the temperature dependence of the surface resistance RS in the graphite intercalated compound (GIC) CaC6, where superconductivity at 11.5 K was recently discovered. Experiments are carried out using a copper dielectrically loaded cavity operating at 7 GHz in a "hot finger" configuration. Bulk CaC6 samples have been synthesized from highly oriented pyrolytic graphite. Microwave data allow to extract unique information on the quasiparticle density and on the nature of pairing in superconductors. The analysis of RS(T) confirms our recent experimental findings that CaC6 behaves as a weakly-coupled, fully gapped, superconductor.

  5. External irradiation models for intracranial 9L glioma studies

    Directory of Open Access Journals (Sweden)

    Feuvret Loïc

    2010-11-01

    Full Text Available Abstract Purpose Radiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI protocol for a rat 9L glioma model. Materials and methods 9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed. Results Irradiated rats had significantly a longer survival (p = 0.01. No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule. Conclusions Delivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.

  6. Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects

    Science.gov (United States)

    Xu, He-Lin; Mao, Kai-Li; Huang, Yin-Ping; Yang, Jing-Jing; Xu, Jie; Chen, Pian-Pian; Fan, Zi-Liang; Zou, Shuang; Gao, Zheng-Zheng; Yin, Jia-Yu; Xiao, Jian; Lu, Cui-Tao; Zhang, Bao-Lin; Zhao, Ying-Zheng

    2016-07-01

    Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g-1. The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the

  7. Pharmacokinetics and the bystander effect in CD::UPRT/5-FC bi-gene therapy of glioma

    Institute of Scientific and Technical Information of China (English)

    SHI De-zhi; HU Wei-xing; LI Li-xin; CHEN Gong; WEI Dong; GU Pei-yuan

    2009-01-01

    Background Cytosine deaminase (CD) converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) in CD/5-FC gene therapy, 5-FU will be mostly converted into nontoxic β-alanine without uracil phosphoribosyltransferase (UPRT). UPRT catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate, which directly kills CD::UPRT-expressing ceils and surrounding cells via the bystander effect. But the pharmacokinetics and the bystander effect of CD::UPRT/5-FC has not been verified in vivo and in vitro. Before the CD::UPRT/5-FC bi-gene therapy system is used in clinical trial, it is essential to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using 19F-magnetic resonance spectroscopy (19F-MRS) and optical imaging to measure non-invasive CD and UPRT expression and its bystander effect.Methods C6 and C6-CD::UPRT cells were cultured with 5-FC. The medium, cells and their mixture were analyzed by 19F-MRS. Rats with intracranial xenografted encephalic C6-CD::UPRT glioma were injected intraperitoneally with 5-FC and their 19F-MRS spectra recorded. Then the pharmacokinetics of 5-FC was proved. Mixtures of C6 and C6-CD::UPRT cells at different ratios were cultured with 5-FC and the cytotoxic efficacy and survival rate of cells recorded. To determine the mechanism of the bystander effect, the culture media from cell comprising 25% and 75% C6-CD::UPRT cells were examined by19F-MRS. A comparative study of mean was performed using analysis of variance (ANOVA). Results 19F-MRS on samples from C6-CD::UPRT cells cultured with 5-FC showed three broad resonance signals corresponding to 5-FC, 5-FU and fluorinated nucleotides (F-Nuctd). For the C6 mixture, only the 5-FC peak was detected. In vivo serial 19F-MRS spectra showed a strong 5-FC peak and a weak 5-FU peak at 20 minutes after 5-FC injection. The 5-FU concentration reached a maximum at about 50 minutes. The F-Nuctd signal appeared after about I hour

  8. Temozolomide in malignant glioma

    Directory of Open Access Journals (Sweden)

    Gregor Dresemann

    2010-07-01

    Full Text Available Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28 (EORTC/NCIC-regime published by R Stupp in 2005 is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no ­contraindication for treatment with temozolomide, although comorbidity and performance status have to be ­considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A ­general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28 is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28 are candidates for clinical studies. Outside of clinical ­studies, dose-dense (7/7, prolonged (21/28, or metronomic (28/28 temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of ­temozolomide allows for various combinations with antitumor agents. None of these ­combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.Keywords: glioblastoma

  9. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    Directory of Open Access Journals (Sweden)

    Mueller-Klieser Wolfgang

    2011-07-01

    Full Text Available Abstract Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2, 3-oxoacid-CoA transferase 1 (OXCT1 and acetyl-CoA acetyltransferase 1 (ACAT1 were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic

  10. Effects of dexamethasone on C6 astrocytoma radiosensitivity

    International Nuclear Information System (INIS)

    Brain-tumor patients often undergo radiation therapy while receiving corticosteroids for the treatment of cerebral edema. Studies have demonstrated that dexamethasone is radioprotective in a number of cell lines. The C6 astrocytoma cell line is well established in vitro and is modulated by dexamethasone treatment. It has therefore been hypothesized that dexamethasone-treated C6 astrocytoma cells would be more resistant to radiation-induced damage. The present study was carried out to assess this hypothesis using both the in vitro C6 astrocytoma monolayer and three-dimensional multicellular spheroid models. Dexamethasone was inhibitory to the C6 astrocytoma cells in the monolayer preparation, increasing their doubling time by 13%. In the spheroid cultures, dexamethasone treatment decreased the number of cells per spheroid by 46%. Dexamethasone did not affect the plating efficiency of either the cells from the monolayer experiment or those dissociated from spheroids, however, suggesting that the inhibitory effect was not tumoricidal. At a clinical concentration (1.94 x 10(-5) M), dexamethasone did not significantly influence plating efficiency of irradiated C6 astrocytoma cells in monolayer or three-dimensional spheroid cultures

  11. BOPP revisited. A study on the toxicity, biodistribution and convection enhanced delivery of BOPP in the 9L intracerebral rat glioma model

    International Nuclear Information System (INIS)

    To evaluate and compare the toxicity and boron biodistribution of the boronated porphyrin BOPP when administered by either intravenous or convection enhanced delivery (CED). For the toxicity study, Fischer 344 rats were injected with graded concentrations of BOPP into the tail vein. For boron biodistribution studies, 9L tumor-bearing rats received BOPP either systematically or by CED. When given i.v. BOPP showed unacceptable toxicity in normal rats receiving doses of ≥60 mg/kg. In contrast, tumor bearing rats receiving BOPP by CED showed no evidence of toxic effects whatsoever. In the biodistribution study, the maximum tumor boron concentration was ∼21 μ/g at 48 h after i.v. injection, at which time the tumor/blood ratio was ∼1.2. Neither of these values is optimal. However, when BOPP was delivered directly into intracerebral tumors with CED, we obtained tumor boron concentrations much greater than those obtained by i.v. injection. For example, convection enhanced delivery of 1.5 mg BOPP produced an average tumor boron level of 519 μg/g and a tumor/blood ratio of ∼1850:1. Tumor/brain ratios of ∼9:1 (ipsilateral) and ∼41:1 (contralateral) were also found at this dose. We conclude that changing the method of BOPP delivery from i.v. to CED significantly enhances the boron concentration in tumors and produces very favorable tumor/blood and tumor/brain ratios with no concomittant systemic toxicity. (author)

  12. 丙泊酚对大鼠胶质瘤细胞侵袭和迁移能力的影响及ADAR2-AMPA受体GluR2通路在其中的作用%Effects of propofol on invasion and migration of glioma cells in rats and the role of ADAR2-AMPA receptor GluR2 pathway

    Institute of Scientific and Technical Information of China (English)

    王欣悦; 王海云; 王国林; 杨卓; 张涛

    2016-01-01

    目的 评价丙泊酚对大鼠胶质瘤细胞侵袭和迁移能力的影响及腺苷脱氨酶(ADAR2)-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体GluR2通路在其中的作用.方法 传代培养大鼠C6胶质瘤细胞,采用随机数字表法分为4组(n=24):对照组(C组)、丙泊酚组(P组)、阴性siRNA转染+丙泊酚组(NP组)和ADAR2-siRNA转染+丙泊酚组(AP组).C组正常培养;NP组和AP组分别将阴性siRNA或ADAR2-siRNA转染至细胞内,48 h后处理同P组;P组加入丙泊酚,终浓度1.2 μg/ml,孵育6h后换为正常培养液,继续培养18h.采用MTT比色分析法检测细胞活力,Transwell侵袭实验测定侵袭细胞数,细胞划痕实验测定迁移率,Western blot法检测胞核ADAR2和胞膜GluR2的表达.结果 与C组比较,P组和NP组细胞活力、侵袭细胞数和迁移率降低,胞核A-DAR2及胞膜GluR2表达上调(P<0.05);与P组比较,AP组细胞活力、侵袭细胞数和迁移率升高,胞核ADAR2及胞膜GluR2表达下调(P<0.05);与NP组比较,AP组细胞活力、侵袭细胞数和迁移率升高,胞核ADAR2及胞膜GluR2表达下调(P<0.05).结论 丙泊酚可抑制大鼠胶质瘤细胞的侵袭和迁移能力,其机制与激活ADAR2-AMPA受体GluR2通路有关.%Objective To evaluate the effects of propofol on the invasion and migration of glioma cells in the rats and the role of adenosine deaminase acting on RNA 2 (ADAR2)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit glutamate 2 (GluR2) pathway.Methods C6 glioma cells were subcuhured and randomly divided into 4 groups (n =24 each) using a random number table:control group (group C);propofol group (group P);negative siRNA transfection + propofol group (group NP);ADAR2-siRNA transfection + propofol group (group AP).The cells were cultured in the common culture medium in group C.In NP and AP groups,negative siRNA and ADAR2-siRNA were transfected into the cells,respectively,and 48 h later the other procedures were similar

  13. Stem cell signatures in glioma

    OpenAIRE

    He, Xiaobing

    2012-01-01

    Gliomas are the most common tumors of the central nervous system in adults. Glioblastoma, the most aggressive form, has a median survival of 15 months regardless of the standard treatment with surgery and temozolomide-based radiochemotherapy. Therefore, it is imperative to improve treatment options for patients with glioblastoma. It has been suggested that the putative tumor stem cells in brain tumors are responsible for glioma initiation, development and resistance to ...

  14. Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy

    Directory of Open Access Journals (Sweden)

    Nicholas K.H. Khoo

    2013-01-01

    Full Text Available Glioma survival is dismal, in part, due to an imbalance in antioxidant expression and activity. Peroxisome proliferator-activated receptor (PPAR agonists have antineoplastic properties which present new redox-dependent targets for glioma anticancer therapies. Herein, we demonstrate that treatment of primary cultures of normal rat astrocytes with PPAR agonists increased the expression of catalase mRNA protein, and enzymatic activity. In contrast, these same agonists had no effect on catalase expression and activity in malignant rat glioma cells. The increase in steady-state catalase mRNA observed in normal rat astrocytes was due, in part, to de novo mRNA synthesis as opposed to increased catalase mRNA stability. Moreover, pioglitazone-mediated induction of catalase activity in normal rat astrocytes was completely blocked by transfection with a PPARγ-dominant negative plasmid. These data suggest that defects in PPAR-mediated signaling and gene expression may represent a block to normal catalase expression and induction in malignant glioma. The ability of PPAR agonists to differentially increase catalase expression and activity in normal astrocytes but not glioma cells suggests that these compounds might represent novel adjuvant therapeutic agents for the treatment of gliomas.

  15. Boldine: a potential new antiproliferative drug against glioma cell lines.

    Science.gov (United States)

    Gerhardt, Daniéli; Horn, Ana Paula; Gaelzer, Mariana Maier; Frozza, Rudimar Luiz; Delgado-Cañedo, Andrés; Pelegrini, Alessandra Luiza; Henriques, Amélia T; Lenz, Guido; Salbego, Christianne

    2009-12-01

    Malignant gliomas are the most common and devastating primary tumors of the central nervous system. Currently no efficient treatment is available. This study evaluated the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on glioma proliferation and cell death. Boldine decreased the cell number of U138-MG, U87-MG and C6 glioma lines at concentrations of 80, 250 and 500 muM. We observed that cell death caused by boldine was cell-type specific and dose-dependent. Exposure to boldine for 24 h did not activate key mediators of apoptosis. However, it induced alterations in the cell cycle suggesting a G(2)/M arrest in U138-MG cells. Boldine had no toxic effect on non-tumor cells when used at the same concentrations as those used on tumor cells. Based on these results, we speculate that boldine may be a promising compound for evaluation as an anti-cancer agent. PMID:19050827

  16. Imaging of adult brainstem gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Purohit, Bela, E-mail: purohitbela@yahoo.co.in; Kamli, Ali A.; Kollias, Spyros S.

    2015-04-15

    Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

  17. Migration capacity of human umbilical cord mesenchymal stem cells towards glioma in vivo*

    Institute of Scientific and Technical Information of China (English)

    Cungang Fan; Dongliang Wang; Qingjun Zhang; Jingru Zhou

    2013-01-01

    High-grade glioma is the most common malignant primary brain tumor in adults. The poor prognosis of glioma, combined with a resistance to currently available treatments, necessitates the ment of more effective tumor-selective therapies. Stem cel-based therapies are emerging as novel cel-based delivery vehicle for therapeutic agents. In the present study, we successful y isolated human umbilical cord mesenchymal stem cel s by explant culture. The human umbilical cord senchymal stem cel s were adherent to plastic surfaces, expressed specific surface phenotypes of mesenchymal stem cel s as demonstrated by flow cytometry, and possessed multi-differentiation potentials in permissive induction media in vitro. Furthermore, human umbilical cord mesenchymal stem cel s demonstrated excel ent glioma-specific targeting capacity in established rat glioma models after intratumoral injection or contralateral ventricular administration in vivo. The excellent glioma-specific targeting ability and extensive intratumoral distribution of human umbilical cord mesenchymal stem cel s indicate that they may serve as a novel cel ular vehicle for delivering the-rapeutic molecules in glioma therapy.

  18. NUMB does not impair growth and differentiation status of experimental gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Euskirchen, Philipp, E-mail: philipp.euskirchen@charite.de [Department of Biomedicine, University of Bergen (Norway); Laboratory for Gene Therapy and Molecular Imaging, Max-Planck-Institute for Neurological Research, Cologne (Germany); Skaftnesmo, Kai-Ove; Huszthy, Peter C.; Brekka, Narve [Department of Biomedicine, University of Bergen (Norway); Bjerkvig, Rolf [Department of Biomedicine, University of Bergen (Norway); NorLux Neuro-Oncology Laboratory, Centre de Public de la Sante, Luxembourg (Luxembourg); Jacobs, Andreas H. [Laboratory for Gene Therapy and Molecular Imaging, Max-Planck-Institute for Neurological Research, Cologne (Germany); European Institute for Molecular Imaging, Muenster (Germany); Miletic, Hrvoje [Department of Biomedicine, University of Bergen (Norway); Department of Pathology, Haukeland University Hospital, Bergen (Norway)

    2011-12-10

    The cell fate determinant NUMB orchestrates asymmetric cell division in flies and mammals and has lately been suggested to have a tumor suppressor function in breast and lung cancer. Here, we studied NUMB in the context of malignant gliomas. We used ectopic expression of NUMB in order to inhibit proliferation and induce differentiation in glioma cells by alteration of Notch, Hedgehog and p53 signaling. We found that NUMB is consistently expressed in glioma biopsies with predominance of NUMB2/4 isoforms as determined by isoform-specific real-time PCR and Western blotting. Upon lentiviral overexpression, in vitro proliferation rate and the grade of differentiation as assessed by morphology and expression of neural and glial markers remained unchanged. Orthotopic xenografts of NUMB-transduced human U87 glioma cells could be established in nude rats without impairing engraftment or causing significant changes in morphology based on magnetic resonance imaging (MRI). The previously reported alteration of Hedgehog and p53 signaling by NUMB could not be recapitulated in glioma cells. We thus show that in experimental gliomas, NUMB overexpression most likely does not exert a tumor suppressor function such as seen in epithelial cancers.

  19. NUMB does not impair growth and differentiation status of experimental gliomas

    International Nuclear Information System (INIS)

    The cell fate determinant NUMB orchestrates asymmetric cell division in flies and mammals and has lately been suggested to have a tumor suppressor function in breast and lung cancer. Here, we studied NUMB in the context of malignant gliomas. We used ectopic expression of NUMB in order to inhibit proliferation and induce differentiation in glioma cells by alteration of Notch, Hedgehog and p53 signaling. We found that NUMB is consistently expressed in glioma biopsies with predominance of NUMB2/4 isoforms as determined by isoform-specific real-time PCR and Western blotting. Upon lentiviral overexpression, in vitro proliferation rate and the grade of differentiation as assessed by morphology and expression of neural and glial markers remained unchanged. Orthotopic xenografts of NUMB-transduced human U87 glioma cells could be established in nude rats without impairing engraftment or causing significant changes in morphology based on magnetic resonance imaging (MRI). The previously reported alteration of Hedgehog and p53 signaling by NUMB could not be recapitulated in glioma cells. We thus show that in experimental gliomas, NUMB overexpression most likely does not exert a tumor suppressor function such as seen in epithelial cancers.

  20. A pH-sensitive hyaluronic acid prodrug modified with lactoferrin for glioma dual-targeted treatment.

    Science.gov (United States)

    Yin, Yatao; Fu, Chaoping; Li, Mei; Li, Xiangpen; Wang, Mengying; He, Lei; Zhang, Li-Ming; Peng, Ying

    2016-10-01

    Gliomas are the most common and lethal type of primary malignant brain tumor. But the existence of blood brain barrier (BBB) and blood-tumor barrier (BTB) hinder drug from reaching the tumor site. To address this problem, we developed a novel prodrug (Lf-HA-DOX) by conjugating hyaluronic acid with doxorubicin (HA-DOX) by an acid-labile hydrazone linkage, which is released in an acidic environment and accumulates in tumor tissues. Lactoferrin (Lf) was coupled for transporting across the BBB. In vitro, the release of DOX from Lf-HA-DOX was pH-dependent. At lower pH (5.0 and 6.0), the release of DOX was much quicker than that at pH7.4. In the cellular uptake studies, flow cytometry analyses and confocal laser scanning microscopy results showed significantly enhanced cellular uptake of Lf-HA-DOX and HA-DOX in C6 cells compared to DOX. In BALB/C mice bearing C6 glioma, enhanced accumulation of Lf-HA-DOX in the glioma was observed by real time fluorescence image. Correspondingly, glioma-bearing mice treated with Lf-HA-DOX displayed the longest median survival time, which was 2-fold longer than that of saline group. In conclusion, Lf-HA-DOX was able to significantly increase drug delivery to the glioma, which might provide a promising strategy for antiglioma therapy. PMID:27287110

  1. Increasing the efficacy of antitumor glioma vaccines by photodynamic therapy and local injection of allogeneic glioma cells

    Science.gov (United States)

    Christie, Catherine E.; Peng, Qian; Madsen, Steen J.; Uzal, Francisco A.; Hirschberg, Henry

    2016-03-01

    Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage vaccines could be increased by: (1) PDT of the priming tumor cells, and (2) injection of allogeneic glioma cells directly into brain tumors. Experiments were conducted in an in vivo brain tumor model using Fisher rats and BT4C (allogeneic) and F98 (syngeneic) glioma cells. Preliminary results showed that vaccination alone had significantly less inhibitory effect on F98 tumor growth compared to the combination of vaccination and allogeneic cell (BT4C) injection.

  2. Paediatric and adult malignant glioma

    DEFF Research Database (Denmark)

    Jones, Chris; Perryman, Lara; Hargrave, Darren

    2012-01-01

    Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

  3. Immunotherapy for malignant glioma

    Directory of Open Access Journals (Sweden)

    Carter M Suryadevara

    2015-01-01

    Full Text Available Malignant gliomas (MG are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM, the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  4. The translocator protein ligand [{sup 18}F]DPA-714 images glioma and activated microglia in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Winkeler, Alexandra; Boisgard, Raphael; Awde, Ali R.; Dubois, Albertine; Theze, Benoit; Zheng, Jinzi [Universite Paris Sud, Inserm, U1023, Laboratoire d' Imagerie Moleculaire Experimentale, Orsay (France); CEA, I2BM, SHFJ, Orsay (France); Ciobanu, Luisa [CEA, DSV, I2BM, NeuroSpin, LRMN, Gif sur Yvette (France); Dolle, Frederic [CEA, I2BM, SHFJ, Orsay (France); Viel, Thomas; Jacobs, Andreas H. [Westfaelische Wilhelm-Universitaet Muenster (WWU), European Institute for Molecular Imaging (EIMI), Muenster (Germany); Tavitian, Bertrand [Universite Paris Sud, Inserm, U1023, Laboratoire d' Imagerie Moleculaire Experimentale, Orsay (France)

    2012-05-15

    In recent years there has been an increase in the development of radioligands targeting the 18-kDa translocator protein (TSPO). TSPO expression is well documented in activated microglia and serves as a biomarker for imaging neuroinflammation. In addition, TSPO has also been reported to be overexpressed in a number of cancer cell lines and human tumours including glioma. Here we investigated the use of [{sup 18}F]DPA-714, a new TSPO positron emission tomography (PET) radioligand to image glioma in vivo. We studied the uptake of [{sup 18}F]DPA-714 in three different rat strains implanted with 9L rat glioma cells: Fischer (F), Wistar (W) and Sprague Dawley (SD) rats. Dynamic [{sup 18}F]DPA-714 PET imaging, kinetic modelling of PET data and in vivo displacement studies using unlabelled DPA-714 and PK11195 were performed. Validation of TSPO expression in 9L glioma cell lines and intracranial 9L gliomas were investigated using Western blotting and immunohistochemistry of brain tissue sections. All rats showed significant [{sup 18}F]DPA-714 PET accumulation at the site of 9L tumour implantation compared to the contralateral brain hemisphere with a difference in uptake among the three strains (F > W > SD). The radiotracer showed high specificity for TSPO as demonstrated by the significant reduction of [{sup 18}F]DPA-714 binding in the tumour after administration of unlabelled DPA-714 or PK11195. TSPO expression was confirmed by Western blotting in 9L cells in vitro and by immunohistochemistry ex vivo. The TSPO radioligand [{sup 18}F]DPA-714 can be used for PET imaging of intracranial 9L glioma in different rat strains. This preclinical study demonstrates the feasibility of employing [{sup 18}F]DPA-714 as an alternative radiotracer to image human glioma. (orig.)

  5. Neuronavigator-guided glioma surgery

    Institute of Scientific and Technical Information of China (English)

    杜固宏; 周良辅; 毛颖

    2003-01-01

    Objective To evaluate the effectiveness of neuronavigator-guided surgery for the resection of gliomas. Methods A total of 80 patients with gliomas underwent surgical treatment under the StealthStation neuronavigator to estimate the extent of the tumors. In 27 cases, the measurements of brain shifts at the dura, cortical surface and lesion margin were recorded during the operations. A technique termed "micro-catheter fence post" was used in superficial gliomas to compensate for brain shift.Results Mean fiducial error and predicted accuracy in the 80 cases were 2.03 mm±0.89 mm and 2.43 mm±0.99 mm, respectively. The shifts at the dura, cortical surface and lesion margin were 3.44 mm±2.39 mm, 7.58 mm±3.75 mm, and 6.55 mm±3.19 mm, respectively. Although neuronavigation revealed residual tumors, operations were discontinued in 5 cases of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation, neurological symptoms were improved or unchanged in 68 cases (85.0%), and worsened in 12 (15.0%). No deaths occurred during the operations and post-operations. Conclusions Intraoperative brain shifts mainly contribute to the fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro-catheter fence post" technique used for glioma surgery is shown to be useful for compensating for intraoperative brain shifts. This technique, thus, contributes to an increase in total tumor removal and a decrease in surgical complications.

  6. Quasiclassical Trajectory Study of Collisional Energy Transfer between Highly Excited C6F6 and N2 ,O2 and Ground State C6F6

    Institute of Scientific and Technical Information of China (English)

    Jian Hua ZHOU; Shao Kun WANG; Zhi Jun YU; Hai Hui JIANG; Yue Shu GU

    2003-01-01

    Quasiclassical trajectory calculation (QCT) is used frequently for studying collisional energy transfer between highly vibrationally excited molecules and bath gases. In this paper, the QCT of the energy transfer between highly vibrationally excited C6F6 and N2 ,O2 and ground state C6F6 were performed. The results indicate that highly vibrationally excited C6F6 transferred vibrational energy to vibrational distribution of N2, O2 and ground state C6F6, so they are V-V energy transfer. Especially it is mainly V-V resonance energy transfer between excited C6F6 and ground state C6F6, excited C6F6 transfers more vibrational energy to ground state C6F6 than to N2 and O2 . The values of QCT , -〈△Evib〉of excited C6F6 are smaller than those of experiments.

  7. Isomerisation of c4-c6 aldoses with zeolites

    DEFF Research Database (Denmark)

    2014-01-01

    temperatures. C6 and C5 aldose sugars such as glucose and xylose, which are available in large amounts from biomass precursors, are isomerized to fructose and xylulose respectively, in a one or two-step process over inexpensive commercially available zeolite catalysts, containing aluminum as the only metal...... in the catalyst. The ketoses obtained are used as sweeteners in the food and/or brewery industry, or treated to obtain downstream platform chemicals such as lactic acid, HMF, levulinic acid, furfural, MMHB, and the like....

  8. 冬凌草甲素诱导C6脑胶质瘤细胞凋亡的初步研究%Apoptosis of C6 astrocytoma cells induced by oridonin

    Institute of Scientific and Technical Information of China (English)

    尹波; 俞利生; 林坚; 盛汉松; 张弩

    2012-01-01

    Objective: To investigate the proliferation suppression and apoptosis inducing effect of oridonin on Rat C6 astrocytoma cells. Methods: C6 cells were treated with different concentrations of oridonin for various time intervals. Oridonin concentration-time viability curve were used to test the effect of oridonin on the C6 cells. The distribution of cell cycle and percentage of apoptosis cells was analyzed with flow cytotnetry. Results: The results of viability curve demonstrated that oridonin induced suppression of prolifera tion in a concentration-and time-dependent manner. Hochest 33258 staining and flow cytometry revealed that oridonin induced apoptosis and arrested the entry into G2/M phase of C6 cells. Conclusion: Oridonin can cause the suppression of proliferation and the cell apoptosis in C6 astrocytoma cells.%目的:研究冬凌草甲素对大鼠C6脑胶质瘤细胞的抑制增殖及诱导凋亡的作用.方法:不同浓度的冬凌草甲素在不同的时间间隔内作用于C6脑胶质瘤细胞,用冬凌草甲素浓度时间生存曲线来测试冬凌草甲素对C6脑胶质瘤细胞的作用.用流式细胞技术来分析细胞周期的分布情况及凋亡细胞的百分数.结果:生存曲线结果证实冬凌草甲素诱导增殖抑制呈浓度依赖和时间依赖.Hochest 33258斑点染色及流式细胞技术揭示冬凌草甲素诱导C6脑胶质瘤细胞凋亡及抑制其进入细胞周期的G2/M相.结论:冬凌草甲素能够抑制C6脑胶质瘤细胞增殖,诱导细胞凋亡.

  9. Superfluid density of bulk CaC 6

    Science.gov (United States)

    Lamura, G.; Aurino, M.; Cifariello, G.; Di Gennaro, E.; Andreone, A.; Emery, N.; Hérold, C.; Marêché, J.-F.; Lagrange, P.

    2007-09-01

    The recent discovery of superconductivity at 11.5 K in the graphite intercalation compound (GIC) CaC6 has opened new perspectives in the physics of graphite. One of the main open questions for superconducting GICs is related to the nature of the pairing mechanism, since the possibility of an unconventional, excitonic or plasmonic, origin of superconductivity has also been invoked as an alternative to a simple electron-phonon interaction. To better understand the origin of pairing mechanism in these compounds, a first step is to determine the symmetry of the superconducting gap function and the nature of the elementary excitations. To this aim, we have performed the first high-resolution measurement of the in-plane magnetic penetration depth, λab(T), in a c-axis oriented polycrystalline CaC6 bulk sample using a high-resolution mutual inductance technique. A clear exponential behavior of λab(T) has been observed at low temperatures, strongly suggesting isotropic s-wave pairing. Data fit using the standard BCS theory yields λab(0) = (720 ± 80) Å and Δ(0) = (1.79 ± 0.08) meV. The ratio 2Δ(0)/kBTC = (3.6 ± 0.2) gives therefore indication for a conventional weakly coupled superconductor. By using these results as fixed parameters, a BCS calculation on the superfluid density in the overall temperature range shows that the sample under test lies in the local dirty limit.

  10. 脑胶质瘤治疗中自由基清除剂的价值%Influence of free radical on the treatment for glioma

    Institute of Scientific and Technical Information of China (English)

    赵心同; 赵洪洋; 姚东晓; 王海均

    2011-01-01

    目的:探讨自由基清除剂依达拉奉(EDA)对肿瘤大小的影响及在肿瘤治疗中的价值.方法:MTT比色法测定EDA对胶质瘤细胞的影响.采用立体定向技术将C6脑胶质瘤细胞接种于大鼠右侧尾状核,建立脑胶质瘤模型,将荷瘤大鼠随机分为EDA高和低剂量组、对照组及空白组4组.空白组用来测定肿瘤组织与正常脑组织中超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量,其他组用EDA或生理盐水干预,观察对肿瘤大小的影响.结果:浓度为1×10-3、1×10-4、1×10-5和1×10-6mol/L的EDA作用48 h后,细胞的增殖率分别为8.3%、13.2%、21.9%和30.6%,呈浓度依赖性.与正常脑组织相比,胶质瘤组织中SOD活性较低,而MDA含量较高,差异均有统计学意义,P=0.000.EDA高剂量组平均肿瘤体积最大,其次为EDA低剂量组,对照组最小.3组荷瘤大鼠肿瘤平均体积差异有统计学意义(F=5.863,P=0.008),EDA高剂量组与其他2组比较差异均有统计学意义,但EDA低剂量组与对照组间差异无统计学意义.结论:自由基清除剂EDA能够促进肿瘤的生长,自由基在肿瘤的综合治疗中有潜在的价值.%OBJECTIVE: To study the influence of edaravone on tumor size, and explore the value of free radicals in the treatment for glioma.METHODS: MTT assay was used to detect the influence of EDA on glioma cells.The suspention of rat C6 glioma cells was stereotaxically injected into right caudate to establish rat C6 glioma model.The rats were randomly classified into 4 groups (EDA group in high dose, EDA group in low dose, control group and blank group).SOD activity and the content of MDA were detected in blank group.Other groups were treated with EDA or normal saline in order to observe their influence on tumor size.RESULTS: After being treated with EDA in dose of 1 × 10-3 , 1 ×10-4 , 1 × 10-5 , 1 × 10-6 mol/L for 48 hours, the proliferation rate of glioma cells was 8.3%, 13.2%, 21.9%, 30.6% respectively

  11. Drug repurposing: sulfasalazine sensitizes gliomas to gamma knife radiosurgery by blocking cystine uptake through system Xc-, leading to glutathione depletion.

    Science.gov (United States)

    Sleire, L; Skeie, B S; Netland, I A; Førde, H E; Dodoo, E; Selheim, F; Leiss, L; Heggdal, J I; Pedersen, P-H; Wang, J; Enger, P Ø

    2015-12-01

    Glioblastomas (GBMs) are aggressive brain tumors that always recur after radiotherapy. Cystine, mainly provided by the system X(c)(-) antiporter, is a requirement for glioma cell synthesis of glutathione (GSH) which has a critical role in scavenging free radicals, for example, after radiotherapy. Thus, we hypothesized that the X(c)(-)-inhibitor sulfasalazine (SAS) could potentiate the efficacy of radiotherapy against gliomas. Here, we show that the catalytic subunit of system X(c)(-), xCT, was uniformly expressed in a panel of 30 human GBM biopsies. SAS treatment significantly reduced cystine uptake and GSH levels, whereas it significantly increased the levels of reactive oxygen species (ROS) in glioma cells in vitro. Furthermore, SAS and radiation synergistically increased DNA double-strand breaks and increased glioma cell death, whereas adding the antioxidant N-acetyl-L-cysteine (NAC) reversed cell death. Moreover, SAS and gamma knife radiosurgery (GKRS) synergistically prolonged survival in nude rats harboring human GBM xenografts, compared with controls or either treatment alone. In conclusion, SAS effectively blocks cystine uptake in glioma cells in vitro, leading to GSH depletion and increased ROS levels, DNA damage and cell death. Moreover, it potentiates the anti-tumor efficacy of GKRS in rats with human GBM xenografts, providing a survival benefit. Thus, SAS may have a role as a radiosensitizer to enhance the efficacy of current radiotherapies for glioma patients.

  12. MicroRNA in Human Glioma

    International Nuclear Information System (INIS)

    Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy

  13. MicroRNA in Human Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mengfeng, E-mail: limf@mail.sysu.edu.cn [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Li, Jun [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Lei; Li, Wei [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yang, Yi [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yuan, Jie [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Key Laboratory of Functional Molecules from Oceanic Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou 510080 (China)

    2013-10-23

    Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy.

  14. Cytochrome c6B of Synechococcus sp. WH 8102 – Crystal structure and basic properties of novel c6-like family representative

    International Nuclear Information System (INIS)

    Highlights: • Crystal structure of cytochrome c6B from Synechococcus sp. WH 8102 was solved. • Basic biophysical properties of cytochrome c6B were determined. • Cytochrome c6B exhibits similar architecture to cytochrome c6. • Organization of heme binding pocket of cytochrome c6B differs from that of c6. • Midpoint potential of cytochrome c6B is significantly lower than of cytochrome c6. - Abstract: Cytochromes c are soluble electron carriers of relatively low molecular weight, containing single heme moiety. In cyanobacteria cytochrome c6 participates in electron transfer from cytochrome b6f complex to photosystem I. Recent phylogenetic analysis revealed the existence of a few families of proteins homologous to the previously mentioned. Cytochrome c6A from Arabidopsis thaliana was identified as a protein responsible for disulfide bond formation in response to intracellular redox state changes and c550 is well known element of photosystem II. However, function of cytochromes marked as c6B, c6C and cM as well as the physiological process in which they take a part still remain unidentified. Here we present the first structural and biophysical analysis of cytochrome from the c6B family from mesophilic cyanobacteria Synechococcus sp. WH 8102. Purified protein was crystallized and its structure was refined at 1.4 Å resolution. Overall architecture of this polypeptide resembles typical I-class cytochromes c. The main features, that distinguish described protein from cytochrome c6, are slightly red-shifted α band of UV–Vis spectrum as well as relatively low midpoint potential (113.2 ± 2.2 mV). Although, physiological function of cytochrome c6B has yet to be determined its properties probably exclude the participation of this protein in electron trafficking between b6f complex and photosystem I

  15. Identification of proteins involved in neural progenitor cell targeting of gliomas

    Directory of Open Access Journals (Sweden)

    Honeth Gabriella

    2009-06-01

    Full Text Available Abstract Background Glioblastoma are highly aggressive tumors with an average survival time of 12 months with currently available treatment. We have previously shown that specific embryonic neural progenitor cells (NPC have the potential to target glioma growth in the CNS of rats. The neural progenitor cell treatment can cure approximately 40% of the animals with malignant gliomas with no trace of a tumor burden 6 months after finishing the experiment. Furthermore, the NPCs have been shown to respond to signals from the tumor environment resulting in specific migration towards the tumor. Based on these results we wanted to investigate what factors could influence the growth and progression of gliomas in our rodent model. Methods Using microarrays we screened for candidate genes involved in the functional mechanism of tumor inhibition by comparing glioma cell lines to neural progenitor cells with or without anti-tumor activity. The expression of candidate genes was confirmed at RNA level by quantitative RT-PCR and at the protein level by Western blots and immunocytochemistry. Moreover, we have developed in vitro assays to mimic the antitumor effect seen in vivo. Results We identified several targets involved in glioma growth and migration, specifically CXCL1, CD81, TPT1, Gas6 and AXL proteins. We further showed that follistatin secretion from the NPC has the potential to decrease tumor proliferation. In vitro co-cultures of NPC and tumor cells resulted in the inhibition of tumor growth. The addition of antibodies against proteins selected by gene and protein expression analysis either increased or decreased the proliferation rate of the glioma cell lines in vitro. Conclusion These results suggest that these identified factors might be useful starting points for performing future experiments directed towards a potential therapy against malignant gliomas.

  16. TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

    International Nuclear Information System (INIS)

    Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro. RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively. RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro. Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy

  17. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  18. Tumor Metabolism of Malignant Gliomas

    Directory of Open Access Journals (Sweden)

    Deliang Guo

    2013-11-01

    Full Text Available Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  19. Single and double ionization in C6++He collisions

    International Nuclear Information System (INIS)

    Single- and double-ionization processes in C6+ collisions with the He atom at an incident energy of 100 MeV/amu are studied by direct solution of the time-dependent Schroedinger equation. A time-dependent close-coupling method based on an expansion of a one-electron three-dimensional wave function in the field of He+ is used to calculate single-ionization cross sections. A time-dependent close-coupling method based on an expansion of a two-electron six-dimensional wave function in the field of He2+ is used to calculate single- and double-ionization cross sections. Electron energy and angle differential cross sections for single ionization are presented for various projectile impact parameters. For relatively large impact parameters, the differential cross sections are in qualitative agreement with ion-atom experiments. Electron energy and angle differential cross sections for double ionization are also presented for a relatively large projectile impact parameter.

  20. 胶质瘤细胞系摄取BPA的实验研究%Experimental study on BPA uptake of glioma cell lines

    Institute of Scientific and Technical Information of China (English)

    杨磊; 赵葵; 王潇; 隋丽; 孔福全; 郝小娟; 郑洁莹; 马南茹; 崔素珍; 刘权卫

    2012-01-01

    Objective: to evaluate the incorporation of BPA by glioma cell lines, and to observe its relationship with the temperature and the concentration of BPA. Methods; C6, U251 and rat astrocyte cells were incubated in a culture medium, in which ' B concentration was 20, 40, 60, 80, 100 μg/mL for 24 h. Boron concentration in the cells was measured induced couple plasma-atomic emission spectroscopy (ICP-AES). C6 cells were pre-incu-bated for 24 h with different boron concentrations in growth medium. Then the mediums were changed to boron-free ones, and boron content was assessed after 1, 2, 3 h. Results; The content of the 10B in cells was increasing with the increasing concentration of BPA, and the boron concentration ratios of glioma cells to astrocyte are 2. 2. The BPA efflux is slower at the lower temperature. Conclusion; BPA has a selectivity for glioma cells, and the results of the efflux assay confirm the temperature dependence of the BPA transport out of the cells.%目的:探讨BPA(2,2-双(4-羟基苯基)丙烷,Bisphenol A)浓度和温度对胶质瘤细胞系摄取和析出10B的影响.方法:将C6和U251两种胶质瘤细胞系,及大鼠正常脑胶质细胞培养在含不同浓度BPA(10B浓度分别为20、40、60、80、100 μg/mL)的培养基中24h后,采用感应耦合等离子体原子发射光谱(ICP-AES)法测定细胞内硼的含量;将C6细胞培养在含不同浓度BPA的培养基中培养24h后,更换为不含10B培养基,在不同温度条件(4、25、37℃)下继续培养,并分别于换液后的1、2、3h,用ICP-AES方法检测细胞内的硼含量.结果:细胞内硼浓度随培养基中BPA浓度的增加而增高,胶质瘤细胞内10B浓度约为正常胶质细胞的2.2倍;温度越高,细胞内硼析出速度越快.结论:BPA对胶质瘤细胞系具有一定亲和力;细胞对10B的析出速率具有温度依赖性.

  1. The anti-tumor effects of calorie restriction are correlated with reduced oxidative stress in ENU-induced gliomas

    Directory of Open Access Journals (Sweden)

    Megan A. Mahlke

    2011-06-01

    Full Text Available The anti-tumor effects of calorie restriction (CR and the possible underlying mechanisms were investigated using ethylnitrosourea (ENU-induced glioma in rats. ENU was given transplacentally at gestational day 15, and male offspring were used in this experiment. The brain from 4-, 6-, and 8-month-old rats fed either ad libitum (AL or calorie-restricted diets (40% restriction of total calories compared to AL rats was studied. Tumor burden was assessed by comparing the number and size of gliomas present in sections of the brain. Immunohistochemical analysis was used to document lipid peroxidation [4-hydroxy-2-nonenal (HNE and malondialdehyde (MDA], protein oxidation (nitrotyrosine, glycation and AGE formation [methylglyoxal (MG and carboxymethyllysine (CML], cell proliferation activity [proliferating cell nuclear antigen (PCNA], cell death [single-stranded DNA (ssDNA], presence of thioredoxin 1 (Trx1, and presence of heme oxygenase-1 (HO-1 associated with the development of gliomas. The results showed that the number of gliomas did not change with age in the AL groups; however, the average size of the gliomas was significantly larger in the 8-month-old group compared to that of the younger groups. Immunopositivity was observed mainly in tumor cells and reactive astrocytes in all histological types of ENU-induced glioma. Immunopositive areas for HNE, MDA, nitrotyrosine, MG, CML, HO-1, and Trx1 increased with the growth of gliomas. The CR group showed both reduced number and size of gliomas, and tumors exhibited less accumulation of oxidative damage, decreased formation of glycated end products, and a decreased presence of HO-1 and Trx1 compared to the AL group. Furthermore, gliomas of the CR group showed less PCNA positive and more ssDNA positive cells, which are correlated to the retarded growth of tumors. Interestingly, we also discovered that the anti-tumor effects of CR were associated with decreased hypoxia-inducible factor-1α (HIF-1α levels

  2. Influence of 12C6+ ion irradiation on mutant avermitilis

    Institute of Scientific and Technical Information of China (English)

    WANG Shu-Yang; CHEN Ji-Hong; LI Wen-Jian; LIANG Jian-Ping; BO Yong-Heng; MA Xiao-Qi; LIU Jing

    2012-01-01

    The effects of 12C+6ion irradiation on colony morphology and mycelia morphology,as well as on mutation rate have been studied in the Bla high-product strains (ZJAV-Y1-203) mutated by heavy ion irradiation and compared with that in the original strain (ZJAV-A-1).After irradiating the rate of a straw hat colony type having a high ability of producing B1a in ZJAV-Y1-203 strains was higher than that found in ZJAV-A-1 strains.When strains were cultured in a liquid medium for 24 hours,the mycelium becoming thinner could be observed in all of the irradiated ZJAV-Y1-203 groups,but only in the ZJAV-A-1 groups irradiated at the dose of 50 Gy or more.The early growth of mycelium was inhibited in the ZJAV-Y1-203 group irradiated with a high dose.The highest positive mutation rate (23.5%) of ZJAV-Y1-203 was reached at the lower dose of 30 Gy while the highest positive mutation rate of 34.2% in ZJAV-A-1 appeared at 50 Gy.These results indicate that the effects of heavy ion irradiation still exist even in the mutated Streptomyces avermitilis,and only the dose is lower and the effects not so strong compared with the one that is first irradiated with optimized heavy ion doses.This is evidence of the one directional mutation being controlled by many more factors in a organism.

  3. Imaging investigations of optic gliomas

    International Nuclear Information System (INIS)

    Objective: To evaluate CT and MR imaging findings of optic gliomas and their clinical significance. Methods: CT and MR imaging findings of 20 patients with pathologically confirmed optic gliomas were analyzed retrospectively. The age of the patients ranged from 8 months to 69 years. Ten patients were female and ten were male. CT scanning was performed in 10 patients with contrast scanning in 2, and MR imaging was performed in 19 patients with contrast scanning in 14. Results: Of the 20 cases with optic gliomas, a fusiform thickening of the optic nerve was found on CT and/or MR imaging in 12, a tubular enlarging and kinking of the optic nerve in 5, a dumb-bell mass of the optic nerve in 2, and an ovoid mass in 1. Enlargement of intraorbital and intracanalicular segments of the optic nerve was seen in all 20 cases, simultaneous enlargement of intracranial segment in 15, a simultaneous mass of intraocular segment in 4, a simultaneous mass of optic chiasm in 6, and simultaneous enlargement of optic tract in 2. CT scanning performed in 10 patients showed iso-density mass. Enhancement of enlarged optic nerve was observed on postcontrast CT in two. MR imaging performed in 19 patients displayed a long T1 and long T2 signal intensity mass in 12, a long T1 and identical T2 signal intensity mass in 5, and an isointense mass on T1- and T2- weighted images in 2. After contrast administration in 14 cases, marked enhancement of the mass was seen in 12 cases, and moderate enhancement was demonstrated in 2. Of the 7 patients associated with neurofibromatosis I, four optic gliomas appeared as a specific sign-isointense in the center on both T1- and T2-weighted images , hypointense on T1- and T2-weighted images in the intermediate portion, and long T1 and long T2 signal intensity in peripheral portion. After statistical analysis, MR imaging was superior to CT in demonstrating the tumor involvement of the intracanalicular and intracranial segments of the optic nerve (P<0

  4. Current treatment of low grade gliomas

    NARCIS (Netherlands)

    M.J. van den Bent (Martin); T.A.B. Snijders (Tom); J.E.C. Bromberg (Jacolien)

    2012-01-01

    textabstractLow grade gliomas affect predominantly young adults, and have a relatively favorable prognosis compared to grade III and grade IV gliomas. The challenge for an optimal management of these patients is to find the balance between an optimal survival and the preservation of neurological fun

  5. Neurofibromatosis Type 1 and Sporadic Optic Gliomas

    OpenAIRE

    J Gordon Millichap

    2002-01-01

    The natural history of sporadic optic gliomas was compared with that of optic gliomas associated with neurofibromatosis type 1 (NF1) in a study using a Children’s Tumor Registry (CTR) and an NF1 Database (NF1DB) at St Mary’s Hospital, Manchester, UK.

  6. Neurofibromatosis Type 1 and Sporadic Optic Gliomas

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-10-01

    Full Text Available The natural history of sporadic optic gliomas was compared with that of optic gliomas associated with neurofibromatosis type 1 (NF1 in a study using a Children’s Tumor Registry (CTR and an NF1 Database (NF1DB at St Mary’s Hospital, Manchester, UK.

  7. IMMUNOHISTOCHEMICAL DETECTION OF P73 PRODUCT IN BRAIN GLIOMAS

    Institute of Scientific and Technical Information of China (English)

    ZHAI Guang; YUAN Xian-hou; PAN Hui-jin; QIU Shang-ming; ZHOU Ming-yong

    1999-01-01

    Objective: To elucidate the role of p73 in the genesis or development of glioma. Methods: P73 and p53expression of 63 gliomas were detected by immunohistochemistry. Results: Out of the 63 gliomas, 17 cases appeared p73 positive. The positive-rate in high grade gliomas was higher than that in low grade gliomas (x2=4.75, P<0.05). Among the 17 cases with p73-positive gliomas, 12 cases overexpressed p53 protein. Conclusion:Overexpression of wild p73 may involve in the genesis or development of glioma.

  8. Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.

    Science.gov (United States)

    Lachance, Daniel H; Yang, Ping; Johnson, Derek R; Decker, Paul A; Kollmeyer, Thomas M; McCoy, Lucie S; Rice, Terri; Xiao, Yuanyuan; Ali-Osman, Francis; Wang, Frances; Stoddard, Shawn M; Sprau, Debra J; Kosel, Matthew L; Wiencke, John K; Wiemels, Joseph L; Patoka, Joseph S; Davis, Faith; McCarthy, Bridget; Rynearson, Amanda L; Worra, Joel B; Fridley, Brooke L; O'Neill, Brian Patrick; Buckner, Jan C; Il'yasova, Dora; Jenkins, Robert B; Wrensch, Margaret R

    2011-09-01

    Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997-2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger among those who did not (odds ratio(allergy-glioma) = 0.40, 95% confidence interval: 0.28, 0.58) versus those who did (odds ratio(allergy-glioma) = 0.76, 95% confidence interval: 0.59, 0.97; P(interaction) = 0.02) carry the 9p21.3 risk allele. However, the inverse association with allergy was stronger among those who carried (odds ratio(allergy-glioma) = 0.44, 95% confidence interval: 0.29, 0.68) versus those who did not carry (odds ratio(allergy-glioma) = 0.68, 95% confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this interaction was not statistically significant (P = 0.14). No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. The authors' observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma. PMID:21742680

  9. Glioma cell line proliferation controlled by different chemical functional groups in vitro

    Institute of Scientific and Technical Information of China (English)

    Su-Ju XU; Fu-Zhai CUI; Xiao-Long YU; Xiang-Dong KONG

    2013-01-01

    Glioma cell line C6 cultured on silicon surfaces modified by different chemical functional groups, including mercapto (-SH), carboxyl (-COOH), amino (-NH2), hydroxyl (-OH) and methyl (-CH3) groups, was studied here to investigate the influence of surface chemistry on the cell proliferation, adhesion and apoptosis. AFM confirmed the similar characteristic of different functional groups occupation. The adhering C6 exhibited morphological changes in response to different chemical functional groups. The C6 adhered to -COOH, -NH2, -OH and -CH3 surfaces and flattened morphology, while those on -SH surface exhibited the smallest contact area with mostly rounded morphology, which led to the death of cancer cells. The results of MTT assay showed that the -COOH and -NH2 groups promoted ceil proliferation, while the -SH significantly inhibited the proliferation. Compared with other chemical functional groups, the -SH group exhibited its unique effect on the fate of cancer cells, which might provide means for the design of biomaterials to prevent and treat glioma.

  10. Frequent Nek1 overexpression in human gliomas.

    Science.gov (United States)

    Zhu, Jun; Cai, Yu; Liu, Pin; Zhao, Weiguo

    2016-08-01

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients' poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. PMID:27251576

  11. Synthesis and characterization of -phosphorylated thioureas RNHC(S)NHP(O)(OPr)2 (R = 2-MeC6H4, 2,6-Me2C6H3, 2,4,6-Me3C6H2)

    Indian Academy of Sciences (India)

    Damir A Safin; Maria G Babashkina; Michael Bolte; Axel Klein

    2010-05-01

    Reaction of O,O'-diisopropylphosphoric acid isothiocyanate (PrO)2P(O)NCS with 2-methylaniline 2-MeC6H4NH2, 2,6-dimethylaniline 2,6-Me2C6H3NH2 or 2,4,6-trimethylaniline 2,4,6-Me3C6H2NH2 leads to the -phosphorylated thioureas RNHC(S)NHP(O)(OPr)2 (R = 2-MeC6H4-, HLI; 2,6-Me2C6H3-, HLII; 2,4,6-Me3C6H2-, HLIII). The new compounds were investigated by 1H and 31P{1H} NMR spectroscopy, and microanalysis. The molecular structure of the thiourea HLIII was elucidated by single crystal X-ray diffraction analysis. Single crystal X-ray diffraction studies showed HLIII forms both intra- and intermolecular hydrogen bonds, which in turn leads to the formation of polymeric chains. One of the intermolecular hydrogen bonds is of the type N-H$\\cdots$S. Moreover, the formation of intermolecular C-H$\\cdots$ 6 -phenyl interactions was established.

  12. Molecular genetic study of human malignant gliomas

    International Nuclear Information System (INIS)

    Loss of heterozygosity for loci on chromosome 10 were found in four of 9 (44%) informative cases of malignant gliomas. Deletions on RB1 locus were seen in six of 11 (54%) informative glioblastomas. LOH on chromosome 17p was found in eight of 16 (50%) malignant gliomas, including 2 cases of anaplastic oligodendroglioma. On the basis of the data presented here, it is possible to associate certain molecular abnormalities with malignant gliomas, LOH on chromosome 10, RB1 gene, and 17p. (Author)

  13. Adult high-grade malignant gliomas

    Directory of Open Access Journals (Sweden)

    Fable Zustovich

    2011-12-01

    Full Text Available Central nervous system (CNS malignant gliomas are relatively rare diseases. Prognosis is poor but has improved over recent years due to the improvement in the multi-disciplinary treatment: surgery, radiotherapy and chemotherapy...

  14. Improving seroreactivity-based detection of glioma.

    Science.gov (United States)

    Ludwig, Nicole; Keller, Andreas; Heisel, Sabrina; Leidinger, Petra; Klein, Veronika; Rheinheimer, Stefanie; Andres, Claudia U; Stephan, Bernhard; Steudel, Wolf-Ingo; Graf, Norbert M; Burgeth, Bernhard; Weickert, Joachim; Lenhof, Hans-Peter; Meese, Eckart

    2009-12-01

    Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 repetitive classifications. We were able to differentiate glioma sera from sera of the healthy controls with a specificity of 90.28%, a sensitivity of 87.31% and an accuracy of 88.84%. We were also able to differentiate World Health Organization grade IV glioma sera from healthy sera with a specificity of 98.45%, a sensitivity of 80.93%, and an accuracy of 92.88%. To rank the antigens according to their information content, we computed the area under the receiver operator characteristic curve value for each clone. Altogether, we found 46 immunogenic clones including 16 in-frame clones that were informative for the classification of glioma sera versus healthy sera. For the separation of glioblastoma versus healthy sera, we found 91 informative clones including 26 in-frame clones. The best-suited in-frame clone for the classification glioma sera versus healthy sera corresponded to the vimentin gene (VIM) that was previously associated with glioma. In the future, autoantibody signatures in glioma not only may prove useful for diagnosis but also offer the prospect for a personalized immune-based therapy. PMID:20019846

  15. Improving Seroreactivity-Based Detection of Glioma

    OpenAIRE

    Nicole Ludwig; Andreas Keller; Sabrina Heisel; Petra Leidinger; Veronika Klein; Stefanie Rheinheimer; Andres, Claudia U; Bernhard Stephan; Wolf-Ingo Steudel; Graf, Norbert M; Bernhard Burgeth; Joachim Weickert; Hans-Peter Lenhof; Eckart Meese

    2009-01-01

    Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 ...

  16. Improving Seroreactivity-Based Detection of Glioma

    Directory of Open Access Journals (Sweden)

    Nicole Ludwig

    2009-12-01

    Full Text Available Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 repetitive classifications. We were able to differentiate glioma sera from sera of the healthy controls with a specificity of 90.28%, a sensitivity of 87.31% and an accuracy of 88.84%. We were also able to differentiate World Health Organization grade IV glioma sera from healthy sera with a specificity of 98.45%, a sensitivity of 80.93%, and an accuracy of 92.88%. To rank the antigens according to their information content, we computed the area under the receiver operator characteristic curve value for each clone. Altogether, we found 46 immunogenic clones including 16 in-frame clones that were informative for the classification of glioma sera versus healthy sera. For the separation of glioblastoma versus healthy sera, we found 91 informative clones including 26 in-frame clones. The best-suited in-frame clone for the classification glioma sera versus healthy sera corresponded to the vimentin gene (VIM that was previously associated with glioma. In the future, autoantibody signatures in glioma not only may prove useful for diagnosis but also offer the prospect for a personalized immune-based therapy.

  17. Targeted Radiolabeled Compounds in Glioma Therapy.

    Science.gov (United States)

    Cordier, Dominik; Krolicki, Leszek; Morgenstern, Alfred; Merlo, Adrian

    2016-05-01

    Malignant gliomas of World Health Organization (WHO) grades II-IV represent the largest entity within the group of intrinsic brain tumors and are graded according to their pathophysiological features with survival times between more than 10 years (WHO II) and only several months (WHO IV). Gliomas arise from astrocytic or oligodendrocytic precursor cells and exhibit an infiltrative growth pattern lacking a clearly identifiable tumor border. The development of effective treatment strategies of the invasive tumor cell front represents the main challenge in glioma therapy. The therapeutic standard consists of surgical resection and, depending on the extent of resection and WHO grade, adjuvant external beam radiotherapy or systemic chemotherapy. Within the last decades, there has been no major improvement of the prognosis of patients with glioma. The consistent overexpression of neurokinin type 1 receptors in gliomas WHO grades II-IV has been used to develop a therapeutic substance P-based targeting system. A substance P-analogue conjugated to the DOTA or DOTAGA chelator has been labeled with different alpha-particle or beta-particle emitting radionuclides for targeted glioma therapy. The radiopharmaceutical has been locally injected into the tumors or the resection cavity. In several clinical studies, the methodology has been examined in adjuvant and neoadjuvant clinical settings. Although no large controlled series have so far been generated, the results of radiolabeled substance P-based targeted glioma therapy compare favorably with standard therapy. Recently, labeling with the alpha particle emitting Bi-213 has been found to be promising due to the high linear energy transfer and the very short tissue range of 0.08 mm. Further development needs to focus on the improvement of the stability of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within the prognostically critical

  18. Suppression of glioma progression by Egln3.

    Directory of Open Access Journals (Sweden)

    Vicki A Sciorra

    Full Text Available Grade IV astrocytoma or glioblastoma has a poor clinical outcome that can be linked to hypoxia, invasiveness and active vascular remodeling. It has recently been suggested that hypoxia-inducible factors, Hifs, increase glioma growth and aggressiveness [1], [2], [3]. Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3, a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma models. Through intracranial tumorigenesis and in vitro assays, we demonstrate for the first time that Egln3 was sufficient to decrease the kinetics of tumor progression and increase survival. We also find that Klf5, a transcription factor important to vascular remodeling, was regulated by hypoxia in glioma. An analysis of the tumor vasculature revealed that elevated Egln3 normalized glioma capillary architecture, consistent with a role for Egln3 in eliciting decreases in the production of Hif-regulated, angiogenic factors. We also find that the hydroxylase-deficient mutant, Egln3(H196A partially maintained tumor suppressive activity. These results highlight a bifurcation of Egln3 signaling and suggest that Egln3 has a non-hydroxylase-dependent function in glioma. We conclude that Egln3 is a critical determinant of glioma formation and tumor vascular functionality.

  19. The combined effect of encapsulating curcumin and C6 ceramide in liposomal nanoparticles against osteosarcoma.

    Science.gov (United States)

    Dhule, Santosh S; Penfornis, Patrice; He, Jibao; Harris, Michael R; Terry, Treniece; John, Vijay; Pochampally, Radhika

    2014-02-01

    This study examines the antitumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared: curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed primary human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested in vivo using a human osteosarcoma xenograft assay. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy.

  20. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Directory of Open Access Journals (Sweden)

    Fine Howard A

    2010-07-01

    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  1. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  2. Opening of the blood-brain barrier through focused ultrasound in combination with drugs to treat glioma%聚焦超声开放血脑屏障治疗脑胶质瘤疗效的实验研究

    Institute of Scientific and Technical Information of China (English)

    潘敏; 张天奉; 王峰; 邹超; 万倩; 吴碧峰; 刘新; 郑海荣

    2015-01-01

    Objective To evaluate the effectiveness of treating glioma in combination with drugs multiply by comparing the size of tumor and the survival time of different groups in rat glioma after targeted blood-brain barrier (BBB ) disruption by MRI-guided focused ultrasound.Methods The stereotaxis instruments and the 10 μl gas-tight syringes were used to inject gliosarcoma cells into the targeted area of the brain in 50 male Sprague-Dawley rats.The glioma-bearing rat model was established.Each rat received either:(1 )no treatment (control;n =8);(2)single liposomal doxorubicin (DOX;n = 10);(3)multiple DOX (n =10);(4)single Avastin (AVS)and DOX (n =10);(5)multiple AVS and DOX (n =10).The SonoVue microbubble ultrasonic contrast agent and DOX or AVS were injected into the tail vein respectively on day 12 after implantation.The tumor size was measured by MRI on pre-treatment,immediacy and once a week of post-treatment after targeted BBB disruption by focused ultrasound,and the life span in rat glioma was recorded.Results The mediam survival of different groups in rat glioma(The range of the life span 13-90 d):no treatment (7 d);single DOX (12 d);multiple DOX (1 5 d);single AVS + DOX (22 d), multiple AVS+ DOX (30 d).There was significant difference of the groups on mediam survival comparison (P < 0.01 ).The tumor growth pattern after post-treatment of different groups in rat glioma except control:single DOX was noticeable fast and multiple AVS+DOX was visibly delayed comparable to other groups,and finally the tumor size of multiple AVS + DOX even became small.Conclusions The microbubble blasting enhances the local tissue permeability and promotes the drug delivery of chemotherapy and anti-angiogenesis locally in glioma-bearing rats by MRI-guided focused ultrasound.Especially,the combination with drugs multiply has a synergism efficacy that may enhance the effectiveness of chemotherapy,reduce tumor growth,and even become small of the tumor size,and increase survival time

  3. A Potential Nanofiber Membrane Device for Filling Surgical Residual Cavity to Prevent Glioma Recurrence and Improve Local Neural Tissue Reconstruction.

    Science.gov (United States)

    Huang, Daoxiang; Lin, Chao; Wen, Xuejun; Gu, Shuying; Zhao, Peng

    2016-01-01

    This study aims to develop a novel device with nanofiber membrane capable of sustained release of temozolomide (TMZ) and neuron growth factor (NGF). An improved bio-availability of TMZ and NGF in surroundings proximal to the device was expected to be attained for a prolonged period of time. The device was developed by integrating TMZ-doped polycaprolactone (PCL) nanofiber (TP) membrane and NGF-coated PCL (NGFP) membrane using sodium alginate hydrogel. TP was prepared by direct electrospinning of TMZ/PCL. NGFP membrane was developed by layer-by-layer assembling technology. The incorporation of TMZ-doped nanofiber and NGFP nanofiber in the device was confirmed by scanning electron microscopy. The number of NGF layer in NGF-coated PCL membrane could be readily measured with energy spectrum analysis. The in vitro release study showed that TP-NGFP-TP membrane could efficiently liberate TMZ to inhibit the growth of C6 glioma cells, and sufficient NGF to induce the differentiation of PC12 neuron cells over four weeks. Such TP-NGFP-TP membrane device can be employed as a tampon to fill up surgical residual cavity and afford residual glioma removal, structural support, hemostasis, and local neural tissue reconstruction in the surgical treatment of glioma. The study opens a horizon to develop multifunctional biomaterial device for maximized glioma treatment efficacy. PMID:27548322

  4. A Potential Nanofiber Membrane Device for Filling Surgical Residual Cavity to Prevent Glioma Recurrence and Improve Local Neural Tissue Reconstruction

    Science.gov (United States)

    Huang, Daoxiang; Lin, Chao; Wen, Xuejun; Gu, Shuying; Zhao, Peng

    2016-01-01

    This study aims to develop a novel device with nanofiber membrane capable of sustained release of temozolomide (TMZ) and neuron growth factor (NGF). An improved bio-availability of TMZ and NGF in surroundings proximal to the device was expected to be attained for a prolonged period of time. The device was developed by integrating TMZ-doped polycaprolactone (PCL) nanofiber (TP) membrane and NGF-coated PCL (NGFP) membrane using sodium alginate hydrogel. TP was prepared by direct electrospinning of TMZ/PCL. NGFP membrane was developed by layer-by-layer assembling technology. The incorporation of TMZ-doped nanofiber and NGFP nanofiber in the device was confirmed by scanning electron microscopy. The number of NGF layer in NGF-coated PCL membrane could be readily measured with energy spectrum analysis. The in vitro release study showed that TP-NGFP-TP membrane could efficiently liberate TMZ to inhibit the growth of C6 glioma cells, and sufficient NGF to induce the differentiation of PC12 neuron cells over four weeks. Such TP-NGFP-TP membrane device can be employed as a tampon to fill up surgical residual cavity and afford residual glioma removal, structural support, hemostasis, and local neural tissue reconstruction in the surgical treatment of glioma. The study opens a horizon to develop multifunctional biomaterial device for maximized glioma treatment efficacy. PMID:27548322

  5. Oncolytic adenoviruses: A thorny path to glioma cure

    OpenAIRE

    Ulasov, I.V.; Borovjagin, A.V.; Schroeder, B.A. (Betsy A.); Baryshnikov, A.Y.

    2014-01-01

    Glioblastoma Multiforme (GBM) is a rapidly progressing brain tumor. Despite the relatively low percentage of cancer patients with glioma diagnoses, recent statistics indicate that the number of glioma patients may have increased over the past decade. Current therapeutic options for glioma patients include tumor resection, chemotherapy, and concomitant radiation therapy with an average survival of approximately 16 months. The rapid progression of gliomas has spurred the development of novel tr...

  6. Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

    International Nuclear Information System (INIS)

    Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist 11C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. 11C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of 11C-SA4503 to C6 cells was increased (∝50%) upon removal and decreased (∝60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC50 progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of 11C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of 11C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

  7. Steroid hormones affect binding of the sigma ligand {sup 11}C-SA4503 in tumour cells and tumour-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van [University of Groningen, Nuclear Medicine and Molecular Imaging, University of Groningen Medical Center, Groningen (Netherlands); Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Tokyo (Japan)

    2009-07-15

    Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist {sup 11}C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. {sup 11}C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of {sup 11}C-SA4503 to C6 cells was increased ({proportional_to}50%) upon removal and decreased ({proportional_to}60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC{sub 50} progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of {sup 11}C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of {sup 11}C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

  8. New similarity search based glioma grading

    Energy Technology Data Exchange (ETDEWEB)

    Haegler, Katrin; Brueckmann, Hartmut; Linn, Jennifer [Ludwig-Maximilians-University of Munich, Department of Neuroradiology, Munich (Germany); Wiesmann, Martin; Freiherr, Jessica [RWTH Aachen University, Department of Neuroradiology, Aachen (Germany); Boehm, Christian [Ludwig-Maximilians-University of Munich, Department of Computer Science, Munich (Germany); Schnell, Oliver; Tonn, Joerg-Christian [Ludwig-Maximilians-University of Munich, Department of Neurosurgery, Munich (Germany)

    2012-08-15

    MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone. (orig.)

  9. New similarity search based glioma grading

    International Nuclear Information System (INIS)

    MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone. (orig.)

  10. Immunoglobulin genes implicated in glioma risk.

    Science.gov (United States)

    Pandey, Janardan P; Kaur, Navtej; Costa, Sandra; Amorim, Julia; Nabico, Rui; Linhares, Paulo; Vaz, Rui; Viana-Pereira, Marta; Reis, Rui M

    2014-01-01

    Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.

  11. Bromelain Reversibly Inhibits Invasive Properties of Glioma Cells

    OpenAIRE

    Tysnes, Berit B.; H. Rainer Maurert; Torsten Porwol; Beatrice Probst; Rolf Bjerkvig; Frank Hoover

    2001-01-01

    Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, and fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell a...

  12. The first potential energy surfaces for the C6H--H2 and C6H--He collisional systems and their corresponding inelastic cross sections

    Science.gov (United States)

    Walker, Kyle M.; Dumouchel, Fabien; Lique, François; Dawes, Richard

    2016-07-01

    Molecular anions have recently been detected in the interstellar and circumstellar media. Accurate modeling of their abundance requires calculations of collisional data with the most abundant species that are usually He atoms and H2 molecules. In this paper, we focus on the collisional excitation of the first observed molecular anion, C6H-, by He and H2. Theoretical calculations of collisional cross sections rely generally on ab initio interaction potential energy surfaces (PESs). Hence, we present here the first PESs for the C6H--H2 and C6H--He van der Waals systems. The ab initio energy data for the surfaces were computed at the explicitly correlated coupled cluster with single, double, and scaled perturbative triple excitations level of theory. The method of interpolating moving least squares was used to construct 4D and 2D analytical PESs from these data. Both surfaces are characterized by deep wells and large anisotropies. Analytical models of the PESs were used in scattering calculations to obtain cross sections for low-lying rotational transitions. As could have been anticipated, important differences exist between the He and H2 cross sections. Conversely, no significant differences exist between the collisions of C6H- with the two species of H2 (para- and ortho-H2). We expect that these new data will help in accurately determining the abundance of the C6H- anions in space.

  13. Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines.

    Science.gov (United States)

    Çiftçi, Gülşen Akalin; Işcan, Arzu; Kutlu, Mehtap

    2015-10-01

    Aesculus hippocastanum (the horse chestnut) seed extract has a wide variety of biochemical and pharmacological effects including anti-inflammatory, antianalgesic, and antipyretic activities. The main active compound of this plant is escin. It is known that several medicinal herbs with anti-inflammatory properties have been found to have a role in the prevention and treatment of cancer. In the present study, the cytotoxic effects of escin in the C6 glioma and A549 cell lines were analyzed by MTT. Apoptotic effects of escin on both cell lines were evaluated by Annexin V binding capacity with flow cytometric analysis. Structural and ultrastructural changes were also evaluated using transmission electron microscopy. The results indicated that escin has potent antiproliferative effects against C6 glioma and A549 cells. These effects are both dose and time dependent. Taken together, escin possesses cell cycle arrest on G0/G1 phase and selective apoptotic activity on A549 cells as indicated by increased Annexin V-binding capacity, bax protein expression, caspase-3 activity and morphological changes obtained from micrographs by transmission electron microscopy. PMID:25906387

  14. Neurotensin promotes the progression of malignant glioma through NTSR1 and impacts the prognosis of glioma patients

    OpenAIRE

    Ouyang, Qing; Gong, Xueyang; Xiao, Hualiang; Zhou, Ji; Xu, Minhui; Dai, Yun; Xu, Lunshan; Feng, Hua; Cui, Hongjuan; Yi, Liang

    2015-01-01

    Background The poor prognosis and minimally successful treatments of malignant glioma indicate a challenge to identify new therapeutic targets which impact glioma progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) overexpression induces neoplastic growth and predicts the poor prognosis in various malignancies. Whether NTS can promote the glioma progression and its prognostic significance for glioma patients remains unclear. Methods NTS precursor (ProNTS), NTS and NTSR1 expr...

  15. Sensitivity of Interstitial combined Chemotherapy against Glioma

    Institute of Scientific and Technical Information of China (English)

    WANG Ming-sheng; LIN Jian-ying; ZHOU Guo-sheng; ZHANG Xin-zhong

    2006-01-01

    Objective To investigate the inhibitory effects of combination chemotherapy of Carboplatin(CBP) ,Teniposide (Vm-26) ,Methasquin(MTX),and Nimodipine(NIM) on glioma,and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells,and to compare the sensitivity of glioma cells to administration of CBP,Vm-26, MTX, and NIM with that of the administration of CBP + NIM, Vm-26 + NIM, MTX + NIM, CBP + Vm-26 + MTX, or CBP + Vm-26 + MTX + NIM respectively. Results The inhibition rate of CBP + Vm-26 + MTX + NIM combination administration against glioma cells was 96.64%,which was higher than that of CBP + NIM (69.03%), Vm-26 + NIM (71.53%), MTX + NIM (52. 75% ), CBP + Vm-26 + MTX(78.59%)(P<0.01),and the dosage of CBP,Vm-26,and MTX was declined to 1/10 ~ 1/100 that of respective use of CBP,Vm-26,and MTX. Conclusions The curative effects of combination administration of CBP,Vm-26, MTX, and NIM was much better than that of respective administration,suggesting a higher inhibition rate and a lower dosage use.

  16. Genetic characterization of adult infratentorial gliomas.

    Science.gov (United States)

    Miwa, Tomoru; Hirose, Yuichi; Sasaki, Hikaru; Ikeda, Eiji; Yoshida, Kazunari; Kawase, Takeshi

    2009-02-01

    Adult infratentorial gliomas are rare and have not been well studied. We therefore conducted genetic analysis of those tumors to see if there was any characteristic that could be relevant in clinical management and understanding of tumorigenesis. Nineteen adult infratentorial gliomas were analyzed for chromosomal aberration by comparative genomic hybridization, and for expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry. The most frequent chromosomal aberration was the gain of 7p, and five of the seven cerebellar or fourth ventricle malignant gliomas had that aberration. However, the gain of 7q, the characteristic abnormality of supratentorial astrocytomas commonly associated with the gaining of 7p, was observed only in 1 of 11 adult infratentorial astrocytic tumors. Combined losses of 1p and 19q, the genetic hallmark of oligodendroglioma, were not observed. Results of immunohistochemistry of p53 and EGFR were comparable to those reported in supratentorial gliomas. Our findings might suggest the presence of distinct tumorigenic pathway in adult infratentorial gliomas.

  17. [Chemotherapy of chiasmal gliomas in children].

    Science.gov (United States)

    Helcl, F

    1995-04-01

    Chiasmal gliomas are rare tumors occurring predominantly in childhood. Their optimal treatment is still controversial. In the past only neurosurgeons (performing partial or subtotal removal of the tumor, biopsy or shunting procedure in hydrocephalus) and radiotherapeutists participated in their treatment. In the middle of the eighties there was only a single article dealing with chemotherapy of these tumors (Rosenstock, 1985). Since that time there was an increased number of articles about harmful effects of radiotherapy on the developing child's brain. Neurosurgeons are aware that they will not solve this problem alone. During the past 7 years we have observed gradual retreat from radiotherapy and an inclination to combined chemotherapy of the chiasmal gliomas in children. The author has been engaged in the research of this clinical entity for more than 10 years and he offers to readers a summary of the contemporary knowledge about chemotherapy of chiasmal gliomas in children. Despite the fact that there is lacking experience with long-term survivors after chemotherapy, which is extremely important especially in this disease, the preliminary short-term results of combined chemotherapy of chiasmal gliomas in children are promising. Rapid development of chemistry and pharmacology in the last few years is promising for the discovery of further, more effective anti-tumor drugs. Their new combinations could improve present non-satisfactory results of treatment of chiasmal gliomas in children. (Ref. 25.)

  18. Molecular Therapeutic Targets for Glioma Angiogenesis

    Directory of Open Access Journals (Sweden)

    Shingo Takano

    2010-01-01

    Full Text Available Due to the prominent angiogenesis that occurs in malignant glioma, antiangiogenic therapy has been attempted. There have been several molecular targets that are specific to malignant gliomas, as well as more broadly in systemic cancers. In this review, I will focus on some topics related to molecular therapeutic targets for glioma angiogenesis. First, important angiogenic factors that could be considered molecular targets are VEGF, VEGF-induced proteins on endothelial cells, tissue factor, osteopontin, v3 integrin, and thymidine phosphorylase as well as endogenous inhibitors, soluble Flt1, and thrombospondin 1. Second, hypoxic areas are also decreased by metronomic CPT11 treatment as well as temozolomide. Third, glioma-derived endothelial cells that are genetically and functionally distinct from normal endothelial cells should be targeted, for example, with SDF-1 and CXCR7 chemokine. Fourth, endothelial progenitor cells (EPCs likely contribute towards glioma angiogenesis in the brain and could be useful as a drug delivery tool. Finally, blockade of delta-like 4 (Dll4 results in a nonfunctioning vasculature and could be another important target distinct from VEGF.

  19. Electron Transfer Reaction between M-C6H6 and M+-C6H6 Complexes in the Gas Phase: Density Functional Theory Study

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    DFT/BLYP method is used to theoretically investigate the electron transfer (ET) reactions between M (Li, Na, Mg)-C6H6 and M+-C6H6 complexes in the gas phase. The geometry optimization of the precursor complexes and the transition state in the process of ET reaction was performed at 6-31G basis set level. The activation energy, the coupling matrix element and the rate constant of the ET reaction are calculated at semi-quantitative level.

  20. Heat of Mixing and Solution of Cyclohexanone C6H10O + C6H12O Cyclohexanol (HMSD1121, LB4187_H)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume A 'Binary Liquid Systems of Nonelectrolytes I' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Heat of Mixing and Solution of Cyclohexanone C6H10O + C6H12O Cyclohexanol (HMSD1121, LB4187_H)' providing data from direct calorimetric measurement of molar excess enthalpy at variable mole fraction and constant pressure and temperature.

  1. Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1212, LB4824_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1212, LB4824_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  2. Vapor-Liquid Equilibrium in the Mixture Cyclohexanone C6H10O + C6H12O Cyclohexanol (EVLM1111, LB5657_E)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume A 'Binary Liquid Systems of Nonelectrolytes I' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Vapor-Liquid Equilibrium in the Mixture Cyclohexanone C6H10O + C6H12O Cyclohexanol (EVLM1111, LB5657_E)' providing data from direct measurement of pressure at variable mole fraction in liquid phase and constant temperature.

  3. Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1111, LB4819_V0029

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1111, LB4819_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  4. Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1511, LB4829_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Benzene C6H6 + C6H10O Cyclohexanone (VMSD1511, LB4829_V)' providing data from direct measurement of low-pressure thermodynamic speed of sound at variable mole fraction and constant temperature, in the single-phase region(s).

  5. 40 CFR 721.2088 - Carboxylic acids, (C6-C9) branched and linear.

    Science.gov (United States)

    2010-07-01

    ... linear. 721.2088 Section 721.2088 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.2088 Carboxylic acids, (C6-C9) branched and linear. (a) Chemical... as carboxylic acids, (C6-C9) branched and linear (PMNs P-93-313, 314, 315, and 316) are subject...

  6. 26 CFR 1.381(c)(6)-1 - Depreciation method.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Depreciation method. 1.381(c)(6)-1 Section 1.381... (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.381(c)(6)-1 Depreciation method. (a) Carryover... (4), the acquiring corporation shall compute its depreciation allowance by the same method used...

  7. Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

    Directory of Open Access Journals (Sweden)

    Holz David

    2008-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Results Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA revealed two discriminating patterns between migrating and stationary glioma cells: i global down-regulation and ii global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF. siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Conclusion Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected

  8. Associations of High-Grade Glioma With Glioma Risk Alleles and Histories of Allergy and Smoking

    OpenAIRE

    Lachance, Daniel H.; Yang, Ping; Johnson, Derek R.; Decker, Paul A.; Kollmeyer, Thomas M.; McCoy, Lucie S.; Rice, Terri; Xiao, Yuanyuan; Ali-Osman, Francis; Wang, Frances; Stoddard, Shawn M.; Sprau, Debra J.; Kosel, Matthew L.; Wiencke, John K.; Wiemels, Joseph L.

    2011-01-01

    Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997–2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). Th...

  9. Prenatal diagnosis of a nasal glioma.

    Science.gov (United States)

    Grzegorczyk, Véronica; Brasseur-Daudruy, Marie; Labadie, Gérard; Cellier, Cécile; Verspyck, Eric

    2010-10-01

    Nasal glioma is a rare congenital midline malformation composed of heterotopic masses of neuroglial tissue. We report a case of fetal nasal glioma diagnosed by sonography at 22 weeks' gestation as a vascular hypoechoic mass located on the left nasal bone. Fetal MRI excluded an underlying bone defect. At birth, the lesion appeared as a reddish mass. Post natal imaging confirmed the vascularisation within the lesion with an arterial low-flow velocity and a high-resistance spectrum, consistent with a glioma. The child underwent surgery at 5 months and final diagnosis was made on pathological examination. Therefore, a vascular lesion and a clinical aspect mimicking a haemangioma should not be considered sufficient to reach the final diagnosis. PMID:20401478

  10. Treatment of malignant glioma using hyperthermia*

    Institute of Scientific and Technical Information of China (English)

    Jiahang Sun; Mian Guo; Hengyuan Pang; Jingtao Qi; Jinwei Zhang; Yunlong Ge

    2013-01-01

    Thirty pathological y diagnosed patients with grade III-IV primary or recurrent malignant glioma (tumor diameter 3-7 cm) were randomly divided into two groups. The control group underwent conventional radiotherapy and chemotherapy. In the hyperthermia group, primary cases received hyperthermia treatment, and patients with recurrent tumors were treated with hyperthermia in com-bination with radiotherapy and chemotherapy. Hyperthermia treatment was administered using a 13.56-MHz radio frequency hyperthermia device. Electrodes were inserted into the tumor with the aid of a CT-guided stereotactic apparatus and heat was applied for 1 hour. During 3 months after hyperthermia, patients were evaluated with head CT or MRI every month. Gliomas in the hyper-thermia group exhibited growth retardation or growth termination. Necrosis was evident in 80%of the heated tumor tissue and there was a decrease in tumor diameter. Our findings indicate that ra-dio frequency hyperthermia has a beneficial effect in the treatment of malignant glioma.

  11. [Surgical treatment of chiasmal gliomas in children].

    Science.gov (United States)

    Helcl, F

    1997-03-01

    Chiasmal gliomas are rare brain tumors occurring especially in children. Their proper treatment is still controversial and consists of surgery, radiotherapy and chemotherapy. Surgical removal of these tumors can usually be only partial or subtotal and radiotherapy frequently follows. There are supporters of surgical approach, as well as its enemies. The author has been engaged in problems of optimal treatment of this entity for more than 10 years. He is offering a review of knowledge from the literature concerning surgical treatment of this disease in children. The great majority of articles in the literature are dealing with retrospective analysis of relatively small series of patients usually treated in single neurosurgical department and the surgical treatment is enclosed like a part of combined therapy. Articles dealing only with surgical treatment of chiasmal gliomas are few and reviews determining the contemporary role of surgery of this entity are also lacking. This was the main impulse for writing this compilation. The short history of surgical therapy is reviewed. Some new trends of this therapy are also mentioned (microsurgery, Cavitron Ultrasonic Surgical Aspirator and peroperative use of visual evoked potentials). Up to date criteria for surgical treatment of chiasmal gliomas in children are given-exploration of chiasmal region and performing a biopsy in all cases, radical surgery only in extrinsic gliomas of the chiasmal region and conservative surgical approach to intrinsic chiasmal gliomas. It is emphasized that the significance of obstructive hydrocephalus in this entity has not been fully estimated till now, as well as the role of shunting procedures. Surgical treatment remains, nevertheless, an important armamentarium in the management of chiasmal gliomas in children. (Ref. 20.)

  12. Mean Diffusional Kurtosis in Patients with Glioma

    DEFF Research Database (Denmark)

    Tietze, A.; Hansen, Mikkel Bo; Østergaard, Leif;

    2015-01-01

    , and the contralateral normal appearing white and grey matter of 34 patients (22 high-grade, 12 low-grade gliomas). MK’ and MD in different grades were compared using a Wilcoxon rank-sum test. Receiver Operating Characteristic curves and the area under the curve were calculated to determine the diagnostic accuracy of MK...... with regard to glioma grading, compare it to conventional DKI and compare the diagnostic accuracy of mean kurtosis (MK’) to that of the widely used mean diffusivity (MD). Material and Methods: MK’ and MD were measured in the contrast-enhancing tumor core, the peri-focal hyperintensity on T2FLAIR...

  13. Using bioluminescence imaging in glioma research.

    Science.gov (United States)

    Luwor, Rodney B; Stylli, Stanley S; Kaye, Andrew H

    2015-05-01

    Glioblastoma multiforme (GBM) is the most common malignant brain tumour and has the worst prognosis. Over the last decade, the use of bioluminescence imaging technology has rapidly become widespread to further understand the mechanisms that drive GBM development and progression. Pre-clinical evaluation and optimisation of therapeutic efficacy in GBM research has also utilised this simple non-invasive technology. Here we summarise recent advances made in glioma biology and therapeutic intervention using bioluminescence imaging. This review also describes the current knowledge regarding the use of luciferase-based reporters in examining the role of specific cancer signalling cascades that promote glioma progression.

  14. Prognostic value of Musashi-1 in gliomas

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Hansen, Steinbjørn; Herrstedt, Jørn;

    2013-01-01

    The aim of this study was to investigate the prognostic value of the RNA-binding protein Musashi-1 in adult patients with primary gliomas. Musashi-1 has been suggested to be a cancer stem cell-related marker in gliomas, and high levels of Musashi-1 have been associated with high tumor grades...... 0.65, p = 0.038). In addition patients with high levels of Musashi-1 benefitted most from post-surgical treatment, indicating that Musashi-1 may be a predictive marker in GBMs. In conclusion, our results suggest that high levels of Musashi-1 are associated with poor survival in patients with WHO...

  15. New naphthoquinone derivatives against glioma cells.

    Science.gov (United States)

    Redaelli, Marco; Mucignat-Caretta, Carla; Isse, Abdirisak Ahmed; Gennaro, Armando; Pezzani, Raffaele; Pasquale, Riccardo; Pavan, Valeria; Crisma, Marco; Ribaudo, Giovanni; Zagotto, Giuseppe

    2015-01-01

    This work was aimed to the development of a set of new naphtoquinone derivatives that can act against glioma. The compounds were tested in order to find out their ability to inhibit the growth of glioma cells, and the results of these assays were correlated with electrochemical analysis and NMR-based reoxidation kinetic studies, suggesting that a redox mechanism underlies and may explain the observed biological behavior. In addition to a full description of the synthetic pathways, electrochemistry, NMR and single crystal X-ray diffraction data are provided. PMID:25916907

  16. Management of Traumatic C6-7 Spondyloptosis with Cord Compression

    OpenAIRE

    Choi, Man-Kyu; Jo, Dae-Jean; Kim, Min-Ki; Kim, Tae-Sung

    2014-01-01

    A case of total spondyloptosis of the cervical spine at C6-7 level with cord compression is described in a 51-year-old male. Because the bodies of C6 and 7 were tightly locked together, cervical traction failed. Then the patient was operated on by a posterior approach. Posterior stabilization and fusion were performed by C4-5 lateral mass and C7-T1 pedicle screw fixation and rod instrumentation with bridging both C4-5's rods to the C7-T1's extended ones. After C6 total laminectomy and foramin...

  17. Reactions of metallic Li or LiC6 with organic solvents for lithium ion battery

    Science.gov (United States)

    Nakajima, Tsuyoshi; Hirobayashi, Yuki; Takayanagi, Yuki; Ohzawa, Yoshimi

    2013-12-01

    DSC (Differential Scanning Calorimetry) study has been made on the reactions of metallic Li or LiC6 with organic solvents for lithium ion battery. Ethylene carbonate (EC) more easily reacts with metallic Li and LiC6 than propylene carbonate (PC). This may be because formation of lithium alkyl carbonate is more difficult for PC than EC. On the other hand, diethyl carbonate (DEC), ethyl methyl carbonate (EMC) and dimethyl carbonate (DMC) react with Li in the same manner. Reactions of Li and LiC6 with organic solvents have been discussed based on the results of quantum calculation.

  18. Lymphoid Cell-Glioma Cell Interaction Enhances Cell Coat Production by Human Gliomas: Novel Suppressor Mechanism

    Science.gov (United States)

    Dick, Steven J.; Macchi, Beatrice; Papazoglou, Savvas; Oldfield, Edward H.; Kornblith, Paul L.; Smith, Barry H.; Gately, Maurice K.

    1983-05-01

    Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these lines in vitro. Coat production is substantially enhanced by the interaction of glioma cells with a macromolecular factor released by human peripheral blood mononuclear cells in culture. This interaction thus constitutes an unusual mechanism by which inflammatory cells may nonspecifically suppress the cellular immune response to at least one class of solid tumors in humans.

  19. Real-time detection of L-glutamate released from C6 glioma cells using a modified enzyme-luminescence method.

    Science.gov (United States)

    Zakir Hossain, S M; Shinohara, Hiroaki; Wang, Feifei; Kitano, Hiromi

    2007-11-01

    There is an increasing interest in new strategies to detect neurotransmitters released from nerve cells in real time for brain science, drug assessment, and so on. Previously we reported real-time monitoring of dopamine release from nerve model cells by enzyme-catalyzed luminescence measurement with tyramine oxidase and peroxidase. In the present study, the system was modified with glutamate oxidase instead of tyramine oxidase to detect L-glutamate sensitively ( approximately 10 nM) and rapidly with high temporal resolution (10 mM) or 5-hydroxytryptamine (>1 microM). The measurement solution was not toxic and therefore the L-glutamate release from the cell was measured by the second stimulation after exchanging the measurement solution. We conclude that the developed monitoring system is suitable for real-time detection of dynamic L-glutamate release from nerve cells in vitro and will be suitable for application in assessment of drugs acting on the nervous system. PMID:17849100

  20. Known glioma risk loci are associated with glioma with a family history of brain tumours

    DEFF Research Database (Denmark)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika;

    2013-01-01

    family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies...... and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain...... tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically...

  1. Photodynamic therapy of supratentorial gliomas

    Science.gov (United States)

    Muller, Paul J.; Wilson, Brian C.

    1997-05-01

    We are reporting the results form intraoperative intracavitary PDT treatment in 56 patients with recurrent supratentorial gliomas who had failed previous surgery and radiotherapy. These patients received 2mg/kg Photofin iv. 12-36 hours prior to surgical resection of their tumor or tumor cyst drainage. The median survival times in weeks for glioblastoma (GBM), malignant astrocytoma (MA), malignant mixed astrocytoma-oligodendroglioma and ependymoma were 30, 40, >56 and >174 weeks, respectively. Eight patients with recurrent GBM who received >60 J/cm2 had a median survival of 58 weeks and 24 patients who received recurrent glioblastoma who undergo surgical treatment alone is only 20 weeks. We are also reporting the results of PDT treatment in 20 patients with newly diagnosed MA or GBM treated with intracavitary Photofin-PDT at the time of their initial craniotomy. The median survival of the whole cohort was 44 weeks with a 1 and 2 year survival of 40 percent and 15 percent, respectively. The median survival of patients with GBM was 37 weeks with a 1 and 2 year actuarial survival of 35 percent and 0 percent, respectively. The median survival of patients with MA as 48 weeks with a 1 and 2 year actuarial survival of 44 percent and 33 percent, respectively. Six patients with a Karnofsky score of >70 who received a light dose of >1260J had a median survival of 92 weeks with a 1 and 2 year survival of 83 percent and 33 percent, respectively. The mortality rate in our total series of 93 PDT treatments or brain tumor is 3 percent. The combined serious mortality-morbidity rate is 8 percent.

  2. Stability of corticosteroids under anaerobic conditions. C6 and C9 fluorine-containing corticosteroids

    NARCIS (Netherlands)

    Dekker, D.; Buijs, D.J.

    1980-01-01

    The decomposition of corticosteroids due to a fluorine atom at C6 and/or C9 is investigated. Chromatographic properties, the isolation and the structure elucidation of decomposition products are given.

  3. Biological effects of 12C6+ heavy ions irradiation on Allium fistulosum L

    International Nuclear Information System (INIS)

    In order to study biological effects of 12C6+ heavy ions irradiation on Allium fistulosum L., the dry seeds were treated by 12C6+ heavy ion beam with different doses. Obvious 'parabola' trends were observed in the characteristics of germination rate and height of Allium fistulosum L. seedling when irradiated doses increased. With irradiation of an appropriate dose of 12C6+ heavy ion beam, 30Gy, the germination rate of Allium fistulosum L. is increased and the seedlings can resist drought and lodging, and grow better than the control. At the same time, the formation frequency of micronucleus and chromosomal aberration were surveyed in root-tip cells. The highest formation frequency of micronucleus and chromosomal aberration treated with 180Gy could reach to 9.09% and 10.03% respectively. This study laid the basis for further work on breeding and improvement of Allium fistulosum L. irradiated by 12C6+ heavy ion beam. (authors)

  4. X-ray diffraction study of p-(alkoxybenzylidene)-p'-toluidines C2H5O-C6H4-CH=N-C6H4-CH3 and C4H9O-C6H4-CH=N-C6H4-CH3

    International Nuclear Information System (INIS)

    The molecular and crystal structures of two p-alkoxybenzylidene)-p'-toluidines C2H5O-C6H4-CH=N-C6H4-CH3 (1) and C4H9O-C6H4-CH=N-C6H4-CH3 (2) are determined by X-ray diffraction. Crystals 1 and 2 contain four and two crystallographically independent molecules, respectively. In 1, the geometry of the independent molecules is almost identical. In 2, the independent molecules differ in the conformation of the alkyl chain, which is disordered in one of them. An analysis of the crystal packing of 2 reveals the alternation of spacious layers formed by loosely packed aliphatic fragments of molecules and layers of closely packed aromatic fragments, which ensures the formation of the mesogenic phase in the course of melting of crystals 2. In crystal 1, loose aliphatic layers are absent.

  5. Structure and Bonding of Ni(C6H4-nFn)(CO)2 (C6H4=benzyne, n=1-4) Complexes

    International Nuclear Information System (INIS)

    The electronic structure and properties of Ni(C6H4-nFn)(CO)2 (C6H4=benzyne, n=1-4) complexes have been investigated using hybrid density functional B3LYP theory. Both aromatic natures and nucleus independent chemical shift (NICS) of the benzyne rings have been analyzed. Among mono-, di-, and tri-fluorinated complexes, 3-F, 3,6-F, and 4-H are the most stable isomers, respectively. NICS values calculated at the several points above the ring centers are consistent with those based on the relative energies of the complexes. The atoms in molecules (AIM) analysis indicates that Ni-C bond distance is well correlated with the electron density of a ring critical point (ρrcp) in all species

  6. Diastereoselective B(C6F5)3-Catalyzed Reductive Carbocyclization of Unsaturated Carbohydrates.

    Science.gov (United States)

    Bender, Trandon A; Dabrowski, Jennifer A; Zhong, Hongyu; Gagné, Michel R

    2016-08-19

    A B(C6F5)3-catalyzed method for the selective conversion of unsaturated carbohydrates to cyclopentanes and cyclopropanes is disclosed. Catalyst activation of tertiary silanes generates the ion pair [(C6F5)3B-H][ROSi2] whose components synergistically activate C-O bonds for diastereoselective C-C bond formation. Sila-THF cations are invoked as key intermediates facilitating carbocyclizations. Complex chiral synthons are thereby obtained in a single pot.

  7. Coordination chemistry of silver(I) with the nitrogen-bridged ligands (C(6)H(5))(2)PN(H)P(C(6)H(5))(2) and (C(6)H(5))(2)PN(CH(3))P(C(6)H(5))(2): the effect of alkylating the nitrogen bridge on ligand bridging versus chelating behavior.

    Science.gov (United States)

    Sekabunga, E J; Smith, Michele L; Webb, T R; Hill, W E

    2002-03-11

    The coordination chemistry of silver(I) with the nitrogen-bridged ligands (C(6)H(5))(2)PN(R)P(C(6)H(5))(2) [R = H (dppa); R = CH(3) (dppma)] has been investigated by (31)P NMR and electrospray mass spectrometry (ESMS). Species observed by (31)P NMR include Ag(2)(mu-dppa)(2+), Ag(2)(mu-dppa)(2)(2+), Ag(2)(mu-dppa)(3)(2+), Ag(2)(mu-dppma)(2+), Ag(2)(mu-dppma)(2)(2+), and Ag(eta(2)-dppma)(2)(+). Species observed by ESMS at low cone voltages were Ag(2)(dppa)(2)(2+), Ag(2)(dppa)(3)(2+), Ag(2)(dppma)(2)(2+), and Ag(dppma)(2)(+). (C(6)H(5))(2)PN(CH(3))P(C(6)H(5))(2) showed a strong tendency to chelate, while (C(6)H(5))(2)PN(H)P(C(6)H(5))(2) preferred to bridge. Differences in the bridging versus chelating behavior of the ligands are assigned to the Thorpe-Ingold effect, where the methyl group on nitrogen sterically interacts with the phenyl groups on phosphorus. The crystal structure of the three-coordinate dinuclear silver(I) complex (Ag(2)[(C(6)H(5))(2)PN(H)P(C(6)H(5))(2)](3))(BF(4))(2) has been determined. Bond distances include Ag-Ag = 2.812(1) A, Ag(1)-P(av) = 2.492(3) A, and Ag(2)-P(av) = 2.509(3) A. The compound crystallizes in the monoclinic space group Cc at 294 K, with a = 18.102(4)(o), Z = 4, V = 7261(3) A(3), R = 0.0503, and R(W) = 0.0670. PMID:11874357

  8. C6 Peptide-Based Multiplex Phosphorescence Analysis (PHOSPHAN for Serologic Confirmation of Lyme Borreliosis.

    Directory of Open Access Journals (Sweden)

    Vera G Pomelova

    Full Text Available A single-tier immunoassay using the C6 peptide of VlsE (C6 from Borrelia burgdorferi sensu stricto (Bb has been proposed as a potential alternative to conventional two-tier testing for the serologic diagnosis of Lyme disease in the United States and Europe.To evaluate the performance of C6 peptide based multiplex Phosphorescence Analysis (PHOSPHAN for the serologic confirmation of Lyme borreliosis (LB in Russian patients.Serum samples (n = 351 were collected from 146 patients with erythema migrans (EM; samples from 131 of these patients were taken several times prior to treatment and at different stages of recovery. The control group consisted of 197 healthy blood donors and 31 patients with other diseases, all from the same highly endemic region of Russia. All samples were analyzed by PHOSPHAN for IgM and IgG to Bb C6, recombinant OspC and VlsE proteins, and C6 peptides from B. garinii and B. afzelii.IgM and IgG to Bb C6 were identified in 43 and 95 out of 131 patients (32.8 and 72.5%, respectively; seroconversion of IgM antibodies was observed in about half of the patients (51.2%, and of IgG antibodies, in almost all of them (88.4%. Additional detection of OspC-IgM and VlsE-IgM or IgG to C6 from B. garinii or B. afzelii did not contribute significantly to the overall sensitivity of the multiplex immunoassay.The multiplex phosphorescence immunoassay is a promising method for simultaneously revealing the spectrum of antibodies to several Borrelia antigens. Detection of IgM and IgG to Bb C6 in the sera of EM patients provides effective serologic confirmation of LB and, with high probability, indicates an active infection process.

  9. Science impact of MODIS C5 calibration degradation and C6+ improvements

    OpenAIRE

    A. Lyapustin; Wang, Y.; Xiong, X; Meister, G.; Platnick, S.; Levy, R.; Franz, B.; S. Korkin; T. Hilker; Tucker, J; Hall, F; Sellers, P.; Wu, A; Angal, A.

    2014-01-01

    The Collection 6 (C6) MODIS (Moderate Resolution Imaging Spectroradiometer) land and atmosphere data sets are scheduled for release in 2014. C6 contains significant revisions of the calibration approach to account for sensor aging. This analysis documents the presence of systematic temporal trends in the visible and near-infrared (500 m) bands of the Collection 5 (C5) MODIS Terra and, to lesser extent, in MODIS Aqua geophysical data sets. Sensor degradation is largest in the b...

  10. ARPP-19 promotes proliferation and metastasis of human glioma.

    Science.gov (United States)

    Jiang, Tao; Zhao, Bing; Li, Xiaocan; Wan, Jinghai

    2016-09-01

    Glioma is the most common and aggressive type of human primary brain tumor with a poor outcome. The molecular mechanisms underlying glioma development and progression are still poorly understood. Recent studies have reported a novel role of ARPP-19 in the regulation of cell mitosis and cancer progression. However, no study has been carried out to determine the role of ARPP-19 in human glioma cells and assess the expression and clinical significance of ARPP-19 in human glioma. In this study, we systematically examined the role of ARPP-19 in glioma A172 cells and examined the expression of ARPP-19 and CD147 in 81 cases of human glioma tissue specimens and correlated them to clinicopathological parameters and patient survival. We found that ARPP-19 promoted both proliferation and metastasis of human glioma cells and the expression of ARPP-19 and CD147 in high-grade glioma was significantly higher than that in the low-grade glioma. Patients whose tumors were positive for expression of ARPP-19 or CD147 showed lower relapse-free survival and overall survival than patients whose tumors were negative for ARPP-19 or CD147, respectively. Pearson correlation analysis indicated that there was a statistically significant correlation between ARPP-19 and CD147. Expressions of ARPP-19 and CD147 may serve as biomarkers for high-grade glioma and poor patient survival. PMID:27380244

  11. Surgical strategies for glioma involving language areas

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong; JIANG Tao; XIE Jian; LIU Fu-sheng; LI Shou-wei; QIAO Hui; WANG Zhong-cheng

    2008-01-01

    Background Successful treatment of gliomas in or adjacent to language areas constitutes a major challenge to neurosurgery. The present study was performed to evaluate the procedure of language mapping via intraoperative direct cortical electrical stimulation under awake anaesthesia when performed prior to resective glioma surgery.Methods Thirty patients with gliomas and left-hemisphere dominance and, who underwent language mapping via intraoperative direct cortical electrical stimulation under awake anaesthesia before resective glioma surgery, were analyzed retrospectively. All patients had tumors in or adjacent to cortical language areas. The brain lesions were removed according to anatomic-functional boundaries with preservation of areas of language function. Both preoperative and postoperative functional findings were evaluated.Results Intraoperative language areas were detected in 20 patients but not in four patients. Language mapping failure for reasons attributable to the anaesthesia or to an intraoperative increase in intracranial pressure occurred in six cases.Seven patients presented with moderate or severe language deficits after six months of follow-up. Total resection was achieved in 14 cases, near-total resection in 12 cases and subtotal resection in four cases.Conclusions Intraoperative cortical electrical stimulation is an accurate and safe approach to identification of the language cortex. Awake craniotomy intraoperative cortical electrical stimulation, in combination with presurgical neurological functional imaging to identify the anatomic-functional boundaries of tumor resection, permits extensive tumor excision while preserving normal language function and minimizing the risk of postoperative language deficits.

  12. Hormone replacement therapy and risk of glioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper;

    2013-01-01

    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  13. Genetics and pharmacogenomics of diffuse gliomas

    NARCIS (Netherlands)

    Thuijl, H.F. van; Ylstra, B.; Wurdinger, T.; Nieuwenhuizen, D. van; Heimans, J.J.; Wesseling, P.; Reijneveld, J.C.

    2013-01-01

    Rapidly evolving techniques for analysis of the genome provide new opportunities for cancer therapy. For diffuse gliomas this has resulted in molecular markers with potential for personalized therapy. Some drugs that utilize pharmacogenomics are currently being tested in clinical trials. In melanoma

  14. Neuromyelitis Optica Lesion Mimicking Brainstem Glioma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-12-01

    Full Text Available A 12-year-old girl who presented with weakness of the left extremities and right sided sixth cranial nerve palsy had neuromyelitis optica (NMO mistaken for brainstem glioma on MRI, in a report from Brain Research Institute, Yonsei University College of Medicine,Seoul, Republic of KoreaNeuromyelitis Optica, Optic-Spinal Syndrome, Spectroscopy.

  15. Changing incidence and improved survival of gliomas

    NARCIS (Netherlands)

    Ho, Vincent K. Y.; Reijneveld, Jaap C.; Enting, Roeline; Bienfait, Henri P.; Robe, Pierre; Baumert, Brigitta G.; Visser, Otto

    2014-01-01

    BACKGROUND: Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma

  16. An incidentally detected third ventricle chordoid glioma

    Directory of Open Access Journals (Sweden)

    Gallina Pasquale

    2007-01-01

    Full Text Available Chordoid glioma is a rare low-grade tumor located in the third ventricle-hypothalamic region. Since its first report, 37 cases have been described in the literature. We report on an additional case that we considered significant because of its incidental detection and its uneventful surgical removal.

  17. A case of radiation-induced glioma

    International Nuclear Information System (INIS)

    A case of malignant cerebellar glioma developing 25 years after radiotherapy for pineal tumor is described. The patient is a 40-year-old male, who was admitted to our department with complaints of dizziness and gait disturbance. neurological examinations revealed symptoms involving the left cerebellar hemisphere and cerebellar vermis. CT scan and MRI demonstrated a circularly enhanced tumor which was located in the left cerebellar hemisphere extending to the vermis. The tumor was diagnosed as malignant glioma. In view of the former radiotherapy, this glioma was suspected to have been induced by radiation. The situation conformed to Walker's criteria for radiation-induced tumor. With the patient under general anesthesia, the tumor was subtotally removed by means of suboccipitel craniectomy. Histopathologically, the tumor was diagnosed as astrocytoma, grade 3. Most radiation-induced gliomas are malignant. There seems to be no significant correlation between the radiation dose; the latent period widely varies, ranging from several years to more than 20 years. Even if the radiation dose is small, there still exists the risk that radiation might induce a tumor. It was concluded that the possibility of radiation-induced tumor should be kept in mind whenever radiation therapy is carried out for brain tumors. (author)

  18. Management of traumatic c6-7 spondyloptosis with cord compression.

    Science.gov (United States)

    Choi, Man-Kyu; Jo, Dae-Jean; Kim, Min-Ki; Kim, Tae-Sung

    2014-05-01

    A case of total spondyloptosis of the cervical spine at C6-7 level with cord compression is described in a 51-year-old male. Because the bodies of C6 and 7 were tightly locked together, cervical traction failed. Then the patient was operated on by a posterior approach. Posterior stabilization and fusion were performed by C4-5 lateral mass and C7-T1 pedicle screw fixation and rod instrumentation with bridging both C4-5's rods to the C7-T1's extended ones. After C6 total laminectomy and foraminotomy, the C6 body was returned to its proper position. Secondly, anterior stabilization and fusion were performed by C6-7 discectomy with a screw-plate system. A postoperative lateral plain radiograph showed good realignment. In this case, we report the clinical presentation and discuss the surgical modalities of C6-7 total spondyloptosis and the failed close reduction. PMID:25132938

  19. 替莫唑胺对胶质瘤侵袭性的影响及可能机制%Effect of temozolomide on the glioma invasiveness and its possible mechanism

    Institute of Scientific and Technical Information of China (English)

    王健; 贾永森; 赵喜庆; 秦丽娟

    2014-01-01

    目的:探讨肿瘤坏死因子-α( tumor necrosis factor-α, TNF-α)在替莫唑胺( temozolomide, TMZ)降低胶质瘤侵袭性过程中的作用及机制。方法对数生长期的C6胶质瘤细胞随机分为TMZ处理10、30、60、120、180和240 min组,每组各15例,动态监测培养液中TNF-α的含量(放射免疫法)、C6细胞内 p53蛋白的表达( Western blot法)和细胞凋亡水平( AnnexinV-FITC法)。制备体外胶质瘤的侵袭模型,利用结晶紫染色法检测胶质瘤的侵袭性。结果 TMZ作用于C6细胞后,培养液中TNF-α的含量明显增加,于120 min时含量最多(P<0.01),其后开始减少。 C6细胞内p53蛋白的表达于处理后120 min达高峰(P<0.01),其后逐渐减少。 TMZ作用于体外胶质瘤侵袭模型后,胶质瘤细胞的侵袭性降低。结论 TNF-α介导TMZ降低胶质瘤侵袭性,此作用可能是由于TMZ促进C6细胞释放TNF-α,增加的TNF-α又促进胶质瘤细胞凋亡所致。%Purpose To explore the role of tumor necrosis factor-α( TNF-α) in the process of temozolomide ( TMZ) reduce glioma in-vasiveness and its possible mechanism. Methods C6 glioma cells of logarithmic phase were randomly divided into TMZ treatment (10, 30, 60, 120, 180, 240 min group) (n=15), dynamic monitoring content of TNF-αin the culture medium was measured by ra-dioimmunoassay, expression of p53 protein in C6 cells was detected with Western blotting method, and cell apoptosis was used with AnnexinV-FITC. A glioma invasiveness model was established in vitro and glioma invasiveness was determined by crystal violet stai-ning. Results For C6 cells, contents of TNF-αin the nutrient fluid and expressions of p53 protein in C6 cells obviously increased af-ter TMZ treatment and they achieved the peak at 120 min (P<0. 01), followed by decrease gradually. Glioma invasiveness was re-duced after TMZ acted on glioma in vitro. Conclusion TMZ can reduce glioma invasiveness by TNF-α, which this role may be is TMZ promote C6

  20. Economics of Malignant Gliomas: A Critical Review

    Science.gov (United States)

    Raizer, Jeffrey J.; Fitzner, Karen A.; Jacobs, Daniel I.; Bennett, Charles L.; Liebling, Dustin B.; Luu, Thanh Ha; Trifilio, Steven M.; Grimm, Sean A.; Fisher, Matthew J.; Haleem, Meraaj S.; Ray, Paul S.; McKoy, Judith M.; DeBoer, Rebecca; Tulas, Katrina-Marie E.; Deeb, Mohammed; McKoy, June M.

    2015-01-01

    Purpose: Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society. Methods: A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the study's publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another. Results: Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from $50,600 to $92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial. Conclusion: With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively. PMID:25466707

  1. Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

    International Nuclear Information System (INIS)

    Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management

  2. Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Bin [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Hu, Zhiqiang, E-mail: zhiqhutg@126.com [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Huang, Hui; Zhu, Guangtong; Xiao, Zhiyong [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Wan, Weiqing; Zhang, Peng; Jia, Wang; Zhang, Liwei [Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050 (China)

    2014-11-07

    Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

  3. Role of Complements C5, C6 in the Pathogenecity of Psoriasis

    Directory of Open Access Journals (Sweden)

    Fayez Muhammad Shaldoum

    2007-03-01

    Full Text Available Background: Psoriasis lesion/scale contains C5a des Arg and C5b-9 (Takematsu et al., 1992; Terui et al., 2000 and Uyemura et al., 1993. These activation products may have arisen from C5-C9 produced supposedly by keratinocytes (KC. In this work we have started with C5 and C6 to prove our hypothesis. Since psoriatic lesions contain several pro-inflammatory cytokines, it is important to find out which pro-inflammatory cytokines can differentially regulate the expected synthesis of C5 and C6 by keratinocytes. Methods: Human KC have been cultured in the absence and the presence of varying concentrations of pro-inflammatory cytokines and the synthesis of C components C5 and C6 have been measured by ELISA at the protein level and RT-PCR at the mRNA level. To test whether KC also secrete these C components, the same measurements have been performed to find out if these late components are present in the supernatant of the medium where these KC were cultured. The keratinocytes cell-line A431 was also used and the monocytes cultures were considered as the positive control. Results: The results showed that resting KC synthesize C5 mRNAs in detectable amounts. C5 mRNA which is synthesized by resting KC is not translated into detectable amount of protein. Although resting KC did not produce C6 mRNA in detectable amounts the levels of C6 protein were detectable. However, These C6 protein levels were minimally secreted by resting KC, into the culture medium. TCGF induced the secretion of C5 and C6 while TGF- induced only the secretion of C6. Conclusion : Normal KC synthesize their own C5 and C6. The synthesis of them is activated by TCGF. While TGF- ² activated the synthesis of C6 other factors might be responsible for activating the synthesis of C5. These factors could be secreted from other cell types than KC in human skin

  4. Transfection of glioma cells with the neural-cell adhesion molecule NCAM

    DEFF Research Database (Denmark)

    Edvardsen, K; Pedersen, P H; Bjerkvig, R;

    1994-01-01

    The tumor growth and the invasive capacity of a rat glioma cell line (BT4Cn) were studied after transfection with the human transmembrane 140-kDa isoform of the neural-cell adhesion molecule, NCAM. After s.c. injection, the NCAM-transfected cells showed a slower growth rate than the parent cell...... line (BT4Cn). Upon intracerebral implantation with BT4Cn cells and different clones of NCAM-transfected cells, all animals developed neurological symptoms within 13-16 days. However, the tumors showed different growth characteristics. The NCAM-transfected BT4Cn cells were localized in the region...... showed a lower cytotoxic response than the spleen cells from rats transplanted with the transfected variants of BT4Cn cells, indicating that the transfection procedure in itself mediated an activation of the immune system. The present data suggest that NCAM may influence the malignant behavior of rat...

  5. Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

    Science.gov (United States)

    2016-10-05

    Childhood Mixed Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

  6. BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

    Directory of Open Access Journals (Sweden)

    Pilar González-Gómez

    2014-01-01

    Full Text Available Astrocytic glioma is the most common brain tumor. The glioma initiating cell (GIC fraction of the tumor is considered as highly chemoresistant, suggesting that GICs are responsible for glioma relapse. A potential treatment for glioma is to induce differentiation of GICs to a more benign and/or druggable cell type. Given BMPs are among the most potent inducers of GIC differentiation, they have been considered as noncytotoxic therapeutic compounds that may be of use to prevent growth and recurrence of glioma. We herein summarize advances made in the understanding of the role of BMP signaling in astrocytic glioma, with a particular emphasis on the effects exerted on GICs. We discuss the prognostic value of BMP signaling components and the implications of BMPs in the differentiation of GICs and in their sensitization to alkylating drugs and oncolytic therapy/chemotherapy. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

  7. Slit2/Robo1 signaling in glioma migration and invasion.

    Science.gov (United States)

    Xu, Yun; Li, Wen-Liang; Fu, Li; Gu, Feng; Ma, Yong-Jie

    2010-12-01

    Slit2/Robo1 is a conserved ligand-receptor system, which greatly affects the distribution, migration, axon guidance and branching of neuron cells. Slit2 and its transmembrane receptor Robo1 have different distribution patterns in gliomas. The expression of Slit2 is at very low levels in pilocytic astrocytoma, fibrillary astrocytoma and glioblastoma, while Robo1 is highly expressed in different grades of gliomas at both mRNA and protein levels. Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Although the specific mechanisms of tumor-suppressive effect of Slit2/Robo1 have not been elucidated, it has been proved that Slit2/Robo1 signaling inhibits glioma cell migration and invasion by inactivation of Cdc42-GTP. With the research development on the molecular mechanisms of Slit2/Robo1 signaling in glioma invasion and migration, Slit2/Robo1 signaling may become a potential target for glioma prevention and treatment.

  8. 蒿甲醚抗SD大鼠原位脑胶质瘤血管生成的实验%Inhibitive Effect of Artemether on Brain Glioma Angiogenesis in SD Rat

    Institute of Scientific and Technical Information of China (English)

    伍治平; 高诚伟; 吴永贵; 朱启顺; 王熙才; 刘馨; 刘淳

    2009-01-01

    目的 探讨蒿甲醚(Artemether)抗SD大鼠原位脑胶质瘤血管生成作用.方法 采用四甲基偶氮唑蓝(MTT)法测定不同浓度蒿甲醚对大鼠C6脑胶质瘤细胞株的生长抑制作用,计算半数抑制浓度(IC50).采用立体定位仪在SD大鼠大脑皮质层接种C6脑胶质瘤细胞(1×106/μl)40只,雌、雄各半;随机分为5组,每组8只.在接种第3天后,各组采用灌胃给药法连续给药10天.于接种后的第20天解剖大鼠,经活体左心室灌注4%多聚甲醛,固定肿瘤的全脑标本.在大鼠脑部接种穿刺点做冠状切口,按垂直和水平方向测量肿瘤大小.肿瘤体积=a2bπ/6(a为肿瘤的短径,b为肿瘤的长径).全脑标本用4%多聚甲醛固定,肿瘤组织做病理观察,免疫组化方法 检测移植瘤组织微血管密度.结果 各实验组血管计数分别为Ⅰ组(39±4),Ⅱ组(29±6),Ⅲ组(12±8),Ⅳ组(10±5),生理盐水组为(52±7).各实验组血管计数均明显少于生理盐水对照组,差异有统计学意义(分别P<0.05,P<0.01).各实验组SD大鼠原位脑胶质瘤体积较对照组显著减小.结论 在一定剂量范围内,蒿甲醚具有明显抑制SD大鼠原位脑胶质瘤血管生成作用;蒿甲醚抑制原位脑胶质瘤生长和转移的机制之一是透过血脑屏障抑制脑胶质瘤血管生成.

  9. LuIII parvovirus selectively and efficiently targets, replicates in, and kills human glioma cells.

    Science.gov (United States)

    Paglino, Justin C; Ozduman, Koray; van den Pol, Anthony N

    2012-07-01

    Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineffective. The four viruses with the greatest oncolytic activity, LuIII, H-1, MVMp, and MVM-G52, were tested for the ability, at a low MOI, to progressively infect the culture over time, causing cell death at a rate higher than that of cell proliferation. LuIII alone was effective in all five human glioblastomas tested. H-1 progressively infected only two of five; MVMp and MVM-G52 were ineffective in all five. To investigate the underlying mechanism of LuIII's phenotype, we used recombinant parvoviruses with the LuIII capsid replacing the MVMp capsid or with molecular alteration of the P4 promoter. The LuIII capsid enhanced efficient replication and oncolysis in MO59J gliomas cells; other gliomas tested required the entire LuIII genome to exhibit enhanced infection. LuIII selectively infected glioma cells over normal glial cells in vitro. In mouse models, human glioblastoma xenografts were selectively infected by LuIII when administered intratumorally; LuIII reduced tumor growth by 75%. LuIII also had the capacity to selectively infect subcutaneous or intracranial gliomas after intravenous inoculation. Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia in vivo but showed a modest infection of developing neurons.

  10. Withania somnifera Suppresses Tumor Growth of Intracranial Allograft of Glioma Cells.

    Science.gov (United States)

    Kataria, Hardeep; Kumar, Sushil; Chaudhary, Harshita; Kaur, Gurcharan

    2016-08-01

    Gliomas are the most frequent type of primary brain tumor in adults. Their highly proliferative nature, complex cellular composition, and ability to escape therapies have confronted investigators for years, hindering the advancement toward an effective treatment. Agents that are safe and can be administered as dietary supplements have always remained priority to be most feasible for cancer therapy. Withania somnifera (ashwagandha) is an essential ingredient of Ayurvedic preparations and is known to eliminate cancer cells derived from a variety of peripheral tissues. Although our previous studies have addressed the in vitro anti-proliferative and differentiation-inducing properties of ashwagandha on neuronal cell lines, in vivo studies validating the same are lacking. While exploring the mechanism of its action in vitro, we observed that the ashwagandha water extract (ASH-WEX) induced the G2/M phase blockade and caused the activation of multiple pro-apoptotic pathways, leading to suppression of cyclin D1, bcl-xl, and p-Akt, and reduced the expression of polysialylated form of neural cell adhesion molecule (PSA-NCAM) as well as the activity of matrix metalloproteinases. ASH-WEX reduced the intracranial tumor volumes in vivo and suppressed the tumor-promoting proteins p-nuclear factor kappa B (NF-κB), p-Akt, vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP70), PSA-NCAM, and cyclin D1 in the rat model of orthotopic glioma allograft. Reduction in glial fibrillary acidic protein (GFAP) and upregulation of mortalin and neural cell adhesion molecule (NCAM) expression specifically in tumor-bearing tissue further indicated the anti-glioma efficacy of ASH-WEX in vivo. Combining this enhanced understanding of the molecular mechanisms of ASH-WEX in glioma with in vivo model system offers new opportunities to develop therapeutic strategy for safe, specific, and effective formulations for treating brain tumors. PMID:26208698

  11. How polarizabilities and C6 coefficients actually vary with atomic volume

    Science.gov (United States)

    Gould, Tim

    2016-08-01

    In this work, we investigate how atomic C6 coefficients and static dipole polarizabilities α scale with effective volume. We show, using confined atoms covering rows 1-5 of the periodic table, that C 6 / C6 R ≈ ( V / VR ) p Z and α / α R ≈ ( V / VR ) pZ ' (for volume V = ∫ d r /4 π 3 r 3 n ( r ) ), where C6 R , αR, and VR are the reference values and effective volume of the free atom. The scaling exponents pZ and pZ ' vary substantially as a function of element number Z = N, in contrast to the standard "rule of thumb" that pZ = 2 and pZ ' = 1 . Remarkably, we find that the polarizability and C6 exponents p' and p are related by p' ≈ p - 0.615 rather than the expected p' ≈ p/2. Results are largely independent of the form of the confining potential (harmonic, cubic, and quartic potentials are considered) and kernel approximation, justifying this analysis.

  12. How polarizabilities and $C_6$ coefficients actually vary with atomic volume

    CERN Document Server

    Gould, Tim

    2016-01-01

    In this work we investigate how atomic $C_6$ coefficients and static dipole polarizabilities $\\alpha$ scale with effective volume. We show, using confined atoms covering rows 1-5 of the periodic table, that $C_6/C_6^R\\approx (V/V^R)^{p_Z}$ and $\\alpha/\\alpha^R\\approx (V/V^R)^{p'_Z}$ (for volume $V=\\int dr \\frac{4\\pi}{3}r^3 n(r)$) where $C_6^R$, $\\alpha^R$ and $V^R$ are the reference values and effective volume of the free atom. The scaling exponents $p_Z$ and $p'_Z$ vary substantially as a function of element number $Z=N$, in contrast to the standard "rule of thumb" that $p_Z=2$ and $p'_Z=1$. Remarkably, We find that the polarizability and $C_6$ exponents $p'$ and $p$ are related by $p'\\approx p-0.615$ rather than the expected $p'\\approx p/2$. Results are largely independent of the form of the confining potential (harmonic, cubic and quartic potentials are considered) and kernel approximation, justifying this analysis.

  13. How polarizabilities and C6 coefficients actually vary with atomic volume.

    Science.gov (United States)

    Gould, Tim

    2016-08-28

    In this work, we investigate how atomic C6 coefficients and static dipole polarizabilities α scale with effective volume. We show, using confined atoms covering rows 1-5 of the periodic table, that C6/C6 (R)≈(V/V(R))(pZ) and α/α(R)≈(V/V(R))(pZ (')) (for volume V=∫dr4π3r(3)n(r)), where C6 (R), α(R), and V(R) are the reference values and effective volume of the free atom. The scaling exponents pZ and pZ (') vary substantially as a function of element number Z = N, in contrast to the standard "rule of thumb" that pZ = 2 and pZ (')=1. Remarkably, we find that the polarizability and C6 exponents p' and p are related by p' ≈ p - 0.615 rather than the expected p' ≈ p/2. Results are largely independent of the form of the confining potential (harmonic, cubic, and quartic potentials are considered) and kernel approximation, justifying this analysis. PMID:27586923

  14. Is cerebral cavernous malformation a pre-glioma lesion?

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ji-yang; MING Zong-yi; WU An-hua

    2012-01-01

    Glioma is the most malignant tumor in the brain,the origin of glioma is still unknown.Recently some papers indicated that glioma may be developed from cerebral cavernous malformation (CCM).We describe a man with a right temporal lobe CCM,after gamma-knife radiotherapy,the patient developed a low-grade astrocytoma in the area of the preexistent CCM.This case,together with other reports,may indicated an oncogenetic properties of CCM,and we proposed that CCM may be a pre-glioma lesion.

  15. Identify paraffin-embedded brain glioma using terahertz pulsed spectroscopy

    Science.gov (United States)

    Li, Ze-ren; Meng, Kun; Chen, Tu-nan; Chen, Tao; Zhu, Li-guo; Liu, Qiao; Li, Zhao; Li, Fei; Zhong, Sen-cheng; Feng, Hua; Zhao, Jian-heng

    2015-01-01

    The refractive indices, absorption coefficients and complex dielectric constants spectra of paraffin-embedded brain glioma and normal brain tissues have been measured by a terahertz time domain spectroscopy (THz-TDS) system in the range of 0.2 - 2.0 THz. The spectral differences between glioma and normal brain tissues were obtained. Our results indicate that, compared with normal tissue, glioma had higher refractive index, absorption coefficient, and dielectric constant. Based on these results, the suitable frequency components for different methods of glioma imaging (intensity imaging, coherent imaging and terahertz pulsed imaging) are analyzed.

  16. Sunitinib in Treating Patients With Recurrent Malignant Gliomas

    Science.gov (United States)

    2016-01-29

    Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

  17. Use of tricyclic antidepressants and risk of glioma

    DEFF Research Database (Denmark)

    Pottegård, Anton; García Rodríguez, Luis Alberto; Rasmussen, Lotte;

    2016-01-01

    inhibitors (SSRIs). RESULTS: We identified 3767 glioma cases and 75 340 population controls. Long-term use of TCAs was inversely associated with risk of glioma (OR 0.72, 95% CI: 0.41-1.25). Long-term SSRI use was not associated with glioma risk (OR 0.93, 95% CI: 0.75-1.16). CONCLUSIONS: Our study indicated...... that long-term use of TCAs may be associated with a reduced risk of glioma, however, the statistical precision was limited. A similar pattern was not observed for use of SSRIs....

  18. Selective migration of neuralized embryonic stem cells to stem cell factor and media conditioned by glioma cell lines

    Directory of Open Access Journals (Sweden)

    Maria Bernard L

    2006-01-01

    Full Text Available Abstract Background Pluripotent mouse embryonic stem (ES cells can be induced in vitro to become neural progenitors. Upon transplantation, neural progenitors migrate toward areas of damage and inflammation in the CNS. We tested whether undifferentiated and neuralized mouse ES cells migrate toward media conditioned by glioma cell lines (C6, U87 & N1321 or Stem Cell Factor (SCF. Results Cell migration assays revealed selective migration by neuralized ES cells to conditioned media as well as to synthetic SCF. Migration of undifferentiated ES cells was extensive, but not significantly different from that of controls (Unconditioned Medium. RT-PCR analysis revealed that all the three tumor cell lines tested synthesized SCF and that both undifferentiated and neuralized ES cells expressed c-kit, the receptor for SCF. Conclusion Our results demonstrate that undifferentiated ES cells are highly mobile and that neural progenitors derived from ES cells are selectively attracted toward factors produced by gliomas. Given that the glioma cell lines synthesize SCF, SCF may be one of several factors that contribute to the selective migration observed.

  19. Selective migration of neuralized embryonic stem cells to stem cell factor and media conditioned by glioma cell lines

    Science.gov (United States)

    Serfozo, Peter; Schlarman, Maggie S; Pierret, Chris; Maria, Bernard L; Kirk, Mark D

    2006-01-01

    Background Pluripotent mouse embryonic stem (ES) cells can be induced in vitro to become neural progenitors. Upon transplantation, neural progenitors migrate toward areas of damage and inflammation in the CNS. We tested whether undifferentiated and neuralized mouse ES cells migrate toward media conditioned by glioma cell lines (C6, U87 & N1321) or Stem Cell Factor (SCF). Results Cell migration assays revealed selective migration by neuralized ES cells to conditioned media as well as to synthetic SCF. Migration of undifferentiated ES cells was extensive, but not significantly different from that of controls (Unconditioned Medium). RT-PCR analysis revealed that all the three tumor cell lines tested synthesized SCF and that both undifferentiated and neuralized ES cells expressed c-kit, the receptor for SCF. Conclusion Our results demonstrate that undifferentiated ES cells are highly mobile and that neural progenitors derived from ES cells are selectively attracted toward factors produced by gliomas. Given that the glioma cell lines synthesize SCF, SCF may be one of several factors that contribute to the selective migration observed. PMID:16436212

  20. Mutagenic effects of Brassica napus by 12C6+ ion beam

    International Nuclear Information System (INIS)

    Dry seeds of Brassica napus were irradiated by 12C6+ ion beams with 30, 90, and 180 Gy, and the mutagenic effects of M1 generation were investigated. In comparison to the control group, the irradiated seeds showed positive changes in emerged seedling rate, plant height and blooming rate, with obvious inhibitive effects on pollen vitality, 1000-seed weight and seed oil content. The 30 Gy irradiation group outperformed the others in pods per plant and seed yield per plant. By means of RAPD method, the results showed specific bands, such as increasing bands, flawing bands and bands with different fluorescence intensity were observed in 13 primers selected. The variation rates under 30 Gy, 90 Gy and 180 Gy 12C6+ irradiation were 22.1%, 23.7% and 36.2%, respectively. The research is valuable to the application of 12C6+ heavy ion beam in improving Brassica napus breeding. (authors)

  1. Identification of Mo-Rich M23C6 Carbides in Alloy 718

    Science.gov (United States)

    Aghajani, Ali; Tewes, Jürgen; Parsa, Alireza Basir; Hoffmann, Thorsten; Kostka, Alexander; Kloewer, Jutta

    2016-09-01

    In the present study, we systematically identify and characterize a (Nb, Mo)-rich M23C6 type of M23C6 carbide with a lattice parameter of 1.094 nm in alloy 718 for the first time using a combination of selected area electron diffraction pattern and powder X-ray diffraction analysis. The time-temperature-precipitation diagrams of the precipitates in both annealed and strained conditions are obtained by particle analysis using an automated scanning electron microscopy method. (Nb, Mo)-rich M23C6 carbides first precipitate after 24 hours at 1223 K (950 °C) annealing, while they form after 10 minutes at 1273 K (1000 °C) in the strained condition. This correlates with the excess dislocations produce during deformation.

  2. 经侧脑室注射人脐带间充质干细胞向胶质瘤趋化能力的实验研究%The experimental investigation of glioma-trophic capacity of human umbilical cord-derived mesenchymal stem cells after intraventricular administration

    Institute of Scientific and Technical Information of China (English)

    范存刚; 王栋梁; 张庆俊; 周景儒

    2013-01-01

    Objective To explore the glioma-trophic migration capacity of human umbilical cordderived mesenchymal stem cells (hUC-MSCs) by intraventricular administration.Methods The umbilical cord tissue were obtained during full-term pregnancy cesarean section under sterile conditions.This study was approved by Ethics Committee and got the informed consent of patient.The hUC-MSCs were isolated by trypsin and collagenase digestion,followed by adherent culture methods.The characteristics of isolated hUC-MSCs were demonstrated by cell morphylogy,phenotype analysis and multi-differentiation potentials into adipocytes,osteoblasts and neural ceils.Then the hUC-MSCs were labeled with CM-DiI and injected into contralateral ventricle of glioma of the C6 glioma-bearing Sprague-Dawley (SD) rats.Two weeks later,the rats were sacrificed and the brains were taken out to examine the migration and distribution of hUCMSCs in the tumor bed,at the interface of tumor and cerebral parenchyma as well as the tumor satelites infiltrating into the normal brain.Results The hUC-MSCs demonstrated plastic-adherent characterization and homogeneous fibroblastic-like morphylogy in culture,expression of specific surface phenotypes of MSCs (CD13,CD29,CD44,CD90) but not endothelial or hematopoietic markers (CD14,CD31,CD34,CD38,CD45,CD133),and muti-differentiatiation potentials into Oil red O stained adipocytes,Alizarin red S stained osteoblasts,neuron-specific enolase (NSE)-positive neurons and glial fibrillary acidic protein (GFAP)positive astrocytes in permissive inducive conditions.Importantly,after labeled hUC-MSCs injection into contralateral ventricle of glioma,the hUC-MSCs migrated from initial injection site to the glioma mass and along the interface of tumor and brain,and some of them "chasing" the glioma satellites infiltrated into the normal parenchyma.Conclusion The hUC-MSCs possess prominent tumor-specific targeting capacity and extensive intratumoral distribution in glioma models.Thus,they may

  3. Simulations of Coarsening Behavior for M23C6 Carbides in AISI H13 Steel

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Based on the local equilibrium assumption, coarsening behavior of M23C6 carbide at 700℃ in H13 steel was simulated by DICTRA software. The results from the calculations were compared with transmission electron microscopy (TEM) observations. The results show the interfacial energy for M23C6 in H13 steel at 700℃ is the coarsening rate was also investigated by simulations. Simulations show a decrease in the coarsening rate when V/Mo ratio is increased, while the coarsening rate increases with increasing temperature.

  4. Two isomers of C6H6F9O9Tb

    International Nuclear Information System (INIS)

    Two isomeric forms of terbium tetrahydrate trifluoroacetate, featuring the composition C6H6F9O9Tb, were prepared as a result of interaction between terbium hydroxide or carbonate and trifluoroacetic acid. The compounds were characterized by the methods of elementary analysis, IR spectroscopy and X-ray diffraction analysis. It has been ascertained that isomerism of the compounds stems from different positions of protons. Crystals of both forms are isostructural, forming a continuous series of solid solutions with C6H6F9O9Eu

  5. Linear and nonlinear electrodynamic responses of bulk CaC6 in the microwave regime

    Science.gov (United States)

    Andreone, A.; Cifariello, G.; Di Gennaro, E.; Lamura, G.; Emery, N.; Hérold, C.; Marêché, J. F.; Lagrange, P.

    2007-08-01

    The linear and nonlinear responses to a microwave electromagnetic field of two c-axis oriented polycrystalline samples of the recently discovered superconductor CaC6 (TC≈11.5K ) is studied in the superconducting state down to 2K. The surface resistance RS and the third order intermodulation distortion, arising from a two-tone excitation, have been measured as a function of temperature and microwave circulating power. Experiments are carried out using a dielectrically loaded copper cavity operating at 7GHz in a "hot finger" configuration. The results confirm recent experimental findings that CaC6 behaves as a weakly coupled, fully gapped, superconductor.

  6. Draft-genome sequence of Shewanella algae strain C6G3

    OpenAIRE

    Aigle, Axel; Michotey, Valerie; Bonin, Patricia

    2015-01-01

    Shewanella algae strain C6G3, isolated from the 2 uppermost centimeters of muddy sediment of Arcachon Bay (SW Atlantic French coast, sampled in October 2007) has the capability to use a large panel of terminal electron acceptors under anaerobic condition, such as nitrate, nitrite and metal-oxide, and presents a great metabolic versatility. Here, we present the non-contiguous draft-genome sequence of Shewanella algae C6G3, which consists of a 4,879,425 bp. The chromosome contains 5792 predicte...

  7. Application of Time-Dependent Density-Functional Theory to C6

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xiao-Lin; BAI Yu-Lin; CHEN Xiang-Rong; YANG Xiang-Dong

    2004-01-01

    @@ We employ a real-space pseudopotential method to determine the ground state structure of the carbon cluster C6 via simulated annealing and the corresponding optical absorption spectra from the adiabatic time-dependent density-functional theory (TDDFT) and the local density approximation (TDLDA). It is found that the ground state structure of the carbon cluster C6 belongs to a monocyclic D3h structure and the calculated spectra exhibit a variety of features that can be used for comparison against future experimental investigations.

  8. Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

    Science.gov (United States)

    2016-06-14

    Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

  9. Antiproliferative activity of melanoidins isolated from heated potato fiber (potex) in glioma cell culture model.

    Science.gov (United States)

    Langner, Ewa; Nunes, Fernando M; Pozarowski, Piotr; Kandefer-Szerszeń, Martyna; Pierzynowski, Stefan G; Rzeski, Wojciech

    2011-03-23

    Potex constitutes a potato fiber preparation widely used as an ingredient to meat and bakery products which thermal treatment results in creation of new compounds. Melanoidins are high molecular weight brown end products of Maillard reaction, and few data presenting tumor cell growth inhibiting activity of melanoidins have been reported. Thus, in present study we utilized water extract of Potex roasted (180 °C for 2 h), whose chemical characterization revealed the presence of melanoidin complexes. Heated Potex extract inhibited C6 glioma cell proliferation in a dose-dependent manner measured by MTT method. High molecular weight components present in initial extract were responsible for stronger antiproliferative effect compared with low molecular weight fraction. Impaired MAPK (mitogen-activated protein kinase) and Akt signaling was found in cells treated with the extract. Moreover, flow cytometry analyses revealed the extract to induce G1/S arrest in glioma cells. Simultaneously, Western blot analysis showed elevated levels of p21 protein with concomitant decrease of cyclin D1. In conclusion, observed antiproliferative activity of melanoidins present in heated Potex was linked to disregulated MAPK and Akt signaling pathways, as well as to cell cycle cessation. These results suggest potential application of Potex preparation as a functional food ingredient and chemopreventive agent.

  10. FTIR spectro-imaging of collagen scaffold formation during glioma tumor development.

    Science.gov (United States)

    Noreen, Razia; Chien, Chia-Chi; Chen, Hsiang-Hsin; Bobroff, Vladimir; Moenner, Michel; Javerzat, Sophie; Hwu, Yeukuang; Petibois, Cyril

    2013-11-01

    Evidence has recently emerged that solid and diffuse tumors produce a specific extracellular matrix (ECM) for division and diffusion, also developing a specific interface with microvasculature. This ECM is mainly composed of collagens and their scaffolding appears to drive tumor growth. Although collagens are not easily analyzable by UV-fluorescence means, FTIR imaging has appeared as a valuable tool to characterize collagen contents in tissues, specially the brain, where ECM is normally devoid of collagen proteins. Here, we used FTIR imaging to characterize collagen content changes in growing glioma tumors. We could determine that C6-derived solid tumors presented high content of triple helix after 8-11 days of growth (typical of collagen fibrils formation; 8/8 tumor samples; 91 % of total variance), and further turned to larger α-helix (days 12-15; 9/10 of tumors; 94 % of variance) and β-turns (day 18-21; 7/8 tumors; 97 % of variance) contents, which suggest the incorporation of non-fibrillar collagen types in ECM, a sign of more and more organized collagen scaffold along tumor progression. The growth of tumors was also associated to the level of collagen produced (P collagen scaffolding is a major event accompanying the angiogenic shift and faster tumor growth in solid glioma phenotypes. PMID:24068168

  11. 聚焦超声开放血脑屏障联合用药治疗脑胶质瘤的实验研究%Opening of the blood-brain barrier through focused ultrasound in combination of drugs to treat glioma

    Institute of Scientific and Technical Information of China (English)

    潘敏; 张天奉; 邹超; 万倩; 刘新; 郑海荣

    2014-01-01

    Objective To evaluate the effectiveness of treating glioma in combination of two kinds of drugs by comparing the size of tumors and the survival time of different groups in rat glioma after targeted blood‐brain barrier (BBB) disruption by focused ultrasound under MRI‐guide. Methods The stereotaxis instruments and the 10 μl gas‐tight syringes were used to inject gliosarcoma cells into the targeted area of the brain in 40 male Sprague‐Dawley rats. The glioma‐bearing rats models were established. Rats were divided into 4 groups to receive different treatment :(1) no treatment (control, n = 8), (2) IV Avastin (Avastin only, n =10), (3) IV liposomal doxorubicin (DOX only, n =10), (4) IV Avastin and liposomal doxorubicin (Avastin+DOX, n =10). The SonoVue microbubbles and DOX or Avastin were injected into the tail vein respectively on the 12th day after implantation. The tumor size was measured by MRI on immediacy, once a week after targeted BBB disruption by focused ultrasound, and the life span in rat glioma was recorded. Results The average survival time of different groups in rat glioma was as follows :no treatment(17 ± 4)d, Avastin(20 ± 4)d, DOX(25 ± 5)d, DOX+ Avastin(40 ± 5)d. The tumor size after post‐treatment of different groups in rat glioma was as follows :no treatment(5 7.0 ± 4 3.0)mm, Avastin(4 3.0 ± 2 5.0)mm, DOX(4 1.2 ± 3 1.0)mm, DOX + Avastin(2. 20 ± 1. 30)mm. There was significant increased in average survival time and decreased in tumor size after a combination treatment DOX+ Avastin compared with other groups( P < 0 0.1). Conclusions The microbubble blasting by MRI‐guided focused ultrasound enhances the local tissue permeability and promotes the drug delivery of chemotherapy and anti‐angiogenesis locally in glioma‐bearing rats. Especially, the combination of two kinds of drugs has a synergism efficacy that may reduce tumor growth and increase survival time significantly after BBB disruption.%目的:采用MRI引导下聚焦

  12. The Internalization of Neurotensin by the Low-Affinity Neurotensin Receptors (NTSR2 and vNTSR2) Activates ERK 1/2 in Glioma Cells and Allows Neurotensin-Polyplex Transfection of tGAS1.

    Science.gov (United States)

    Ayala-Sarmiento, Alberto E; Martinez-Fong, Daniel; Segovia, José

    2015-08-01

    Glioblastoma is the most malignant primary brain tumor and is very resistant to treatment; hence, it has a poor prognosis. Neurotensin receptor type 1 (NTSR1) plays a key role in cancer malignancy and has potential therapeutic applications. However, the presence and function of neurotensin (NTS) receptors in glioblastoma is not clearly established. RT-PCR assays showed that healthy (non-tumor) astroglial cells and C6 glioma cells express NTSR2 and its isoform (vNTSR2) rather than NTSR1. In glioma cells, NTS promotes the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK 1/2), an effect that was completely abolished by blocking the internalization of the NTS/NTSR complex. We demonstrated pharmacologically that the internalization is dependent on the activation of NTSR2 receptors and it was prevented by levocabastine, a NTSR2 receptor antagonist. The internalization of NTSR2 and vNTSR2 was further demonstrated by its ability to mediate gene transfer (transfection) via the NTS-polyplex system. Expression of reporter transgenes and of the pro-apoptotic soluble form of growth arrest specific 1 (tGAS1) was observed in glioma cells. A significant reduction on the viability of C6 cells was determined when tGAS1 was transfected into glioma cells. Conversely, astroglial cells could neither internalize NTS nor activate ERK 1/2 and could not be transfected by the NTS-polyplex. These results demonstrate that the internalization process of NTSR2 receptors is a key regulator necessary to trigger the activation of the ERK 1/2. Our data support a new internalization pathway in glioma C6 cells that involve NTSR2/vNTSR2, which can be used to selectively transfer therapeutic genes using the NTS-polyplex system.

  13. Trends in Malignant Glioma Monoclonal Antibody Therapy

    Science.gov (United States)

    Chekhonin, Ivan; Gurina, Olga

    2015-01-01

    Although new passive and active immunotherapy methods are emerging, unconjugated monoclonal antibodies remain the only kind of biological preparations approved for high-grade glioma therapy in clinical practice. In this review, we combine clinical and experimental data discussion. As antiangiogenic therapy is the standard of care for recurrent glioblastoma multiforme (GBM), we analyze major clinical trials and possible therapeutic combinations of bevacizumab, the most common monoclonal antibody to vascular endothelial growth factor (VEGF). Another humanized antibody to gain recognition in GBM is epidermal growth factor (EGFR) antagonist nimotuzumab. Other antigens (VEGF receptor, platelet-derived growth factor receptor, hepatocyte growth factor and c-Met system) showed significance in gliomas and were used to create monoclonal antibodies applied in different malignant tumors. We assess the role of genetic markers (isocitrate dehydrogenase, O6-methylguanine-DNA methyltransnsferase) in GBM treatment outcome prediction. Besides antibodies studied in clinical trials, we focus on perspective targets and briefly list other means of passive immunotherapy.

  14. Bright Solitary Waves in Malignant Gliomas

    OpenAIRE

    Pérez-García, Víctor M.; Calvo, Gabriel F.; Belmonte-Beitia, Juan; Diego, D.; Pérez-Romasanta, Luis

    2011-01-01

    We put forward a nonlinear wave model describing the fundamental physio-pathologic features of an aggressive type of brain tumors: glioblastomas. Our model accounts for the invasion of normal tissue by a proliferating and propagating rim of active glioma cancer cells in the tumor boundary and the subsequent formation of a necrotic core. By resorting to numerical simulations, phase space analysis and exact solutions, we prove that bright solitary tumor waves develop in such systems.

  15. CURRENT APPROACHES TO CHEMORADIOTHERAPY FOR MALIGNANT GLIOMAS

    Directory of Open Access Journals (Sweden)

    Ye. L. Choinzonov

    2014-01-01

    Full Text Available High-grade malignant gliomas (WHO grade G III–IV account for more than 50% of all primary brain tumors. Despite aggressive treatment, survival rates are still very low with a median reported survival of no more than 1.5 years.Radiation therapy is an integral part of the combined treatment, but often does not influence lethally on resistant tumor cells. Thereby, in recent decades there has been an active search for novel approaches to the treatment of malignant gliomas (chemotherapeutic drugs, biological modifiers, local hyperthermia. Experimental data showed that the effect of high temperatures has both a direct damaging effect on tumor cells and a sensitizing effect. Significant advantages are achieved when the complex treatment of different malignant tumorsincludes local hyperthermia. However data on the treatment of patients with primary and recurrent gliomas G III–IV using local hyperthermia are scarce.The literature review is given in the article provides an overview of the existing treatment methods for brain tumors.

  16. Metabolic Targeting of Lactate Efflux by Malignant Glioma Inhibits Invasiveness and Induces Necrosis: An In Vivo Study

    Directory of Open Access Journals (Sweden)

    Chaim B Colen

    2011-07-01

    Full Text Available Glioblastoma multiforme (GBM are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs. We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA, a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion. Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity.

  17. Dexamethasone inhibits the HSV-tk/ ganciclovir bystander effect in malignant glioma cells

    International Nuclear Information System (INIS)

    HSV-tk/ ganciclovir (GCV) gene therapy has been extensively studied in the setting of brain tumors and largely relies on the bystander effect. Large studies have however failed to demonstrate any significant benefit of this strategy in the treatment of human brain tumors. Since dexamethasone is a frequently used symptomatic treatment for malignant gliomas, its interaction with the bystander effect and the overall efficacy of HSV-TK gene therapy ought to be assessed. Stable clones of TK-expressing U87, C6 and LN18 cells were generated and their bystander effect on wild type cells was assessed. The effects of dexamethasone on cell proliferation and sensitivity to ganciclovir were assessed with a thymidine incorporation assay and a MTT test. Gap junction mediated intercellular communication was assessed with microinjections and FACS analysis of calcein transfer. The effect of dexamethasone treatment on the sensitivity of TK-expressing to FAS-dependent apoptosis in the presence or absence of ganciclovir was assessed with an MTT test. Western blot was used to evidence the effect of dexamethasone on the expression of Cx43, CD95, CIAP2 and BclXL. Dexamethasone significantly reduced the bystander effect in TK-expressing C6, LN18 and U87 cells. This inhibition results from a reduction of the gap junction mediated intercellular communication of these cells (GJIC), from an inhibition of their growth and thymidine incorporation and from a modulation of the apoptotic cascade. The overall efficacy of HSV-TK gene therapy is adversely affected by dexamethasone co-treatment in vitro. Future HSV-tk/ GCV gene therapy clinical protocols for gliomas should address this interference of corticosteroid treatment

  18. EGFR-directed Affibody for fluorescence-guided glioma surgery: time-dose analysis (Conference Presentation)

    Science.gov (United States)

    Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason R.; Elliott, Jonathan T.; Samkoe, Kimberley S.; Paulsen, Keith D.; Draney, Daniel R.; Feldwisch, Joachim

    2016-03-01

    The key to fluorescence guided surgical oncology is the ability to create specific contrast between normal and glioma tissue. The blood brain barrier that limits the delivery of substances to the normal brain is broken in tumors, allowing accumulation of agents in the tumor interior. However, for a clinical success, imaging agents should be in the infiltrative edges to minimize the resection of normal brain while enable the removal of tumor. The aberrant overexpression and/or activation of EGFR is associated with many types of cancers, including glioblastoma and the injection of a fluorescent molecule targeted to these receptors would improve tumor contrast during fluorescence guided surgery. Affibody molecules have intentional medium affinity and high potential specificity, which are the desirable features of a good surgical imaging agent. The aim of this study was evaluate the brain/glioma uptake of ABY029 labeled with near-infrared dye IRDye800CW after intravenous injection. Rats were either inoculated with orthotopic implantations of U251 human glioma cell line or PBS (shams control) in the brain. The tumors were allowed to grow for 2-3 weeks before carrying out fluorescent tracer experiments. Fluorescent imaging of ex vivo brain slices from rats was acquired at different time points after infection of fluorescently labeled EGFR-specific affibody to verify which time provided maximal contrast tumor to normal brain. Although the tumor was most clearly visualized after 1h of IRDye800CW-labeled ABY029 injection, the tumor location could be identified from the background after 48h. These results suggest that the NIR-labeled affibody examined shows excellent potential to increase surgical visualization for confirmed EGFR positive tumors.

  19. Superoxide mediates direct current electric field-induced directional migration of glioma cells through the activation of AKT and ERK.

    Directory of Open Access Journals (Sweden)

    Fei Li

    Full Text Available Direct current electric fields (DCEFs can induce directional migration for many cell types through activation of intracellular signaling pathways. However, the mechanisms that bridge extracellular electrical stimulation with intracellular signaling remain largely unknown. In the current study, we found that a DCEF can induce the directional migration of U87, C6 and U251 glioma cells to the cathode and stimulate the production of hydrogen peroxide and superoxide. Subsequent studies demonstrated that the electrotaxis of glioma cells were abolished by the superoxide inhibitor N-acetyl-l-cysteine (NAC or overexpression of mitochondrial superoxide dismutase (MnSOD, but was not affected by inhibition of hydrogen peroxide through the overexpression of catalase. Furthermore, we found that the presence of NAC, as well as the overexpression of MnSOD, could almost completely abolish the activation of Akt, extracellular-signal-regulated kinase (Erk1/2, c-Jun N-terminal kinase (JNK, and p38, although only JNK and p38 were affected by overexpression of catalase. The presenting of specific inhibitors can decrease the activation of Erk1/2 or Akt as well as the directional migration of glioma cells. Collectively, our data demonstrate that superoxide may play a critical role in DCEF-induced directional migration of glioma cells through the regulation of Akt and Erk1/2 activation. This study provides novel evidence that the superoxide is at least one of the "bridges" coupling the extracellular electric stimulation to the intracellular signals during DCEF-mediated cell directional migration.

  20. Microstructural and superconducting properties of C6H6 added bulk MgB2 superconductor

    Science.gov (United States)

    Babaoğlu, Meral G.; Safran, Serap; Çiçek, Özlem; Ağıl, Hasan; Ertekin, Ercan; Hossain, Md. Shahriar A.; Yanmaz, Ekrem; Gencer, Ali

    2012-10-01

    The effect of aromatic hydrocarbon (benzene, C6H6) addition on lattice parameters, microstructure, critical temperature (Tc), critical current density (Jc) of bulk MgB2 has been studied. In this work only 2 mol% C6H6 addition was found to be very effective in increasing the Jc values, while resulting in slight reduction of the Tc. Jc values of 2 mol% C6H6 added MgB2 bulks reached to 1.83×106 A/cm2 at 15 K and 0 T. Microstructural analyses suggest that Jc enhancement is associated with the substitution of carbon with boron and which also results in the smaller MgB2 grain size. The change in the lattice parameters or the lattice disorder is claimed as a cause of the slight reduction in the Tc by carbon addition. We note that our results show the advantages of C6H6 addition include homogeneous mixing of precursor powders, avoidance of expansive nanoadditives, production of highly reactive C, and significant enhancement in Jc of MgB2, compared to un-doped samples.

  1. 40 CFR 721.524 - Alcohols, C6-12, ethoxylated, reaction product with maleic anhydride.

    Science.gov (United States)

    2010-07-01

    ... product with maleic anhydride. 721.524 Section 721.524 Protection of Environment ENVIRONMENTAL PROTECTION... with maleic anhydride. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alcohols, C6-12, ethoxylated, reaction product with...

  2. Novel bioluminescent coelenterazine derivatives with imidazopyrazinone C-6 extended substitution for Renilla luciferase.

    Science.gov (United States)

    Jiang, Tianyu; Yang, Xiaofeng; Yang, Xingye; Yuan, Mingliang; Zhang, Tianchao; Zhang, Huateng; Li, Minyong

    2016-06-21

    Two series of novel coelenterazine analogues (alkynes and triazoles) with imidazopyrazinone C-6 extended substitution have been designed and synthesized successfully for the extension of bioluminescent substrates. After extensive evaluation, some compounds display excellent bioluminescence properties compared with DeepBlueC in cellulo, thus becoming potential molecules for bioluminescence techniques. PMID:27197767

  3. Endothelial PKCα-MAPK/ERK-phospholipase A2 pathway activation as a response of glioma in a triple culture model. A new role for pericytes?

    Science.gov (United States)

    Anfuso, Carmelina Daniela; Motta, Carla; Giurdanella, Giovanni; Arena, Valeria; Alberghina, Mario; Lupo, Gabriella

    2014-04-01

    In view of understanding the molecular mechanisms through which angiogenic switch on happens in the early phases of reciprocal interaction between tumor and cells constituting microvessel, a triple culture model in which endothelial cells (EC), pericytes (PC) and glioma C6 cells were cultured together. In the present work, we observed that C6 enhanced EC proliferation. This effect was reduced by cytosolic and Ca(2+)-independent phospholipase A2 (cPLA2 and iPLA2), cyclooxygenase-2 (COX-2), PI3-K, MEK-1, and ERK1/2 inhibitors and by siRNAs against both PLA2s. In EC, C6 induced an increase in iPLA2, cPLA2 and COX-2 total protein expression. Moreover, the increase in endothelial cPLA2 phosphorylation was attenuated by kinase inhibitors. Both EC proliferation and signal protein phosphorylation were attenuated when PC were in triple culture. In EC/C6 supernatants, and, in a lesser extent, in EC/PC co-cultures, an enhancement in prostaglandins E2 (PGE2) was found. The presence of PC in triple-cultures caused a decrease in production of PGE2 respect to EC/C6 double-cultures. In all systems, AACOCF3 and BEL significantly reduced PGE2 secretion. In Matrigel-based assays, emerging branch points from EC cell bodies and tubule-like structures were observed. C6 conditioned EC/PC co-cultures in constituting poorly organized tubules. Transfection of EC with c- and iPLA2 siRNA strongly reduced in vitro tubulogenesis. Data here reported indicate that PKCα, ERK kinase phosphorylation, PLA2s and COX-2 activation, and PGE2 production in EC stimulated by tumor cells are coincident phenomena and could represent therapeutic targets in chemoprevention of glioma. Moreover, PC exhibited an important "modulating" role in the initial stages of angiogenesis driven by a brain tumor.

  4. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) of photodynamic therapy (PDT) outcome and associated changes in the blood-brain barrier following Pc 4-PDT of glioma in an athymic nude rat model

    Science.gov (United States)

    Belle, Vaijayantee; Anka, Ali; Cross, Nathan; Thompson, Paul; Mott, Eric; Sharma, Rahul; Gray, Kayla; Zhang, Ruozhen; Xu, Yueshuo; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David

    2012-02-01

    Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) appears to provide an unambiguous means of tracking the outcome of photodynamic therapy (PDT) of brain tumors with the photosensitizer Pc 4. The increase in Gd enhancement observed after Pc 4-PDT may be due to a temporary opening of the blood-brain-barrier which, as noted by others, may offer a therapeutic window. Methods: We injected 2.5 x 105 U87 cells into the brains of 9 athymic nude rats. After 8-9 days peri-tumor DCE-MRI images were acquired on a 7.0 T microMRI scanner before and after the administration of 150 μL Gd. DCE-MRI scans were repeated three times following Pc 4-PDT. Results: The average, normalized peak enhancement in the tumor region, approximately 30-90 seconds after Gd administration, was 1.31 times greater than baseline (0.03 Standard Error [SE]) prior to PDT and was 1.44 (0.02 SE) times baseline in the first Post-PDT scans (Day 11), a statistically significant (p ~ 0.014, N=8) increase over the Pre- PDT scans, and was 1.38 (0.02 SE) times baseline in the second scans (Day 12), also a statistically significant (p ~ 0.008, N=7) increase. Observations were mixed in the third Post-PDT scans (Day 13), averaging 1.29 (0.03 SE) times baseline (p ~ 0.66, N=7). Overall a downward trend in enhancement was observed from the first to the third Post-PDT scans. Discussion: DCE-MRI may provide an unambiguous indication of brain tumor PDT outcome. The initial increase in DCE-MRI signal may correlate with a temporary, PDT-induced opening of the blood-brain-barrier, creating a potential therapeutic window.

  5. VapC6, a ribonucleolytic toxin regulates thermophilicity in the crenarchaeote Sulfolobus solfataricus.

    Science.gov (United States)

    Maezato, Yukari; Daugherty, Amanda; Dana, Karl; Soo, Edith; Cooper, Charlotte; Tachdjian, Sabrina; Kelly, Robert M; Blum, Paul

    2011-07-01

    The phylum Crenarchaeota includes hyperthermophilic micro-organisms subjected to dynamic thermal conditions. Previous transcriptomic studies of Sulfolobus solfataricus identified vapBC6 as a heat-shock (HS)-inducible member of the Vap toxin-antitoxin gene family. In this study, the inactivation of the vapBC6 operon by targeted gene disruption produced two recessive phenotypes related to fitness, HS sensitivity and a heat-dependent reduction in the rate of growth. In-frame vapBC6 deletion mutants were analyzed to examine the respective roles of each protein. Since vapB6 transcript abundance was elevated in the vapC6 deletion, the VapC6 toxin appears to regulate abundance of its cognate antitoxin. In contrast, vapC6 transcript abundance was reduced in the vapB6 deletion. A putative intergenic terminator may underlie these observations by coordinating vapBC6 expression. As predicted by structural modeling, recombinant VapC6 produced using chaperone cosynthesis exhibited heat-dependent ribonucleolytic activity toward S. solfataricus total RNA. This activity could be blocked by addition of preheated recombinant VapB6. In vivo transcript targets were identified by assessing the relative expression of genes that naturally respond to thermal stress in VapBC6-deficient cells. Preferential increases were observed for dppB-1 and tetR, and preferential decreases were observed for rpoD and eIF2 gamma. Specific VapC6 ribonucleolytic action could also be demonstrated in vitro toward RNAs whose expression increased in the VapBC6-deficient strain during heat shock. These findings provide a biochemical mechanism and identify cellular targets underlying VapBC6-mediated control over microbial growth and survival at temperature extremes.

  6. Interaction between 5 genetic variants and allergy in glioma risk

    DEFF Research Database (Denmark)

    Schoemaker, Minouk J; Robertson, Lindsay; Wigertz, Annette;

    2010-01-01

    The etiology of glioma is barely known. Epidemiologic studies have provided evidence for an inverse relation between glioma risk and allergic disease. Genome-wide association data have identified common genetic variants at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756...

  7. Effect of Vascular Endothelial Growth Factor on Remodeling of Glioma Tissue in vivo%血管内皮细胞生长因子对胶质瘤组织重构的作用

    Institute of Scientific and Technical Information of China (English)

    林志雄; 杨丽娟; 黄强; 林建华; 陈振斌; 周玲英; 张鹏飞

    2008-01-01

    BACKGROUND & OBJECTIVE:Pathological characteristics and biological behaviom of tumors were considered as a result from histological remodeling regulated by interaction among factors in miemecosystem(TMES). Vascular endothelial growth factor (VEGF) probably plays an important role in the process of the tissue remodeling. This study was a comprehensive investigation of the effect of VEGF on remodeling of glioma structure in vivo.METHODS:C6 cells with expression vectors containing sense (C6/VEGF+) or antisense (C6/VEGF-) VEGF164 cDNA or an empty vector (C6/vec) were implanted into athymic mice, which served as in vivo model with divergent levels of VEGF expression. The VEGF expression, water content and morphologies of these tumoral tissues were assayed. RESULTS: The expression of VEGF and the water content in C6/VEGF- gliorna (C6/ VEGF-G) tissues were lower than that in C6,C6/VEGF+and C6/vec glioma (C6G,C6/VEGF+G ,C6/vecG)(P<0.01,P<0.01,P<0.05),and the water content conelated with VEGF expression (r=0.791,P=0.000). In C6/VEGF-G,the tumor cells demonstrated no tight adherence to vascular walls, the basal lamina surrounded by collagen fibers were monolayer and discontinued. While in C6G,C6/VEGF+and C6/vecG,the tumor cells were very close to vascular walls with some of them extending their process to the wall; More over, loose basal lamina surrounded by little amounts of collagen fibers were multilayer and integrated as well as continuously. Vesicular vacuolar organelle (VVO) structures was observed in plasma of endothelial cells (VECs) and significant correlation was found between VEGF expression levels and the VVO density (r=0.844,P=0.00). No correlation was found between VEGF expression and fenestrac formation in VECs, and neither fenestrae in VECs nor intercellular clefts were correlated with the water content of tumor tissue (r=0.01, P=0.970). CONCLUSION:These results demonstrate that VEGF can aggravate the edema in tumor tissues by increasing VVOs and played

  8. Autophagy involved in resveratrol increased radiosensitivity in glioma stem cells

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of Resveratrol combined with X-ray on radiosensitivity in glioma stem cells. Methods: The proliferation inhibition of glioma stem cells induced by X-rays and Resveratrol was assessed with MTT assay. The activation of proapoptotic effect was characterized by Hoechst 33258 stain. MDC stain and Western blot analysis were used to analyze the autophagy mechanism in X-rays-induced death of glioma stem cells. Results: MTT assay indicated that X-rays and Resveratrol decreased the viability of glioma stem cells (P<0.05); we found the proliferative inhibition of glioma stem cells was declined when we used 3-MA to inhibit autophagy(P<0.05). When the cells were treated by the Resveratrol and x-rays, their spherical shape were changed. Apoptosis was induced in glioma stem cells by combined X-rays and Resveratrol as detected by Hoechst 33258 staining. In addition, autophagy was induced in glioma stem cells in the combined treatment group as detected by MDC staining. Western blotting showed that Bcl-2 expression was decreased. in the combined treatment group (P<0.01), and the LC3-Ⅱ expression was increased in the combined treatment group (P<0.01). Conclusion: Resveratrol can increased the radiation sensitivity of glioma stem cells, the apoptosis and autophagy was induced in the glioma stem cells in the combined treatment X-rays and Resveratrol. Our results suggest that autophagy plays an essential role in the regulation of radiosensitization of glioma stem cells. (authors)

  9. Glioma Association and Balancing Selection of ZFPM2.

    Directory of Open Access Journals (Sweden)

    Shui-Ying Tsang

    Full Text Available ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350, non-glioma cancer (n = 354 and healthy control (n = 463 by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69 of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016, and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005 or non-glioma cancers (P = 0.020. ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002, with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028. In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.

  10. Science impact of MODIS C5 calibration degradation and C6+ improvements

    Directory of Open Access Journals (Sweden)

    A. Lyapustin

    2014-07-01

    Full Text Available The Collection 6 (C6 MODIS land and atmosphere datasets are scheduled for release in 2014. C6 contains significant revisions of the calibration approach to account for sensor aging. This analysis documents the presence of systematic temporal trends in the visible and near-infrared (500 m bands of the Collection 5 (C5 MODIS Terra, and to lesser extent, in MODIS Aqua geophysical datasets. Sensor degradation is largest in the Blue band (B3 of the MODIS sensor on Terra and decreases with wavelength. Calibration degradation causes negative global trends in multiple MODIS C5 products including the dark target algorithm's aerosol optical depth over land and Ångström Exponent over the ocean, global liquid water and ice cloud optical thickness, as well as surface reflectance and vegetation indices, including the normalized difference vegetation index (NDVI and enhanced vegetation index (EVI. As the C5 production will be maintained for another year in parallel with C6, one objective of this paper is to raise awareness of the calibration-related trends for the broad MODIS user community. The new C6 calibration approach removes major calibrations trends in the Level 1B (L1B data. This paper also introduces an enhanced C6+ calibration of the MODIS dataset which includes an additional polarization correction (PC to compensate for the increased polarization sensitivity of MODIS Terra since about 2007, as well as de-trending and Terra–Aqua cross-calibration over quasi-stable desert calibration sites. The PC algorithm, developed by the MODIS ocean biology processing group (OBPG, removes residual scan angle, mirror side and seasonal biases from aerosol and surface reflectance (SR records along with spectral distortions of SR. Using the Multi-Angle Implementation of Atmospheric Correction (MAIAC algorithm over deserts, we have also developed a de-trending and cross-calibration method which removes residual decadal trends on the order of several tenths of one

  11. Cognitive impairments in patients with low grade gliomas and high grade gliomas

    Directory of Open Access Journals (Sweden)

    Eliane C. Miotto

    2011-08-01

    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

  12. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  13. Glioma Cell Proliferation Controlled by ERK Activity-Dependent Surface Expression of PDGFRA

    OpenAIRE

    Dongfeng Chen; Duo Zuo; Cheng Luan; Min Liu; Manli Na; Liang Ran; Yingyu Sun; Annette Persson; Elisabet Englund; Leif G Salford; Erik Renström; Xiaolong Fan; Enming Zhang

    2014-01-01

    Increased PDGFRA signaling is an essential pathogenic factor in many subtypes of gliomas. In this context the cell surface expression of PDGFRA is an important determinant of ligand sensing in the glioma microenvironment. However, the regulation of spatial distribution of PDGFRA in glioma cells remains poorly characterized. Here, we report that cell surface PDGFRA expression in gliomas is negatively regulated by an ERK-dependent mechanism, resulting in reduced proliferation of glioma cells. G...

  14. Design, Synthesis and Biological Evaluation of C(6-Modified Celastrol Derivatives as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Kaiyong Tang

    2014-07-01

    Full Text Available New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468. The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84–0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

  15. PCl3-C6H6 heterodimers: evidence for Pπ phosphorus bonding at low temperatures.

    Science.gov (United States)

    Ramanathan, N; Sankaran, K; Sundararajan, K

    2016-07-28

    A phosphorous trichloride (PCl3)-benzene (C6H6) heterodimer was generated in a low temperature N2 matrix and was characterized using infrared spectroscopy. The structure of the heterodimer produced in the matrix isolation experiment was discerned through ab initio computations. Computations disclosed that the experimentally detected dimer is stabilized through strong non-covalent phosphorus bonded Pπ interaction, considered as a class of pnicogen bonding. This experimentally unmapped Pπ interaction so far has been reconnoitered using atoms in molecules and natural bond orbital and energy decomposition analyses. The influence of substitutions on both the PCl3 and C6H6 monomeric units of the heterodimer was subsequently examined to understand the strength of Pπ interaction as a result of these substitutions. PMID:27374927

  16. Sequencing of complete mitochondrial genome of brown algal Saccharina sp. ye-C6.

    Science.gov (United States)

    Xu, Le; Wang, Shuai; Fan, Xiao; Xu, Dong; Zhang, Xiaowen; Miao, Yu; Ye, Naihao

    2016-09-01

    The complete mitochondrial sequence (37 657 bp) of the Saccharina sp. ye-C6 was obtained from the assembled and annotated genome data sequenced by Illumina sequencing technology (KT271760). The circular genome contains 38 protein-coding genes (PCG), three ribosomal RNA (rRNA), and 25 transfer RNA (tRNA) genes. Base composition of genome is A (28.41%), T (36.29%), C (14.72%), and G (20.58%). Through a phylogenetic analysis based on the mitochondrial genomes of brown algae, we found that Saccharina sp. ye-C6 and Saccharina japonica are the most closely related species and strongly supports their close phylogenetic affinity. PMID:26403617

  17. Misdiagnosed bilateral C5-C6 dislocation causing cervical spine instability: a case report

    OpenAIRE

    Gelalis, Ioannis D.; Christoforou, Georgios; Arnaoutoglou, Christina M.; Politis, Angelos N.; Manoudis, Gregory; Xenakis, Theodoros A

    2009-01-01

    Introduction The diagnosis of cervical spine injuries remains a significant problem in many blunt trauma patients. Correct and early diagnosis of these injuries is imperative as delayed or missed diagnoses result in increased morbidity and mortality. Case presentation A 57-year-old Caucasian woman presented with a misdiagnosed bilateral C5-C6 dislocation one month after a fall and head injury, without clearance of the cervical spine in her previous visits to two physicians and having already ...

  18. Cervical pedicle screw fixation at C6 and C7 A cadaveric study

    Directory of Open Access Journals (Sweden)

    Ye Li

    2015-01-01

    Conclusion: The intersection of the horizontal line through the midpoint of the transverse process root and vertical line through the intersection of the posterolateral and posterior planes of the isthmus can be used as an entry point for C6 and C7 pedicle screw fixation. The screws should be inserted at 60 or 90° with the posterolateral isthmus in the horizontal plane and at 75° with the posterior isthmus in the sagittal plane. The LSC should not exceed 30 mm.

  19. Isolation of Rickettsia felis in the Mosquito Cell Line C6/36

    OpenAIRE

    Horta, Maurício C.; Labruna, Marcelo B.; Edison L. Durigon; Teresinha T.S. Schumaker

    2006-01-01

    We report the isolation and establishment of Rickettsia felis in the C6/36 cell line. Rickettsial growth was intense, always with 90 to 100% of cells being infected after few weeks. The rickettsial isolate was confirmed by testing infected cells by PCR and sequencing fragments of three major Rickettsia genes (gltA, ompB, and the 17-kDa protein gene).

  20. Positive pressure dependence of the superconducting transition temperature in C6Yb

    International Nuclear Information System (INIS)

    We have made a preliminary study of the evolution, with hydrostatic pressure, of the recently discovered superconductivity in the graphite intercalation compound C6Yb. We present a pressure-temperature phase diagram established by electrical transport and magnetization measurements. In the range 0-1.2GPa, the superconducting transition temperature increases linearly with pressure (dTc/dP=+0.389+/-0.005K/GPa)

  1. Three-dimensional structure determination of capsid of Aedes albopicus C6/36 cell densovirus

    Institute of Scientific and Technical Information of China (English)

    CHENG Lingpeng; CHEN Senxiong; Jenifer M.Brannan; Joanita Jakana; ZHANG Qinfen; Z.H.Zhou; ZHANG Jingqiang

    2004-01-01

    The three-dimensional structure of capsid of Aedes albopictus C6/36 densovirus was determined to 14-(A) resolution by electron cryomicroscopy and computer reconstruction. The triangulation number of the capsid is 1. There are 12 holes in each triangular face and a spike on each 5-fold vertex. The validity of the capsid and nucleic acid densities in the reconstructions was discussed.

  2. Relativistic calculations of $C_6$ and $C_8$ coefficients for strontium dimers

    CERN Document Server

    Porsev, S G; Clark, Charles W

    2014-01-01

    The electric dipole and quadrupole polarizabilities of the $5s5p~^3\\!P_1^o$ state and the $C_6$ and $C_8$ coefficients for the $^1\\!S_0 +\\, ^1\\!S_0$ and $^1\\!S_0 +\\, ^3\\!P_1^o$ dimers of strontium are calculated using a high-precision relativistic approach that combines configuration interaction and linearized coupled-cluster methods. Our recommended values of the long range dispersion coefficients for the $0_u$ and $1_u$ energy levels are $C_6(0_u)=3771(32)$ a.u. and $C_6(1_u)= 4001(33)$ a.u., respectively. They are in good agreement with recent results from experimental photoassociation data. We also calculate $C_8$ coefficients for Sr dimers, which are needed for precise determination of long-range interaction potential. We confirm the experimental value for the magic wavelength, where the Stark shift on the $^1\\!S_0$-$^3\\!P_1^o$ transition vanishes. The accuracy of calculations is analyzed and uncertainties are assigned to all quantities reported in this work.

  3. First astronomical detection of the cumulene carbon chain molecule H2C6 in TMC-1

    Science.gov (United States)

    Langer, W. D.; Velusamy, T.; Kuiper, T. B.; Peng, R.; McCarthy, M. C.; Travers, M. J.; Kovacs, A.; Gottlieb, C. A.; Thaddeus, P.; Levin, S. M. (Principal Investigator)

    1997-01-01

    The cumulene carbenes are important components of hydrocarbon chemistry in low-mass star-forming cores. Here we report the first astronomical detection of the long-chain cumulene carbene H2C6 in the interstellar cloud TMC-1, from observations of two of its rotational transitions: J(K,K') = 7(1,7) --> 6(1,6) at 18.8 GHz and 8(1,8) --> 7(1,7) at 21.5 GHz, using NASA's Deep Space Network 70 m antenna at Goldstone, California. In addition we also observed the shorter cumulene carbene H2C4 at the same position. The fractional abundance of H2C6 relative to H2 is about 4.7 x 10(-11) and that of H2C4 is about 4.1 x 10(-9). The abundance of H2C6 is in fairly good agreement with gas-phase chemical models for young molecular cloud cores, but the abundance of H2C4 is significantly larger than predicted.

  4. Zero-Point Corrections for Isotropic Coupling Constants for Cyclohexadienyl Radical, C6H7 and C6H6Mu: Beyond the Bond Length Change Approximation

    Directory of Open Access Journals (Sweden)

    Bruce S. Hudson

    2013-04-01

    Full Text Available Zero-point vibrational level averaging for electron spin resonance (ESR and muon spin resonance (µSR hyperfine coupling constants (HFCCs are computed for H and Mu isotopomers of the cyclohexadienyl radical. A local mode approximation previously developed for computation of the effect of replacement of H by D on 13C-NMR chemical shifts is used. DFT methods are used to compute the change in energy and HFCCs when the geometry is changed from the equilibrium values for the stretch and both bend degrees of freedom. This variation is then averaged over the probability distribution for each degree of freedom. The method is tested using data for the methylene group of C6H7, cyclohexadienyl radical and its Mu analog. Good agreement is found for the difference between the HFCCs for Mu and H of CHMu and that for H of CHMu and CH2 of the parent radical methylene group. All three of these HFCCs are the same in the absence of the zero point average, a one-parameter fit of the static HFCC, a(0, can be computed. That value, 45.2 Gauss, is compared to the results of several fixed geometry electronic structure computations. The HFCC values for the ortho, meta and para H atoms are then discussed.

  5. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    Science.gov (United States)

    2015-03-02

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  6. CT image digital measurement and clinical significance of C4 -C6 anterior fixed parameter

    Institute of Scientific and Technical Information of China (English)

    LI Xiaohe; LI Zhijun; GAO Shang

    2015-01-01

    Objective:To measure C3-C5 anterior fixed parametersment for the segmental anterior fixation surgery. Methods:The examination of the cervical spine in patients with CT imaging data were randomly selected from January 2009 - December 2012 , C4 - C6 cervical no lesions in 35 cases of imaging data were selected (20 males and 5 females , 25 to 50 years old, average 41. 2 years) ,The image data were rebuilded and measured di-ameter by Mimics 16. 01 software, vertebral body height, vertebrae transverse process hole diameter and diameter around, the left and right sides of the horizontal distance between the flange hole inside, left and right sides of the axis of the pedicle and sagittal axis and the horizontal axis angle and length were measured. Results and conclu-sion:the vertebral body diameter of C4-C6, (26. 67±0. 25) mm gradually increased to (32. 89±0. 12) mm, an-terior and posterior diameter of C4 -C6 ,(6. 89±0. 12) mm gradually increased to (8. 85±0. 44) mm, comparing differences between different segments were statistical significance;Vertebral body midline sagittal anterior, middle and posterior height from C4 [anterior was (7. 99 ±0. 51) mm, middle was(7. 09±0. 42) mm, posterior was (7. 76±0. 49) mm]. To C6 [anterior was (9. 89±0. 45 mm, middle was (8. 42±0. 75) mm, posterior was (8. 84±0. 26) mm], vertebral bodies were significant difference (P<0. 05); the vertebrae transverse process hole diameter and diameter around anterior and posterior were gradually increased with the increase of the sequence; on both sides of C4~C6 were by transverse process hole inside edge distance ( 25 . 10 ± 0 . 45 ) mm gradually increased to (28. 89±0. 56) mm, comparing differences between different segments were statistical significance;Pedicle axis , the sagittal axis and horizontal axis angle and length were gradually increasing with the increase of the cervical spine ordinal, difference is statistically significant.

  7. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  8. Telomere maintenance and the etiology of adult glioma.

    Science.gov (United States)

    Walsh, Kyle M; Wiencke, John K; Lachance, Daniel H; Wiemels, Joseph L; Molinaro, Annette M; Eckel-Passow, Jeanette E; Jenkins, Robert B; Wrensch, Margaret R

    2015-11-01

    A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk has remained elusive. Recent data address this question and are reviewed here. Common inherited variants near the telomerase-component genes TERC and TERT are associated both with longer telomere length and increased risk of glioma. Exome sequencing of glioma patients from families with multiple affected members has identified rare inherited mutations in POT1 (protection of telomeres protein 1) as high-penetrance glioma risk factors. These heritable POT1 mutations are also associated with increased telomere length in leukocytes. Tumor sequencing studies further indicate that acquired somatic mutations of TERT and ATRX are among the most frequent alterations found in adult gliomas. These mutations facilitate telomere lengthening, thus bypassing a critical mechanism of apoptosis. Although future research is needed, mounting evidence suggests that glioma is, at least in part, a disease of telomere dysregulation. Specifically, several inherited and acquired variants underlying gliomagenesis affect telomere pathways and are also associated with increased telomere length. PMID:26014050

  9. Current status of cerebral glioma surgery in China

    Institute of Scientific and Technical Information of China (English)

    WU Jin-song; ZHANG Jie; ZHUANG Dong-xiao; YAO Cheng-jun; QIU Tian-ming; LU Jun-feng; ZHU Feng-ping; MAO Ying; ZHOU Liang-fu

    2011-01-01

    The treatment of gliomas is highly individualized.Surgery for gliomas is essentially for histological diagnosis,to alleviate mass effect,and most importantly,to favor longer survival expectancy.During the past two decades,many surgical techniques and adjuvants have been applied to glioma surgery in China,which lead to a rapid development in the field of cerebral glioma surgery.This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China.A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China.The following databases were searched:the Pubmed (January 1995 to date);China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date).A selection criterion was established to exclude duplicates and irrelevant studies.The outcome measures were extracted from included studies.A total of 3307 articles were initially searched.After excluded by abstracts and full texts,69 studies conducted in the mainland of China were included and went through further analysis.The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change.Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients.The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention.The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

  10. P01.23NEUROTENSIN PROMOTES THE PROGRESSION OF MALIGNANT GLIOMA THROUGH NTSR1 AND IMPACTS THE PROGNOSIS OF GLIOMA PATIENTS

    OpenAIRE

    Yi, L.; Xu, M.; Xu, L.; Feng, H.; Cui, H.

    2014-01-01

    BACKGROUND: Neurotensin (NTS) functions as a neuromodulator and induces cellular proliferation and migration in various solid tumors. However, whether NTS can promote the progression of malignant glioma and its prognostic significance for glioma patients remain unclear. METHODS: NTS and its high-affinity receptor (NTSR1) expression levels in clinical glioma samples were detected by immunohistochemistry and immunobloting. The prognostic analysis in glioma patients were conducted online by R2 m...

  11. Somatostatin-receptor positive brain stem glioma visualized by octreoscan.

    Science.gov (United States)

    Pichler, Robert; Pichler, Josef; Mustafa, Hamdy; Nussbaumer, Karin; Zaunmüller, Thomas; Topakian, Raffi

    2007-06-01

    In diffuse brainstem gliomas often surgical biopsies cannot be obtained. The diagnosis relies upon imaging criteria, first line being MRI. Gliomas generally express somatostatin receptors (SSTR), which might enable receptor imaging. We present the case of a female adolescent with acute onset of hallucinations, dysphagia and diplopia. MRI detected a suggestive large pontine glioma. This lesion presented with marked In-111-pentreotide tracer uptake. SSTR-scan provided information about SSTR-expression, tumour viability and extension. Radiopeptide therapy for selected patients might be discussed. PMID:17627256

  12. A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

    OpenAIRE

    Butowski, Nicholas; Bankiewicz, Krystof; Kells, Adrian; Martin, Alastair; Berger, Mitchell; Aghi, Manish; Prados, Michael; Chang, Susan; Clarke, Jennifer

    2014-01-01

    BACKGROUND: Chemotherapy for high grade glioma (HGG) is limited by poor activity of available agents and compromised delivery across the blood brain barrier (BBB). Convection enhanced delivery (CED) improves chemotherapy delivery by utilizing fluid convection established as a result of a pressure gradient, obviating the challenges of crossing the BBB while minimizing systemic toxicity. CED of nanoliposomal irinotecan (MM-398) has been optimized in rat, dog, and primate models. A recent study ...

  13. Analysis on Biomechanical Characteristics of Post-operational Vertebral C5-C6 Segments

    Directory of Open Access Journals (Sweden)

    Heqiang Tian

    2016-03-01

    Full Text Available Both anterior cervical decompression and fusion (ACDF and artificial cervical disc replacement (ACDR have obvious advantages in the treatment of cervical spondylosis. To analyze the operation results, it is absolutely necessary to study the biomechanics of the movement range of post-operational vertebral C5-C6 segments, especially the biomechanical characteristics in cervical tissues in actual movements. In this study, using the human vertebral 3D graph gained by imaging diagnosis (CT, a vertebral solid model is established by the 3D reconstruction algorithm and reverse engineering technology. After that, with cervical soft tissue structure added to the solid model and set with a joint contact mechanism, a finite element model with a complete, accurate cervical C5-C6 kinematic unit is constructed, based on relevant physiological anatomical knowledge. This model includes vertebral segments, an intervertebral disc, ligament and zygopophysis in the cervical C5-C6 kinematic unit. In the created vertebral finite element model, the model is amended, referring to ACDF and ACDR, and the load and constraint are applied to a normal group, a fusion group and a displacement group, so as to analyze the biomechanical characteristics of the cervical vertebra after ACDF and ACDR. By comparing the finite element simulation results of different surgeries, this paper is intended to evaluate the functions and biomechanical behaviors of the post-operational vertebra, and explore the influence of the operation on the biomechanical stability of the cervical vertebra. This will provide theoretical guidance for implementation and optimization of ACDF and ACDR.

  14. Hydrostatic pressure testing of graphite/epoxy cylinder C6-1

    Energy Technology Data Exchange (ETDEWEB)

    Blake, H.W.; Starbuck, J.M.

    1992-07-01

    This report details the design, fabrication, and testing of IM6 graphite cylinder C6-1, which achieved a record pressure in hydrotest without failure. Included are the details of the cylinder construction, the design calculations for stress and buckling, and the cylinder failure predictions. Also provided are the design details of the metal end closures including the design calculations for the linear tapered end plugs. Finally, the test data and observations from the hydrotest are summarized. This work is performed under the Oak Ridge National Laboratory, Laboratory Directed Research and Development Program. The project is funded by the Director as a three-year project.

  15. Angular Differential Cross-Section for Ionization of Helium in C6+ Ion Collision

    Institute of Scientific and Technical Information of China (English)

    A.C.Gagyi-Pálffy; I.F.Barna; L.Gulyás; K.T(o)kési

    2004-01-01

    With the help of the density operator, the angular differential cross-section for ionization of helium is calculated within the framework of the one-centre atomic-orbital close-coupling method. We consider a naked C6+ ion as projectile with an energy of 2.5 MeV/a.u. Our result agrees well with the experimental data and the other theoretical calculations such as the first Born approximation, various Distorted Wave models and the classical trajectory Monte Carlo simulation.

  16. Isochoric thermal conductivity of solid n-alkanes: hexane C6H14

    International Nuclear Information System (INIS)

    The isochoric thermal conductivity of solid n-hexane C6H14 has been investigated on three samples of different density in the temperature interval from 100 K to the onset of melting. In all the cases the isochoric thermal conductivity varied following a dependence which is weaker than A is proportional to 1/T. The results obtained are compared with the thermal conductivities of other representatives of n-alkanes. The contributions of low-frequency phonons and 'diffuse modes' to the thermal conductivity are calculated.

  17. Experimental Evidence of s-Wave Superconductivity in Bulk CaC6

    Science.gov (United States)

    Lamura, G.; Aurino, M.; Cifariello, G.; di Gennaro, E.; Andreone, A.; Emery, N.; Hérold, C.; Marêché, J.-F.; Lagrange, P.

    2006-03-01

    The temperature dependence of the in-plane magnetic penetration depth, λab(T), has been measured in a c-axis oriented polycrystalline CaC6 bulk sample using a high-resolution mutual inductance technique. A clear exponential behavior of λab(T) has been observed at low temperatures, strongly suggesting isotropic s-wave pairing. Data fit using the standard BCS theory yields λab(0)=(720±80)Å and Δ(0)=(1.79±0.08)meV. The ratio 2Δ(0)/kBTc=(3.6±0.2) gives indication for a weakly coupled superconductor.

  18. Angular Distribution of the 12C(6He, 7Li)11B Reaction

    Institute of Scientific and Technical Information of China (English)

    LI Er-Tao; LI Zhi-Hong; LI Yun-Ju; YAN Sheng-Quan; BAI Xi-Xiang; GUO Bing; SU Jun; WANG You-Bao; WANG Bao-Xiang; LIAN Gang; ZENG Sheng; FANG Xiao; ZHAO Wei-Juan; LIU Wei-Ping

    2009-01-01

    Angular distribution of the 12C(6He, 7Li)11B transfer reaction is measured with a secondary 6He beam of 36.4 Me V for the first time. The experimental angular distribution is well reproduced by the distorted-wave Born approxima-tion (DWBA) calculation. The success of the present experiment shows that it is feasible to measure one-nucleon transfer reaction on a light nucleus target with the secondary beam facility of the HI-13 tandem accelerator at China Institute of Atomic Energy (CIAE), Beifing.

  19. Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate

    OpenAIRE

    Wei-Lien Chuang; Joshua Pacheco; Samantha Cooper; Kingsbury, Jonathan S.; John Hinds; Pavlina Wolf; Petra Oliva; Joan Keutzer; Cox, Gerald F.; Kate Zhang

    2015-01-01

    Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann–Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann–Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the...

  20. FLUORESCENT, SHORT-CHAIN C-6-NBD-SPHINGOMYELIN, BUT NOT C-6-NBD-GLUCOSYLCERAMIDE, IS SUBJECT TO EXTENSIVE DEGRADATION IN THE PLASMA-MEMBRANE - IMPLICATIONS FOR SIGNAL-TRANSDUCTION RELATED TO CELL-DIFFERENTIATION

    NARCIS (Netherlands)

    KOK, JW; BABIA, T; KLAPPE, K; HOEKSTRA, D

    1995-01-01

    The involvement of the plasma membrane in the metabolism of the sphingolipids sphingomyelin (SM) and glucosylceramide (GlcCer) was studied, employing fluorescent short-chain analogues of these lipids, 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]hexanoylsphingosylphosphorylcholine (C-6-NBD-SM), C-6-

  1. Terahertz pulsed spectroscopy of paraffin-embedded brain glioma

    Science.gov (United States)

    Meng, Kun; Chen, Tu-nan; Chen, Tao; Zhu, Li-guo; Liu, Qiao; Li, Zhao; Li, Fei; Zhong, Sen-cheng; Li, Ze-ren; Feng, Hua; Zhao, Jian-heng

    2014-07-01

    The refractive indices, absorption coefficients, and complex dielectric constants of paraffin-embedded brain glioma and normal brain tissues have been measured by a terahertz time-domain spectroscopy (THz-TDS) system in the 0.2- to 2.0-THz range. The spectral differences between gliomas and normal brain tissues were obtained. Compared with normal brain tissue, our results indicate that paraffin-embedded brain gliomas have a higher refractive index, absorption coefficient, and dielectric constant. Based on these results, the best THz frequencies for different methods of paraffin-embedded brain glioma imaging, such as intensity imaging, coherent imaging with continuum THz sources, and THz pulsed imaging with short-pulsed THz sources, are analyzed.

  2. Research and application progress of MGMT promoter methylation in gliomas

    Directory of Open Access Journals (Sweden)

    Cui-yun SUN

    2014-07-01

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT is an important DNA repair enzyme. The promoter methylation status of MGMT gene has recently become a biomarker of gliomas. Methylation of the MGMT promoter not only is an important biomarker to evaluate the sensitivity to the chemotherapy with alkylating agents, but also contributes to predicting prognosis and distinguishing between recurrence and pseudoprogression in glioma patients. Especially in the elderly, MGMT promoter methylation status has recently been introduced to be a biomarker for glioma classification and personalized treatment strategies. This review gives a short summary of the function of MGMT and clinical application of MGMT promoter methylation in personalized treatment strategies, prognosis evaluation and differentiation of recurrence and pseudoprogression of glioma. doi: 10.3969/j.issn.1672-6731.2014.07.017

  3. Cognitive rehabilitation in patients with gliomas : a randomized, controlled trial

    NARCIS (Netherlands)

    Gehring, Karin; Sitskoorn, Margriet M; Gundy, Chad M; Sikkes, Sietske A M; Klein, Martin; Postma, Tjeerd J; van den Bent, Martin J; Beute, Guus N; Enting, Roelien H.; Kappelle, Arnoud C; Boogerd, Willem; Veninga, Theo; Twijnstra, Albert; Boerman, Dolf H; Taphoorn, Martin J B; Aaronson, Neil K

    2009-01-01

    PURPOSE: Patients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients

  4. 360 degree decompresion and stabilisation of the C6-C7 cervical spine luxation - case study.

    Science.gov (United States)

    Chrzanowski, Robert; Godlewski, Bartosz; Klauz, Grzegorz; Janeczko, Łukasz

    2012-01-01

    We present the operative technique employed in a young man with cervical spine luxation at the level of C6-C7 with clinical signs of damage to the spinal cord at the level of C5. In order to achieve an optimal therapeutic effect (decompression of neural structures and spinal stabilisation) during one surgical procedure, the positioning of the patient was changed twice during the procedure. Considering the positioning of the patient at the beginning of the procedure, the body position was changed by 360 degrees. The first part of the procedure was performed from an anterior approach with the patient in the supine position. It involved a C6-C7 discectomy and removal of the upper surface of the body of C7, which was protruding into the vertebral canal and compressing the spinal cord. Intraoperative inspection showed that a posterior approach was necessary to reduce the luxation. Therefore, for the second part of the operation, the patient was turned by 180 degrees and placed in the prone position. For the last (third) part of the surgical procedure, the patient was again turned by 180 degrees and placed in the supine position in order to insert an anterior spine fixator. We believe that a procedure utilising different surgical approaches and different positioning of the patient in order to achieve optimal therapeutic effect may be used in selected cases in everyday clinical practice. PMID:23382285

  5. Cytological effects and RAPD analysis of Allium fistulosum L. irradiated by 12C6+ heavy ions

    International Nuclear Information System (INIS)

    Cytological effects and RAPD analysis of root-tip cells of Allium fistulosum L., the dry seeds were irradiated by 12 C6+ heavy ions, were studied. Micronucleus and chromosomal aberration observed in the root-tip cells showed that obvious 'linear rise' trend was in the frequency of micronucleus, multi-micronucleus and total chromosomal aberration. But a 'U- formed' trend was observed only in the chromosomal aberration frequency. At the same time, RAPD analysis revealed 12C6+ heavy ions exerted great effect on DNA variation of Allium fistulosum L.. Flawing bands, increasing bands and the ones with different transport ratios were observed in amplified bands of 28 selected primers. The DNA variation rate for 30, 90 and 180Gy treatments was 29.91%, 41.05% and 22.14%, respectively. This study also found that high micronucleus frequency and chromosomal variation lead to high lethality, resulting in low DNA variation rate in the survived plants which seeds were irradiated with high doses. (authors)

  6. Oxygen subsurface adsorption on the Cu(110)-c(6 × 2) surface

    Science.gov (United States)

    Li, Liang; Zhou, Guangwen

    2013-09-01

    To understand the initial steps of the oxidation of Cu(110), we applied density functional theory (DFT) calculations to study oxygen subsurface adsorption at the Cu(110)-c(6 × 2) reconstructed surface by increasing oxygen coverage. A transition from oxygen octahedral occupancy to tetrahedral preference occurs when the coverage reaches 1 monolayer, which may signal the onset of bulk oxidation that initially forms highly distorted Cusbnd O tetrahedrons by comparing the bond lengths and angles of the resulting Cusbnd O tetrahedron with the bulk Cu2O structure. These results suggest that a critical oxygen coverage is required for such a crossover from the oxygen chemisorption to bulk oxide formation. A comparison with the oxygen subsurface adsorption at Cu(100) suggests that the Cu(110) surface has a larger tendency to form Cusbnd O tetrahedrons. We model oxygen subsurface adsorption at the Cu(110)-c(6 × 2) reconstructed surface. Increasing O coverage leads to O tetrahedral preference over octahedral occupancy. The resulting Cusbnd O tetrahedrons show resemblance to that of the Cu2O structure. Cu(110) shows a stronger tendency than Cu(100) to form Cu2O-like tetrahedrons.

  7. Successful propagation of Alkhumra (misnamed as Alkhurma) virus in C6/36 mosquito cells.

    Science.gov (United States)

    Madani, Tariq A; Kao, Moujahed; Azhar, Esam I; Abuelzein, El-Tayeb M E; Al-Bar, Hussein M S; Abu-Araki, Huda; Ksiazek, Thomas G

    2012-03-01

    Epidemiological data suggest that Alkhumra (misnamed as Alkhurma) virus (ALKV) is transmitted from livestock animals to humans by direct contact with animals or by the mosquito bites, but not by ticks. To assess the ability of the virus to replicate in mosquito cells, serum and plasma of seven acutely febrile patients with clinically suspected ALKV infection reported in Najran, Saudi Arabia in 2009 were inoculated onto Aedes albopictus mosquito cells (C6/36) and directly examined with ALKV-RNA-specific real time RT-PCR as well as indirect immunfluorescence assay (IFA) using ALKV-specific polyclonal antibodies. The isolated virus was titrated in the mammalian rhesus monkey kidney cells (LLC-MK2). Five of the seven specimens were RT-PCR- and culture-positive demonstrating cytopathic effects in the form of cell rounding and aggregation appearing on day 3 post inoculation with syncytia eventually appearing on day 8 post inoculation. Identification of ALKV-RNA in the cell culture was confirmed with RT-PCR and IFA. The virus titre was 3.2×10(6) tissue culture infective dose 50 (TCID(50)) per mL. Three more viral passages were successfully made in the C6/36 cells. This is the first description of propagation of ALKV in mosquito cells. PMID:22154975

  8. Ca intercalated bilayer graphene as a thinnest limit of superconducting C6Ca.

    Science.gov (United States)

    Kanetani, Kohei; Sugawara, Katsuaki; Sato, Takafumi; Shimizu, Ryota; Iwaya, Katsuya; Hitosugi, Taro; Takahashi, Takashi

    2012-11-27

    Success in isolating a 2D graphene sheet from bulky graphite has triggered intensive studies of its physical properties as well as its application in devices. Graphite intercalation compounds (GICs) have provided a platform of exotic quantum phenomena such as superconductivity, but it is unclear whether such intercalation is feasible in the thinnest 2D limit (i.e., bilayer graphene). Here we report a unique experimental realization of 2D GIC, by fabricating calcium-intercalated bilayer graphene C(6)CaC(6) on silicon carbide. We have investigated the structure and electronic states by scanning tunneling microscopy and angle-resolved photoemission spectroscopy. We observed a free-electron-like interlayer band at the Brillouin-zone center, which is thought to be responsible for the superconductivity in 3D GICs, in addition to a large π* Fermi surface at the zone boundary. The present success in fabricating Ca-intercalated bilayer graphene would open a promising route to search for other 2D superconductors as well as to explore its application in devices.

  9. Gas-phase synthesis of the benzyl radical (C(6)H(5)CH(2)).

    Science.gov (United States)

    Dangi, Beni B; Parker, Dorian S N; Yang, Tao; Kaiser, Ralf I; Mebel, Alexander M

    2014-04-25

    Dicarbon (C2 ), the simplest bare carbon molecule, is ubiquitous in the interstellar medium and in combustion flames. A gas-phase synthesis is presented of the benzyl radical (C6 H5 CH2 ) by the crossed molecular beam reaction of dicarbon, C2 (X(1) Σg (+) , a(3) Πu ), with 2-methyl-1,3-butadiene (isoprene; C5 H8 ; X(1) A') accessing the triplet and singlet C7 H8 potential energy surfaces (PESs) under single collision conditions. The experimental data combined with ab initio and statistical calculations reveal the underlying reaction mechanism and chemical dynamics. On the singlet and triplet surfaces, the reactions involve indirect scattering dynamics and are initiated by the barrierless addition of dicarbon to the carbon-carbon double bond of the 2-methyl-1,3-butadiene molecule. These initial addition complexes rearrange via multiple isomerization steps, leading eventually to the formation of C7 H7 radical species through atomic hydrogen elimination. The benzyl radical (C6 H5 CH2 ), the thermodynamically most stable C7 H7 isomer, is determined as the major product.

  10. Glioma-Associated Antigen HEATR1 Induces Functional Cytotoxic T Lymphocytes in Patients with Glioma

    Directory of Open Access Journals (Sweden)

    Zhe Bao Wu

    2014-01-01

    Full Text Available A2B5+ glioblastoma (GBM cells have glioma stem-like cell (GSC properties that are crucial to chemotherapy resistance and GBM relapse. T-cell-based antigens derived from A2B5+ GBM cells provide important information for immunotherapy. Here, we show that HEAT repeat containing 1 (HEATR1 expression in GBM tissues was significantly higher than that in control brain tissues. Furthermore, HEATR1 expression in A2B5+ U87 cells was higher than that in A2B5−U87 cells (P=0.016. Six peptides of HEATR1 presented by HLA-A*02 were selected for testing of their ability to induce T-cell responses in patients with GBM. When peripheral blood mononuclear cells from healthy donors (n=6 and patients with glioma (n=33 were stimulated with the peptide mixture, eight patients with malignant gliomas had positive reactivity with a significantly increased number of responding T-cells. The peptides HEATR1682–690, HEATR11126–1134, and HEATR1757–765 had high affinity for binding to HLA-A*02:01 and a strong capacity to induce CTL response. CTLs against HEATR1 peptides were capable of recognizing and lysing GBM cells and GSCs. These data are the first to demonstrate that HEATR1 could induce specific CTL responses targeting both GBM cells and GSCs, implicating that HEATR1 peptide-based immunotherapy could be a novel promising strategy for treating patients with GBM.

  11. Dose enhancement by synchrotron radiation and heavy atoms for the treatment of gliomas

    International Nuclear Information System (INIS)

    High grade gliomas are brain tumors of bad prognosis. The standard therapeutic treatment combines surgery, radiotherapy and sometimes use of temozolomide (chemotherapy agent). Healthy tissues radio-sensitivity is a major limitation for radiotherapy treatment. The stereotactic radiotherapy by synchrotron radiation is an innovative technique which combines a low energy radiation (lower 100 keV) with the presence of heavy atoms in the tumoral zone. Such an approach is used to increase the differential of dose deposited in the tumor compared to surrounding healthy tissues. In this study, several compounds containing heavy atoms such as chemotherapy agents: cisplatin/carbo-platin, a DNA base analog: 5-iodo-2'-deoxyuridine (IUdR) and gold nano-particles were considered. The dose enhancement factor induced by the presence of these compounds located for some of them in the extracellular medium or inside the cells for others, was determined using in vitro studies. Thereafter, in vivo studies on rats bearing gliomas, were performed to study the toxicity, the kinetic of distribution and the localization of these compounds together with their potential efficacy of treatment combining intracerebral injection with low energy radiation. (author)

  12. Galunisertib inhibits glioma vasculogenic mimicry formation induced by astrocytes

    OpenAIRE

    Chao Zhang; Wenliang Chen; Xin Zhang; Bin Huang; Aanjing Chen; Ying He; Jian Wang; Xingang Li

    2016-01-01

    Gliomas are among the most lethal primary brain tumors found in humans. In high-grade gliomas, vasculogenic mimicry is often detected and has been correlated with prognosis, thus suggesting its potential as a therapeutic target. Vasculogenic mimicry mainly forms vascular-like channels independent of endothelial cells; however, little is known about the relationship between astrocytes and vasculogenic mimicry. In our study, we demonstrated that the presence of astrocytes promoted vasculogenic ...

  13. P47THE IDENTIFICATION OF NOVEL APTAMERS TO GLIOMA

    OpenAIRE

    Norris, Karl; Shaw, Lisa; Alder, Jane Elizabeth; Lawrence, Clare Louise

    2014-01-01

    INTRODUCTION: Glioma represent less than 2% of all cancer cases in the UK, however, 80% of these tumours are glioblastoma (GBM). GBM is a highly aggressive tumour with poor patient survival rates, despite treatment involving surgery and radiotherapy with adjuvant chemotherapy. Delivery systems that have the ability to distinguish neoplasms from non-cancerous tissues, such as aptamers, may improve patient outcome. Aptamers have previously been shown to selectively target glioma cell lines. Apt...

  14. Improving Seroreactivity-Based Detection of Glioma1

    OpenAIRE

    Ludwig, Nicole; Keller, Andreas; Heisel, Sabrina; Leidinger, Petra; Klein, Veronika; Rheinheimer, Stefanie; Andres, Claudia U; Stephan, Bernhard; Steudel, Wolf-Ingo; Graf, Norbert M; Burgeth, Bernhard; Weickert, Joachim; Lenhof, Hans-Peter; Meese, Eckart

    2009-01-01

    Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 ...

  15. Research and application progress of MGMT promoter methylation in gliomas

    OpenAIRE

    Cui-yun SUN; Shi-zhu YU

    2014-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) is an important DNA repair enzyme. The promoter methylation status of MGMT gene has recently become a biomarker of gliomas. Methylation of the MGMT promoter not only is an important biomarker to evaluate the sensitivity to the chemotherapy with alkylating agents, but also contributes to predicting prognosis and distinguishing between recurrence and pseudoprogression in glioma patients. Especially in the elderly, MGMT promoter methylation stat...

  16. Effects of metformin treatment on glioma-induced brain edema

    Science.gov (United States)

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

  17. Galunisertib inhibits glioma vasculogenic mimicry formation induced by astrocytes.

    Science.gov (United States)

    Zhang, Chao; Chen, Wenliang; Zhang, Xin; Huang, Bin; Chen, Aanjing; He, Ying; Wang, Jian; Li, Xingang

    2016-01-01

    Gliomas are among the most lethal primary brain tumors found in humans. In high-grade gliomas, vasculogenic mimicry is often detected and has been correlated with prognosis, thus suggesting its potential as a therapeutic target. Vasculogenic mimicry mainly forms vascular-like channels independent of endothelial cells; however, little is known about the relationship between astrocytes and vasculogenic mimicry. In our study, we demonstrated that the presence of astrocytes promoted vasculogenic mimicry. With suspension microarray technology and in vitro tube formation assays, we identified that astrocytes relied on TGF-β1 to enhance vasculogenic mimicry. We also found that vasculogenic mimicry was inhibited by galunisertib, a promising TGF-β1 inhibitor currently being studied in an ongoing trial in glioma patients. The inhibition was partially attributed to a decrease in autophagy after galunisertib treatment. Moreover, we observed a decrease in VE-cadherin and smooth muscle actin-α expression, as well as down-regulation of Akt and Flk phosphorylation in galunisertib-treated glioma cells. By comparing tumor weight and volume in a xenograft model, we acquired promising results to support our theory. This study expands our understanding of the role of astrocytes in gliomas and demonstrates that galunisertib inhibits glioma vasculogenic mimicry induced by astrocytes. PMID:26976322

  18. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

    International Nuclear Information System (INIS)

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases

  19. Role of MicroRNAs in Malignant Glioma

    Institute of Scientific and Technical Information of China (English)

    Bao-Cheng Wang; Jie Ma

    2015-01-01

    Objective:This overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.Data Sources:Using the keyword terms "glioma" and "miRNA," we performed the literature search in PubMed,Ovid,and web.metstr.com databases from their inception to October 2014.Study Selection:In screening out the quality of the articles,factors such as clinical setting of the study,the size of clinical samples were taken into consideration.Animal studied for verification and reviews article were also included in our data collection.Results:Despite many advance in miRNA for malignant glioma,further studies were still required to focus on the following aspects:(i) Improving the understanding about biogenesis of miRNA and up-down regulation;(ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma;(iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.Conclusions:We discussed the most promising miRNA,correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.

  20. Ion channel gene expression predicts survival in glioma patients.

    Science.gov (United States)

    Wang, Rong; Gurguis, Christopher I; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

    2015-08-03

    Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.

  1. EXPRESSION AND SWITCHING OF TH 1/TH2 TYPE CYTOKINES GENE IN HUMAN GLIOMAS

    Institute of Scientific and Technical Information of China (English)

    Yong-sheng Hu; Xin-gang Li; Qing-lin Zhang; Dong-hai Wang; Song-feng Gong

    2005-01-01

    Objective To study the expression and switching of Th1/Th2 cytokines gene in hman gliomas and its effects on occurring and developing of human gliomas.Methods Interleukin(IL)-2 and intefferon-γ represent Th1 type cytokines. IL-4, IL-6, IL-10, and IL-13 represent Th2 type cytokines. The gene expressions of Th1/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes,and glioma cell lines were detected by reverse transcription polymerase chain reaction (RT-PCR). The biological activity of cytokines in the supematant of glioma cell lines was assayed by enzyme-linked immunosorbent assay (ELISA)method.Results The total positive rates of Th1 and Th2 type cytokines gene in human glioma cells were 14.77% and 75%. The total positive rates of Thl and Th2 type cytokines gene in glioma infiltrating lymphocytes were 22.73% and 68.17%. There was obviously predominant expression of Th2 type cytokines in human glioma tissues, glioma infiltrating lymphocytes, and glioma cell lines. There was no unbalanced expression of Th1/Th2 cytokines in normal brain tissues.Conclusion There is a predominant expression of Th2 type cytokines in human glioma cells. The switching of Th1/Th2 cytokines gene may play an important role in the occurring and developing of human gliomas.

  2. Microglia in close vicinity of glioma cells: correlation between phenotype and metabolic alterations.

    Directory of Open Access Journals (Sweden)

    Pierre Voisin

    2010-10-01

    Full Text Available Microglia are immune cells within the central nervous system. In brain-developing tumors, gliomas are able to silence the defense and immune functions of microglia, a phenomenon which strongly contributes to tumor progression and treatment resistance. Being activated and highly motile, microglia infiltrate tumors and secrete macrophagic chemoattractant factors. Thereafter, tumor cells shut down their immune properties and stimulate the microglia to release tumor growth-promoting factors. The result of such modulation is that a kind of symbiosis occurs between microglia and tumor cells, in favor of tumor growth.However, little is known about microglial phenotype and metabolic modifications in a tumoral environment. Co-cultures were performed using CHME5 microglia cells grown on collagen beads or on coverslips and placed on monolayer of C6 cells, limiting cell/cell contacts. Phagocytic behavior and expression of macrophagic and cytoskeleton markers were monitored. Respiratory properties and energetic metabolism were also studied with regard to the activated phenotype of microglia. In co-cultures, transitory modifications of microglial morphology and metabolism were observed linked to a concomitant transitory increase of phagocytic properties. Therefore, after 1h of co-culture, microglia were activated but when longer in contact with tumor cells, phagocytic properties appear silenced. Like the behavior of the phenotype, microglial respiration showed a transitory readjustment although the mitochondria maintained their perinuclear relocation. Nevertheless, the energetic metabolism of the microglia was altered, suggesting a new energetic steady state. The results clearly indicate that like the depressed immune properties, the macrophagic and metabolic status of the microglia is quickly driven by the glioma environment, despite short initial phagocytic activation. Such findings question the possible contribution of diffusible tumor factors to the

  3. Water-soluble L-cysteine-coated FePt nanoparticles as dual MRI/CT imaging contrast agent for glioma.

    Science.gov (United States)

    Liang, Shuyan; Zhou, Qing; Wang, Min; Zhu, Yanhong; Wu, Qingzhi; Yang, Xiangliang

    2015-01-01

    Nanoparticles (NPs) are advantageous for the delivery of diagnosis agents to brain tumors. In this study, we attempted to develop an L-cysteine coated FePt (FePt-Cys) NP as MRI/CT imaging contrast agent for the diagnosis of malignant gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was characterized by transmission electron microscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251) as the model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was evaluated using three different cell lines (ECV304, L929, and HEK293) as the model. The results showed that FePt-Cys NPs displayed excellent biocompatibility and good MRI/CT imaging ability, thereby indicating promising potential as a dual MRI/CT contrast agent for the diagnosis of brain malignant gliomas.

  4. Radiosensitization of human glioma cells in vitro and in vivo with acyclovir and mutant HSV-TK75 expressed from adenovirus

    International Nuclear Information System (INIS)

    Purpose: We recently reported that an adenovirus-expressing mutant HSV-TK75 (AdCMV-TK75) radiosensitized rat syngeneic gliomas in combination with low concentrations of acyclovir (ACV) much more effectively than a virus expressing wild-type herpes simplex virus thymidine kinase (HSV-TK). In this report we have examined whether similar radiosensitizing effects are also seen with human glioma cells in vitro and in vivo. Methods and Materials: Human U87 MG glioma cells were transduced with AdCMV-TK75 and exposed to ACV followed by single-dose irradiation and colony-forming survival assays. Similarly, U87 MG xenografts were infused with AdCMV-TK75 or Adβgal control virus, followed by ACV administration and fractionated irradiation. Therapeutic efficacy was monitored by tumor growth. Results: U87 MG cells transduced with AdCMV-TK75 were significantly more sensitive to ACV (3 μM) than cells transduced with either wild-type HSV-TK or control virus. To determine whether human cells also demonstrate improved radiosensitization similar to that seen with rat glioma cells and tumors, we transduced U87 MG cells with either AdCMV-TK75, AdCMV-TK, expressing wild-type HSV-TK, or Adβgal and then treated the cells with 3 μM of ACV. Cells transduced with AdCMV-TK75 were significantly more radiosensitive (dose enhancement ratio [D37]: 2.6) by colony-forming survival assay than cells transduced with either AdCMV-TK or Adβgal. Furthermore, we found that U87 MG xenografts infused with AdCMV-TK75 by slow positive pressure infusion were more radiosensitive after administration of ACV than tumors infused with Adβgal. A more dramatic result was achieved when fractionated irradiation was carried out concurrently with ACV administration, in which case AdCMV-TK75-treated tumors did not grow at all. Conclusions: These results demonstrate that transduction of human glioma cells in vitro and infusion of xenografts in vivo with AdCMV-TK75 and treatment with concentrations of ACV that can be

  5. Intraoperative radiation therapy for malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Noboru; Yamada, Hiromu; Andoh, Takashi; Takada, Mitsuaki; Hirata, Toshifumi; Funakoshi, Takashi; Doi, Hidetaka; Yanagawa, Shigeo (Gifu Univ. (Japan). Faculty of Medicine)

    1989-04-01

    Intraoperative radiation therapy (IOR) is an ideal means of exterminating residual tumor after surgical resection. In this study, the clinical results of IOR using a Scanditronix Microtron MM-22 were evaluated in 14 patients with malignant glioma, five of whom had recurrent tumors. Between July, 1985 and October, 1986, 11 patients with glioblastoma multiforme (GB) were irradiated 18 times (mean, 1.6 times/case), and three with astrocytoma (Kernohan grade III) underwent IOR once each. The target-absorbed dose at 1 to 2 cm deeper than the tumor resection surface was 15 to 50 Gy. During irradiation, a cotton bolus was placed in the dead space after over 91% of the tumor had been resected. As a rule, external irradiation therapy was also given postoperatively at a dose of 30 to 52 Gy. One patient died of pneumonia and disseminated intravascular coagulation syndrome 1 month postoperatively. The 1- and 2-year survival rates of the ramaining 13 patients were 84.6% and 61.5%, respectively; among the 10 with GB, they were 80% and 50%. Generally, the smaller the tumor size, the better the results. There were no adverse effects, despite the dose 15 to 50 Gy applied temporally to the tumor bed. IOR was especially effective against small, localized tumors, but was not always beneficial in cases of large tumors, particularly those with a contralateral focus. The improved survival rate in this series demonstrates that IOR is significantly effective in the 'induction of remission' following surgical excision of malignant gliomas. (author).

  6. First-Principles Prediction of High-Pressure Phase of CaC6

    Institute of Scientific and Technical Information of China (English)

    LI Yan; ZHANG Li-Jun; GUI Tian; LIU Yan-Hui; MA Yan-Ming; ZOU Guang-Tian

    2007-01-01

    The lattice dynamics of rhombohedral CaCe is studied as a function of pressure to probe its high pressure phase with low superconducting transition temperature using the density functional liner-response theory. The pressure-induced phase transition in CaC6 is attributable to the softening transverse acoustic (TA) phonon mode at the zone boundary X (0.5, 0.0, 0.5) point. The high pressure phase is then explored by performing fully structural optimization in the supercell which accommodates the atomic displacements corresponding to the eigenvectors of the unstable mode of TA(X). The high-pressure phase is predicted to be a monoclinic unit cell with space group P21/m.

  7. Unilateral hyperplasia of the left posterior arch and associated vertebral schisis at C6 level

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Giuseppe; Bonis, Pasquale de; Tamburrini, Gianpiero; Massimi, Luca; Rocco, Concezio di [Catholic University, School of Medicine, Department of Pediatric Neurosurgery, Rome (Italy); Byvaltsev, Vadim [Irkutsk Railway Clinical Hospital, Department of Neurosurgery, Irkutsk (Russian Federation); Leone, Antonio [Catholic University, School of Medicine, Department of Bioimaging and Radiological Sciences, Rome (Italy)

    2009-12-15

    We report on a 5-year-old girl with unilateral hyperplasia of the left posterior arch of C6 associated with spina bifida occulta at the same level. Anteroposterior and lateral radiographs of the cervical spine showed hypertrophy of the left lamina as well as overgrowth and elongation of the left spinous process of the sixth cervical vertebra. Computed tomography (CT) examination better depicted this congenital variant and clearly showed the associated schisis of the posterior arch at the same level. Magnetic resonance (MR) imaging examination ruled out other spinal anomalies. The neck pain, the young age of the patient and the local aesthetic abnormality contributed to the surgical indication. To the best of our knowledge, this is the first case in the English literature of unilateral hyperplasia of a posterior cervical arch. Only one previous study has reported a similar congenital anomaly, but it was limited to the left side of the spinous process. (orig.)

  8. Development of C6+ laser ion source and RFQ linac for carbon ion radiotherapy

    Science.gov (United States)

    Sako, T.; Yamaguchi, A.; Sato, K.; Goto, A.; Iwai, T.; Nayuki, T.; Nemoto, K.; Kayama, T.; Takeuchi, T.

    2016-02-01

    A prototype C6+ injector using a laser ion source has been developed for a compact synchrotron dedicated to carbon ion radiotherapy. The injector consists of a laser ion source and a 4-vane radio-frequency quadrupole (RFQ) linac. Ion beams are extracted from plasma and directly injected into the RFQ. A solenoid guides the low-energy beams into the RFQ. The RFQ is designed to accelerate high-intensity pulsed beams. A structure of monolithic vanes and cavities is adopted to reduce its power consumption. In beam acceleration tests, a solenoidal magnetic field set between the laser ion source and the RFQ helped increase both the peak currents before and after the RFQ by a factor of 4.

  9. Unilateral hyperplasia of the left posterior arch and associated vertebral schisis at C6 level

    International Nuclear Information System (INIS)

    We report on a 5-year-old girl with unilateral hyperplasia of the left posterior arch of C6 associated with spina bifida occulta at the same level. Anteroposterior and lateral radiographs of the cervical spine showed hypertrophy of the left lamina as well as overgrowth and elongation of the left spinous process of the sixth cervical vertebra. Computed tomography (CT) examination better depicted this congenital variant and clearly showed the associated schisis of the posterior arch at the same level. Magnetic resonance (MR) imaging examination ruled out other spinal anomalies. The neck pain, the young age of the patient and the local aesthetic abnormality contributed to the surgical indication. To the best of our knowledge, this is the first case in the English literature of unilateral hyperplasia of a posterior cervical arch. Only one previous study has reported a similar congenital anomaly, but it was limited to the left side of the spinous process. (orig.)

  10. Comparing MODIS C6 'Deep Blue' and 'Dark Target' Aerosol Data

    Science.gov (United States)

    Hsu, N. C.; Sayer, A. M.; Bettenhausen, C.; Lee, J.; Levy, R. C.; Mattoo, S.; Munchak, L. A.; Kleidman, R.

    2014-01-01

    The MODIS Collection 6 Atmospheres product suite includes refined versions of both 'Deep Blue' (DB) and 'Dark Target' (DT) aerosol algorithms, with the DB dataset now expanded to include coverage over vegetated land surfaces. This means that, over much of the global land surface, users will have both DB and DT data to choose from. A 'merged' dataset is also provided, primarily for visualization purposes, which takes retrievals from either or both algorithms based on regional and seasonal climatologies of normalized difference vegetation index (NDVI). This poster present some comparisons of these two C6 aerosol algorithms, focusing on AOD at 550 nm derived from MODIS Aqua measurements, with each other and with Aerosol Robotic Network (AERONET) data, with the intent to facilitate user decisions about the suitability of the two datasets for their desired applications.

  11. Fully differential cross sections for C6+single ionization of helium

    Institute of Scientific and Technical Information of China (English)

    Li Xia; Ma Xiao-Yan; Sun Shi-Yan; Jia Xiang-Fu

    2012-01-01

    The three-Coulomb-wave (3C) model is applied to study the single ionization of helium by 2 MeV/amu C6+impact.Fully differential cross sections (FDCS) are calculated in the scattering plane and the results are compared with experimental data and other theoretical predictions.It is shown that the 3C results of the recoil peak are in very good agreement with experimental observations,and variation of the position of the binary peak with increasing momentum transfer also conforms better to the experimental results.Furthermore,the contributions of different scattering amplitudes are discussed.It turns out that the cross sections are strongly influenced by the interference of these amplitudes.

  12. Study on Aromatization of C6 Aliphatic Hydrocarbons on ZRP Zeolite Catalyst

    Institute of Scientific and Technical Information of China (English)

    Wang Yongjun; Xie Chaogang

    2004-01-01

    The performance of ZRP zeolite catalysts for aromatization of C6 aliphatic hydrocarbons was investigated in a pulsed microreactor. The influence of metal modified ZRP zeolites on aromatization reaction was also studied, coupled with comparison of aromatization tendencies of olefins, paraffins and paraffins with different degrees of chain branching. Test results had shown that the lower the silicon/aluminum ratio in the ZRP zeolite, the higher the aromatization reactivity of aliphatic hydrocarbons. Modification of ZRP zeolite by zinc and its zinc content had apparent impact on the yield and distribution of aromatics. The aromatization tendency of olefins was apparently better than paraffins, while the aromatization tendency of monomethyl paraffins was better than that of straight-chain paraffins with the exception of dimethyl paraffins, which had worse aromatization tendency because of their steric hindrance.

  13. Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate.

    Science.gov (United States)

    Chuang, Wei-Lien; Pacheco, Joshua; Cooper, Samantha; Kingsbury, Jonathan S; Hinds, John; Wolf, Pavlina; Oliva, Petra; Keutzer, Joan; Cox, Gerald F; Zhang, Kate

    2015-06-01

    Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann-Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann-Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the sodium taurocholate detergent concentration in the assay buffer lowered the activity levels of these two patients into the range observed with other patients with clear separation from normal controls. PMID:26937397

  14. Ne matrix spectra of the sym-C6Br3F3+ radical cation

    Science.gov (United States)

    Bondybey, V.E.; Sears, T.J.; Miller, T.A.; Vaughn, C.; English, J.H.; Shiley, R.S.

    1981-01-01

    The electronic absorption and laser excited, wavelength resolved fluorescence spectra of the title cation have been observed in solid Ne matrix and vibrationally analysed. The vibrational structure of the excited B2A2??? state shows close similarity to the parent compound. The X2E??? ground state structure is strongly perturbed and irregular owing to a large Jahn-Teller distortion. The data are analysed in terms of a recently developed, sophisticated multimode Jahn-Teller theoretical model. We have generated the sym-C6Br3F3+ cations in solid Ne matrix and obtained their wavelength resolved emission and absorption spectra. T ground electronic X2E??? state exhibits an irregular and strongly perturbed vibrational structure, which can be successfully modeled using sophisticated multimode Jahn-Teller theory. ?? 1981.

  15. Identificación de regiones isofuncionales en el citocromo c6 y en la plastocianina

    OpenAIRE

    Molina Heredia, Fernando Publio

    2001-01-01

    Una de las líneas de investigación mas intereses de la bioquímica contemporánea es el estudio de la relación entre la estructura y la función de las macromoléculas biológicas, o reconocimiento molecular. Como sistema objeto de este estudio, se ha escogido el citocromo c6(Cit) y la plastocianina (Pc), dos proteínas con estructuras diferentes pero con idéntica función, cual es transportar electrones entre los complejos de membrana citocromo b6-f y fotosistema I(PSI). La conexión entre ambos ...

  16. Cellular senescence induced by prolonged subculture adversely affects glutamate uptake in C6 lineage.

    Science.gov (United States)

    Pereira, Mery Stéfani Leivas; Zenki, Kamila; Cavalheiro, Marcela Mendonça; Thomé, Chairini Cássia; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido; de Souza, Diogo Onofre Gomes; de Oliveira, Diogo Losch

    2014-05-01

    Several researchers have recently used C6 cells to evaluate functional properties of high-affinity glutamate transporters. However, it has been demonstrated that this lineage suffers several morphological and biochemical alterations according to the number of passages in culture. Currently, there are no reports showing whether functional properties of high-affinity glutamate transporters comply with these sub culturing-dependent modifications. The present study aimed to compare the functional properties of high-affinity glutamate transporters expressed in early (EPC6) and late (LPC6) passage C6 cells through a detailed pharmacological and biochemical characterization. Between 60-180 min of L-[(3)H]glu incubation, LPC6 presented an intracellular [(3)H] 55% lower than EPC6. Both cultures showed a time-dependent increase of intracellular [(3)H] reaching maximal levels at 120 min. Cultures incubated with D-[(3)H]asp showed a time-dependent increase of [(3)H] until 180 min. Moreover, LPC6 have a D-[(3)H]asp-derived intracellular [(3)H] 30-45% lower than EPC6 until 120 min. Only EAAT3 was immunodetected in cultures and its total content was equal between them. PMA-stimulated EAAT3 trafficking to membrane increased 50% of L-[(3)H]glu-derived intracellular [(3)H] in EPC6 and had no effect in LPC6. LPC6 displayed characteristics that resemble senescence, such as high β-Gal staining, cell enlargement and increase of large and regular nuclei. Our results demonstrated that LPC6 exhibited glutamate uptake impairment, which may have occurred due to its inability to mobilize EAAT3 to cell membrane. This profile might be related to senescent process observed in this culture. Our results suggest that LPC6 cells are an inappropriate glial cellular model to investigate the functional properties of high-affinity glutamate transporters.

  17. DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

  18. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    Science.gov (United States)

    2015-12-14

    Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

  19. In vivo single voxel H MR spectroscopy in cerebral glioma

    International Nuclear Information System (INIS)

    To assess the metabolite ratios in gliomas to determine whether the metabolic information obtained by using in vivo single voxel 1H magnetic resonance spectroscopy (MRS) can be used as a marker for the grading of malignancy. A total of 28 1H MR spectra from brain tumors in 27 patients with pathologically-proven gliomas were recorded. Seven patients had low grade gliomas (grade II astrocytoma in three, oligodendroglioma in three and mixed glioma in one), six had anaplastic gliomas (grade III astrocytoma in three and oligodendroglioma n three), and 14 had glioblastoma multiformes (grade IV). 1H MRS was performed on a 1.5T MR unit using PRESS sequence with a TR of 2000ms, a TE of 270 or 135ms and a voxel size of cm for all spectra. Relative lactate levels, NAA/Cho, NAA/ Cr and Cho/Cr ratios were measured based on the peak heights of each resonance and compared among gliomas. Most tumors demonstrated decreased NAA, elevated Cho and lactate. Relatively high lactate and Cho levels and markedly decreased NAA level were more frequently observed in the high grade gliomas than in low grade gliomas. Marked elevation of lactated level in the solid component of the tumor was mostly observed in high grade gliomas. In a patient with gliomatosis cerebri, 1H MRS demonstrated a spectral pattern of tumor infiltration in an area that on MR images was apparently normal. However, NAA/Cr, NAA/Cho and Cho/Cr ratios did not significantly correlate, however, with the histologic grading of malignancy. Because of the partial volume effect, the heterogeneity of tumors containing solid and cystic or necrotic components within a voxel limited the interpretation of 1H MRS data for the grading of malignancy. The results suggest that in some patients in vivo single voxel 1H MRS may be useful for grading the malignancy of gilomas and evaluating the exact extent of tumors. In solid gliomas, the relative level of lactate appears to be a good marker for the grading of malignancy

  20. Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy

    DEFF Research Database (Denmark)

    Khan, Z.; Knecht, Wolfgang; Willer, Mette;

    2010-01-01

    The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen...... phosphorylates its substrate AZT not only to AZT monophosphate, but also to AZT diphosphate, with excellent kinetics. The efficiency of the toTK1/AZT system was confirmed when toTK1-transduced human glioblastoma (GBM) cells displayed a 500-fold increased sensitivity to AZT compared with wild-type cells....... In addition, when neural progenitor cells were used as delivery vectors for toTK1 in intracranial GBM xenografts in nude rats, substantial attenuation of tumor growth was achieved in animals exposed to AZT, and survival of the animals was significantly improved compared with controls. The novel toTK1/AZT...

  1. Irreversible blockade of the high and low affinity (3H) naloxone binding sites by C-6 derivatives of morphinane-6-ones

    International Nuclear Information System (INIS)

    C-6 derivatives-hydrazones, phenylhydrazones, dinitrophenylhydrazones, oximes and semicarbazones - of morphinane-6-ones were synthesized and their binding characteristics were studied on rat brain membranes. The dihydromorphinone and oxymorphone derivatives compete for the (3H)naloxone binding sites with high affinity, while the dihydrocodeinone and oxycodone derivatives are less potent. The affinity of the new compounds is decreased for the delta sites as compared to the parent ligands. The ligands bearing bulky substituents also bind with low affinity to the kappa sites. The modification decreased the Na+-index of compounds indicating their mixed agonist-antagonist character. The dihydromorphinone derivatives are all capable to block irreversibly the high affinity binding site of (3H)naloxone, whereas the dihydrocodeinone derivatives block irreversibly the low affinity site. A possible mechanism for the inhibition is suggested

  2. Irreversible blockade of the high and low affinity ( sup 3 H) naloxone binding sites by C-6 derivatives of morphinane-6-ones

    Energy Technology Data Exchange (ETDEWEB)

    Krizsan, D. (EGIS Pharmaceutical Works, Budapest (Hungary)); Varga, E.; Benyhe, S.; Szucs, M.; Borsodi, A. (Biological Research Center of the Hungarian Academy of Sciences, Szeged (Hungary)); Hosztafi, S. (Alkaloida Chemical Works, Tiszavasvari (Hungary))

    1991-01-01

    C-6 derivatives-hydrazones, phenylhydrazones, dinitrophenylhydrazones, oximes and semicarbazones - of morphinane-6-ones were synthesized and their binding characteristics were studied on rat brain membranes. The dihydromorphinone and oxymorphone derivatives compete for the ({sup 3}H)naloxone binding sites with high affinity, while the dihydrocodeinone and oxycodone derivatives are less potent. The affinity of the new compounds is decreased for the delta sites as compared to the parent ligands. The ligands bearing bulky substituents also bind with low affinity to the kappa sites. The modification decreased the Na{sup +}-index of compounds indicating their mixed agonist-antagonist character. The dihydromorphinone derivatives are all capable to block irreversibly the high affinity binding site of ({sup 3}H)naloxone, whereas the dihydrocodeinone derivatives block irreversibly the low affinity site. A possible mechanism for the inhibition is suggested.

  3. The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

    Directory of Open Access Journals (Sweden)

    Abdi Khosro

    2008-11-01

    Full Text Available Abstract Background Experimental studies indicate that gamma linolenic acid (GLA and docosahexaenoic acid (DHA may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo. Methods GLA oil (GLAO; 72% GLA, DHA oil (DHAO; 73% DHA were fed to adult wistar rats (1 mL/rat/day starting one week prior to C6 glioma cells implantation and continued for two weeks after implantation. Control group were fed same amount of high linoleic acid safflower oil (74–77% linoleic acid. Fatty acid composition of tumor samples was determined in a set of 8–12 animals in each group and serum fatty acid in 6 animals per each group. Gene expression of tumor fatty acid binding protein 7 (FABP7, epidermal growth factor receptor (EGFR, peroxisome proliferator activated receptor γ (PPAR-γ and retinoid × receptor-α (RXR-α were determined in a set of 18 animals per group. Results DHAO feeding increased EPA of brain tumors and decreased ratio of n-6/n-3 fatty acids. Serum levels of EPA were also increased in DHAO group. A similar trend in serum and tumor levels of DHA were observed in DHAO group but it did not achieve statistical significance. GLAO increased serum concentration of GLA but had no significant effect on tumor GLA or dihomo-gamma linolenic acid (DGLA concentrations. Gene expression of FABP7 was up-regulated in tumors of DHAO group but no other significant effects were observed on EGFR, PPAR-γ or RXR-α expression, and expression of these genes in tumors of GLAO were not different from SFO group. Conclusion Dietary supplementation of DHA containing oil could be an effective way to increase levels of long chain n-3 fatty acids in brain tumors and this increase may be mediated partly by up-regulation of FABP7 expression.

  4. Human ClC-6 is a late endosomal glycoprotein that associates with detergent-resistant lipid domains.

    Directory of Open Access Journals (Sweden)

    Sofie Ignoul

    Full Text Available BACKGROUND: The mammalian CLC protein family comprises nine members (ClC-1 to -7 and ClC-Ka, -Kb that function either as plasma membrane chloride channels or as intracellular chloride/proton antiporters, and that sustain a broad spectrum of cellular processes, such as membrane excitability, transepithelial transport, endocytosis and lysosomal degradation. In this study we focus on human ClC-6, which is structurally most related to the late endosomal/lysomal ClC-7. PRINCIPAL FINDINGS: Using a polyclonal affinity-purified antibody directed against a unique epitope in the ClC-6 COOH-terminal tail, we show that human ClC-6, when transfected in COS-1 cells, is N-glycosylated in a region that is evolutionary poorly conserved between mammalian CLC proteins and that is located between the predicted helices K and M. Three asparagine residues (N410, N422 and N432 have been defined by mutagenesis as acceptor sites for N-glycosylation, but only two of the three sites seem to be simultaneously N-glycosylated. In a differentiated human neuroblastoma cell line (SH-SY5Y, endogenous ClC-6 colocalizes with LAMP-1, a late endosomal/lysosomal marker, but not with early/recycling endosomal markers such as EEA-1 and transferrin receptor. In contrast, when transiently expressed in COS-1 or HeLa cells, human ClC-6 mainly overlaps with markers for early/recycling endosomes (transferrin receptor, EEA-1, Rab5, Rab4 and not with late endosomal/lysosomal markers (LAMP-1, Rab7. Analogously, overexpression of human ClC-6 in SH-SY5Y cells also leads to an early/recycling endosomal localization of the exogenously expressed ClC-6 protein. Finally, in transiently transfected COS-1 cells, ClC-6 copurifies with detergent-resistant membrane fractions, suggesting its partitioning in lipid rafts. Mutating a juxtamembrane string of basic amino acids (amino acids 71-75: KKGRR disturbs the association with detergent-resistant membrane fractions and also affects the segregation of ClC-6

  5. Treating malignant glioma in Chinese patients: update on temozolomide

    Directory of Open Access Journals (Sweden)

    Chang L

    2014-02-01

    Full Text Available Liang Chang,1 Jun Su,1 Xiuzhi Jia,2,3 Huan Ren2,3 1Department of Neurosurgery, The Tumor Hospital of Harbin Medical University, 2Department of Immunology, Harbin Medical University, 3Key Lab Infection and Immunity, Heilongjiang Province, Harbin, People's Republic of China Abstract: Malignant glioma, ie, anaplastic astrocytoma and glioblastoma, is the most common type of primary malignant brain tumor in the People's Republic of China, and is particularly aggressive. The median survival of patients with newly diagnosed glioblastoma is only 12–14 months despite advanced therapeutic strategies. Treatment of malignant glioma consists mainly of surgical resection followed by adjuvant radiation and chemotherapy. Temozolomide (TMZ, a second-generation oral alkylating agent, is playing an increasingly important role in the treatment of malignant glioma in Chinese patients. Since the publication of a study by Stupp et al in 2005, which used a protocol of conventional fractionated irradiation with concomitant TMZ followed by standard TMZ for six cycles, many clinical studies in the People's Republic of China have demonstrated that such a treatment strategy has significantly improved efficacy with limited side effects for newly diagnosed glioblastoma after surgery as compared with strategies that do not contain TMZ. However, as a relatively new agent, the history and development of TMZ for malignant glioma is not well documented in Chinese patients. Multicenter, randomized controlled trials including appropriately sized patient populations investigating multiple aspects of TMZ therapy and related combination therapies are warranted in patients with malignant glioma. This review provides an update on the efficacy, mechanism of action, adverse reactions, and clinical role of TMZ in the treatment of malignant glioma in Chinese patients. Keywords: malignant glioma, chemotherapy, temozolomide, efficacy, side effect, People's Republic of China

  6. IDH1 mutation detection by droplet digital PCR in glioma.

    Science.gov (United States)

    Wang, Jing; Zhao, Yi-ying; Li, Jian-feng; Guo, Cheng-cheng; Chen, Fu-rong; Su, Hong-kai; Zhao, Hua-fu; Long, Ya-kang; Shao, Jian-yong; To, Shing shun Tony; Chen, Zhong-ping

    2015-11-24

    Glioma is the most frequent central nervous system tumor in adults. The overall survival of glioma patients is disappointing, mostly due to the poor prognosis of glioblastoma (Grade IV glioma). Isocitrate dehydrogenase (IDH) is a key factor in metabolism and catalyzes the oxidative decarboxylation of isocitrate. Mutations in IDH genes are observed in over 70% of low-grade gliomas and some cases of glioblastoma. As the most frequent mutation, IDH1(R132H) has been served as a predictive marker of glioma patients. The recently developed droplet digital PCR (ddPCR) technique generates a large amount of nanoliter-sized droplets, each of which carries out a PCR reaction on one template. Therefore, ddPCR provides high precision and absolute quantification of the nucleic acid target, with wide applications for both research and clinical diagnosis. In the current study, we collected 62 glioma tissue samples (Grade II to IV) and detected IDH1 mutations by Sanger direct sequencing, ddPCR, and quantitative real-time PCR (qRT-PCR). With the results from Sanger direct sequencing as the standard, the characteristics of ddPCR were compared with qRT-PCR. The data indicated that ddPCR was much more sensitive and much easier to interpret than qRT-PCR. Thus, we demonstrated that ddPCR is a reliable and sensitive method for screening the IDH mutation. Therefore, ddPCR is able to applied clinically in predicting patient prognosis and selecting effective therapeutic strategies. Our data also supported that the prognosis of Grade II and III glioma was better in patients with an IDH mutation than in those without mutation.

  7. Description of selected characteristics of familial glioma patients – Results from the Gliogene Consortium

    DEFF Research Database (Denmark)

    Sadetzki, Siegal; Bruchim, Revital; Oberman, Bernice;

    2013-01-01

    While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained...

  8. Invasion of primary glioma- and cell line-derived spheroids implanted into corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Nørregaard, Annette; Christensen, Karina;

    2013-01-01

    Gliomas are highly invasive tumors and the pronounced invasive features of gliomas prevent radical surgical resection. In the search for new therapeutics targeting invasive glioma cells, in vivo-like in vitro models are of great interest. We developed and evaluated an in vivo-like in vitro model ...

  9. [18F]-fluoro-l-thymidine PET and advanced MRI for preoperative grading of gliomas

    Directory of Open Access Journals (Sweden)

    S. Collet

    2015-01-01

    Conclusion: Whereas advanced MRI parameters give indications for the grading of gliomas, the addition of [18F]-FLT-PET could be of interest for the accurate preoperative classification of diffuse gliomas, particularly for identification of doubtful grade III and IV gliomas.

  10. Synthesis of two pentaarylated [ 60 ]fullerene derivatives Ar5C60-H (Ar = p-MeC6H4, m-MeC6H4) and their novel electrochemical properties

    Institute of Scientific and Technical Information of China (English)

    SONG, Li-Cheng(宋礼成); LIU, Peng-Chong(刘鹏蹟); HU, Qing-Mei(胡青眉); ZANELLO, Piero; FONTANI, Marco

    2000-01-01

    Through one pot reaction of C60 with organocopper/magnesium reagent ( p -MeC6 H4 )2 CuMgBr or ( m- MeC6 H4 )2-CuMgBr prepared from CuBr· Me2S and p-MeC6H4MgBr or m-MeC6H4MgBr and subsequent quenching with aqueous NHeCl, two pentaarylated [60] fullerene derivatives (p-MeC6H4)5C60H (1) and (m-MeC6H4)5C60H (2) have been synthesized in 94% and 96% yields, respectively. While known compound 1 prepared via this improved method is unambiguously identified, new compound 2 is fully characterized by elemental analysis, IR, UV-vis, 1H NMR and 13C NMR spectroscopies. Additionally, electrochemical study shows that the two [60] fullerene derivatives 1 and 2 in dichloromethane solution display two sequential one-electron reductions which are shifted by about 0.4 V towards more negative potential values with respect to free C60. Such remarkable cathodic shift is attributed to the multiple breakage of the double-bond conjugation within the fullerene core.

  11. Water-soluble l-cysteine-coated FePt nanoparticles as dual MRI/CT imaging contrast agent for glioma

    Directory of Open Access Journals (Sweden)

    Liang SY

    2015-03-01

    Full Text Available Shuyan Liang,1 Qing Zhou,1 Min Wang,2,3 Yanhong Zhu,1 Qingzhi Wu,2,3 Xiangliang Yang1 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, People’s Republic of China; 3Biomedical Material and Engineering Center of Hubei Province, Wuhan University of Technology, Wuhan, People’s Republic of China Abstract: Nanoparticles (NPs are advantageous for the delivery of diagnosis agents to brain tumors. In this study, we attempted to develop an l-cysteine coated FePt (FePt-Cys NP as MRI/CT imaging contrast agent for the diagnosis of malignant gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was characterized by transmission electron microscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251 as the model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was evaluated using three different cell lines (ECV304, L929, and HEK293 as the model. The results showed that FePt-Cys NPs displayed excellent biocompatibility and good MRI/CT imaging ability, thereby indicating promising potential as a dual MRI/CT contrast agent for the diagnosis of brain malignant gliomas. Keywords: CT, glioma, MRI

  12. Topoisomerase I inhibitors, shikonin and topotecan, inhibit growth and induce apoptosis of glioma cells and glioma stem cells.

    Directory of Open Access Journals (Sweden)

    Feng-Lei Zhang

    Full Text Available Gliomas, the most malignant form of brain tumors, contain a small subpopulation of glioma stem cells (GSCs that are implicated in therapeutic resistance and tumor recurrence. Topoisomerase I inhibitors, shikonin and topotecan, play a crucial role in anti-cancer therapies. After isolated and identified the GSCs from glioma cells successfully, U251, U87, GSCs-U251 and GSCs-U87 cells were administrated with various concentrations of shikonin or topotecan at different time points to seek for the optimal administration concentration and time point. The cell viability, cell cycle and apoptosis were detected using cell counting kit-8 and flow cytometer to observe the inhibitory effects on glioma cells and GSCs. We demonstrated that shikonin and topotecan obviously inhibited proliferation of not only human glioma cells but also GSCs in a dose- and time-dependent manner. According to the IC50 values at 24 h, 2 μmol/L of shikonin and 3 μmol/L of topotecan were selected as the optimal administration concentration. In addition, shikonin and topotecan induced cell cycle arrest in G0/G1 and S phases and promoted apoptosis. The down-regulation of Bcl-2 expression with the activation of caspase 9/3-dependent pathway was involved in the apoptosis process. Therefore, the above results showed that topoisomerase I inhibitors, shikonin and topotecan, inhibited growth and induced apoptosis of GSCs as well as glioma cells, which suggested that they might be the potential anticancer agents targeting gliomas to provide a novel therapeutic strategy.

  13. Facing Contrast-Enhancing Gliomas: Perfusion MRI in Grade III and Grade IV Gliomas according to Tumor Area

    Directory of Open Access Journals (Sweden)

    Anna Luisa Di Stefano

    2014-01-01

    Full Text Available Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV, calculated with Dynamic Susceptibility Contrast (DSC Perfusion-Weighted Imaging (PWI, allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV. Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp., the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78, P=0.036. In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading.

  14. Radiotherapy in supratentorial gliomas. A study of 821 cases

    Energy Technology Data Exchange (ETDEWEB)

    Heesters, M. [Dept. of Radiotherapy, Groningen Univ. Hospital (Netherlands); Molenaar, W. [Dept. of Pathology, Groningen Univ. Hospital (Netherlands); Go, G.K. [Dept. of Neurosurgery, Groningen Univ. Hospital (Netherlands)

    2003-09-01

    Purpose: Analysis of the results of radiotherapy in a large group of cerebral gliomas with identification of prognostic factors and the outcome with respect to different decades of treatment. Patients and Methods: Two decades (1979-1999) of radiotherapy in supratentorial astrocytic and oligodendroglial tumors (n = 821) at the University Hospital Groningen were retrospectively evaluated. Prognostic factors for survival were analyzed. Two decades of radiotherapy treatment were compared with respect to radiotherapy dose and treatment-field design. Results: Glioblastoma multiforme, including gliosarcoma, was the most frequent supratentorial glioma (n = 442) with a poor survival, i.e., median survival time (MST) 7 months, especially in patients > 50 years of age and with poor performance. Patients with good performance were selected for radiotherapy with an optimum dose of 60 Gy local-field irradiation. However, in patients with poor prognosis, no radiotherapy was applied or a shorter treatment scheme was given. Anaplastic astrocytomas (n = 131) were treated in the same way as glioblastoma multiforme. Over time, a decrease in radiation dose (from 60 to 45 Gy) and from whole brain irradiation to local-field treatment was observed, following the literature. In low-grade gliomas, prognostic factors for survival were age, performance, and extent of resection. Gemistocytic astrocytoma (n = 15) had an inferior survival compared to astrocytoma (MST 46 vs. 54 months), but a superior survival compared to anaplastic astrocytoma (MST 10 months). The presence of an oligodendroglial component in a glioma implied a superior survival compared to the astrocytic gliomas. The inherent biology of the glioma is reflected by the study of recurrent tumors with progression to higher grades of malignancy in 32-40% and by the histology of recurrent oligodendroglial tumors. In comparing two decades of radiotherapy in gliomas, no differences in survival were observed despite the technological

  15. Radiotherapy in supratentorial gliomas. A study of 821 cases

    International Nuclear Information System (INIS)

    Purpose: Analysis of the results of radiotherapy in a large group of cerebral gliomas with identification of prognostic factors and the outcome with respect to different decades of treatment. Patients and Methods: Two decades (1979-1999) of radiotherapy in supratentorial astrocytic and oligodendroglial tumors (n = 821) at the University Hospital Groningen were retrospectively evaluated. Prognostic factors for survival were analyzed. Two decades of radiotherapy treatment were compared with respect to radiotherapy dose and treatment-field design. Results: Glioblastoma multiforme, including gliosarcoma, was the most frequent supratentorial glioma (n = 442) with a poor survival, i.e., median survival time (MST) 7 months, especially in patients > 50 years of age and with poor performance. Patients with good performance were selected for radiotherapy with an optimum dose of 60 Gy local-field irradiation. However, in patients with poor prognosis, no radiotherapy was applied or a shorter treatment scheme was given. Anaplastic astrocytomas (n = 131) were treated in the same way as glioblastoma multiforme. Over time, a decrease in radiation dose (from 60 to 45 Gy) and from whole brain irradiation to local-field treatment was observed, following the literature. In low-grade gliomas, prognostic factors for survival were age, performance, and extent of resection. Gemistocytic astrocytoma (n = 15) had an inferior survival compared to astrocytoma (MST 46 vs. 54 months), but a superior survival compared to anaplastic astrocytoma (MST 10 months). The presence of an oligodendroglial component in a glioma implied a superior survival compared to the astrocytic gliomas. The inherent biology of the glioma is reflected by the study of recurrent tumors with progression to higher grades of malignancy in 32-40% and by the histology of recurrent oligodendroglial tumors. In comparing two decades of radiotherapy in gliomas, no differences in survival were observed despite the technological

  16. Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy

    Directory of Open Access Journals (Sweden)

    Sadhak Sengupta

    2012-01-01

    Full Text Available Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.

  17. Possible novel therapy for malignant gliomas with secretable trimeric TRAIL.

    Directory of Open Access Journals (Sweden)

    Moonsup Jeong

    Full Text Available Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI. Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl-1-nitrosourea (BCNU, a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas.

  18. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    International Nuclear Information System (INIS)

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  19. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    Energy Technology Data Exchange (ETDEWEB)

    Peres, Elodie A.; Valable, Samuel [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Guillamo, Jean-Sebastien [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Departement de Neurologie, CHU de Caen (France); Marteau, Lena [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Bernaudin, Jean-Francois [Service d' Histologie-Biologie Tumorale, ER2UPMC, Universite Paris 6, Hopital Tenon, Paris (France); Roussel, Simon [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Lechapt-Zalcman, Emmanuele [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Service d' Anatomie Pathologique, CHU de Caen (France); Bernaudin, Myriam [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Petit, Edwige, E-mail: epetit@cyceron.fr [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)

    2011-10-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  20. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Science.gov (United States)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  1. Sulfonic acid heterogeneous catalysts for dehydration of C6-monosaccharides to 5-hydroxymethylfurfural in dimethyl sulfoxide

    Institute of Scientific and Technical Information of China (English)

    Gabriel Morales; Juan A.Melero; Marta Paniagua; Jose Iglesias; Blanca Hernández; María Sanz

    2014-01-01

    Sulfonic acid-functionalized heterogeneous catalysts have been evaluated in the catalytic dehydra-tion of C6 monosaccharides into 5-hydroxymethylfurfural (HMF) using dimethyl sulfoxide (DMSO) as solvent. Sulfonic commercial resin Amberlyst-70 was the most active catalyst, which was as-cribed to its higher concentration of sulfonic acid sites as compared with the other catalysts, and it gave 93 mol%yield of HMF from fructose in 1 h. With glucose as the starting material, which is a much more difficult reaction, the reaction conditions (time, temperature, and catalyst loading) were optimized for Amberlyst-70 by a response surface methodology, which gave a maximum HMF yield of 33 mol%at 147°C with 23 wt%catalyst loading based on glucose and 24 h reaction time. DMSO promotes the dehydration of glucose into anhydroglucose, which acts as a reservoir of the substrate to facilitate the production of HMF by reducing side reactions. Catalyst reuse without a regeneration treatment showed a gradual but not very significant decay in catalytic activity.

  2. Physical properties of new cerium palladium phosphide with C6Cr23-type structure

    Directory of Open Access Journals (Sweden)

    T. Abe

    2014-01-01

    Full Text Available We have found that a cerium palladium phosphide crystallizes into a C6Cr23-type structure with atomic disorder. Prepared polycrystalline samples show a homogeneity range in the ternary Ce–Pd–P phase diagram. The physical properties of the highest-quality sample of Ce2.4Pd20.7P5.9 were investigated by measuring the magnetization, electrical resistivity and specific heat. No pronounced phase transition was observed down to 0.5 K. The Kondo screening of localized 4f electrons in metallic Ce2.4Pd20.7P5.9 appears to be weaker than that in the isostructural compounds of Ce3Pd20Si6 and Ce3Pd20Ge6. By a comparative study of Ce2.4Pd20.7P5.9 and Ce3Pd20X6 (X = Si, Ge, the competition between the Kondo temperature and ordering temperatures including the quadrupolar ordering temperature is briefly discussed.

  3. Assessment of biological changes in wheat seedlings induced by 12C6+-ion irradiation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Luwei; ZHANG Hong; ZHANG Xiaofu; ZHU Jianlan

    2008-01-01

    The present study was designed to evaluate the effect of 12C6+ ion beam (10~80 Gy) on biological changes of wheat seedlings. Reactive oxygen species (ROS)-related biomarkers and the quantification of plant survival and growth were examined at 10 day after carbon ions irradiation (LET: 30.8keV/μm). The results showed that heavy ions obviously enhanced ROSs reflected by the production of O2 and H2O2 as well as TBARS, and treatment with 20 Gy achieved the peak value, suggesting that higher mutagenic potential may occur at 20 Gy. Simultaneously, increase of SOD activity was induced by heavy ions to counteract ROS accumulation. On the other hand, higher doses at 40 and 80 Gy inhibited wheat growth and survival in comparison with the control, and reversely lower doses at 10 or 20 Gy stimulated wheat growth and survival. In conclusion, the above observations imply that a dose range of 20~40 Gy is likely promised for wheat mutation breeding.

  4. Genetic analysis of benzothiophene biodesulfurization pathway of Gordonia terrae strain C-6.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available Sulfur can be removed from benzothiophene (BT by some bacteria without breaking carbon-carbon bonds. However, a clear mechanism for BT desulfurization and its genetic components have not been reported in literatures so far. In this study, we used comparative transcriptomics to study differential expression of genes in Gordonia terrae C-6 cultured with BT or sodium sulfate as the sole source of sulfur. We found that 135 genes were up-regulated with BT relative to sodium sulfate as the sole sulfur source. Many of these genes encode flavin-dependent monooxygenases, alkane sulfonate monooxygenases and desulfinase, which perform similar functions to those involved in the 4S pathway of dibenzothiophene (DBT biodesulfurization. Three of the genes were found to be located in the same operon, designated bdsABC. Cell extracts of pET28a-bdsABC transfected E. coli Rosetta (DE3 converted BT to a phenolic compound, identified as o-hydroxystyrene. These results advance our understanding of enzymes involved in the BT biodesulfurization pathway.

  5. Evaluation of radioiodinated C6-O- and N-iodoallyl analogues of diprenorphine as ligands for cerebral opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lever, J.R.; Scheffel, U.; Stathis, M. [The Johns Hopkins Medical Institutions, Baltimore, MD (United States)] [and others

    1994-05-01

    Analogues of diprenorphine (DPN) having C6-O-iodoallyl (O-IA-DPN) and N-iodoallyl (N-IA-DPN) substituents can be I-125 labeled in good yield with high specific activity by radioiododestannylation. When tested in vitro against [H-3]-DPN in rat brain membranes, the apparent affinity (Ki) of O-IA-DPN (1.35 nM) proved 17-fold stronger than that of N-IA-DPN (23.4 nM). Against selective [H-3]-ligands, O-IA-DPN showed high apparent affinities for {mu}(1.9 nM), {gamma}(1.1 nM) and {kappa}(0.9 nM) sites. Consistent with the low apparent affinity in vitro, [I-125]-N-IA- DPN did not allow localization of cerebral opioid receptors after i.v. administration to mice. By contrast, [I-125]-O-IA-DPN exhibited a regional brain distribution which reflects binding to multiple opioid receptors. The highest radioactivity concentrations were in superior colliculi, hypothalamus, olfactory tubercles, thalamus and striatum. Peak levels (2.5-3.5 %ID/g) were maintained over the first 60 min. At all times, the lowest levels of radioactivity were in the cerebellum. Binding in vivo was saturable by O-IA-DPN, was blocked by (-)- but not by (+)-naloxone, and was inhibited by naltrexone in dose-dependent fashion. Specific binding was 83-93% for all tissues except cerebellum, where 50% blockade was noted with naltrexone (5.0 mg/kg). Using naltrexone blockade to define non-specific binding, the highest ratio of specific to non-specific binding (> 14 to 1) was noted for superior colliculi at 60 min. Inhibition studies with drugs selective for {mu}, {gamma} or {kappa} sites established that multiple opioid receptors are labeled. [123I]-O-IA-DPN has been prepared (84%, >2400 mCi/{mu}mol), and allows visualization of opioid receptors in mouse brain by ex vivo autoradiography. Together, these results suggest that [123I]-O-IA-DPN is suitable for SPECT studies of multiple opioid receptors.

  6. Functional compensative mechanism of upper limb with root avulsion of C5-C6 of brachial plexus after ipsilateral C7 transfer

    Institute of Scientific and Technical Information of China (English)

    SONG Jie; CHEN Liang; GU Yu-dong

    2008-01-01

    Objective: To investigate the compensative mechanism of no further impairment of the upper limb after ipsilateral C7 transfer for treatment of root avuision of C5-C6 of the bra- chial plexus. Methods: Sixty Sprague Dawley SD rats were randomly divided into a CT-transection group and a control group, 30 rats each. In the C7-transection group, the left forelimbs of the animals underwent transection of ipsilat- eral C7 nerve root while C5 and C6 nerve roots were avulsed. In the control group, the left forelimbs only underwent C5 and C6 root avulsion. The representative muscles of C7 innervated mainly by C7 including latissimus dorsi, triceps, extensor carpi radialis brevis and extensor digitorum com- munis were evaluated with neurophysiological investigation, muscular histology and motor end plate histomorphometry 3, 6 and 12 weeks after operation. The right forelimbs of all rats were taken as the control sides. Results: Three weeks after operation, the recovery rates of amplitudes of compound muscle action potential CMAP and CMAP latency, muscular wet weight and cross-sec-tional area of muscle fibers, and area of postsynaptic membranes of those four representative muscles in the C7transection group were significantly lower than those of the control group P <0.05 or P <0.01. Six weeks postoperatively, the recovery rates of CMAP amplitude and latency of the triceps showed no significant difference between the C7transection group and the control group P0.05. For the extensor carpi radialis brevis and the extensor digitorum communis, the recovery rates of the cross-sectional area of muscle fibers, the amplitude and latency of CMAP and the area of postsynaptic membranes showed no significant difference between the two groups P 0.05, while the rest parameters were still significantly different between the two group P <0.05 or P <0.01. As far as the ultramicrostructure was concerned in the C7-transection group, more motor end plates of four representative muscles were

  7. The rise and fall of "biopsy and radiate": a history of surgical nihilism in glioma treatment.

    Science.gov (United States)

    Han, Seunggu J; Sughrue, Michael E

    2012-04-01

    Many neurosurgeons take a nihilistic approach to surgical treatment of gliomas, stating the inability to achieve a cure. Where this idea comes from is somewhat nebulous to most neurosurgeons. A review of the scientific studies supporting the commonly held beliefs about gliomas shows that these ideas regarding the surgical treatment of gliomas are based on overgeneralizations of data from older studies. One should avoid the temptation to apply them to the greater concept of what gliomas are, how they behave, and what should be done, but rather we should continue to scientifically evaluate the role of surgical resection in glioma treatment. PMID:22440864

  8. Relapse of herpes encephalitis induced by temozolomide-based chemoradiation in a patient with malignant glioma.

    Science.gov (United States)

    Okada, Masaki; Miyake, Keisuke; Shinomiya, Aya; Kawai, Nobuyuki; Tamiya, Takashi

    2013-02-01

    The authors report on a case of concurrent herpes simplex encephalitis (HSE) and malignant glioma. The co-occurrence of HSE and malignant glioma is very rare, but it can occur during glioma treatment. Both radiotherapy and chemoradiation with temozolomide can induce viral reactivation, leading to HSE relapse. Careful observation for HSE is necessary when administering chemoradiation to patients with a history of HSE. Antiviral therapy for HSE must be initiated immediately, and the chemoradiation for glioma should be stopped; however, it is not clear what antitumor therapy is optimal when HSE co-occurs during the treatment of glioma.

  9. Comparative evaluation of gadoteridol versus gadopentetate dimeglumine for contrast-enhanced MRI in a rat brain glioma model at 1.5 and 3.0 T%钆特醇及钆喷替酸葡甲胺在1.5、3.0 TMR下鼠脑胶质瘤模型增强扫描中的应用比较研究

    Institute of Scientific and Technical Information of China (English)

    艾飞; Val M Runge; John N Morelli; Lan.Vu; Jeremy Cannel; Alan T Loynachan; 漆剑频; 李小明

    2010-01-01

    计学意义(t值分别为31.503、5.137,P值均<0.05),而两者CE均值差异无统计学意义(t=2.033,P>0.05).结论 利用鼠脑胶质瘤模型,在1.5及3.0 T MR下注射钆特醇和Gd-DTPA行增强扫描,两者增强效果无明显差异;3.0 T MR下注射钆特醇行增强扫描,效果明显优于在1.5 T条件下使用;3.0 T MR下使用半剂量钆特醇与在1.5 T下使用标准剂量增强效果相仿,同样能取得满意的增强效果.因此,使用钆特醇可在保证增强效果的同时,在一定程度上降低使用MRI对比剂的风险,增加安全性.%Objective To compare gadoteridol and gadopentetate dimeglumine (Gd-DTPA) with respect to lesion enhancement in a rat brain glioma model at 1.5 and 3.0 T. Methods Glioma cells were injected into the brains of 42 male CDF ( Fisher 344) rats through implanted cannula to create Glioma animal model. One week after implantation, all rats were randomly divided in to four groups which included 12,10,10,10 rats. The comparisons included the contrast effect of gadoteridol versus gadopentetate dimeglumine at both 1.5 and 3.0 T. In addition, gadoteridol alone was evaluated by comparing the standard dose at both two field strengths and half dose at 3.0 T to a standard full dose at 1.5 T. Two MRI scans for different contrast agent injections were performed in each animal model with an interval of 24 hours. T1 -weighted images were analyzed pre-contrast and at five time points ( 1, 3, 5, 7 and 9 min) post-contrast with respect to lesion signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast enhancement (CE). Student t test was used for statistics. Results The mean SNR, CNR, and CE were respectively 54. 4 ± 3. 2, 17.0 ± 3.3 and 20. 8 ± 3.4 with gadopentetate dimeglumine versus 53.2 ± 3.2, 17.2 ± 3. 1 and 20. 8 ± 3.2 with gadoteridol at 1.5 T at every postcontrast time point ( t = 2. 247, 0. 403, 0. 076, P > 0. 05 ). The mean SNR, CNR, and CE were respectively 94.8 ± 7.1, 38.0 ± 6.0 and 45.0 ± 6.3 with

  10. RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

    OpenAIRE

    Bao, Zhao-Shi; Chen, Hui-min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; HU, HUI-MIN

    2014-01-01

    Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent ...

  11. Glioma-initiating cells and molecular pathology: implications for therapy.

    Science.gov (United States)

    Natsume, Atsushi; Kinjo, Sayano; Yuki, Kanako; Kato, Takenori; Ohno, Masasuke; Motomura, Kazuya; Iwami, Kenichiro; Wakabayashi, Toshihiko

    2011-02-01

    There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.

  12. Targeting autophagy to sensitive glioma to temozolomide treatment.

    Science.gov (United States)

    Yan, Yuanliang; Xu, Zhijie; Dai, Shuang; Qian, Long; Sun, Lunquan; Gong, Zhicheng

    2016-02-02

    Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, the efficacy of TMZ is often limited by the development of resistance. Recently, studies have found that TMZ treatment could induce autophagy, which contributes to therapy resistance in glioma. To enhance the benefit of TMZ in the treatment of glioblastomas, effective combination strategies are needed to sensitize glioblastoma cells to TMZ. In this regard, as autophagy could promote cell survival or autophagic cell death, modulating autophagy using a pharmacological inhibitor, such as chloroquine, or an inducer, such as rapamycin, has received considerably more attention. To understand the effectiveness of regulating autophagy in glioblastoma treatment, this review summarizes reports on glioblastoma treatments with TMZ and autophagic modulators from in vitro and in vivo studies, as well as clinical trials. Additionally, we discuss the possibility of using autophagy regulatory compounds that can sensitive TMZ treatment as a chemotherapy for glioma treatment.

  13. MR imaging of optic chiasmatic glioma

    International Nuclear Information System (INIS)

    To evaluate the MR findings of optic chiasmatic glioma (OCG). MR images were reviewed in 14 patients with histologically proven OCGs and one with neurofibromatosis type 1 (male: female=8:7, mean age=8.5 years.) Tumors were evaluated retrospectively with respect to their size, involvement of the optic pathway, transverse/vertical diameter ratio based on the coronal plane, signal intensities, enhancement pattern, and the presence of a cyst or calcification. Tumors was measured 1.7-5.5 (mean, 3.3) cm in maximum diameter. In ten patients, the optic tracts were involved, and in three, the optic nerves. In 12 patients, tumors had a transverse/vertical diameter ratio of over one, and showed iso (n=5) or low signal intensity (n=10) compared with gray matter at T1-weighted imaging and high signal intensity (n=15) at T2-weighted imaging. Cyst formations were ween in eight patients, and tumors were enhanced strongly and homogeneously in nine and peripherally in four. In seven three was associated hydrocephalus, and in one, calcification. OCG is a suprasellar tumor which can extend into the optic pathway, has a transverse/vertical diameter ratio of more than one, and shows strong and homogeneous enhancement. These MR imaging findings are useful for the differentiation of OCG from other suprasellar tumors

  14. Epigenetic aberrations and therapeutic implications in gliomas.

    Science.gov (United States)

    Natsume, Atsushi; Kondo, Yutaka; Ito, Motokazu; Motomura, Kazuya; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-06-01

    Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.

  15. MR imaging of optic chiasmatic glioma

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seong Sook; Lee, Ho Kyu; Kim, Hyun Jin; Ryu, Meung Sun; Goo, Hyun Woo; Yoon, Chong Hyun; Choi, Choong Gon; Suh, Dae Chul; Ra, Young Shin; Khang, Shin Kwang [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2002-08-01

    To evaluate the MR findings of optic chiasmatic glioma (OCG). MR images were reviewed in 14 patients with histologically proven OCGs and one with neurofibromatosis type 1 (male: female=8:7, mean age=8.5 years.) Tumors were evaluated retrospectively with respect to their size, involvement of the optic pathway, transverse/vertical diameter ratio based on the coronal plane, signal intensities, enhancement pattern, and the presence of a cyst or calcification. Tumors was measured 1.7-5.5 (mean, 3.3) cm in maximum diameter. In ten patients, the optic tracts were involved, and in three, the optic nerves. In 12 patients, tumors had a transverse/vertical diameter ratio of over one, and showed iso (n=5) or low signal intensity (n=10) compared with gray matter at T1-weighted imaging and high signal intensity (n=15) at T2-weighted imaging. Cyst formations were ween in eight patients, and tumors were enhanced strongly and homogeneously in nine and peripherally in four. In seven three was associated hydrocephalus, and in one, calcification. OCG is a suprasellar tumor which can extend into the optic pathway, has a transverse/vertical diameter ratio of more than one, and shows strong and homogeneous enhancement. These MR imaging findings are useful for the differentiation of OCG from other suprasellar tumors.

  16. Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases.

    Science.gov (United States)

    Fernández, Francisco; Deviers, Alexandra; Dally, Claire; Mogicato, Giovanni; Delverdier, Maxence; Cauzinille, Laurent; Gnirs, Kirsten; Añor, Sònia; de la Fuente, Cristian; Fondevila, Dolors; Pumarola, Martí

    2016-03-01

    Gliomas are the most common primary brain tumours in humans and are associated with a poor prognosis. An accurate animal model of human glioma tumorigenesis is needed to test new treatment strategies. Dogs represent a promising model because they develop spontaneous diffusely-infiltrating gliomas. This study investigated whether spontaneous canine gliomas contain cancer stem cells previously identified in all grades of human gliomas. Twenty spontaneous cases of canine gliomas were graded according to the human WHO classification. The expression of different markers of lineage differentiation was evaluated with immunohistochemistry as follows: nestin and CD133 for neural stem cells, doublecortin for neuronal progenitor cells, Olig2 for glial progenitor cells, glial fibrillary acidic protein, vimentin and S-100 for mature glial cells, and NeuN and βIII-tubulin for mature neurons. Gliomas were characterised as follows: five grade II (oligodendrogliomas); nine grade III (seven anaplastic oligodendrogliomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma); six grade IV (glioblastomas). Immunohistochemical evaluation revealed that (1) nestin and CD133 were expressed in all grades of gliomas with a higher proportion of positive cells in high-grade gliomas; (2) the expression of S-100 protein and Olig2 did not differ substantially between astrocytic and oligodendroglial tumours, and (3) all gliomas were negative for mature neuron markers. The results demonstrated the presence of undifferentiated neural progenitors in all grades of spontaneous canine gliomas, confirming the relevance of this animal model for further studies on cancer stem cells. PMID:26831167

  17. Upregulation of p-Smad2 contributes to FAT10-induced oncogenic activities in glioma.

    Science.gov (United States)

    Dai, Bin; Zhang, Yisong; Zhang, Peng; Pan, Changcun; Xu, Cheng; Wan, Weiqing; Wu, Zhen; Zhang, Junting; Zhang, Liwei

    2016-07-01

    The human leukocyte antigen f-associated transcript 10 (FAT10) has a similar structure and function with ubiquitin, which efficiently mediate proteasome degradation in an ubiquitin-independent manner. FAT10 expression is upregulated in many tumor tissues and plays a vital role in cell cycle regulation and tumor genesis. However, its role in glioma has not been illuminated. The aim of this study was to evaluate the prognostic value of FAT10 and investigate its functional roles in glioma. The expression of FAT10 in glioma patient samples was examined using quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry methods. Glioma cell lines with either FAT10 overexpression or knockdown were created. The effect of FAT10 on glioma cell migration and invasion was investigated using these cells. In the present study, we had shown that FAT10 was elevated significantly in glioma samples and correlated with tumor pathological grade. FAT10 high-expression glioma is associated with a poor clinical prognosis. Overexpression of FAT10 promoted proliferation, invasion, migration, and sphere formation of glioma cells, whereas downregulation of FAT10 had an opposite effect. Overexpression of FAT10 also promoted the growth of glioma cells in vivo. Moreover, FAT10 enhanced the phosphorylation of Smad2, which contributes to FAT10-induced oncogenic activities in glioma. In conclusion, these findings indicate that FAT10 is a critical regulator potential therapeutic target of glioma. PMID:26733179

  18. FT-IR study on interactions between medroxyprogesterone acetate and solvent in CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems

    Science.gov (United States)

    Shi, Jie-hua; Fan, Chun-hui

    2012-09-01

    The intermolecular interactions between medroxyprogesterone acetate (MPA) and CHCl3 and CCl4 solvent in CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems have been studied by Fourier transform infrared spectroscopy (FT-IR). The experimental results showed that there are hydrogen bonding interactions between oxygen atoms of all carbonyl groups in MPA and hydrogen atom of CHCl3 so as to form 1:3 complex of MPA with CHCl3 and produce three new absorption bands at 1728.9-1736.1, 1712.7-1717.4 and 1661.9-1673.8 cm-1, respectively. And, 1:1 complex of MPA with CCl4 is formed in CCl4/cyclo-C6H12 binary solvent as a result of hydrogen bonding interaction between C3 carbonyl group and empty d-orbital in chlorine atom of CCl4 leading to producing new absorption band at 1673.2-1674.2 cm-1. However, all free carbonyl and associated carbonyl stretching vibrations of MPA in CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems shift to lower wavenumbers with the increasing of volume fraction of CHCl3 and CCl4 in binary solvent systems owing to the dipole-dipole interaction and the dipole-induced dipole interaction between MPA and solvents.

  19. Cyclinac medical accelerators using pulsed C6+/H2+ ion sources

    International Nuclear Information System (INIS)

    Charged particle therapy, or so-called hadrontherapy, is developing very rapidly. There is large pressure on the scientific community to deliver dedicated accelerators, providing the best possible treatment modalities at the lowest cost. In this context, the Italian research Foundation TERA is developing fast-cycling accelerators, dubbed 'cyclinacs'. These are a combination of a cyclotron (accelerating ions to a fixed initial energy) followed by a high gradient linac boosting the ions energy up to the maximum needed for medical therapy. The linac is powered by many independently controlled klystrons to vary the beam energy from one pulse to the next. This accelerator is best suited to treat moving organs with a 4D multipainting spot scanning technique. A dual proton/carbon ion cyclinac is here presented. It consists of an Electron Beam Ion Source, a superconducting isochronous cyclotron and a high-gradient linac. All these machines are pulsed at high repetition rate (100-400 Hz). The source should deliver both C6+ and H2+ ions in short pulses (1.5 μs flat-top) and with sufficient intensity (at least 108 fully stripped carbon ions per pulse at 300 Hz). The cyclotron accelerates the ions to 120 MeV/u. It features a compact design (with superconducting coils) and a low power consumption. The linac has a novel C-band high-gradient structure and accelerates the ions to variable energies up to 400 MeV/u. High RF frequencies lead to power consumptions which are much lower than the ones of synchrotrons for the same ion extraction energy. This work is part of a collaboration with the CLIC group, which is working at CERN on high-gradient electron-positron colliders.

  20. Double Electron Processes in Low Energy Isotope Bare Ions 13C6+ with Helium Collisions

    Institute of Scientific and Technical Information of China (English)

    YU De-Yang; SHAO Jian-Xiong; DING Bao-Wei; YANG Zhi-Hu; CHEN Xi-Meng; CAI Xiao-Hong; LU Rong-Chun; SHAO Cao-Jie; LU Jun; RUAN Fang-Fang; ZHANG Hong-Qiang; CUI Ying; XU Xu

    2005-01-01

    @@ The isotopic bare ion 13C6+ was employed to collide with helium at 4.15-11.08keV/u. The relative partial cross sections were measured by position-sensitive and time-of-flight coincident techniques. It is shown that the direct-ionization (DI) process can be completely ignored in this region, the transfer ionization (TI) process is the most important double-electron channel, and the probability of the pure double-electron capture (DC) process is quite small. The cross-section ratio of the total double-electron (DE) process (i.e. DC+TI) to the single-electron capture (SC) process is experimentally determined to be approximately a constant of 0.09 ± 0.03 in this region,and this value is obviously smaller than the predictions of the classical over-barrier models and the semi-empirical scaling laws. It is found that the cross-section ratio of pure DC to DE decreases obviously as the projectile velocity increases. Because the pure DC process only comes from the radiation de-excitation following the DC process and are competed by the TI process (comes from the auto-ionization following the DC process), this implies that the population of the two captured electrons depends distinctly on the collision velocity. Comparison with works on Ar16+-He by Wu et al. [Phys. Rev. A 48 (1993) 3617] reveals that the strong projectile-dependent character of the pure DC process exists.

  1. Progress of temozolomide in the treatment of recurrent high-grade gliomas

    Directory of Open Access Journals (Sweden)

    LI Jin-duo

    2013-12-01

    Full Text Available High-grade gliomas are central nervous system malignancies which are difficult to treat. Surgery, temozolomide combined with radiotherapy postoperatively and adjuvant chemotherapy with temozolomide have been established as the standard treatment options for high-grade gliomas. Nevertheless, the prognosis of patients with high-grade gliomas remains poor. At present, there is no standard therapy for recurrent or relapsed high-grade gliomas. Temozolomide is still an effective drug for the treatment of recurrent high-grade gliomas. According to the characteristics of patients, there have been many kinds of temozolomide administration and other treatments in combination. Individual therapy were paid more attention, so that the patients with high-grade gliomas recurrence could get greater survival benefit. This paper aims to introduce the progress of temozolomide in the treatment of recurrent high-grade gliomas in recent years.

  2. Expression of FOXG1 is associated with the malignancy of human glioma

    Institute of Scientific and Technical Information of China (English)

    Zhiwei Shao; Beibei Cong; Aihua Sui; Kai Meng; Yihe Dou

    2014-01-01

    Objective: Recent evidence indicates that the increased expression of FOXG1 is associated with tumor genesis. This study was designed to explore the expression and role which FOXG1 plays in human glioma. Methods: We detected the expression of FOXG1 by immunohistochemistry in glioma tissue samples. Fol owing the down-regulation of FOXG1 in glioma cel lines by a specific short hairpin RNA, the function of FOXG1 in proliferation and apoptosis was assessed. Results:Glioma tissues exhibited notably higher expression of FOXG1 compared with control brain tissues and was positively corre-lated with histological malignancy. The down-regulation of FOXG1 in glioma cel s led to a cel apoptosis in vitro. Conclusion:The overexpression of FOXG1 is a novel glioma malignancy marker, and FOXG1 may be used as a new target in therapeutic strategies for human glioma.

  3. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

    2014-09-10

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

  4. Radiation effects on human glia and glioma cells in vitro

    International Nuclear Information System (INIS)

    The radiosensitivity of human glia and glioma cells has been studied in vitro, and a new cloning method has been developed to overcome the difficulties due to the very low cloning efficiency of these cells. The cells were confined to small palladium areas surrounded by agarose, which increased the cell density, but kept the clones separated. Using this method, the glia cells were found to be very sensitive to gamma irradiation (D0=1.0-1.5 Gy and n=1) in comparision with the glioma cells (D0=1.5-2.5 Gy and n=3.5). The induction and repair of DNA strand breaks were studied with two DNA unwinding techniques. No differences between the two cell-lines were detected when induction and fast repair were studied with the single-labelling method, while the glioma cells showed less unrepaired DNA strand breaks than the glia cells after 1, 2 and 3 hours, when the double-labelling method was used. Detachment, attachment and growth kinetics were studied using the palladium-agarose cloning method. All of the glioma cell-lines studied, detached and attached themselves at rates higher than the normal diploid glia cell-lines. All of the cell-lines contained clones with different properties. Some clones were rapidly growing, others maintained a nearly constant number of cells or even decreased. The effects of chronic hypoxia were tested in a few experiments. Low oxygen tension in the culture medium reduced the rate of growth and the DNA synthesis of the glioma cells. The present study indicates that cultured human glioma cells are less radiosensitive than cultured glia cells. The palladium-agarose technique, enable studying growth kinetics detachment, attachment and radiosensitivity in a quantitative manner for cells with low cloning efficiency. (author)

  5. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK

  6. NESS038C6, a novel selective CB1 antagonist agent with anti-obesity activity and improved molecular profile.

    Science.gov (United States)

    Mastinu, Andrea; Pira, Marilena; Pani, Luca; Pinna, Gérard Aimè; Lazzari, Paolo

    2012-10-01

    The present work aims to study the effects induced by a chronic treatment with a novel CB1 antagonist (NESS038C6) in C57BL/6N diet-induced obesity (DIO) mice. Mice treated with NESS038C6 and fed with a fat diet (NESS038C6 FD) were compared with the following three reference experimental groups: DIO mice fed with the same fat diet used for NESS038C6 and treated with vehicle or the reference CB1 antagonist/inverse agonist rimonabant, "VH FD" and "SR141716 FD", respectively; DIO mice treated with vehicle and switched to a normal diet (VH ND). NESS038C6 chronic treatment (30 mg/kg/day for 31 days) determined a significant reduction in DIO mice weight relative to that of VH FD. The entity of the effect was comparable to that detected in both SR141716 FD and VH ND groups. Moreover, if compared to VH FD, NESS038C6 FD evidenced: (i) improvement of cardiovascular risk factors; (ii) significant decrease in adipose tissue leptin expression; (iii) increase in mRNA expression of hypothalamic orexigenic peptides and a decrease of anorexigenic peptides; (iv) expression increase of metabolic enzymes and peroxisome proliferator-activated receptor-α in the liver; (v) normalization of monoaminergic transporters and neurotrophic expression in mesolimbic area. However, in contrast to the case of rimonabant, the novel CB1 antagonist improved the disrupted expression profile of genes linked to the hunger-satiety circuit, without altering monoaminergic transmission. In conclusion, the novel CB1 antagonist compound NESS038C6 may represent a useful candidate agent for the treatment of obesity and its metabolic complications, without or with reduced side effects relative to those instead observed with rimonabant. PMID:22771813

  7. Glioma Stem Cells but Not Bulk Glioma Cells Upregulate IL-6 Secretion in Microglia/Brain Macrophages via Toll-like Receptor 4 Signaling.

    Science.gov (United States)

    a Dzaye, Omar Dildar; Hu, Feng; Derkow, Katja; Haage, Verena; Euskirchen, Philipp; Harms, Christoph; Lehnardt, Seija; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut

    2016-05-01

    Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive and tumor-supportive phenotype in these glioma-associated microglia/brain macrophages (GAMs). A subpopulation of glioma cells acts as glioma stem cells (GSCs). We explored the interaction between GSCs and GAMs. Using CD133 as a marker of stemness, we enriched for or deprived the mouse glioma cell line GL261 of GSCs by fluorescence-activated cell sorting (FACS). Over the same period of time, 100 CD133(+ )GSCs had the capacity to form a tumor of comparable size to the ones formed by 10,000 CD133(-) GL261 cells. In IL-6(-/-) mice, only tumors formed by CD133(+ )cells were smaller compared with wild type. After stimulation of primary cultured microglia with medium from CD133-enriched GL261 glioma cells, we observed an selective upregulation in microglial IL-6 secretion dependent on Toll-like receptor (TLR) 4. Our results show that GSCs, but not the bulk glioma cells, initiate microglial IL-6 secretion via TLR4 signaling and that IL-6 regulates glioma growth by supporting GSCs. Using human glioma tissue, we could confirm the finding that GAMs are the major source of IL-6 in the tumor context.

  8. IgE, Allergy, and Risk of Glioma: Update from the San Francisco Bay Area Adult Glioma Study in the Temozolomide Era

    OpenAIRE

    Wiemels, Joseph L.; Wilson, David; Patel, Chirag; Patoka, Joseph; McCoy, Lucie; Rice, Terri; Schwartzbaum, Judith; Heimberger, Amy; Sampson, John H; Chang, Susan; Prados, Michael; Wiencke, John K.; Wrensch, Margaret

    2009-01-01

    The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that IgE levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechanism that inhibits or prevents glioma. We sought to extend these results with a new and larger series of patients (n=535 with questionnaire data; 393 with IgE measures) and controls (n=532 with questionnaire data; 470 with IgE measures). As expected, glioma cas...

  9. Molecular biology of gliomas: present and future challenges.

    Science.gov (United States)

    Altieri, R; Agnoletti, A; Quattrucci, F; Garbossa, D; Calamo Specchia, F M; Bozzaro, M; Fornaro, R; Mencarani, C; Lanotte, M; Spaziante, R; Ducati, A

    2014-09-01

    Malignant brain tumours are one of the most relevant causes of morbidity and mortality across a wide range of individuals. Malignant glioma is the most common intra axial tumor in the adult. Many researches on this theme brought advances in the knowledge of gliomas biology and pathogenesis and to the development of new agents for targeted molecular therapy. Recent studies focused on either tumor metabolism analysis or epigenetic regulation in the pathogenesis or maintenance of brain tumors. This Review summarizes these developments analyzing molecular pathology and possible further developments for targeted therapies.

  10. Brain Mitochondrial Lipid Abnormalities in Mice Susceptible to Spontaneous Gliomas

    OpenAIRE

    Kiebish, M.A.; Han, X; Cheng, H; Chuang, J H; Seyfried, T N

    2008-01-01

    Alterations in mitochondrial function have long been considered a hallmark of cancer. We compared the lipidome and electron transport chain activities of non-synaptic brain mitochondria in two inbred mouse strains, the C57BL/6J (B6) and the VM/Dk (VM). The VM strain is unique in expressing a high incidence of spontaneous brain tumors (1.5%) that are mostly gliomas. The incidence of gliomas is about 210-fold greater in VM mice than in B6 mice. Using shotgun lipidomics, we found that the mitoch...

  11. Targetting hypoxia in gliomas: From mathematics to bedside.

    OpenAIRE

    Martínez González, Alicia

    2014-01-01

    Esta Tesis explora la utilización de modelos matemáticos como herramientas para ayudar a entender la complejidad de los tumores y su entorno. El estudio presta especial atención a los gliomas, que son tumores cerebrales primarios, originados por células de la glia: astrocitos u oligodendrocitos. Estos tumores abarcan desde los astrocitomas de bajo grado, como el astrocitoma difuso, de crecimiento lento, a los gliomas de más alto grado, como el más maligno y de más incidencia: el glioblastoma ...

  12. Epigenetic biomarkers of T-cells in human glioma

    OpenAIRE

    Wiencke, John K.; Accomando, William P.; Zheng, Shichun; Patoka, Joe; Dou, Xiaoqin; Phillips, Joanna J.; Hsuang, George; Christensen, Brock C.; Houseman, E. Andres; Koestler, Devin C; Bracci, Paige; Wiemels, Joseph L.; Wrensch, Margaret; Nelson, Heather H.; Kelsey, Karl T.

    2012-01-01

    Immune factors are thought to influence glioma risk and outcomes, but immune profiling studies to further our understanding of the immune response are limited by current immunodiagnostic methods. We developed a new assay to capture glioma immune biology based on quantitative methylation specific PCR (qMSP) of two T-cell genes (CD3Z: T-cells, and FOXP3: Tregs). Flow cytometry of T-cells correlated well with the CD3Z demethylation assay (r = 0.93; p < 2.2 × 10−16), demonstrating the validity of...

  13. The functional role of Notch signaling in human gliomas

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2010-01-01

    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now......Gliomas are among the most devastating adult tumors for which there is currently no cure. The tumors are derived from brain glial tissue and comprise several diverse tumor forms and grades. Recent reports highlight the importance of cancer-initiating cells in the malignancy of gliomas. These cells...

  14. Synthesis of the molecular amalgam [{AuHg2(o-C6F4)3}{Hg3(o-C6F4)3}](-): a rare example of a heterometallic homoleptic metallacycle.

    Science.gov (United States)

    Lasanta, Tania; López-de-Luzuriaga, José M; Monge, Miguel; Olmos, M Elena; Pascual, David

    2016-04-12

    The preparation of homoleptic heterometallic complexes still remains a challenge. Herein, we report the synthesis and characterization of [Au(PMe3)2][{AuHg2(o-C6F4)3}{Hg3(o-C6F4)3}] (), a gold-mercury homoleptic metallacycle. The crystal structure of displays two [Hg2M(o-C6F4)3] (M = Au(I), Hg(II)) units linked through a short AuHg contact of 3.097(2) Å, the strongest unsupported Au(I)Hg(II) interaction described to date. Theoretical calculations quantify the interaction between the trimetalic units as -199 kJ mol(-1), a surprisingly strong value. PMID:26983855

  15. Involvement of triacylglycerol in the metabolism of fatty acids by cultured neuroblastoma and glioma cells

    International Nuclear Information System (INIS)

    The metabolism (chain elongation, desaturation, and incorporation into complex lipids) of thirteen different radiolabeled fatty acids and acetate was examined in N1E-115 neuroblastoma and C-6 glioma cell lines in culture. During 6-hr incubations, all fatty acids were extensively (14-80%) esterified to complex lipids, mainly choline phosphoglycerides and triacylglycerol. With trienoic and tetraenoic substrates, inositol and ethanolamine phosphoglycerides also contained up to 30% of the labeled fatty acids; plasmalogen contained up to half of the label in the ethanolamine phosphoglyceride fraction of neuroblastoma cells. Chain elongation and delta 9, delta 6, and delta 5 desaturation occurred in both cell lines; delta 4 desaturation was not observed. Seemingly anomalous utilization of arachidic acid and some selectivity based on the geometric configuration of double bonds was observed. These studies indicate that these cell lines are capable of modulating cellular membrane composition by a combination of selective exclusion and removal of inappropriate acyl chains and of modification of other acyl chains by desaturation and chain elongation. The time courses and patterns of modification and incorporation of exogenous substrates into phospholipids and triacylglycerol suggest that exogenous unsaturated fatty acid may be incorporated into triacylglycerol and later released for further metabolism and incorporation into phospholipids. This supports a role for triacylglycerol in the synthesis of membrane complex lipids in cell lines derived from neural tissue

  16. Role of C6ORF120, an N-glycosylated protein, is implicated in apoptosis of CD4+T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    LI Xin; QIAO Yong; CHANG Lu-si; XIAO Fan; LU Lian-he; HAO Xiao-hua; ZHANG Ren-wen; WU Hao; WEI Hong-shan

    2011-01-01

    Background Although CD4+ T cell apoptosis and CD8+ T cell responses have been extensively studied during HIV infection,how apoptosis signals being initiated in CD4+ T cells still need to be elucidated.The present study was designed to characterize the function-unknown gene,C6orf120,and elucidates its primary role in tunicamycin-induced CD4+ T apoptosis.Methods The C6orf120 coding sequence was amplified from peripheral blood mononuclear cel