Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

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Ishola, I O; Chaturvedi, J P; Rai, S; Rajasekar, N; Adeyemi, O O; Shukla, R; Narender, T

2013-03-27

Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. Rat astrocytoma cells (C6) were stimulated with LPS (10μg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3μg/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. LPS (10μg/ml) significantly (PTHP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (Ptest. It produced time course significant (P<0.05) decrease in oedema formation in rodents. Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The molecular biology of WHO grade I astrocytomas.

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Marko, Nicholas F; Weil, Robert J

2012-12-01

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

Prognostic parameters in benign astrocytomas

DEFF Research Database (Denmark)

Westergaard, L; Gjerris, F; Klinken, L

1993-01-01

astrocytomas treated in the period 1956 to 1991. The pilocytic type of astrocytoma was found to have an outstandingly good prognosis and should be regarded as a distinct nosological entity. For the non-pilocytic supratentorial astrocytomas, a multivariate regression analysis showed that age, tumour site...

miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK.

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Feng Zhi

Full Text Available Astrocytomas are common malignant intracranial tumors that comprise the majority of adult primary central nervous system tumors. MicroRNAs (miRNAs are small, non-coding RNAs (20-24 nucleotides that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In our previous studies, we found that the downregulation of miR-106a-5p in astrocytomas is associated with poor prognosis. However, its specific gene target(s and underlying functional mechanism(s in astrocytomas remain unclear. In this study, we used mRNA microarray experiments to measure global mRNA expression in the presence of increased or decreased miR-106a-5p levels. We then performed bioinformatics analysis based on multiple target prediction algorithms to obtain candidate target genes that were further validated by computational predictions, western blot analysis, quantitative real-time PCR, and the luciferase reporter assay. Fas-activated serine/threonine kinase (FASTK was identified as a direct target of miR-106a-5p. In human astrocytomas, miR-106a-5p is downregulated and negatively associated with clinical staging, whereas FASTK is upregulated and positively associated with advanced clinical stages, at both the protein and mRNA levels. Furthermore, Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the increased expression of FASTK is significantly associated with poor survival outcome. These results further supported the finding that FASTK is a direct target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and FASTK during astrocytoma progression. Through gain-of-function and loss-of-function studies, we demonstrated that miR-106a-5p can significantly inhibit cell proliferation and migration and can promote cell apoptosis in vitro. The knockdown of FASTK induced similar effects on astrocytoma cells as those induced by the overexpression of miR-106a-5p. These

Integrated analysis of mismatch repair system in malignant astrocytomas.

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Irene Rodríguez-Hernández

Full Text Available Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

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Jian-jun Sun

2015-01-01

Full Text Available This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133 + and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133 + cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133 + astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

Retinal astrocytoma in a dog.

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Kuroki, Keiichi; Kice, Nathan; Ota-Kuroki, Juri

2017-09-01

A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic protein, vimentin, and S-100 and largely negatively for oligodendrocyte transcription factor 2 by immunohistochemistry. The clinical and histopathological features of canine retinal astrocytomas are discussed.

Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

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Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A; Ostrosky-Wegman, Patricia

2015-01-01

Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

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Maraziotis Theodore

2007-10-01

Full Text Available Abstract Background Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Methods Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were used. The labeling index (LI, defined as the percentage of positive (labeled cells out of the total number of tumor cells counted, was determined. Results Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (~1% in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were

Phase II trial of carmustine, cisplatin, and oral etoposide chemotherapy before radiotherapy for grade 3 astrocytoma (anaplastic astrocytoma): Results of North Central Cancer Treatment Group trial 98-72-51

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Rao, Ravi D.; Krishnan, Sunil; Fitch, Tom R.; Schomberg, Paula J.; Dinapoli, Robert P.; Nordstrom, Kathleen; Scheithauer, Bernd; O'Fallon, Judith R.; Maurer, Matthew J. M.S.; Buckner, Jan C.

2005-01-01

Purpose: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. Methods and materials: Therapy consisted of carmustine (40 mg/m 2 /d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m 2 /d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. Results: A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. Conclusion: Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma

Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

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Natalia Bailon-Moscoso

Full Text Available Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL, a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

International Nuclear Information System (INIS)

Assimakopoulou, Martha; Kondyli, Maria; Gatzounis, George; Maraziotis, Theodore; Varakis, John

2007-01-01

Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75 NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75 NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75 NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75 NTR , and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75 NTR and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75 NTR receptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor

Childhood Astrocytoma Treatment (PDQ®)—Patient Version

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Childhood astrocytomas can be benign (not cancer) or malignant (cancer). Learn more about the types of astrocytoma, signs and symptoms, diagnosis, prognosis, and treatment of astrocytomas that are newly diagnosed or have come back after treatment in this expert-reviewed summary.

A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.

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Rubén Martín

Full Text Available Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA. Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.

MR imaging characteristics of protoplasmic astrocytomas

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Tay, Kevin L. [Royal Melbourne Hospital, Department of Radiology, Parkville, Victoria (Australia); Royal North Shore Hospital, Department of Radiology, St Leonards, New South Wales (Australia); Tsui, Alpha [Royal Melbourne Hospital, Department of Pathology, Parkville, Victoria (Australia); Phal, Pramit M.; Tress, Brian M. [Royal Melbourne Hospital, Department of Radiology, Parkville, Victoria (Australia); Drummond, Katharine J. [Royal Melbourne Hospital, Department of Neurosurgery, Parkville, Victoria (Australia)

2011-06-15

Protoplasmic astrocytomas are a poorly recognized and uncommon subtype of astrocytoma. While usually categorized with other low-grade gliomas, there is literature to suggest that protoplasmic astrocytomas have differences in biology compared to other gliomas in this group. This paper presents the MR imaging characteristics of a series of eight protoplasmic astrocytomas. We retrospectively reviewed MR images and histopathology of eight consecutive cases of histologically proven protoplasmic astrocytomas. Patients ranged from 17 to 51 years of age with a 5:3 male to female ratio. The tumors were located in the frontal or temporal lobes and tended to be large, well defined, and had a very high signal on T2 (close to cerebrospinal fluid). Generally, a large proportion of the tumor showed substantial signal suppression on T2 fluid-attenuated inversion recovery (FLAIR). Six of the eight lesions also demonstrated a partial or complete rim of reduced apparent diffusion coefficient (ADC) around the T2 FLAIR suppressing portion. The possibility that a primary cerebral neoplasm represents a protoplasmic astrocytoma should be considered in a patient with a large frontal or temporal tumor that has a very high signal on T2 with a large proportion of the tumor showing substantial T2 FLAIR suppression. A further clue is a partial or complete rim of reduced ADC. (orig.)

Errantum: Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins

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Lai JCK

2010-12-01

Full Text Available Lai JCK, Ananthakrishnan G, Jandhyam S, et al. Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins. Int J Nanomedicine. 2010;5:715–723.The wrong image was used in Figure 5 on page 719.

201Thallium SPECT, accuracy in astrocytoma diagnosis and treatment evaluation

International Nuclear Information System (INIS)

Kaellen, K.

1999-10-01

The aims of the studies included in this thesis were: - to investigate the reliability of 201 Thallium single photon emission computed tomography. Tl SPECT for preoperative diagnosis and histological staging of malignant astrocytomas in comparison with CT; - to develop a method for quantification of cerebral thallium uptake, and to evaluate the quantitative measurement in comparison with CT, for astrocytoma treatment follow-up purposes; - to compare quantitative Tl SPECT and proton magnetic resonance spectroscopy (H-MRS) with conventional MR imaging for astrocytoma monitoring, and to evaluate associations between change of morphological tumour characteristics during treatment and changes of cerebral thallium uptake and metabolic ratios. Results and conclusions: - High TI-index, calculated as a ratio comparing tumour uptake to uptake in the contralateral hemisphere, is an indicator of highly malignant astrocytoma. Differentiation between the high-grade astrocytomas, the low-grade astrocytomas, and infectious lesions is only partial, with an overlap of Tl-indexes between these groups. High-grade astrocytomas that do not show contrast enhancement on CT, and astrocytomas with central necrosis and moderate ring-enhancement, tend to be underestimated when evaluated by Tl-index calculation. Tl SPECT is not a reliable method for non-invasive tumour staging among the group of highly malignant astrocytomas. - Quantification of cerebral TI-uptake, defining the volume of viable tumour tissue, is a new method for astrocytoma chemotherapy monitoring. Results suggest that the method provides prognostic information, and information of treatment efficacy, at an earlier stage than CT. - We did not find a higher accuracy of quantitative Tl SPECT than of MR for monitoring purposes and our results indicated that treatment induced MR changes were interrelated with TI-uptake variations. - Multi-voxel H-MRS was difficult to apply for astrocytoma treatment monitoring, due to the anatomical

Complement activation in astrocytomas: deposition of C4d and patient outcome

International Nuclear Information System (INIS)

Mäkelä, Katri; Helén, Pauli; Haapasalo, Hannu; Paavonen, Timo

2012-01-01

C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann–Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement

The emerging role of m-TOR up-regulation in brain Astrocytoma.

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Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

2017-05-01

The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

13N-NH3 PET in the diagnosis of astrocytomas: preliminary result

International Nuclear Information System (INIS)

Zhang Xiangsong; He Zuoxiang; Tang Anwu

2004-01-01

Objective: To evaluate the feasibility of diagnosing the astrocytoma with 13N-NH3 PET imaging. Methods 13N-NH3 and 18F-fluorodeoxyglucose (FDG) PET imaging were performed in seven cases of astrocytomas including 3 anteoperative astrocytomas, 2 recurrent astrocytomas, 2 brain injury or necrosis after the operation and radiotherapy. The radioactivity ratios of the tumor and normal white matter (T/WM) were calculated. Results: The tumor lesions in 3 anteoperative astrocytomas and 2 recurrent astrocytomas all uptake 13N-NH3. The average T/WM on 13N-NH3 images was 1.82±0.21, and T/WM on 13N-NH3 and 18F-FDG images were 1.98 and 0.97 for one case with grade 1 astrocytoma. 13N-NH3 and 18F-FDG PET imaging both showed decreased uptake in 2 brain injury or necrosis after the operation and radiotherapy of astrocytomas. Conclusions: 13N-NH3 was uptaken in astrocytomas. 13N-NH3 can be useful in the diagnosis of astrocytoma, and potentially improve diagnostic accuracy of astrocytoma, especially in low-grade astrocytoma. (authors)

13N-NH3 PET in the diagnosis of astrocytomas: preliminary result

International Nuclear Information System (INIS)

Zhang Xiangsong; He Zuoxiang; Tang Anwu

2004-01-01

Objective: To evaluate the feasibility of diagnosing the astrocytoma with 13N-NH3 PET imaging. Methods: 13N-NH3 and 18F-fluorodeoxyglucose (FDG) PET imaging were performed in seven cases of astrocytomas including 3 anteoperative astrocytomas, 2 recurrent astrocytomas, 2 brain injury or necrosis after the operation and radiotherapy. The radioactivity ratios of the tumor and normal white matter (T/WM) were calculated. Results: The tumor lesions in 3 anteoperative astrocytomas and 2 recurrent astrocytomas all uptake 13N-NH3 .The average T/WM on 13N-NH3 images was 1.82±0.21, and T/WM on 13N-NH3 and 18F-FDG images were 1.98 and 0.97 for one case with grade 1 astrocytoma. 13N-NH3 and 18F-FDG PET imaging both showed decreased uptake in 2 brain injury or necrosis after the operation and radiotherapy of astrocytomas. Conclusions: 13N-NH3 was uptaken in astrocytomas. 13N-NH3 can be useful in the diagnosis of astrocytoma, and potentially improve diagnostic accuracy of astrocytoma, especially in low-grade astrocytoma. (authors)

Prognosis and Treatment of Spinal Cord Astrocytoma

International Nuclear Information System (INIS)

Minehan, Kiernan J.; Brown, Paul D.; Scheithauer, Bernd W.; Krauss, William E.; Wright, Michael P.

2009-01-01

Purpose: To identify the prognostic factors for spinal cord astrocytoma and determine the effects of surgery and radiotherapy on outcome. Methods and Materials: This retrospective study reviewed the cases of consecutive patients with spinal cord astrocytoma treated at Mayo Clinic Rochester between 1962 and 2005. Results: A total of 136 consecutive patients were identified. Of these 136 patients, 69 had pilocytic and 67 had infiltrative astrocytoma. The median follow-up for living patients was 8.2 years (range, 0.08-37.6), and the median survival for deceased patients was 1.15 years (range, 0.01-39.9). The extent of surgery included incisional biopsy only (59%), subtotal resection (25%), and gross total resection (16%). Patients with pilocytic tumors survived significantly longer than those with infiltrative astrocytomas (median overall survival, 39.9 vs. 1.85 years; p < 0.001). Patients who underwent resection had a worse, although nonsignificant, median survival than those who underwent biopsy only (pilocytic, 18.1 vs. 39.9 years, p = 0.07; infiltrative, 19 vs. 30 months, p = 0.14). Postoperative radiotherapy, delivered in 75% of cases, gave no significant survival benefit for those with pilocytic tumors (39.9 vs. 18.1 years, p = 0.33) but did for those with infiltrative astrocytomas (24 vs. 3 months; Wilcoxon p = 0.006). On multivariate analysis, pilocytic histologic type, diagnosis after 1984, longer symptom duration, younger age, minimal surgical extent, and postoperative radiotherapy predicted better outcome. Conclusion: The results of our study have shown that histologic type is the most important prognostic variable affecting the outcome of spinal cord astrocytomas. Surgical resection was associated with shorter survival and thus remains an unproven treatment. Postoperative radiotherapy significantly improved survival for patients with infiltrative astrocytomas but not for those with pilocytic tumors

Cystic astrocytomas in children. The contribution of MRI

International Nuclear Information System (INIS)

Vilgrain, V.; Sellier, N.; Lalande, G.; Demange, P.; Kalifa, G.

1988-01-01

Three cases of cystic astrocytomas are reported in children. Two are supratentorial and one is a cerebellar tumor. The authors insist on the difficulties of the diagnosis. They emphasize the role of NMR which enables distinction between cystic astrocytomas and other cysts. In agreement with Kjos, the 3 cystic astrocytomas demonstrate an increased T1 and T2 and belong to the group of cystic tumors (type II) [fr

Postradiation astrocytoma. Report of two cases

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Kitanaka, C.; Shitara, N.; Nakagomi, T.; Nakamura, H.; Genka, S.; Nakagawa, K.; Akanuma, A.; Aoyama, H.; Takakura, K.

1989-01-01

The authors describe two cases of malignant astrocytomas associated with previous radiation therapy in childhood for intracranial germinoma and craniopharyngioma. In both patients, there was no recurrence at the primary tumor site. Because of a geometric coincidence between the tumor location and the radiation field, radiotherapy was strongly implicated as a cause of these two astrocytomas.33 references

{sup 201}Thallium SPECT, accuracy in astrocytoma diagnosis and treatment evaluation

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Kaellen, K

1999-10-01

The aims of the studies included in this thesis were: - to investigate the reliability of {sup 201}Thallium single photon emission computed tomography. Tl SPECT for preoperative diagnosis and histological staging of malignant astrocytomas in comparison with CT; - to develop a method for quantification of cerebral thallium uptake, and to evaluate the quantitative measurement in comparison with CT, for astrocytoma treatment follow-up purposes; - to compare quantitative Tl SPECT and proton magnetic resonance spectroscopy (H-MRS) with conventional MR imagingfor astrocytoma monitoring, and to evaluate associations between change of morphological tumour characteristics during treatment and changes of cerebral thallium uptake and metabolic ratios. Results and conclusions: - High TI-index, calculated as a ratio comparing tumour uptake to uptake in the contralateral hemisphere, is an indicator of highly malignant astrocytoma. Differentiation between the high-grade astrocytomas, the low-grade astrocytomas, and infectious lesions is only partial, with an overlap of Tl-indexes between these groups. High-grade astrocytomas that do not show contrast enhancement on CT, and astrocytomas with central necrosis and moderate ring-enhancement, tend to be underestimated when evaluated by Tl-index calculation. Tl SPECT is not a reliable method for non-invasive tumour staging among the group of highly malignant astrocytomas. - Quantification of cerebral TI-uptake, defining the volume of viable tumour tissue, is a new method for astrocytoma chemotherapy monitoring. Results suggest that the method provides prognostic information, and information of treatment efficacy, at an earlier stage than CT. - We did not find a higher accuracy of quantitative Tl SPECT than of MR for monitoring purposes and our results indicated that treatment induced MR changes were interrelated with TI-uptake variations. - Multi-voxel H-MRS was difficult to apply for astrocytoma treatment monitoring, due to the

AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

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Fassina, L; Magenes, G; Inzaghi, A; Palumbo, S; Allavena, G; Miracco, C; Pirtoli, L; Biggiogera, M; Comincini, S

2012-10-11

An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

Radiotherapy Results of Brain Astrocytoma and Glioblastoma Multiforme

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Choi, Doo Ho; Kim, Il Han; Ha, Sung Whan; Chi, Je Geun

1988-01-01

A retrospective analysis was performed on 49 patients with astrocytoma of glioblastoma multiforme of brain who received postoperative radiotherapy in the period between February 1979 and December 1985. Fourteen patients had grade I astrocytoma, 11 patients grade II, 14 patients grade III, and 10 patients glioblastoma multiforme. Three year actuarial survival rates were 85.7%, 44.6% and 23.1% for grade I, II, and III astrocytomas, respectively. One and 2 year actuarial survival rates for patients with glioblastoma multiforme were 54.5% and 27.3%, respectively. Histologic grade, age, extent of operation and tumor location were revealed to be prognosticators

Gemistocytic astrocytoma in the spinal cord in a dog: a case report

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R.O. Chaves

2016-08-01

Full Text Available ABSTRACT This paper reports a case of a rare variant of the cervical spinal cord astrocytoma diagnosed in a dog with progressive neurological signs, initially asymmetrical, not ambulatory tetraparesis, segmental reflexes and normal muscle tone in all four limbs and absence of pain upon palpation of the cervical spine. Myelography revealed attenuation of the ventral and dorsal contrast line in the third region of the fifth cervical vertebra. At necropsy intramedullary cylindrical mass that stretched from the third to the sixth cervical vertebra, which replaced all the gray matter of the spinal cord was observed. In the histological study, there was the replacement of the substance by neoplastic cells mantle arranged loosely. The cells were large and slightly rounded. The eosinophilic cytoplasm was well defined, sometimes forming processes interconnecting cells. The nucleus was eccentric, round, oval or kidney-shaped, and the nucleolus was evident. Thus, the microscopic changes observed in the cervical spinal cord were consistent with gemistocytic astrocytoma.

Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

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Choi, Seo Young; Kim, Myung Soon; Kim, Young Ju

2014-01-01

Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

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John Meshki

Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

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Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

2017-03-01

Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Anaplasia in pilocytic astrocytoma predicts aggressive behavior.

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Rodriguez, Fausto J; Scheithauer, Bernd W; Burger, Peter C; Jenkins, Sarah; Giannini, Caterina

2010-02-01

The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.

The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.

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Bissler, John J; Franz, David N; Frost, Michael D; Belousova, Elena; Bebin, E Martina; Sparagana, Steven; Berkowitz, Noah; Ridolfi, Antonia; Kingswood, J Christopher

2018-01-01

Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m 2 /day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged 20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding ≥ grade 2. Tolerability was also assessed. Overall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (≥80%) achieved clinically relevant reductions in angiomyolipoma volume (≥50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity. Although everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA.

Pilocytic Astrocytoma Presenting as an Orbital Encephalocele: A Case Report

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Amy Bruzek

2015-04-01

Full Text Available We describe the case of a 29-year-old male who presented with new-onset seizures. He was subsequently found to have an orbital encephalocele containing a focus of pilocytic astrocytoma. We believe that this is the first report of a pilocytic astrocytoma located within the orbit that did not originate from the optic pathway. It is also the first case of a pilocytic astrocytoma completely contained within an encephalocele. This case suggests a close pathological examination of encephaloceles for underlying diseases.

Computed tomography of benign supratentorial astrocytomas of infancy and childhood

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Pedersen, H.; Gjerris, F.; Klinken, L.

1981-01-01

The CT findings of 15 benign supratentorial astrocytomas in children less than 15 years of age are compared with the CT findings of 19 supratentorial tumors of other histological types in the same age group. Astrocytomas were more often hypodense, lacked calcification and showed greater contrast enhancement than other tumors. Seven of the 15 astrocytomas were hypodense, without calcification and showed contrast enhancement of more than 10 Hounsfield units, whereas this coexistence was not present in any of the 19 tumors of the other histological types. (orig.)

Imaging characteristics of pilomyxoid astrocytomas in comparison with pilocytic astrocytomas

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Lee, In Ho; Kim, Ji Hye; Suh, Yeon-Lim; Eo, Hong; Shin, Hyung Jin; Yoo, So-Young; Lee, Kyung Soo

2011-01-01

Purpose: Pilomyxoid astrocytoma (PMA) is a recently described astrocytic tumor that has been previously diagnosed as pilocytic astrocytoma (PA). The purpose of this study was to describe the imaging features of PMAs in comparison with PAs. Materials and methods: We retrospectively reviewed CT/MR images and medical records of 10 patients with PMA and 38 patients with PA. The mean ages of patients with PMA and PA were 10 and 15 years, respectively. Imaging features including location, composition, enhancement pattern, presence of calcification, hemorrhage, and leptomeningeal dissemination were compared in patients with two tumor types. Results: Six PMAs (60%) occurred at the suprasellar area and the cerebellum was the most common (45%) site of PA. Solid component was dominant in eight PMAs (80%) and in 19 PAs (50%). All of the PMAs containing solid mass (n = 8) included non-enhancing portion while 12/37 (32%) PAs included non-enhancing solid portion (p < 0.05). Leptomeningeal dissemination was noted in five PMAs (50%) and one PA (3%) (p < 0.05). Other imaging findings were not significantly different. Conclusion: A younger age, more frequent occurrence at the suprasellar area, mainly solid mass containing non-enhancing portion, and more frequent leptomeningeal dissemination are helpful differential features of PMAs as compared to PAs.

Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors

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Majid Kheirollahi

2017-01-01

Full Text Available Background: Patients affected by gliomas have a poor prognosis. Astrocytoma is a subtype of glioma. Identification of biomarkers could be an effective way to an early diagnosis of tumor or to distinguish more aggressive tumors that need more intensive therapy. In this study, we investigated whether the expression of miR-362 was increased or decreased in patients with different grades of astrocytoma. Materials and Methods: miR-362 expression was compared in 25 patients with astrocytoma with that of 4 normal nonneoplastic brain tissues. Results: In all tumor tissues, the expression of miR-362 was significantly decreased relative to its expression in normal brain tissues. However, there was no significant difference between miR-362 expressions in high and low grades of astrocytoma. Conclusions: In conclusion, miR-362 showed a down-regulation pattern in astrocytoma tissues that was different from the pattern obtained from previously published microarray studies.

An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

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Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

2015-09-04

Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

Postoperative irradiation of incompletely excised gemistocytic astrocytomas. Clinical outcome and prognostic factors

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Nowak-Sadzikowska, J.; Glinski, B.; Szpytma, T.; Pluta, E.

2005-01-01

Background and purpose: although gemistocytic astrocytomas are considered slow-growing tumors, they often behave aggressively and carry the least favorable prognosis among low-grade astrocytomas. The aim of this study is to evaluate the outcomes and prognostic factors of patients with incompletely excised gemistocytic astrocytomas irradiated postoperatively. Patients and methods: records of 48 patients with incompletely excised gemistocytic astrocytoma, irradiated between 1976 and 1998 at the department of radiation oncology, Maria Sklodowska-curie Memorial Cancer Center, Cracow, Poland, were reviewed. The total dose ranged from 50 to 60 Gy (mean: 59.35, median: 60 Gy) delivered in daily fractions of 2 Gy, 5 days a week. The treatment volume covered the residual tumor with a margin of 1-2 cm. Results: toxicity was acceptable. The overall actuarial survival rates at 5 and 10 years were 30% and 17%, respectively. Age and gender had an influence on overall survival by univariate and multivariate analysis (p < 0.05). Patients ≤ 35 years of age and female patients carried the best prognosis. Conclusion: in most patients with gemistocytic astrocytoma, combined surgery and postoperative radiotherapy result in only short-term survival. Older age is the most important unfavorable prognostic factor in patients with gemistocytic astrocytoma. (orig.)

Malignant transformation of a chiasmatic pilocytic astrocytoma in a patient with diencephalic syndrome

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Wal, Ester P.J. van der; Edwards-Brown, Mary; Azzarelli, Biagio

2003-01-01

Chiasmatic gliomas with metastatic spread are rare in children and are usually associated with diencephalic syndrome. They are mostly pilocytic astrocytomas and their transformation to high-grade astrocytomas has never previously been reported in the pediatric population. We report leptomeningeal spread of a chiasmatic pilocytic astrocytoma in a child presenting with diencephalic syndrome. He was treated with chemotherapy and radiation. The tumor recurred with transformation into a high-grade astrocytoma. Radiation therapy may have played a role in transformation of the tumor, but more research is needed to further clarify the biological behavior of this tumor. (orig.)

Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.

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Jones, Tania A; Jeyapalan, Jennie N; Forshew, Tim; Tatevossian, Ruth G; Lawson, Andrew R J; Patel, Sheena N; Doctor, Gabriel T; Mumin, Muhammad A; Picker, Simon R; Phipps, Kim P; Michalski, Antony; Jacques, Thomas S; Sheer, Denise

2015-12-18

Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas. Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B. These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs.

RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.

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Jin, Tian-Bo; Zhang, Jia-Yi; Li, Gang; Du, Shu-Li; Geng, Ting-Ting; Gao, Jing; Liu, Qian-Ping; Gao, Guo-Dong; Kang, Long-Li; Chen, Chao; Li, Shan-Qu

2013-12-01

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

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Teng, Chih-Chuan [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan (China); Kuo, Hsing-Chun [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Cheng, Ho-Chen [Department of General Education, Chang Gung University of Science and Technology, CGUST, Taiwan (China); Wang, Ting-Chung [Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi Center, Chiayi, Taiwan (China); Graduate Institute of Clinical Medical Sciences, Chang Gung University, Gueishan, Taiwan (China); Sze, Chun-I, E-mail: szec@mail.ncku.edu.tw [Institute of Basic Medicine Science, Department of Cell Biology and Anatomy and Pathology, National Cheng Kung University, Tainan, Taiwan (China)

2012-08-15

CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0 μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr{sup 15} and Cdc25cSer{sup 216}. Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer{sup 216} expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer{sup 216} in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer{sup 216} cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells. -- Highlights: ► We show the effects of CIL-102 on the G2/M arrest of human astrocytoma cells. ► ROS and the Ras/ERK1/2 triggering pathways are involved in the CIL-102 treatment. ► CIL-102 induces sustained activation of ERK1/2 and Cdc25c and ROS are required.

The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

International Nuclear Information System (INIS)

Teng, Chih-Chuan; Kuo, Hsing-Chun; Cheng, Ho-Chen; Wang, Ting-Chung; Sze, Chun-I

2012-01-01

CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0 μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr 15 and Cdc25cSer 216 . Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer 216 expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer 216 in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer 216 cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells. -- Highlights: ► We show the effects of CIL-102 on the G2/M arrest of human astrocytoma cells. ► ROS and the Ras/ERK1/2 triggering pathways are involved in the CIL-102 treatment. ► CIL-102 induces sustained activation of ERK1/2 and Cdc25c and ROS are required.

Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

International Nuclear Information System (INIS)

Hepler, J.R.; Harden, T.K.

1986-01-01

Formation of the inositol phosphates (InsP), InsP 3 , InsP 2 , and InsP 1 was increased in a concentration dependent manner (K/sub 0.5/ ∼ 5 μM) by GTPΣS in washed membranes prepared from 3 H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTPγS and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 μM GTPγS, carbachol stimulated (K/sub 0.5/ ∼ 10 μ M) the formation of InsP above the level achieved with GTPγS alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 μM carbachol was GTPγS > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTPγS or GTPγS plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTPγS in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells

A case of astrocytoma, 19 year history after BNCT

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Kamano, Shuji

2006-01-01

A 39-year-old man had received Boron Neutron Capture Therapy (BNCT) in 1987 for a Grade II Astrocytoma. He gradually exacerbated and received a second operation in 1994. The mass taken in the second operation is almost competent with radiation necrosis. Following that, he shows no signs of recurrence. Currently, he has returned to full time employment in physical labor. This case suggests effectiveness of BNCT for rather low-grade astrocytomas. (author)

Evaluation of invasiveness of astrocytoma using 1H-magnetic resonance spectroscopy: correlation with expression of matrix metalloproteinase-2

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Zhang, Kai; Li, Chuanfu; Ma, Xiangxing; Meng, Xiangshui; Feng, Dechao; Liu, Ying; Li, Li

2007-01-01

Even low-grade astrocytomas infiltrate the entire brain, a feature that precludes their successful therapy. So to assess the invasive potential of astrocytoma is very important. The aim of this study was determine whether there is a significant correlation between the results of 1 H-magnetic resonance spectroscopy ( 1 H-MRS) and tumor invasive potential of astrocytoma, which is reflected by expression of matrix metalloproteinase-2 (MMP-2). The 1 H-MRS spectra of 41 histologically verified astrocytomas were obtained on a 3-T MR scanner. According to the World Health Organization classification criteria for central nervous system tumors, there were 16 low-grade astrocytomas (2 pilocytic astrocytomas, 14 grade II astrocytomas) and 25 high-grade astrocytomas (5 anaplastic astrocytomas, 20 glioblastomas).The choline/N-acetylaspartate (Cho/NAA) and choline/creatine (Cho/Cr) ratios were calculated. Of the 41 astrocytomas, 19 (8 low-grade and 11 high-grade) were analyzed immunohistochemically. Expression of MMP-2 was determined using streptavidin-peroxidase complex (SP) staining which was quantified by calculating its calibrated opacity density (COD) using an image analysis system. The correlations between metabolite ratios and the quantitative data from the immunohistochemical tests in the 19 astrocytomas were determined. The Cho/NAA and Cho/Cr ratios of high-grade astrocytoma were both significantly greater than those of low-grade astrocytoma (t = -6.222, P = 0.000; t = -6.533, P = 0.000, respectively). MMP-2 COD values of high-grade astrocytomas were also significantly greater than those of low-grade astrocytomas (t = -5.892, P 0.000). There were strong positive correlations between Cho/NAA ratio and MMP-2 COD (r = 0.669, P = 0.002), and between Cho/Cr ratio and MMP-2 COD (r = 0.689, P = 0.001). 1 H-MRS is helpful in evaluating the invasiveness of astrocytomas and predicting prognosis preoperatively by determining the Cho/NAA and Cho/Cr ratios. (orig.)

ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas

International Nuclear Information System (INIS)

Tomaselli, Sara; Galeano, Federica; Massimi, Luca; Di Rocco, Concezio; Lauriola, Libero; Mastronuzzi, Angela; Locatelli, Franco; Gallo, Angela

2013-01-01

High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients. Total RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR). A significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival. High-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas

Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas

DEFF Research Database (Denmark)

Ramachandran, Rahimsan K.; Sørensen, Mia D.; Aaberg-Jessen, Charlotte

2017-01-01

with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2...... of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed...

Anorexia: an early sign of fourth ventricle astrocytoma in children.

Science.gov (United States)

Leroy, Henri-Arthur; Baroncini, Marc; Delestret, Isabelle; Florent, Vincent; Vinchon, Matthieu

2014-12-01

Paediatric low-grade astrocytomas of the fourth ventricle are rare tumours, generally revealed by hydrocephalus. However, some patients present with a history of severe anorexia. It might be a harbinger, which if recognized, could lead to earlier diagnosis. We decided to examine our database in order to evaluate the incidence and signification of anorexia in this context. Retrospective monocentric study of cases of low-grade astrocytomas of the fourth ventricle operated between 1991 and 2012 in our paediatric neurosurgery department. We particularly observed the clinical presentation and long-term clinical, oncological and radiological evolution. Non-parametrical tests were used (Mann-Whitney, Fisher). We reviewed 34 cases, 31 pilocytic astrocytomas and 3 diffuse astrocytomas, 16 boys and 18 girls, (M/F ratio 0.89). Mean age at diagnosis was 8 years old. Seven presented with notable anorexia, the average BMI in this group was ≤2 standard deviation (SD); with clinical signs evolving for 11.5 months. Twenty-seven children had no anorexia; average BMI in this group was +1 SD, with clinical evolution for 6 months on an average of p anorexia, body mass index improved markedly in the postoperative follow-up, which lasted, on average, for 6 years. Anorexia with stunted body weight curve is a non-exceptional presentation in children with low-grade astrocytomas of the fourth ventricle. Unexplained or atypical anorexia with negative etiologic assessment should prompt cerebral imaging. Clinical improvement after surgical resection, could suggest a possible interaction between tumour tissue and appetite-suppressing peptide secretion.

Methylation profiles of thirty four promoter-CpG islands and concordant methylation behaviours of sixteen genes that may contribute to carcinogenesis of astrocytoma

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Wang Yifei

2004-09-01

Full Text Available Abstract Background Astrocytoma is a common aggressive intracranial tumor and presents a formidable challenge in the clinic. Association of altered DNA methylation patterns of the promoter CpG islands with the expression profile of cancer-related genes, has been found in many human tumors. Therefore, DNA methylation status as such may serve as an epigenetic biomarker for both diagnosis and prognosis of human tumors, including astrocytoma. Methods We used the methylation specific PCR in conjunction with sequencing verification to establish the methylation profile of the promoter CpG island of thirty four genes in astrocytoma tissues from fifty three patients (The WHO grading:. I: 14, II: 15, III: 12 and IV: 12 cases, respectively. In addition, compatible tissues (normal tissues distant from lesion from three non-astrocytoma patients were included as the control. Results Seventeen genes (ABL, APC, APAF1, BRCA1, CSPG2, DAPK1, hMLH1, LKB1, PTEN, p14ARF, p15INK4b, p27KIP1, p57KIP2, RASSF1C, RB1, SURVIVIN, and VHL displayed a uniformly unmethylated pattern in all the astrocytoma and non-astrocytoma tissues examined. However, the MAGEA1 gene that was inactivated and hypermethylated in non-astrocytoma tissues, was partially demethylated in 24.5% of the astrocytoma tissues (co-existence of the hypermethylated and demethylated alleles. Of the astrocytoma associated hypermethylated genes, the methylation pattern of the CDH13, cyclin a1, DBCCR1, EPO, MYOD1, and p16INK4a genes changed in no more than 5.66% (3/53 of astrocytoma tissues compared to non-astrocytoma controls, while the RASSF1A, p73, AR, MGMT, CDH1, OCT6,, MT1A, WT1, and IRF7 genes were more frequently hypermethylated in 69.8%, 47.2%, 41.5%, 35.8%, 32%, 30.2%, 30.2%, 30.2% and 26.4% of astrocytoma tissues, respectively. Demethylation mediated inducible expression of the CDH13, MAGEA1, MGMT, p73 and RASSF1A genes was established in an astrocytoma cell line (U251, demonstrating that expression of

Holocord low grade astrocytoma - Role of radical irradiation and chemotherapy

International Nuclear Information System (INIS)

Goyal, S.; Puri, T.; Julka, R.K.

2015-01-01

Spinal intradural tumors, especially those extending along the entire length of the spinal cord, termed as ‘holocord’ tumors are uncommon. Most of these are gliomas, with astrocytomas (low grade) predominating in children and ependymomas in adults. Other histologies, though reported, are even rarer. Management is debatable, with both surgery and radiotherapy of such extensive tumors posing challenges. We describe a case of a 14-year-old girl with holocord astrocytoma extending from cervicomedullary junction till lumbar spine, who recovered full neurological function following radical irradiation of entire spine followed by temozolomide-based chemotherapy. No grade 3/4 bone marrow morbidity was seen. Five years following treatment, she maintained normal neurological function and apparently normal pubertal and skeletal growth despite residual disease visible on imaging. Literature review of existing reports of holocord astrocytomas highlighting management and outcome is presented.

Radical proposal for the treatment of malignant astrocytoma

International Nuclear Information System (INIS)

Karlsson, U.; Black, P.; Nair, S.; Yablon, J.S.; Brady, L.W.

1991-01-01

The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

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Cléciton Braga Tavares

Full Text Available Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

Science.gov (United States)

Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

2016-01-01

Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

Current treatment of low grade astrocytoma

DEFF Research Database (Denmark)

Pedersen, Christina Louise; Romner, Bertil

2013-01-01

Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have a v...... effective in discriminating between tumour progression and radiation necrosis. The research into biomarkers is currently limited with regards to their applications in LGA diagnostics, and therefore further studies including larger patient populations are needed.......Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have...... as the course of disease. The current literature seems to support the idea that treatment with radical tumour resection, where possible, yields better long term outcome for patients with LGA. However, adjuvant therapy is often necessary. Administering early postoperative radiotherapy to patients with partially...

Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

International Nuclear Information System (INIS)

Shahi, Mehdi H; Afzal, Mohammad; Sinha, Subrata; Eberhart, Charles G; Rey, Juan A; Fan, Xing; Castresana, Javier S

2010-01-01

The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes

Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell lines

International Nuclear Information System (INIS)

Qian Yongchang; Venkatraj, Jijayanagaram; Barhoumi, Rola; Pal, Ranadip; Datta, Aniruddha; Wild, James R.; Tiffany-Castiglioni, Evelyn

2007-01-01

The objective of this study was to evaluate the comparative non-cholinergic neurotoxic effects of paraoxon, which is acutely neurotoxic, and diisopropyl fluorophosphate (DFP), which induces OPIDN, in the human neuroblastoma SY5Y and the human astrocytoma cell line CCF-STTG1. SY5Y cells have been studied extensively as a model for OP-induced neurotoxicity, but CCF cells have not previously been studied. We conducted a preliminary human gene array assay of OP-treated SY5Y cells in order to assess at the gene level whether these cells can distinguish between OP compounds that do and do not cause OPIDN. Paraoxon and DFP induced dramatically different profiles of gene expression. Two genes were upregulated and 13 downregulated by at least 2-fold in paraoxon-treated cells. In contrast, one gene was upregulated by DFP and none was downregulated at the 2-fold threshold. This finding is consistent with current and previous observations that SY5Y cells can distinguish between OPs that do or do not induce OPIDN. We also examined gene array results for possible novel target proteins or metabolic pathways for OP neurotoxicity. Protein levels of glucose regulated protein 78 (GRP78) revealed that paraoxon exposure at 3 μM for 24 h significantly reduced GRP78 levels by 30% in neuroblastoma cells, whereas DFP treatment had no effect. In comparison with SY5Y neuroblastoma cells, paraoxon and DFP (3 μM for 24 h) each significantly increased GRP78 levels by 23-24% in CCF astrocytoma cells. As we have previously evaluated intracellular changes in Ca 2+ levels in SY5Y cells, we investigated the effects of paraoxon and DFP on cellular Ca 2+ homeostasis in CCF by studying cytosolic and mitochondrial basal calcium levels. A significant decrease in the ratio of mitochondrial to cytosolic Ca 2+ fluorescence was detected in CCF cultures treated for either 1 or 3 days with 1, 3, 10, or 30 μM paraoxon. In contrast, treatment with DFP for 1 day had no significant effect on the ratio of

Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma

Energy Technology Data Exchange (ETDEWEB)

Heo, Young Jin [Inje University, Busan Paik Hospital, Department of Radiology, Busan (Korea, Republic of); Park, Ji Eun; Kim, Ho Sung; Lee, Ji Ye; Jung, Seung Chai; Choi, Choong Gon; Kim, Sang Joon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Nam, Soo Jeong [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

2017-07-15

To determine if gemistocytic grade II astrocytoma (GemA) and its MR imaging characteristics are associated with a shorter time-to-progression (TTP) compared with non-gemistocytic grade II astrocytoma (non-GemA). We enrolled 78 patients who were followed up more than 5 years (29 pathologically proven GemA and 49 non-GemA) during a 10-year period. Contrast-enhanced T1-weighted, diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC), and MR spectroscopy (MRS) and clinical data were retrospectively reviewed. Clinical and MR imaging features were analyzed as possible prognostic factors of high-grade transformation, and multivariate analysis of TTP was performed using Cox proportional modeling. GemA showed more frequent high-grade features than non-GemA, including diffusion restriction (P <.001), increased choline/creatine (P =.02), and increased choline/NAA ratio (P =.015). Patients with GemA had a significantly shorter median TTP (53.1 vs 68 months; P <.001). A gemistocytic histopathology (hazard ratio = 3.42; P =.015) and low ADC (hazard ratio = 3.61; P =.001) were independently associated with a shorter TTP. GemA can present with MR imaging findings mimicking high-grade glioma at initial diagnosis and transforms to high-grade disease earlier than non-GemA. Low ADC on DWI might be useful in stratifying the risk of progression in patients with grade II astrocytoma. (orig.)

Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma

NARCIS (Netherlands)

Münch, C.; Penndorf, A.; Schwalenstöcker, B.; Troost, D.; Ludolph, A. C.; Ince, P.; Meyer, T.

2001-01-01

A loss of the glutamate transporter EAAT2 has been reported in the neoplastic transformation of astrocytic cells and astrocytoma. The RNA expression of EAAT2 and five 5'-regulatory splice variants was investigated to identify alterations of the post-transcriptional EAAT2 gene regulation in human

Effects of γ-radiation on cell growth, cell cycle and promoter methylation of 22 cell cycle genes in the 1321NI astrocytoma cell line.

Science.gov (United States)

Alghamian, Yaman; Abou Alchamat, Ghalia; Murad, Hossam; Madania, Ammar

2017-09-01

DNA damage caused by radiation initiates biological responses affecting cell fate. DNA methylation regulates gene expression and modulates DNA damage pathways. Alterations in the methylation profiles of cell cycle regulating genes may control cell response to radiation. In this study we investigated the effect of ionizing radiation on the methylation levels of 22 cell cycle regulating genes in correlation with gene expression in 1321NI astrocytoma cell line. 1321NI cells were irradiated with 2, 5 or 10Gy doses then analyzed after 24, 48 and 72h for cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu bromide) assay. Flow cytometry were used to study the effect of 10Gy irradiation on cell cycle. EpiTect Methyl II PCR Array was used to identify differentially methylated genes in irradiated cells. Changes in gene expression was determined by qPCR. Azacytidine treatment was used to determine whether DNA methylation affectes gene expression. Our results showed that irradiation decreased cell viability and caused cell cycle arrest at G2/M. Out of 22 genes tested, only CCNF and RAD9A showed some increase in DNA methylation (3.59% and 3.62%, respectively) after 10Gy irradiation, and this increase coincided with downregulation of both genes (by 4 and 2 fold, respectively). with azacytidine confirmed that expression of CCNF and RAD9A genes was regulated by methylation. 1321NI cell line is highly radioresistant and that irradiation of these cells with a 10Gy dose increases DNA methylation of CCNF and RAD9A genes. This dose down-regulates these genes, favoring G2/M arrest. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

Energy Technology Data Exchange (ETDEWEB)

Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

2010-08-15

A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

Directory of Open Access Journals (Sweden)

Eberhart Charles G

2010-11-01

Full Text Available Abstract Background The Sonic hedgehog (Shh signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63% and primary astrocytoma tumor samples (32%, but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.

Clinical Implications of the Epidermal Growth Factor Receptor overexpression in the High-grade Astrocytomas

International Nuclear Information System (INIS)

Hong, Seong Eon; Kang, Jin Oh; Lee, Hye Kyoung; Yang, Moon Ho; Leem, Won; Cho, Kyung Sam

1996-01-01

To determine the incidence and prognostic effects of EGFR overexpression in the high-grade astrocytomas. With 23 paraffin blocks of the high-garde astrocytomas, expression of EGFR were evaluated by immunohistochemical staining employing polyclonal antibody raised to short cytoplasmic domain of the molecule. Two out of 7 anaplastic astrocytomas and 9 out of 16 glioblastoma multiform patients showed overexpression of EGFR(p=0.44). Three out of 11 patients of age below 55 and 8 out of 12 patients of age over 54 showed EGFR overexpression(p=0.141). Median survival of the EGFR negative anaplastic astrocytoma patient was 37 months. Median survival of the glioblastoma multiform patients were 11 months in EGFR negative group and 7 months in EGFR positive group. But survival difference was not significant(p=0.17). There was a marked trend of increasing overexpression of EGFR in older patients. But survival of the glioblastoma multiform decreased by the overexpression of the EGFR without significant

Clinical significance of changes of serum expression of IGF-I in patients with astrocytoma

International Nuclear Information System (INIS)

Liu Jianbo; Ding Dongmei; Yang Fubing

2005-01-01

Objective: To investigate the serum expression of IGF-I in patients with astrocytoma of different degrees of malignancy as well as the changes of levels after operative removal of the tumor. Methods: Serum IGF-I contents were measured with IRMA in 16 patients with Grade I-II astrocytoma and 14 patients with Grade III-IV astrocytoma both before and after operation as well as in 30 controls. Results: The serum contents of IGF-I in both groups of patients were significantly higher than those in controls (P<0.05). The levels in Grade III-IV patients were significantly higher than those in Grade I-II patients (P < 0.05 ). After operation, the levels dropped significantly (vs before operation, P<0.05). Conclusion: The serum contents of IGF - I in patients with astrocytoma were positively correlated with the degree of malignancy. Post-operative decrease of IGF-I contents was related to the decrease of tumor burden. (authors)

[Diagnostic imaging of high-grade astrocytoma: heterogeneity of clinical manifestation, image characteristics, and histopathological findings].

Science.gov (United States)

Okajima, Kaoru; Ohta, Yoshio

2012-10-01

Recent developments in diagnostic radiology, which have enabled accurate differential diagnoses of brain tumors, have been well described in the last three decades. MR and PET imaging can also provide information to predict histological grades and prognoses that might influence treatment strategies. However, high-grade astrocytomas consist of many different subtypes that are associated with different imaging and histological characteristics. Hemorrhage and necrosis results in a variety of imaging features, and infiltrative tumor growth entrapping normal neurons may cause different clinical manifestations. We reviewed patients with high-grade astrocytomas that showed various imaging characteristics, with special emphasis on initial symptoms and histological features. Clinicopathological characteristics of astrocytomas were also compared with other malignant tumors. Neurological deficits were not notable in patients with grade 3-4 astrocytomas when they showed infiltrative tumor growth, while brain metastases with compact cellular proliferation caused more neurological symptoms. Infiltrative tumors did not show any enhancing masses on MR imaging, but these tumors may show intratumor heterogeneity. Seizures were reported to be more frequent in low-grade glioma and in secondary glioblastoma. Tumor heterogeneity was also reported in molecular genetic profile, and investigators identified some subsets of astrocytomas. They investigated IHD1/2 mutation, EGFR amplification, TP53 mutation, Ki-67 index, etc. In summary, high-grade astrocytomas are not homogenous groups of tumors, and this is associated with the heterogeneity of clinical manifestation, image characteristics, and histopathological findings. Molecular studies may explain the tumor heterogeneity in the near future.

Treatment results of non-pilocytic cerebral astrocytomas in adults treated by surgery, radiation therapy and chemotherapy

International Nuclear Information System (INIS)

Matsutani, Masao; Nishikawa, Ryo; Sugiyama, Satoshi; Fujimaki, Takamitsu; Nakamura, Osamu

1999-01-01

Non-pilocytic cerebral astrocytomas in adults are oncopathologically defined as well-differentiated carcinoma of the brain. They grow invasively and can not be cured by extensive surgery followed by radiation therapy. We performed multidisciplinary treatments consisting of surgery, radiation therapy and chemotherapy in 26 adult patients with non-pilocytic cerebral astrocytomas. The 5- and 10-year survival rates of the patients were 90.9% and 75.6%, respectively; these were better than reported survival rates of patients treated by postoperative radiation therapy alone. Precise analysis of clinical findings of astrocytic tumors suggested that glioblastomas growing superficially might be derived from preexisting astrocytomas. This hypothesis proposes that multidisciplinary treatments for astrocytomas in early stages could cure the disease and could ultimately decrease a number of glioblastomas. (author)

Malignant astrocytoma following radiotherapy for craniopharyngioma

Energy Technology Data Exchange (ETDEWEB)

Maat-Schieman, M.L.C.; Bots, G.T.A.M.; Thomeer, T.W.M.; Vielvoye, G.J. (Rijksuniversiteit Leiden (Netherlands). Hospital)

1985-05-01

The case report describes a boy with a malignant astrocytoma in the mid-line of the cerebellum 14 years after X-ray therapy for craniopharyngioma. In Leiden University Hospital this is the first case of a suspected radiation-induced brain tumour in 66 patients treated for cranial lesions by radiotherapy between 1969 and 1979 who have survived more than 5 years.

Malignant astrocytoma following radiotherapy for craniopharyngioma

International Nuclear Information System (INIS)

Maat-Schieman, M.L.C.; Bots, G.T.A.M.; Thomeer, T.W.M.; Vielvoye, G.J.

1985-01-01

The case report describes a boy with a malignant astrocytoma in the mid-line of the cerebellum 14 years after X-ray therapy for craniopharyngioma. In Leiden University Hospital this is the first case of a suspected radiation-induced brain tumour in 66 patients treated for cranial lesions by radiotherapy between 1969 and 1979 who have survived more than 5 years. (author)

Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

Directory of Open Access Journals (Sweden)

Maher Kurdi

2014-01-01

Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

Study on the correlation between VEGF and peritumoral edema and tumor border in astrocytoma by CT

International Nuclear Information System (INIS)

Ye Yuxiang; Tan Siping; Liu Bo; Liu Guorui; Zhen Zhichao; Fan Miao

2004-01-01

Objective: To study the correlation between VEGF and peritumoral edema and tumor border in human astrocytoma, investigate the significance of its CT features in molecular-biology. Methods: The VEGF was examined by means of SP immunohistochemical technique in 52 cases of astrocytoma proved by pathology. The correlation of tumor VEGF with peritumoral edema, and tumor border was analyzed. Results: The peritumoral edema, tumor border and mass effect of astrocytoma was positively correlated with its VEGF. The VEGF increased with peritumoral edema and mass effect (P<0.01). VEGF were significantly higher in uncertain border group than those the clear border group (P<0.05), which VEGF were 69.2 ± 19.0. Conclusion: The over expression of VEGF obviously effect CT features in astrocytoma, such as peritumoral edema and tumor border

Estimation of radiotherapy and MCNU versus radiotherapy and MCNU plus interferon-[beta] for the treatment of anaplastic astrocytoma

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Kiya, Katsuzo; Uozumi, Tohru; Kurisu, Kaoru; Ogasawara, Hidenori; Sugiyama, Kazuhiko; Maeda, Hitoshi; Harada, Kunyu (Hiroshima Univ. (Japan). School of Medicine)

1993-02-01

The efficacy of radiotherapy and MCNU (MR) was estimated in comparison with radiotherapy and MCNU plus interferon-[beta] (IMR) in 25 patients with anaplastic astrocytoma. The MR group received irradiation with 50[approx]60 Gy and intravenous administration of 2 mg/kg of MCNU on the initial day of irradiation and following every 6[approx]8 weeks interval. The IMR group also received the same regimen in addition to intravenous infusion of 2 x 10[sup 6] IU/m[sup 2] of interferon-[beta] for 5 serial days every eight weeks and following once every two weeks. There were no significant differences between the two groups in terms of background. The response rates of MR and IMR group were 38.5% and 66.7%, respectively. The times to tumor progression (TTP) in the two groups were 11.9[+-]5.8 months and 13.6[+-]7.7 months, respectively. Thus, IMR therapy seems to be more efficacious for patients with anaplastic astrocytoma than MR therapy, but further trials are necessary. (author).

astrocytoma – diagnostic pitfalls. A review

Directory of Open Access Journals (Sweden)

Ewa Matyja

2016-10-01

Full Text Available Pilocytic astrocytomas (PAs are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome – neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK pathway have been considered to underlie the development of PAs. The most

Childhood Astrocytomas Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Astrocytoma is the most common type of glioma in children. Get detailed information about the clinical features, molecular and diagnostic evaluation, classification, prognosis, and treatment of newly diagnosed and recurrent disease low-grade and high-grade gliomas in this comprehensive summary for clinicians.

Adenosine Receptors Differentially Regulate the Expression of Regulators of G-Protein Signalling (RGS 2, 3 and 4 in Astrocyte-Like Cells.

Directory of Open Access Journals (Sweden)

Till Nicolas Eusemann

Full Text Available The "regulators of g-protein signalling" (RGS comprise a large family of proteins that limit by virtue of their GTPase accelerating protein domain the signal transduction of G-protein coupled receptors. RGS proteins have been implicated in various neuropsychiatric diseases such as schizophrenia, drug abuse, depression and anxiety and aggressive behaviour. Since conditions associated with a large increase of adenosine in the brain such as seizures or ischemia were reported to modify the expression of some RGS proteins we hypothesized that adenosine might regulate RGS expression in neural cells. We measured the expression of RGS-2,-3, and -4 in both transformed glia cells (human U373 MG astrocytoma cells and in primary rat astrocyte cultures stimulated with adenosine agonists. Expression of RGS-2 mRNA as well as RGS2 protein was increased up to 30-fold by adenosine agonists in astrocytes. The order of potency of agonists and the blockade by the adenosine A2B-antagonist MRS1706 indicated that this effect was largely mediated by adenosine A2B receptors. However, a smaller effect was observed due to activation of adenosine A2A receptors. In astrocytoma cells adenosine agonists elicited an increase in RGS-2 expression solely mediated by A2B receptors. Expression of RGS-3 was inhibited by adenosine agonists in both astrocytoma cells and astrocytes. However while this effect was mediated by A2B receptors in astrocytoma cells it was mediated by A2A receptors in astrocytes as assessed by the order of potency of agonists and selective blockade by the specific antagonists MRS1706 and ZM241385 respectively. RGS-4 expression was inhibited in astrocytoma cells but enhanced in astrocytes by adenosine agonists.

Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

DEFF Research Database (Denmark)

Therkildsen, C; Ladelund, S; Rambech, E

2015-01-01

.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical...

Combined value of susceptibility weighted imaging and dynamic susceptibility-weighted contrast-enhanced MR perfusion-weighted imaging in brain astrocytoma grading

International Nuclear Information System (INIS)

Wang Xiaochun; Zhang Hui; Qin Jiangbo; Wang Le; Wu Xiaofeng

2012-01-01

Objective: To assess the value of combination of susceptibility weighted imaging (SWI) and dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion-weighted magnetic resonance imaging in astrocytoma grading. Methods: SWI and DSC scans were performed in 82 patients with pathologically confirmed astrocytoma. The patient group consisted of grade Ⅱ (15), grade Ⅲ (10), and grade Ⅳ (57). The intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max were used to determine the grade of astrocytomas by Kruskal Wallis test, Welch test, Spearman correlation coefficients, Pearson correlation coefficients, and receiver operating characteristic curve (ROC)statistic methods. Results: There were no ITSS in 14 cases of low-grade astrocytomas, the degree of ITSS were grade 1 to 3 in anaplastic astrocytomas, the degree of ITSS were grade 3 in all of the glioblastomas, the degree of ITSS were significant difference in all grades (H=71.96, P<0.01). rCBV max in grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were 1.26 ± 0.42, 3.59 ± 2.09 and 8.34 ± 1.16 respectively, rCBV max were significant difference in all grades (F'=681.72, P<0.01). ITSS showed significant correlation with rCBV max (r=0.72, P<0.01) and tumor grades (r=0.89, P<0.01), and rCBV and tumor grades showed significant correlation (r=0.78, P<0.01). Area under the ROC curve application SWI, DSC, SWI and DSC in differentiation of the grade Ⅱ and grade Ⅲ astrocytomas were 0.99, 0.93, 1.00, differentiate grade Ⅲ from grade Ⅳ were 0.70, 0.94, 0.94, and differentiate high-grade from low-grade astrocytomas were 1.00, 0.99, 1.00. Conclusions: ITSS is helpful to determine the grade of astrocytomas. The use of SWI in combination with DSC may improve the diagnostic accuracy of astrocytoma grading. (authors)

Chondrogenic differentiation of ATDC5-cells under the influence of Mg and Mg alloy degradation

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Martinez Sanchez, Adela H., E-mail: adela.martinez@hzg.de [Helmholtz-Zentrum Geesthacht, Institute of Material Research, Department for Structural Research on Macromolecules, Geesthacht (Germany); Feyerabend, Frank; Laipple, Daniel; Willumeit-Römer, Regine [Helmholtz-Zentrum Geesthacht, Institute of Material Research, Department for Structural Research on Macromolecules, Geesthacht (Germany); Weinberg, Annelie [Department of Orthopedics and Orthopedic Surgery, Medical University of Graz (Austria); Luthringer, Bérengère J.C. [Helmholtz-Zentrum Geesthacht, Institute of Material Research, Department for Structural Research on Macromolecules, Geesthacht (Germany)

2017-03-01

Biodegradable magnesium (Mg)-based materials are a potential alternative to permanent implants for application in children. Nevertheless effects of those materials on growth plate cartilage and chondrogenesis have not been previously evaluated. In vitro differentiation of ATDC5 cells was evaluated under the influence of pure Mg (PMg), Mg with 10 wt% of gadolinium (Mg-10Gd) and Mg with 2 wt% of silver (Mg-2Ag) degradation products (extracts) and direct cell culture on the materials. Gene expression showed an inhibitory effect on ATDC5 mineralization with the three extracts and a chondrogenic potential of Mg-10Gd. Cells cultured in Mg-10Gd and Mg-2Ag extracts showed the same proliferation and morphology than cells cultured in growth conditions. Mg-10Gd induced an increase in production of ECM and a bigger cell size, similar to the effects found with differentiation conditions. An increased metabolic activity was observed in cells cultured under the influence of Mg-10Gd extracts, indicated by an acidic pH during most of the culture period. After 7 days of culture on the materials, ATDC5 growth, distribution and ECM synthesis were higher on Mg-10Gd samples, followed by Mg-2Ag and PMg, which was influenced by the homogeneity and composition of the degradation layer. This study confirmed the tolerance of ATDC5 cells to Mg-based materials and a chondrogenic effect of Mg-10Gd. Further studies in vitro and in vivo are necessary to evaluate cell reactions to those materials, as well as the effects on bone growth and the biocompatibility of the alloying system in the body. - Highlights: • Degradation of PMg, and Mg-2Ag do not influence ATDC5 cells growth and chondrogenic redifferentiation. • Mg-10Gd enhances fast chondrogenic redifferentiation and expression of hyperthrophic markers on ATDC5 cells. • Further evaluation of the effects of PMg, Mg-10Gd and Mg-2Ag in vivo are necessary to confirm its potential for application in growing bones.

Chondrogenic differentiation of ATDC5-cells under the influence of Mg and Mg alloy degradation

International Nuclear Information System (INIS)

Martinez Sanchez, Adela H.; Feyerabend, Frank; Laipple, Daniel; Willumeit-Römer, Regine; Weinberg, Annelie; Luthringer, Bérengère J.C.

2017-01-01

Biodegradable magnesium (Mg)-based materials are a potential alternative to permanent implants for application in children. Nevertheless effects of those materials on growth plate cartilage and chondrogenesis have not been previously evaluated. In vitro differentiation of ATDC5 cells was evaluated under the influence of pure Mg (PMg), Mg with 10 wt% of gadolinium (Mg-10Gd) and Mg with 2 wt% of silver (Mg-2Ag) degradation products (extracts) and direct cell culture on the materials. Gene expression showed an inhibitory effect on ATDC5 mineralization with the three extracts and a chondrogenic potential of Mg-10Gd. Cells cultured in Mg-10Gd and Mg-2Ag extracts showed the same proliferation and morphology than cells cultured in growth conditions. Mg-10Gd induced an increase in production of ECM and a bigger cell size, similar to the effects found with differentiation conditions. An increased metabolic activity was observed in cells cultured under the influence of Mg-10Gd extracts, indicated by an acidic pH during most of the culture period. After 7 days of culture on the materials, ATDC5 growth, distribution and ECM synthesis were higher on Mg-10Gd samples, followed by Mg-2Ag and PMg, which was influenced by the homogeneity and composition of the degradation layer. This study confirmed the tolerance of ATDC5 cells to Mg-based materials and a chondrogenic effect of Mg-10Gd. Further studies in vitro and in vivo are necessary to evaluate cell reactions to those materials, as well as the effects on bone growth and the biocompatibility of the alloying system in the body. - Highlights: • Degradation of PMg, and Mg-2Ag do not influence ATDC5 cells growth and chondrogenic redifferentiation. • Mg-10Gd enhances fast chondrogenic redifferentiation and expression of hyperthrophic markers on ATDC5 cells. • Further evaluation of the effects of PMg, Mg-10Gd and Mg-2Ag in vivo are necessary to confirm its potential for application in growing bones.

Chondrogenic differentiation of ATDC5-cells under the influence of Mg and Mg alloy degradation.

Science.gov (United States)

Martinez Sanchez, Adela H; Feyerabend, Frank; Laipple, Daniel; Willumeit-Römer, Regine; Weinberg, Annelie; Luthringer, Bérengère J C

2017-03-01

Biodegradable magnesium (Mg)-based materials are a potential alternative to permanent implants for application in children. Nevertheless effects of those materials on growth plate cartilage and chondrogenesis have not been previously evaluated. In vitro differentiation of ATDC5 cells was evaluated under the influence of pure Mg (PMg), Mg with 10wt% of gadolinium (Mg-10Gd) and Mg with 2wt% of silver (Mg-2Ag) degradation products (extracts) and direct cell culture on the materials. Gene expression showed an inhibitory effect on ATDC5 mineralization with the three extracts and a chondrogenic potential of Mg-10Gd. Cells cultured in Mg-10Gd and Mg-2Ag extracts showed the same proliferation and morphology than cells cultured in growth conditions. Mg-10Gd induced an increase in production of ECM and a bigger cell size, similar to the effects found with differentiation conditions. An increased metabolic activity was observed in cells cultured under the influence of Mg-10Gd extracts, indicated by an acidic pH during most of the culture period. After 7days of culture on the materials, ATDC5 growth, distribution and ECM synthesis were higher on Mg-10Gd samples, followed by Mg-2Ag and PMg, which was influenced by the homogeneity and composition of the degradation layer. This study confirmed the tolerance of ATDC5 cells to Mg-based materials and a chondrogenic effect of Mg-10Gd. Further studies in vitro and in vivo are necessary to evaluate cell reactions to those materials, as well as the effects on bone growth and the biocompatibility of the alloying system in the body. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

International Nuclear Information System (INIS)

Guss, Zachary D.; Moningi, Shalini; Jallo, George I.; Cohen, Kenneth J.; Wharam, Moody D.; Terezakis, Stephanie A.

2013-01-01

Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

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Guss, Zachary D.; Moningi, Shalini [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland (United States); Jallo, George I. [Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland (United States); Cohen, Kenneth J. [Division of Pediatric Oncology, Johns Hopkins Hospital, Baltimore, Maryland (United States); Wharam, Moody D. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: stereza1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland (United States)

2013-04-01

Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

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Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S. [Department of Radiation Oncology, Methodist Hospital, Houston, TX (United States); Chintagumpala, Murali [Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Paulino, Arnold C., E-mail: apaulino@tmhs.org [Department of Radiation Oncology, Methodist Hospital, Houston, TX (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States)

2012-10-01

Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD). Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria. Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields. Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.

Leptomeningeal dissemination of an astrocytoma causing hypophyseal insufficiency

International Nuclear Information System (INIS)

Suzan, S.; Cigdem, O.; Furkan, U.; Baki, A.

2012-01-01

Full text: Introduction: Hypophyseal insufficiency is an unusual clinical presentation of metastatic disease. Objectives: In this report, a case of leptomeningeal metastasis of an astrocytoma to the infundibular recess, causing hypophyseal insufficiency is presented with its magnetic resonance imaging (MRI) findings. Materials and methods: A 27-year-old woman presented with nausea, vomiting and generalized weakness. Her laboratory results were consistent with hypopituitarism. She had an operation history for astrocytoma. She was referred to radiology department for brain MRI study. Contrast-enhanced MRI scan showed extensive wall enhancement of ventricles consistent with leptomeningeal metastases. A nodular mass with pronounced contrast enhancement was also detected at the infundibular stalk. Results: Because suprasellar cistern was normal and extensive leptomeningeal metastases was detected, the nodular mass at the infundibular stalk thought to be secondary to leptomeningeal involvement of the infundibular recess. Conclusion: When a patient with a known malignancy presented with hypophyseal insufficiency, it should be thought that leptomeningeal metastases to the infundibular recess may also be a cause. The neuroimaging, especially contrast-enhanced studies, is necessary for the confirmation

The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells.

Science.gov (United States)

Alaimo, Agustina; Gorojod, Roxana M; Kotler, Mónica L

2011-08-01

Manganese (Mn) is a trace element known to be essential for maintaining the proper function and regulation of many biochemical and cellular reactions. However, chronic exposure to high levels of Mn in occupational or environmental settings can lead to its accumulation in the brain resulting in a degenerative brain disorder referred to as Manganism. Astrocytes are the main Mn store in the central nervous system and several lines of evidence implicate these cells as major players in the role of Manganism development. In the present study, we employed rat astrocytoma C6 cells as a sensitive experimental model for investigating molecular mechanisms involved in Mn neurotoxicity. Our results show that C6 cells undergo reactive oxygen species-mediated apoptotic cell death involving caspase-8 and mitochondrial-mediated pathways in response to Mn. Exposed cells exhibit typical apoptotic features, such as chromatin condensation, cell shrinkage, membrane blebbing, caspase-3 activation and caspase-specific cleavage of the endogenous substrate poly (ADP-ribose) polymerase. Participation of the caspase-8 dependent pathway was assessed by increased levels of FasL, caspase-8 activation and Bid cleavage. The involvement of the mitochondrial pathway was demonstrated by the disruption of the mitochondrial membrane potential, the opening of the mitochondrial permeability transition pore, cytochrome c release, caspase-9 activation and the increased mitochondrial levels of the pro-apoptotic Bcl-2 family proteins. In addition, our data also shows for the first time that mitochondrial fragmentation plays a relevant role in Mn-induced apoptosis. Taking together, these findings contribute to a deeper elucidation of the molecular signaling mechanisms underlying Mn-induced apoptosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Association of invasive breast carcinoma and multicentric high grade astrocytoma: a case report with a review.

Science.gov (United States)

Pour, P Hossein; Forouzandeh, M; Beni, A Naderi; Beni, Z Naderi; Hoseinpour, P

2011-03-01

Breast cancer is the most common cancer in women. Multicentric gliomas are uncommon lesions of the central nervous system (CNS) with an unprecise rate of occurrence that diffusely infiltrate large portions of the brain. High grade astrocytoma is the most agressive form of gliomas and often has a distinct neuroimaging pattern with a poor prognosis. We report a case of a 29-year-old woman patient with primary breast carcinoma and high grade astrocytoma subsequently developed. The woman was treated by mastectomy and 20 months post-diagnosis of the cancer she exhibited a transient facial paralysis. Magnetic resonance imaging (MRI) revealed two cranial masses suspicious of metastasis. A complete tumor removal from the brain was performed. On histological examination, this tumor was a high grade astrocytoma.

[Familial astrocytoma associated with von Recklinghausen's disease: report of two cases].

Science.gov (United States)

Ito, Y; Oki, S; Mikami, T; Ogasawara, H; Kawamoto, Y; Sato, H; Yamaguchi, S; Hayashi, Y; Shindo, H

1997-03-01

Two cases of astrocytoma associated with von Recklinghausen's disease (neurofibromatosis type; NF-1) were reported. The first case wes a 60-year-old man who had been diagnosed as von Recklinghausen's disease on the basis of skin findings. Magnetic resonance imaging (MRI) showed a tumor in the left temporal lobe. Partial removal was performed with neuronavigator, and because of the existence of Rosenthal fiber the histological diagnosis was pilocytic astrocytoma. Radiation therapy was performed. The second case was a 6-year-old boy suffering from headache and left hemiparesis including his face. MRI showed a tumor with a cyst in the right thalamus and obstructive hydrocephalus. Initially CT-guided stereotactic biopsy was performed, and the histological diagnosis, on the basis of increased cellularity, pleomorphism and nuclear atypia without necrosis or vascular proliferation, was anaplastic astrocytoma. Radiation and chemo-immuno therapy were carried out after V-P shunt. It is well known that von Recklinghausen's disease (NF-1) is often associated with optic glioma (5-36%). In the literature, the glioma seldom occurs in other parts of the brain, supratentorial glioma especially is rare. Only two familial cases of supratentorial glioma associated with von Recklinghausen's disease have been reported. The prognosis of supratentorial glioma associated with NF-1 was poor in these reports. In this paper, the diagnostic and therapeutic problems are discussed.

Vascular endothelial growth factor and basic fibroblast growth factor expression positively correlates with angiogenesis and peritumoural brain oedema in astrocytoma

International Nuclear Information System (INIS)

Jang, F.F.; Wei, W.

2008-01-01

Astrocytoma is the most malignant intracranial neoplasm and is characterized by high neovascularization and peritumoural brain oedema. Angiogenesis is a complicated process in oncogenesis regulated by the balance between angiogenic and antiangiogenic factors. The expression of two angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor were investigated using immunohistochemistry for astrocytoma from 82 patients and 11 normal human tissues. The expression of vascular endothelial growth factor and basic fibroblast growth factor positively correlate with the pathological grade of astrocytoma, microvessel density numbers and brain oedema, which may be responsible for the increased tumour neovascularization and peritumoural brain oedema. The results support the idea that inhibiting vascular endothelial growth factor and basic fibroblast growth factor are useful for the treatment of human astrocytoma and to improve patient's clinical outcomes and prognosis. (author)

Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

Science.gov (United States)

Muallaoglu, Saik; Besen, Ali Ayberk; Ata, Alper; Mertsoylu, Huseyin; Arican, Ali; Kayaselcuk, Fazilet; Ozyilkan, Ozgur

2014-01-01

Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

MRS of pilocytic astrocytoma: The peak at 2 ppm may not be NAA.

Science.gov (United States)

Tamrazi, Benita; Nelson, Marvin D; Blüml, Stefan

2017-08-01

To determine whether the chemical shift of residual N-acetylaspartate (NAA) signal in pilocytic astrocytomas (PA) is consistent with the position of the NAA peak in controls. MR spectra from 27 pediatric World Health Organization (WHO) grade I pilocytic astrocytoma patients, fifteen patients with WHO grade II and high-grade (III-IV) astrocytomas, and 36 controls were analyzed. All spectra were acquired with a short echo time (35 ms), single voxel point-resolved spectroscopy sequence on clinical 3 tesla scanners. Fully automated LCModel software was used for processing, which included the fitting of peak positions for NAA and creatine (Cr). The chemical shift difference between the NAA and Cr peaks was significantly smaller (by 0.016 ± 0.005 parts per million, P NAA peak in PAs is not consistent with NAA. The signal likely originates from an N-acetyl group of one or more other chemicals such as N-acetylated sugars. Magn Reson Med 78:452-456, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Astrocytoma of the pituitary gland (pituicytoma): case report

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Uesaka, T.; Miyazono, M.; Nishio, S.; Iwaki, T.

2002-01-01

A 34-year-old man presented with a 4-month history of visual obscuration. Magnetic resonance imaging showed a solid, discrete, contrast-enhancing pituitary mass with suprasellar extension. Surgery, which was performed via a transsphenoidal approach, disclosed the pituitary tumor to be a fibrillary astrocytoma (pituicytoma). This case report contains the clinical and neuroimaging features of this rare tumor of the neurohypophysis, which masqueraded as a pituitary adenoma. (orig.)

FLAIR MR sequence in the diagnosis and follow-up of low-grade astrocytomas

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Stošić-Opinćal Tatjana

2005-01-01

Full Text Available Aim. To evaluate the sensitivity of fluid-attenuated inversion recovery (FLAIR sequence in the diagnosis and follow-up of the patients with low-grade astrocytomas compared with T2-weighted (T2W sequence. Methods. Twenty-four patients with biopsy- confirmed low-grade astrocytoma (age range, 15-66 years underwent T1- weighted (T1W, T2W and FLAIR imaging with a superconducting unit 1.0 T. FLAIR images were qualitatively evaluated by comparison with T2W images by the three experienced neuroradiologists. To evaluate the diagnostic value of FLAIR, the neuroradiologists individually assessed the possibilities of the detection of lesions, as well as the possibilities of the differentiation of tumor from the surrounding edema on FLAIR vs. T2W images. Every examiner ranked FLAIR sequence vs. T2W in three degrees: worse, equal and better. Results. The comparison of FLAIR with T2W spin-echo (SE images with regard to the detection of the lesions showed that 82.8% of FLAIR studies were superior, 17.2% were of similar diagnostic value, and none was inferior to the T2W images. The comparison of images with regard to the differentiation of tumor boundaries vs. surrounding edema showed that 92.5% of FLAIR studies were superior, 7.5% were of similar diagnostic value, and none was inferior to the T2W images. Conclusion. Our results were similar to the previous studies' results concerning the advantages of FLAIR sequence in the diagnosis of low grade astrocytomas over T2W sequence. FLAIR was better at showing different tumor components, and at distinguishing CSF from the cystic component, and the postoperative cavity, compared with T2W images. Our conclusion was that FLAIR could be routinely used in the evaluation and follow-up of low-grade astrocytomas.

Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line

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Mollace Vincenzo

2009-05-01

Full Text Available Abstract Background Oxidative stress plays a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV-1 infection causing apoptosis of astroglia cells and neurons. Recent data have shown that oxidative stress is also responsible for the acceleration of human fibroblast telomere shortening in vitro. In the present study we analyzed the potential relations occurring between free radicals formation and telomere length during HIV-1 mediated astroglial death. Results To this end, U373 human astrocytoma cells have been directly exposed to X4-using HIV-1IIIB strain, for 1, 3 or 5 days and treated (where requested with N-acetylcysteine (NAC, a cysteine donor involved in the synthesis of glutathione (GSH, a cellular antioxidant and apoptosis has been evaluated by FACS analysis. Quantitative-FISH (Q-FISH has been employed for studying the telomere length while intracellular reduced/oxidized glutathione (GSH/GSSG ratio has been determined by High-Performance Liquid Chromatography (HPLC. Incubation of U373 with HIV-1IIIB led to significant induction of cellular apoptosis that was reduced in the presence of 1 mM NAC. Moreover, NAC improved the GSH/GSSG, a sensitive indicator of oxidative stress, that significantly decreased after HIV-1IIIB exposure in U373. Analysis of telomere length in HIV-1 exposed U373 showed a statistically significant telomere shortening, that was completely reverted in NAC-treated U373. Conclusion Our results support the role of HIV-1-mediated oxidative stress in astrocytic death and the importance of antioxidant compounds in preventing these cellular damages. Moreover, these data indicate that the telomere structure, target for oxidative damage, could be the key sensor of cell apoptosis induced by oxidative stress after HIV infection.

Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

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2013-01-15

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

Low-Grade Astrocytoma Associated with Abscess Formation: Case Report and Literature Review

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Tai-Hsin Tsai

2008-05-01

Full Text Available A rare case of low-grade astrocytoma associated with abscess formation occurred in a 52-year-old man presenting with Broca's aphasia. He underwent craniotomy and tumor removal under the impression of brain tumor with necrotic cystic change. Abscess accumulation within the intra-axial tumor was found intraoperatively. Literature related to brain abscess with brain tumor is reviewed, with an emphasis on abscesses with astrocytoma. We discuss the common brain tumors that are associated with abscess, pathogens that coexist with brain tumor, and the pathogeneses of coexisting brain abscess and tumor. It is very important to know how to differentiate between and diagnose a brain abscess and tumor, or brain abscess with tumor, preoperatively from clinical presentation and through the use of computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging or magnetic resonance spectroscopy.

The value of diffusion weighted imaging in differentiating intracranial tuberculomas from high-grade astrocytomas and metastases

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Peng Juan; Luo Tianyou; Lv Fajin; Fang Weidong; Wu Jingquan; Ouyang Yu; Li Yongmei

2007-01-01

Objective: To explore the value of diffusion weighted imaging (DWI) in differentiating intracranial tuberculomas from high-grade astrocytomas and metastases. Methods: The conventional MR imaging and DWI were performed in 50 eases (14 cases with intracranial tuberculomas, 15 cases with high- grade astrocytomas, and 21 cases with metastases) before treatment or operation. The mean apparent diffusion coefficient (ADC) values and relative apparent diffusion coefficient (rADC) values were calculated from the mass as well as from the peripheral edema regions of intracranial lesions. Results: The mean ADC values and rADC values were (1.2±0.2) x 10 -3 mm 2 ·s -1 and 1.6±0.3 in the mass of intracranial tuberculomas respectively; (0.8±0.1) x 10 -3 mm 2 ·s -1 and 1.1±0.1 in the parenehyma of high-grade astrocytomas; (0.8±0.1) x 10 -3 mm 2 ·s -1 and 1.0±0.2 in the parenchyma of metastases. There was significant difference of the mean ADC values (F=33.57, P -3 mm 2 ·s -1 and 2.5±0.2 in the peripheral edema regions of intracranial tuberculomas respectively; (1.4±0.2) x 10 -3 mm 2 ·s -1 and 1.8±0.3 in the peripheral edema regions of high-grade astrocytomas; and (1.9±0.2) x 10 -3 mm 2 ·s -1 and 2.3±0.5 in the peripheral edema regions of metastases. There was also significant difference in the mean ADC values (F23.17, P<0.01) or rADC values (F=5.94, P<0.01) among the peripheral edema regions of the three groups. Conclusion: The ADC values and rADC values are quite effective in differentiating intracranial tuberculoma from high-grade astrocytoma and metastasis. (authors)

MR signal of the solid portion of pilocytic astrocytoma on T2-weighted images: is it useful for differentiation from medulloblastoma?

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Arai, Kiyokazu; Yagi, Akiko; Taketomi-Takahashi, Ayako; Morita, Hideo; Koyama, Yoshinori; Endo, Keigo; Sato, Noriko; Aoki, Jun; Oba, Hiroshi; Ishiuchi, Shogo; Saito, Nobuhito

2006-01-01

Background and purpose: Although imaging features of cerebellar pilocytic astrocytoma and medulloblastoma have been described in many texts, original comparisons of magnetic resonance intensity between these two tumours are limited. In the present study the results of magnetic resonance imaging (MRI) were reviewed, focusing especially on the signal intensity of the solid portion of these neoplasms. Methods: MR images of ten cerebellar pilocytic astrocytomas and ten medulloblastomas were reviewed. The signal intensities of the solid components were graded on a scale of 1 to 5, with higher scores indicating a signal intensity closer to that of water. The degree of enhancement, tumour cysts and peripheral oedema were evaluated on MR images. When the solid portion was heterogeneous (i.e. mixed signal intensity or degree of enhancement), the dominant area was selected for evaluation. On T2-weighted images, the signal intensity of the solid portion was equal to that of cerebrospinal fluid (CSF) in 50% of pilocytic astrocytomas. No medulloblastomas showed such hyperintensity. Most medulloblastomas (80%) were isointense to grey matter. On T1-weighted images, the signal intensity varied widely in pilocytic astrocytomas; however, all medulloblastomas were iso- or hypointense to grey matter. The MR enhancement pattern, cystic component and peripheral oedema all varied in both tumour types and no specific features were identified. A signal intensity of the solid portion isointense to CSF on T2-weighted images was characteristic of cerebellar pilocytic astrocytomas; this was not observed in medulloblastomas. Attention to T2-weighted imaging of the solid portions of a tumour is easy and helpful in differentiating between cerebellar pilocytic astrocytoma and medulloblastoma. (orig.)

First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

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Frenay, M P; Fontaine, D; Vandenbos, F; Lebrun, C

2005-09-01

At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.

Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

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Quintero Eliana A

2008-04-01

Full Text Available Abstract Background This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7 in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13 did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12. The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere and the affectation (or not of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories, Digits span (WISC-R verbal scale and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74 years from surgery in CE group and at 6.47 (SD = 2.77 in CE+ group. Results The Medulloblastoma group showed severe executive deficit (≤ 1.5 SD below normal mean in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category and moderate to slight deficit in Stroop (word and colour tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables

Geometrical study of astrocytomas through fractals and scaling analysis

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Torres H, F.; Baena N, R.; Vergara V, J.; Guerrero M, M.

2017-10-01

The tumor growth is a complex process characterized by the proliferation of uncontrollable cells which invade neighbor tissues. The understanding process of this type of phenomena is very relevant in order to establish diagnosis and proper therapy strategies and to start the valorization of its complexity with proper descriptors produced by the scaling analysis, which define the tumor growth geometry. In this work, obtained results through the scaling analysis for pilocytic astrocytomas, anaplastic and diffuse, are shown, which tumors of primary origin are. On them, it is calculated the fractal dimension and critic exponents of local roughness to characterize in vivo three-dimensional tumor growth. The acquisition of the images for this type of injuries was carried out according to the standard protocol used for brain radiotherapy and radiosurgery, i.e., axial, coronal and sagittal magnetic resonance T1 weighted images and comprising the brain volume for image registration. Image segmentation was performed by the application the K-means procedure upon contrasted images. The results show significant variations of the parameters depending on the tumor stage and its histological origin. (Author)

Conformal proton radiation therapy for pediatric low-grade astrocytomas

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Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D.; Liwnicz, B.

2002-01-01

Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

The value of multi ultra high-b-value DWI in grading cerebral astrocytomas and its association with aquaporin-4.

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Tan, Yan; Zhang, Hui; Wang, Xiao-Chun; Qin, Jiang-Bo; Wang, Le

2018-06-01

To investigate the value of multi-ultrahigh-b-value diffusion-weighted imaging (UHBV-DWI) in differentiating high-grade astrocytomas (HGAs) from low-grade astrocytomas (LGAs), analyze its association with aquaporin (AQP) expression. 40 astrocytomas divided into LGAs (N = 15) and HGAs (N = 25) were studied. Apparent diffusion coefficient (ADC) and UHBV-ADC values in solid parts and peritumoral edema were compared between LGAs and HGAs groups by the t-test. Using receiver operating characteristic curves to identify the better parameter. Using real time polymerase chain reaction to assess AQP messenger ribonucleic acid (mRNA). Using spearman correlation analysis to assess the correlation of AQP mRNA with each parameter. ADC values in solid parts of HGAs were significantly lower than LGAs (p = 0.02), while UHBV-ADC values of HGAs were significantly higher than LGAs (p  0.05); ADC value showed a negative correlation with AQP4 mRNA (r = -0.357; p = 0.024). UHBV-ADC value positively correlated with the AQP4 mRNA (r = 0.646; p value may be related with the AQP4 mRNA levels. UHBV-DWI could be of value in the assessment of astrocytoma. Advances in knowledge: UHBV-DWI generated by multi UHBV could have particular value for astrocytoma grading, and the level of AQP4 mRNA might be potentially linked to the change of UHBV-DWI parameter, and we might find the exact reason for the difference of UHBV-ADC between the LGAs and HGAs.

Tuberous schlerosis complex and astrocytoma: a case report, Hiroshima

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Rudnick, P A; Hoshino, N; Kitaoka, T; Miura, M

1961-02-10

This case report concerned a young woman with cutaneous, osseous, and retinal changes of tuberous sclerosis, referred to ABCC for evaluation of blindness and increased intracranial pressure. A right lateral ventricle astrocytoma was successfully removed, but the patient's sight was not restored. The development of cerebral neoplasms in these patients is discussed. A careful search for resectable brain lesions should be made in all patients with tuberous sclerosis who have signs and symptoms of increased intracranial pressure. 14 references, 6 figures.

Tuberous schlerosis complex and astrocytoma: a case report, Hiroshima

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Rudnick, P.A.; Hoshino, N.; Kitaoka, T.; Miura, M.

1961-02-10

This case report concerned a young woman with cutaneous, osseous, and retinal changes of tuberous sclerosis, referred to ABCC for evaluation of blindness and increased intracranial pressure. A right lateral ventricle astrocytoma was successfully removed, but the patient's sight was not restored. The development of cerebral neoplasms in these patients is discussed. A careful search for resectable brain lesions should be made in all patients with tuberous sclerosis who have signs and symptoms of increased intracranial pressure. 14 references, 6 figures.

(-)[125I]-iodopindolol, a new highly selective radioiodinated beta-adrenergic receptor antagonist: measurement of beta-receptors on intact rat astrocytoma cells

International Nuclear Information System (INIS)

Barovsky, K.; Brooker, G.

1980-01-01

(-)-Pindolol, one of the most potent beta-adrenergic receptor antagonists, was radioiodinated using chloramine-T oxidation of carrier-free Na 125I and separated from unreacted pindolol to yield 2200 Ci/mmole (-)-[125I]-iodopindolol ((-)-[125I]-IPin). Mass and ultraviolet spectra confirmed that the iodination occurred on the indole ring, presumably at the 3 position. The binding of radiolabeled (-)-[125I]-IPin to beta-adrenergic receptors has been studied using intact C6 rat astrocytoma cells (2B subclone) grown in monolayer cultures. Binding of (-)[125IPin was saturable with time and concentration. Using 13 pM (-)-[125I]IPin, binding equilibrium was reached in 90 min at 21-22 degrees C. The reverse rate constant was 0.026 min-1 at 21 0 C. Specific binding (expressed as 1 microM(-)-propranolol displaceable counts) of (-)-[125I]-IPin was 95% of total binding. Scatchard analysis of (-)-[125I]-I]Pin binding revealed approximately 4300 receptors/cell and a dissociation constant of 30 pM. This was in excellent agreement with the kinetically determined dissociation constant of 35 pM. Displacement by propranolol and isoproterenol showed that (-)-[125I]-IPin binding sites were pharmacologically and stereospecifically selective. These results indicate that (-)-[125I]-IPin, a pure (-)-stereoisomer, high specific activity radioligand, selectively binds to beta-adrenergic receptors in whole cells with a high percentage of specific binding and should therefore be useful in the study and measurement of cellular beta-adrenergic receptors

Cerebral hemisphere astrocytoma: Treatment results

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Boyages, J.; Tiver, K.W.

1987-01-01

Eighty two adult patients with histologically proven cerebral astrocytomas of grades I to IV received post-operative radiotherapy at Westmead Hospital between January 1980 and February 1985. Seventy one patients completed a course of megavoltage irradiation, the majority having received a tumour dose of at least 60 Gy. Patients who underwent surgical resection had a greater median survival than those undergoing biopsy, but the difference was not statistically significant. By grade, the difference reached statistical significance only for grade III tumours. Patients with high grade tumours had a significantly lower survival than those patients with tumours of low grade. After adjustment for grade, various dosage levels did not significantly affect survival, although there was a trend towards improved median survival with higher doses in grade III tumours. When included in a multivariate analysis, the extent of surgery did not significantly influence survival, but increasing tumour grade and increasing age were significant adverse prognostic factors. (Auth.)

Outcome and patterns of failure following limited-volume irradiation for malignant astrocytomas

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Garden, A.S.; Maor, M.H.; Yung, W.K.A.; Bruner, J.M.; Woo, Shiao Y.; Moser, R.P.; Lee, Ya-Yen (Anderson (M.D.) Hospital and Tumor Inst., Houston, TX (USA))

1991-02-01

Between January 1982 and June 1986, 60 consecutive patients with high-grade astrocytomas (39 glioblastoma multiforme (GBM), 21 anaplastic astrocytoma (AA)) were treated with radiation therapy after biopsy (13 patients) or resection (47 patients). 53 patients were treated with limited-volume irradiation, 7 received whole-brain irradiation. The mean tumor dose was 65.4 Gy. In 35 patients, chemotherapy was given as part of their initial treatment. The 1- and 2-year survivals for GBM patients were 40 and 14 percent, respectively. Survival figures for AA patients were 76 and 52 percent at 1 and 2 years, respectively. The progression-free rate at 1 year was 13 percent in GBM and 29 percent in AA patients. 34 of 48 patients who received limited-volume irradiation had evidence of progression on postirradiation CT scans. 6 patients (3 GBM, 3 AA) had evidence of a new intracranial metastatic site on CT scan. In 3 patients the metastasis was within the previously irradiated volume, and in 3 other patients, it was outside this volume. All 6 had evidence of progression of their primary tumor at the original location on CT scan prior to the discovery of the metastatic site. 21 patients (15 GBM, 6 AA) had at least 1 postirradiation reoperation for a recurrent mass. 19 patients had recurrent tumors in the primary site, and 2 patients had necrosis but no tumor. Patients who received limited-volume irradiation for high-grade astrocytomas achieved the same survival results as patients treated previously with whole brain irradiation. New intra-cranial metastases did not influence the outcome, since these were always antedated by tumor progression at the primary site. (author). 16 refs.; 8 figs.; 2 tabs.

Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial

International Nuclear Information System (INIS)

Payne, D.G.; Simpson, W.J.; Keen, C.; Platts, M.E.

1982-01-01

A prospective randomized trial of 157 patients with malignant astrocytomas (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m 2 ) six weekly and hydroxyurea (HU, 3.5 gm/m 2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks). Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P<0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimes had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease

Multifunctional MgO Layer in Perovskite Solar Cells.

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Guo, Xudong; Dong, Haopeng; Li, Wenzhe; Li, Nan; Wang, Liduo

2015-06-08

A multifunctional magnesium oxide (MgO) layer was successfully introduced into perovskite solar cells (PSCs) to enhance their performance. MgO was coated onto the surface of mesoporous TiO(2) by the decomposition of magnesium acetate and, therefore, could block contact between the perovskite and TiO(2). X-ray photoelectron spectroscopy and infrared spectroscopy showed that the amount of H(2)O/hydroxyl absorbed on the TiO(2) decreased after MgO modification. The UV/Vis absorption spectra of the perovskite with MgO modification revealed an enhanced photoelectric performance compared with that of unmodified perovskite after UV illumination. In addition to the photocurrent, the photovoltage and fill factor also showed an enhancement after modification, which resulted in an increase in the overall efficiency of the cell from 9.6 to 13.9 %. Electrochemical impedance spectroscopy (EIS) confirmed that MgO acts as an insulating layer to reduce charge recombination. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea.

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Fukushima, Takao; Katayama, Yoichi; Watanabe, Takao; Yoshino, Atsuo; Ogino, Akiyoshi; Ohta, Takashi; Komine, Chiaki

2005-02-15

In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.

Correlation between E-cadherin-regulated cell adhesion and human osteosarcoma MG-63 cell anoikis.

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Lin, Ding-Sheng; Cai, Le-Yi; Ding, Jian; Gao, Wei-Yang

2014-01-01

The aim of this study was to investigate the relationship between cell adhesion and anoikis evasion among human osteosarcoma cells (MG-63), and to further study the molecular mechanisms. Human osteosarcoma cells (MG-63) were assessed for apoptosis, and caspase-3, E-cadherin and β-catenin expression in EDTA and control non-EDTA groups. MG-63 cells were predominantly aggregated when in suspension, and the suspended cells were more dispersed in the EDTA group. Following culture in suspension for 24 h, 48 h, or 72 h, the rates of apoptosis were 34.88%±3.64%, 59.3%±7.22% and 78.5%±5.21% in the experimental group and 7.34%±2.13%, 14.7%±3.69%, and 21.4%±3.60% in the control group, respectively. Caspase-3 expression progressively increased and E-cadherin and β-catenin were decreased in the experimental group, whereas there was no change in the control group. MG-63 cells could avoid anoikis through cell adhesion, and E-cadherin might play a role in this process.

Optic nerve pilomyxoid astrocytoma in a patient with Noonan syndrome.

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Nair, Sushmita; Fort, John A; Yachnis, Anthony T; Williams, Charles A

2015-06-01

Noonan syndrome (NS; MIM 163950) is an autosomal dominant syndrome which is clinically diagnosed by the distinct facial features, short stature, cardiac anomalies and developmental delay. About 50% of cases are associated with gain of function mutations in PTPN11 gene which leads to activation of the RAS/mitogen-activated protein kinase signaling pathway. This is known to have a role in tumorigenesis. Despite this, only limited reports of solid tumors (Fryssira H, Leventopoulos G, Psoni S, et al. Tumor development in three patients with Noonan syndrome. Eur J Pediatr 2008;167:1025-1031; Schuettpelz LG, McDonald S, Whitesell K et al. Pilocytic astrocytoma in a child with Noonan syndrome. Pediatr Blood Cancer 2009;53:1147-1149; Sherman CB, Ali-Nazir A, Gonzales-Gomez I, et al. Primary mixed glioneuronal tumor of the central nervous system in a patient with Noonan syndrome. J Pediatr Hematol Oncol 2009;31:61-64; Sanford RA, Bowman R, Tomita T, et al. A 16 year old male with Noonan's syndrome develops progressive scoliosis and deteriorating gait. Pediatr Neurosurg 1999;30:47-52) and no prior reports of optic gliomas have been described in patients with NS. We present here a patient with NS with a PTPN11 mutation and an optic pathway pilomyxoid astrocytoma. © 2015 Wiley Periodicals, Inc.

High dose rate brachytherapy in treatment of high grade astrocytomas

International Nuclear Information System (INIS)

Garcia-Alejo, R.; Delgado, J.M.; Cerro, E. del; Torres, J.J.; Martinez, R.

1996-01-01

From May 1994 to June 1995, 18 patients with high grade astrocytomas were entered prospectively on a selective protocol combining surgery, external beam radiotherapy, stereotactic interstitial implantation with HDR Iridium 192 and chemotherapy. Only those patients with tumor size 100cc or less average dimension, high grade astrocytoma, Karnofsky 70 or greater, unilateral, circumscribed, unifocal, tumor stable or responding to external radiation and supratentorial were included in the study. Ages ranged from 16 to 69 years. There were 13 males and 5 females. Surgery consisted of biopsy only in 3 patients, subtotal resection in 11, and gross total resection in 4 patients. Focal external beam radiation portals included the contrast enhancing mass on CT scan plus a 3 cm margin. The protocol called for minimum tumor dose of 60 Gy to be given in 2 Gy daily fractions. An interstitial brachytherapy boost was to be performed two weeks after the conclusion of external beam radiation. The dose was 30 Gy in 4 fractions. The authors analyze on basis on their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically possible with negligible acute morbidity and mortality, and appeared to be effective and may provide for an increase in tumor control in selected cases

MR Findings of Desmoplastic Cerebral Astrocytoma of Infancy. A case report

International Nuclear Information System (INIS)

Kim, J.H.; Kim, I.O.; Kim, W.S.; Kim, K.H.; Park, C. M.; Yeon, K.M.

2003-01-01

Desmoplastic cerebral astrocytoma of infancy (DCAI) presents as a large supratentorial mass consisting of a central cystic component and an enhancing solid component associated with peripheral dural attachment. We report the unusual MR findings of a DCAI that differed from previously reported cases in terms of the presence of calcification, which is not considered a feature of this tumor, and the absence of an enhancing peripheral dural component

Preliminary individualized chemotherapy for malignant astrocytomas based on O6-methylguanine-deoxyribonucleic acid methyltransferase methylation analysis.

Science.gov (United States)

Watanabe, Takao; Katayama, Yoichi; Ogino, Akiyoshi; Ohta, Takashi; Yoshino, Atsuo; Fukushima, Takao

2006-08-01

O(6)-methylguanine-deoxyribonucleic acid methyltransferase gene (MGMT) methylation is apparently correlated with responsiveness to nitrosourea chemotherapy, suggesting this alkylating agent should be effective against MGMT-methylated tumors. MGMT appears not to be linked to platinum resistance, so platinum chemotherapy should be used for MGMT-unmethylated tumors. This study was a preliminary trial of individualized chemotherapy based on MGMT methylation status in a total of 20 patients with newly diagnosed malignant astrocytomas (9 anaplastic astrocytomas and 11 glioblastomas multiforme). The procarbazine, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, and vincristine (PAV) regimen was administered to seven patients with MGMT-methylated tumors, and the carboplatin and etoposide (CE) regimen was administered to 13 patients with MGMT-unmethylated tumors. Objective response to the PAV therapy was noted in all three patients with measurable residual tumor (2 complete responses and 1 partial response). Five of the seven patients continued to be disease-free after initiation of the PAV therapy. Objective response to the CE therapy was seen in only one of seven patients with measurable residual tumor (1 partial response). Three of the 13 patients were free from progression, whereas the remaining 10 patients showed early progression. The PAV regimen is effective against MGMT-methylated malignant astrocytomas, but the CE regimen is not useful at the given dose and schedule in MGMT-unmethylated tumors.

From the Cover: Vulnerability of C6 Astrocytoma Cells After Single-Compound and Joint Exposure to Type I and Type II Pyrethroid Insecticides.

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Romero, Delfina M; Berardino, Bruno G; Wolansky, Marcelo J; Kotler, Mónica L

2017-01-01

A primary mode-of-action of all pyrethroid insecticides (PYRs) is the disruption of the voltage-gated sodium channel electrophysiology in neurons of target pests and nontarget species. The neurological actions of PYRs on non-neuronal cells of the nervous system remain poorly investigated. In the present work, we used C6 astrocytoma cells to study PYR actions (0.1-50 μM) under the hypothesis that glial cells may be targeted by and vulnerable to PYRs. To this end, we characterized the effects of bifenthrin (BF), tefluthrin (TF), α-cypermethrin (α-CYP), and deltamethrin (DM) on the integrity of nuclear, mitochondrial, and lysosomal compartments. In general, 24- to 48-h exposures produced concentration-related impairment of cell viability. In single-compound, 24-h exposure experiments, effective concentration (EC) 15 s 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT assay) were computed as follows (in μM): BF, 16.1; TF, 37.3; α-CYP, 7.8; DM, 5.0. We found concentration-related damage in several C6-cell subcellular compartments (mitochondria, nuclei, and lysosomes) at ≥ 10 -1 μM levels. Last, we examined a mixture of all PYRs (ie, Σ individual EC 15 ) using MTT assays and subcellular analyses. Our findings indicate that C6 cells are responsive to nM levels of PYRs, suggesting that astroglial susceptibility may contribute to the low-dose neurological effects caused by these insecticides. This research further suggests that C6 cells may provide relevant information as a screening platform for pesticide mixtures targeting nervous system cells by expected and unexpected toxicogenic pathways potentially contributing to clinical neurotoxicity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Surgical Management of Pilocytic Astrocytoma of the Optic Nerve: A Case Report and Review of the Literature

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Ifeoluwa Apanisile

2017-01-01

Full Text Available Optic nerve astrocytomas (ONAs are frequent types of optic nerve gliomas (ONGs, which can affect the visual pathway. An 18-year-old male patient was admitted to our department with right-sided intraorbital/retrobulbar swelling, which progressively grew over several months. Clinical examination showed right-sided diplopia, mydriasis, low visual acuity (0.4, exophthalmus (3 cm, epiphora, and severe retrobulbar pain. There was a family history of high-grade (IV astrocytomas in which two of the family members died due to the disease. Preoperative MRI scan revealed a soft tissue mass around the retrobulbar area of the right eye with intact orbital bony walls. Surgery was performed whereby it was dissected freely from the muscles and was separated from the optic nerve and the globe. Histopathologic analysis confirmed a benign astrocytoma. The follow-up examination revealed no recurrent or residual tumor. A systemic review of the literature indicates that early diagnosis and experienced multidisciplinary management are required in case of unilateral, resectable forms of ONAs with no distant metastasis, in order to provide a long-time survival of patients. Surgical intervention of unilateral ONAs is a relatively safe procedure, allowing complete or partial tumor removal with minimal morbidity and low recurrence rate.

Supratentorial juvenile pilocytic astrocytoma in a young adult with Silver-Russell syndrome.

LENUS (Irish Health Repository)

Fenton, E

2008-12-01

Silver-Russell syndrome is a rare genetically heterogeneous disorder in which patients demonstrate intrauterine and postnatal growth retardation, triangular facies, excessive sweating during early childhood, late closure of the anterior fontanelle and skeletal asymmetry. An association with malignancy exists and only one previous intracranial tumour has been reported, a craniopharyngioma. We report the first case of Silver-Russell syndrome associated with a supratentorial juvenile pilocytic astrocytoma.

Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

NARCIS (Netherlands)

Sie, M.; de Bont, E. S. J. M.; Scherpen, F. J. G.; Hoving, E. W.; den Dunnen, W. F. A.

2010-01-01

Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study

Pilocytic astrocytoma: a retrospective review

International Nuclear Information System (INIS)

Wen, B.-C.; Mayr, Nina A.; Hitchon, Patrick W.; Kao, S.; Hussey, David H.

1996-01-01

Purpose: The principle objective of this study is to determine the role of radiation therapy in the management of pilocytic astrocytoma. The specific aims are to assess the results of surgical resection +/- radiation therapy, the dose-response relationships for local tumor control, and the prognostic indicators. Materials and methods: Between Jan. 1970 and Dec. 1995, 60 patients with pilocytic astrocytomas (27 cerebellum, 23 hypothalmus/brain stem, 4 temporal, 3 frontal, and 3 occipital) were seen. All pathologic slides were reviewed and confirmed. Of these, 30 patients had surgery only (8 subtotal resections and 22 total resections), 8 had biopsy followed by radiotherapy (6) or chemotherapy (2), 21 had surgery and postoperative radiotherapy (20 subtotal resections and 1 total resection) and 1 was observed only. The radiation dose was 40.6 Gy/31fr/44ds to 60.2 Gy/35fr/49ds (mean = 52.1 Gy). Results: The overall 5- and 10-year actuarial survival rate was 93% and 93%, and the relapse-free survival rate was 86% and 80%, respectively. Eight patients developed local recurrence and one had leptomeningeal spread. Two patients receiving chemotherapy (vincristine + carboplatin) had persistent but stable disease. The one patient who was observed eventually required surgical resection 25 months later. Subtotal resection without RT: The local recurrence rate was 38% ((3(8))) if no RT was given after subtotal resection. Only 2 of the 3 recurrences were salvaged. All 22 patients who had tumor totally resected had local tumor control. Subtotal resection/biopsy only plus RT: Radiation therapy was effective in controlling the gross disease in 75% ((15(20))) of patients with subtotal resection, and 100% ((6(6))) of patients with biopsy only. In 14 patients receiving a tumor dose ≥ 51 Gy, 13 (93%) had local control, in comparison, to (11(15)) (73%) receiving a tumor dose <51 Gy had tumor control. Location of tumor: Sixty-three percent ((17(27))) of patients with tumor in cerebellum

Maraba MG1 Virus Enhances Natural Killer Cell Function via Conventional Dendritic Cells to Reduce Postoperative Metastatic Disease

Science.gov (United States)

Zhang, Jiqing; Tai, Lee-Hwa; Ilkow, Carolina S; Alkayyal, Almohanad A; Ananth, Abhirami A; de Souza, Christiano Tanese; Wang, Jiahu; Sahi, Shalini; Ly, Lundi; Lefebvre, Charles; Falls, Theresa J; Stephenson, Kyle B; Mahmoud, Ahmad B; Makrigiannis, Andrew P; Lichty, Brian D; Bell, John C; Stojdl, David F; Auer, Rebecca C

2014-01-01

This study characterizes the ability of novel oncolytic rhabdoviruses (Maraba MG1) to boost natural killer (NK) cell activity. Our results demonstrate that MG1 activates NK cells via direct infection and maturation of conventional dendritic cells. Using NK depletion and conventional dendritic cells ablation studies in vivo, we established that both are required for MG1 efficacy. We further explored the efficacy of attenuated MG1 (nonreplicating MG1-UV2min and single-cycle replicating MG1-Gless) and demonstrated that these viruses activate conventional dendritic cells, although to a lesser extent than live MG1. This translates to equivalent abilities to remove tumor metastases only at the highest viral doses of attenuated MG1. In tandem, we characterized the antitumor ability of NK cells following preoperative administration of live and attenuated MG1. Our results demonstrates that a similar level of NK activation and reduction in postoperative tumor metastases was achieved with equivalent high viral doses concluding that viral replication is important, but not necessary for NK activation. Biochemical characterization of a panel of UV-inactivated MG1 (2–120 minutes) revealed that intact viral particle and target cell recognition are essential for NK cell–mediated antitumor responses. These findings provide mechanistic insight and preclinical rationale for safe perioperative virotherapy to effectively reduce metastatic disease following cancer surgery. PMID:24695102

High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin

NARCIS (Netherlands)

Albrecht, K. W.; de Witt Hamer, P. C.; Leenstra, S.; Bakker, P. J.; Beijnen, J. H.; Troost, D.; Kaaijk, P.; Bosch, A. D.

2001-01-01

The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because

Prognostic significance of multiple kallikreins in high-grade astrocytoma

International Nuclear Information System (INIS)

Drucker, Kristen L.; Gianinni, Caterina; Decker, Paul A.; Diamandis, Eleftherios P.; Scarisbrick, Isobel A.

2015-01-01

Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival. Grade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6- or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score. These data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival. The online version of this article (doi:10.1186/s12885-015-1566-5) contains supplementary material, which is available to authorized users

Interplay of Mg2+, ADP, and ATP in the cytosol and mitochondria: unravelling the role of Mg2+ in cell respiration.

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Gout, Elisabeth; Rébeillé, Fabrice; Douce, Roland; Bligny, Richard

2014-10-28

In animal and plant cells, the ATP/ADP ratio and/or energy charge are generally considered key parameters regulating metabolism and respiration. The major alternative issue of whether the cytosolic and mitochondrial concentrations of ADP and ATP directly mediate cell respiration remains unclear, however. In addition, because only free nucleotides are exchanged by the mitochondrial ADP/ATP carrier, whereas MgADP is the substrate of ATP synthase (EC 3.6.3.14), the cytosolic and mitochondrial Mg(2+) concentrations must be considered as well. Here we developed in vivo/in vitro techniques using (31)P-NMR spectroscopy to simultaneously measure these key components in subcellular compartments. We show that heterotrophic sycamore (Acer pseudoplatanus L.) cells incubated in various nutrient media contain low, stable cytosolic ADP and Mg(2+) concentrations, unlike ATP. ADP is mainly free in the cytosol, but complexed by Mg(2+) in the mitochondrial matrix, where [Mg(2+)] is tenfold higher. In contrast, owing to a much higher affinity for Mg(2+), ATP is mostly complexed by Mg(2+) in both compartments. Mg(2+) starvation used to alter cytosolic and mitochondrial [Mg(2+)] reversibly increases free nucleotide concentration in the cytosol and matrix, enhances ADP at the expense of ATP, decreases coupled respiration, and stops cell growth. We conclude that the cytosolic ADP concentration, and not ATP, ATP/ADP ratio, or energy charge, controls the respiration of plant cells. The Mg(2+) concentration, remarkably constant and low in the cytosol and tenfold higher in the matrix, mediates ADP/ATP exchange between the cytosol and matrix, [MgADP]-dependent mitochondrial ATP synthase activity, and cytosolic free ADP homeostasis.

The Characteristics of Astrocytomas and Oligodendrogliomas Are Caused by Two Distinct and Interchangeable Signaling Formats

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Chengkai Dai

2005-04-01

Full Text Available Chronic platelet-derived growth factor (PDGF signaling in glial progenitors leads to the formation of oligodendrogliomas in mice, whereas chronic combined Ras and Akt signaling leads to astrocytomas. Different histologies of these tumors imply that the pathways activated by these two oncogenic stimulations are different, and that the apparent lineage of the tumor cells may result from specific signaling activity. Therefore, we have investigated the signaling effects of PDGF in culture and in gliomas in vivo. In culture, PDGF transiently activates ERK1/2 and Akt, and subsequently elevates p21 and PCNA expression similar to chronic PDGF autocrine signaling in cultured astrocytes and PDGF-induced oligodendrogliomas in vivo. Culture experiments show that autocrine PDGF stimulation, and combined active Ras and Akt generate signaling patterns that are in some ways mutually exclusive. Furthermore, forced Akt activity in the context of chronic PDGF stimulation results in cells with an astrocytic differentiation pattern both in culture and in vivo. These data imply that these two interconvertible signaling motifs are distinct in mice and lead to gliomas resembling the two major glioma histologies found in humans. The ability of signaling activity to convert tumor cells from one lineage to another presents a mechanism for the development of tumors apparently comprised of cells from multiple lineages.

Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

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Gulati Michel

2010-03-01

Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

Live microbial cells adsorb Mg2+ more effectively than lifeless organic matter

Science.gov (United States)

Qiu, Xuan; Yao, Yanchen; Wang, Hongmei; Duan, Yong

2018-03-01

The Mg2+ content is essential in determining different Mg-CaCO3 minerals. It has been demonstrated that both microbes and the organic matter secreted by microbes are capable of allocating Mg2+ and Ca2+ during the formation of Mg-CaCO3, yet detailed scenarios remain unclear. To investigate the mechanism that microbes and microbial organic matter potentially use to mediate the allocation of Mg2+ and Ca2+ in inoculating systems, microbial mats and four marine bacterial strains ( Synechococcus elongatus, Staphylococcus sp., Bacillus sp., and Desulfovibrio vulgaris) were incubated in artificial seawater media with Mg/Ca ratios ranging from 0.5 to 10.0. At the end of the incubation, the morphology of the microbial mats and the elements adsorbed on them were analyzed using scanning electronic microscopy (SEM) and energy diffraction spectra (EDS), respectively. The content of Mg2+ and Ca2+ adsorbed by the extracellular polysaccharide substances (EPS) and cells of the bacterial strains were analyzed with atomic adsorption spectroscopy (AAS). The functional groups on the surface of the cells and EPS of S. elongatus were estimated using automatic potentiometric titration combined with a chemical equilibrium model. The results show that live microbial mats generally adsorb larger amounts of Mg2+ than Ca2+, while this rarely is the case for autoclaved microbial mats. A similar phenomenon was also observed for the bacterial strains. The living cells adsorb more Mg2+ than Ca2+, yet a reversed trend was observed for EPS. The functional group analysis indicates that the cell surface of S. elongatus contains more basic functional groups (87.24%), while the EPS has more acidic and neutral functional groups (83.08%). These features may be responsible for the different adsorption behavior of Mg2+ and Ca2+ by microbial cells and EPS. Our work confirms the differential Mg2+ and Ca2+ mediation by microbial cells and EPS, which may provide insight into the processes that microbes use to

[The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas].

Science.gov (United States)

Revert Ventura, A J; Sanz Requena, R; Martí-Bonmatí, L; Pallardó, Y; Jornet, J; Gaspar, C

2014-01-01

To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (K(trans)), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and K(trans), both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. The quantification of the volume parameters of the entire region of the tumor with BV, BF, and K(trans) is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

A Sensitive and Specific Diagnostic Panel to Distinguish Diffuse Astrocytoma from Astrocytosis: Chromosome 7 Gain with Mutant Isocitrate Dehydrogenase 1 and p53

Science.gov (United States)

Camelo-Piragua, Sandra; Jansen, Michael; Ganguly, Aniruddha; Kim, J. ChulMin; Cosper, Arjola K.; Dias-Santagata, Dora; Nutt, Catherine L.; Iafrate, A. John; Louis, David N.

2011-01-01

One of the major challenges of surgical neuropathology is the distinction of diffuse astrocytoma (World Health Organization [WHO] grade II) from astrocytosis. The most commonly used ancillary tool to solve this problem is p53 immunohistochemistry (IHC), but this is neither sensitive nor specific. Isocitrate dehydrogenase 1 (IDH1) mutations are common in lower grade gliomas, with most causing a specific amino acid change (R132H) that can be detected with a monoclonal antibody. IDH2 mutations are rare, but also occur in gliomas. In addition, gains of chromosome 7 are common in gliomas. In this study we assessed the status of p53, IDH1/2 and chromosome 7 to determine the most useful panel to distinguish astrocytoma from astrocytosis. We studied biopsy specimens from 21 WHO grade II diffuse astrocytomas and 20 reactive conditions. The single most sensitive test to identify astrocytoma is fluorescence in situ hybridization (FISH) for chromosome 7 gain (76.2%). The combination of p53 and mutant IDH1 IHC provides a higher sensitivity (71.4%) than either test alone (47.8%); this combination offers a practical initial approach for the surgical pathologist. The best overall sensitivity (95%) is achieved when FISH for chromosome 7 gain is added to the p53-mutant IDH1 IHC panel. PMID:21343879

Pre-surgical integration of FMRI and DTI of the sensorimotor system in transcortical resection of a high-grade insular astrocytoma

Directory of Open Access Journals (Sweden)

Chelsea eEkstrand

2016-03-01

Full Text Available Herein we report on a patient with a WHO Grade III astrocytoma in the right insular region in close proximity to the internal capsule who underwent a right frontotemporal craniotomy. Total gross resection of insular gliomas remains surgically challenging based on the possibility of damage to the corticospinal tracts. However, maximizing the extent of resection has been shown to decrease future adverse outcomes. Thus, the goal of such surgeries should focus on maximizing extent of resection while minimizing possible adverse outcomes. In this case, pre-surgical planning included integration of functional magnetic resonance imaging (fMRI and diffusion tensor imaging (DTI, to localize motor and sensory pathways. Novel fMRI tasks were individually developed for the patient to maximize both somatosensory and motor activation simultaneously in areas in close proximity to the tumor. Information obtained was used to optimize resection trajectory and extent, facilitating gross total resection of the astrocytoma. Across all three motor-sensory tasks administered, fMRI revealed an area of interest just superior and lateral to the astrocytoma. Further, DTI analyses showed displacement of the corona radiata around the superior dorsal surface of the astrocytoma, extending in the direction of the activation found using fMRI. Taking into account these results, a transcortical superior temporal gyrus surgical approach was chosen in order to avoid the area of interest identified by fMRI and DTI. Total gross resection was achieved and minor post-surgical motor and sensory deficits were temporary. This case highlights the utility of comprehensive pre-surgical planning, including fMRI and DTI, to maximize surgical outcomes on a case-by-case basis.

FGFR1 tyrosine kinase domain duplication in pilocytic astrocytoma with anaplasia.

Science.gov (United States)

Ballester, Leomar Y; Penas-Prado, Marta; Leeds, Norman E; Huse, Jason T; Fuller, Gregory N

2018-04-01

We report the case of a 27-yr-old male with visual field loss who had a 4.9-cm complex cystic mass in the right occipital lobe. Histologic examination showed pilocytic astrocytoma (PA) with anaplasia, and molecular characterization revealed FGFR1 duplication with additional variants of unknown significance in several genes ( ARID1A, ARID1B, CHEK2, EPHA5, and MLL2 ). This is one of only a very few reported cases of anaplastic PA with characterization of molecular alterations. © 2018 Ballester et al.; Published by Cold Spring Harbor Laboratory Press.

Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

Science.gov (United States)

2017-04-27

Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

Cytotoxicity assessment of adipose-derived mesenchymal stem cells on synthesized biodegradable Mg-Zn-Ca alloys

Energy Technology Data Exchange (ETDEWEB)

Fazel Anvari-Yazdi, Abbas [Department of Biomedical Engineering, Materials and Biomaterials Research Center (MBMRC), Tehran, IR (Iran, Islamic Republic of); Tahermanesh, Kobra, E-mail: tahermanesh.k@iums.ac.ir [Endometriosis and Gynecologic Disorders Research Center, Department of Ob. & Gyn., Rasoul-e Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, IR (Iran, Islamic Republic of); Hadavi, Seyed Mohammad Mehdi [Materials and Energy Research Center (MERC), Karaj, IR (Iran, Islamic Republic of); Talaei-Khozani, Tahereh [Tissue Engineering Lab, Anatomy Department, School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, IR (Iran, Islamic Republic of); Razmkhah, Mahboobeh [Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, IR (Iran, Islamic Republic of); Abed, Seyedeh Mehr [School of Medicine, Yasuj University of Medical Sciences (YUMS), Yasuj, IR (Iran, Islamic Republic of); Mohtasebi, Maryam Sadat [Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences (SUMS), Shiraz, IR (Iran, Islamic Republic of)

2016-12-01

Magnesium (Mg)-based alloys have been extensively considered as biodegradable implant materials for orthopedic surgery. Mg and its alloys are metallic biomaterials that can degrade in the body and promote new bone formation. In this study, the corrosion behavior and cytotoxicity of Mg-Zn-Ca alloys are evaluated with adipose-derived mesenchymal stem cells (ASCs). Mg-2Zn and Mg-2Zn-xCa (x = 1, 2 and 3 wt.%) alloys were designated. Mg alloys were analyzed with scanning electron microscopy and potentiodynamic polarization. To understand the in-vitro biocompatibility and cytotoxicity of Mg-2Zn and Mg-2Zn-xCa alloys, ASCs were cultured for 24 and 72 h in contact with 10%, 50% and 100% extraction of all alloys prepared in DMEM. Cell cytotoxicity and viability of ASCs were examined by MTT assay. Alloying elements including Zn and Ca improved the corrosion resistance of alloys were compared with pure Mg. The cytotoxicity results showed that all alloys had no significant adverse effects on cell viability in 24 h. After 72 h, cell viability and proliferation increased in the cells exposed to pure Mg and Mg-2Zn-1Ca extracts. The release of Mg, Zn and Ca ions in culture media had no toxic impacts on ASCs viability and proliferation. Mg-2Zn-1Ca alloy can be suggested as a good candidate to be used in biomedical applications. - Highlights: • Short and long term corrosion behavior of Mg-Zn-Ca alloys studied • Viability and toxicity of Adipose-derived Stem cells studied with Mg-Zn-Ca alloys • Understanding the morphology of cultured adipose stem cells on Mg alloys • Stem cells on Mg-Zn-Ca alloys could proliferate and expand.

Cytotoxicity assessment of adipose-derived mesenchymal stem cells on synthesized biodegradable Mg-Zn-Ca alloys

International Nuclear Information System (INIS)

Fazel Anvari-Yazdi, Abbas; Tahermanesh, Kobra; Hadavi, Seyed Mohammad Mehdi; Talaei-Khozani, Tahereh; Razmkhah, Mahboobeh; Abed, Seyedeh Mehr; Mohtasebi, Maryam Sadat

2016-01-01

Magnesium (Mg)-based alloys have been extensively considered as biodegradable implant materials for orthopedic surgery. Mg and its alloys are metallic biomaterials that can degrade in the body and promote new bone formation. In this study, the corrosion behavior and cytotoxicity of Mg-Zn-Ca alloys are evaluated with adipose-derived mesenchymal stem cells (ASCs). Mg-2Zn and Mg-2Zn-xCa (x = 1, 2 and 3 wt.%) alloys were designated. Mg alloys were analyzed with scanning electron microscopy and potentiodynamic polarization. To understand the in-vitro biocompatibility and cytotoxicity of Mg-2Zn and Mg-2Zn-xCa alloys, ASCs were cultured for 24 and 72 h in contact with 10%, 50% and 100% extraction of all alloys prepared in DMEM. Cell cytotoxicity and viability of ASCs were examined by MTT assay. Alloying elements including Zn and Ca improved the corrosion resistance of alloys were compared with pure Mg. The cytotoxicity results showed that all alloys had no significant adverse effects on cell viability in 24 h. After 72 h, cell viability and proliferation increased in the cells exposed to pure Mg and Mg-2Zn-1Ca extracts. The release of Mg, Zn and Ca ions in culture media had no toxic impacts on ASCs viability and proliferation. Mg-2Zn-1Ca alloy can be suggested as a good candidate to be used in biomedical applications. - Highlights: • Short and long term corrosion behavior of Mg-Zn-Ca alloys studied • Viability and toxicity of Adipose-derived Stem cells studied with Mg-Zn-Ca alloys • Understanding the morphology of cultured adipose stem cells on Mg alloys • Stem cells on Mg-Zn-Ca alloys could proliferate and expand

Development of pure Mg open-cell foams as structured CO{sub 2} captor

Energy Technology Data Exchange (ETDEWEB)

Figueroa, I.A., E-mail: iafiguera@unam.mx [Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior S/N, Cd. Universitaria, C.P. 04510 México, D.F. (Mexico); Suarez, M.A.; Velasco-Castro, M.; Pfeiffer, H.; Alcántar-Vázquez, B.; González, G. [Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior S/N, Cd. Universitaria, C.P. 04510 México, D.F. (Mexico); Alfonso, I. [Instituto de Investigaciones en Materiales, Unidad Morelia, Universidad Nacional Autónoma de México, Campus Morelia UNAM, Antigua Carretera a Pátzcuaro No. 8701, Col. Ex-Hacienda de San José de la Huerta, C.P. 58190 Morelia, Michoacán (Mexico); Lara-Rodríguez, G.A. [Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior S/N, Cd. Universitaria, C.P. 04510 México, D.F. (Mexico)

2015-12-10

Highlights: • The CO{sub 2} capture capacity of the open-cell Mg foams was studied at low temperatures. • Open-cell Mg foams with pore size of 350 μm were used for the CO{sub 2} capture study. • The highest amount of CO{sub 2} captured was obtained at 60 °C and 80% of relative humidity. • A CO{sub 2} capture capacity of 0.87 mmol/g was obtained for the open-cell Mg foams. • The oxidized open-cell Mg foams can be used as CO{sub 2} captors. - Abstract: The CO{sub 2} capture capacity of the superficial oxide layer formed in pure open-cell Mg foams was studied at low temperatures (40–60 °C) varying the relative humidity from 40 to 80%. Mg foam samples with pore size of 350 μm and surface area of 5.4 m{sup 2}/g were used for these analyses. Optical microscopy and X-ray diffraction techniques were used to characterize the cell structure and the superficial oxide formed in the cell-foams, respectively. The final products formed after the CO{sub 2}–H{sub 2}O capture experiments were identified by scanning electron microscopy and attenuated total reflexion-Fourier transform infrared spectroscopy (ATR-FTIR). The MgCO{sub 3} and other products, formed after CO{sub 2} + H{sub 2}O capture process, were thermally decomposed, to quantify the amount of CO{sub 2} captured by the superficial MgO layer using standard thermogravimetric analysis. The results showed that the highest amount of CO{sub 2} captured was obtained at 60 °C and 80% of relative humidity, with a CO{sub 2} capture capacity of 0.87 mmol/g, which is comparable with others CO{sub 2} MgO-based captors. The considerable CO{sub 2} capture capacity at low temperatures supports the potential of the pure open-cell Mg foams to be used as structured CO{sub 2} captors.

Sustained response to weekly vinblastine in 2 children with pilomyxoid astrocytoma associated with diencephalic syndrome.

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Singh, Gurpreet; Wei, Xing Chang; Hader, Walter; Chan, Jennifer A; Bouffet, Eric; Lafay-Cousin, Lucie

2013-03-01

Diencephalic syndrome (DS) related to hypothalamic/chiasmatic region tumor has mainly been reported with low-grade glioma. We described 2 young children with DS related to pilomyxoid astrocytoma. Despite the recognized more agressive clinical behavior of this histologic subtype, we report successful resolution of DS and sustained tumor response with prolonged use of single-agent vinblastine.

Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I

NARCIS (Netherlands)

Fischer, U.; Heckel, D.; Michel, A.; Janka, M.; Hulsebos, T.; Meese, E.

1997-01-01

Gene amplification, which is generally considered to occur late in tumor development, is a common feature of high grade glioma. Up until now, there have been no reports on amplification in astrocytoma grade I. In this study, we report cloning and sequencing of a cDNA termed glioma-amplified sequence

Pediatric spinal cord astrocytomas: a retrospective study of 348 patients from the SEER database.

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Luksik, Andrew S; Garzon-Muvdi, Tomas; Yang, Wuyang; Huang, Judy; Jallo, George I

2017-06-01

OBJECTIVE Intramedullary spinal cord tumors comprise 1%-10% of all childhood central nervous system neoplasms, with astrocytomas representing the most common subtype. Due to their rarity and poor prognosis, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of improving outcome. The authors undertook this retrospective study to explore factors that may influence survival in pediatric patients with spinal cord astrocytomas. METHODS Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a prospective cancer registry, the authors retrospectively assessed survival in histologically confirmed, primary spinal cord astrocytomas in patients 21 years of age and younger. Survival was described with Kaplan-Meyer curves, and a multivariate regression analysis was used to assess the association of several variables with survival while controlling for confounding variables. RESULTS This analysis of 348 cases showed that age (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.017), nonwhite race (HR 1.74, 95% CI 1.11-2.74, p = 0.014), high-grade tumor status (HR 14.67, 95% CI 6.69-32.14, p < 0.001), distant or invasive extension of the tumor (HR 2.37, 95% CI 1.02-5.49, p = 0.046), and radiation therapy (HR 3.74, 95% CI 2.18-6.41, p < 0.001) were associated with decreased survival. Partial resection (HR 0.37, 95% CI 0.16-0.83, p = 0.017) and gross-total resection (HR 0.39, 95% CI 0.16-0.95, p = 0.039) were associated with improved survival. CONCLUSIONS Younger age appears to be protective, while high-grade tumors have a much worse prognosis. Early diagnosis and access to surgery appears necessary for improving outcomes, while radiation therapy has an unclear role. There is still much to learn about this disease in the hope of curing children with the misfortune of having one of these rare tumors.

Characterization of cells recovered from the xenotransplanted NG97 human-derived glioma cell line subcultured in a long-term in vitro

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Heinrich Juliana K

2008-10-01

Full Text Available Abstract Background In order to elucidate tumoral progression and drug resistance, cultured cell lines are valuable tools applied on tumor related assays provided they are well established and characterized. Our laboratory settled the NG97 cell line derived from a human astrocytoma grade III, which started to develop and express important phenotypical characteristics of an astrocytoma grade IV after injection in the flank of nude mice. Astrocytomas are extremely aggressive malignancies of the Central Nervous System (CNS and account for 46% of all primary malignant brain tumors. Progression to worse prognosis occurs in 85% of the cases possibly due to changes in cell tumor microenvironment and through biological pathways that are still unclear. Methods This work focused on characterizing the NG97 cell line specifically after being recovered from the xenotransplant, who maintained their undifferentiated characteristics along the following 60th passages in vitro. These cells were subcultivated to evaluate the possible contribution of these undifferentiated characteristics to the malignant progression phenotype. These characteristics were the expression of molecules involved in the processes of migration, dedifferentiation and chromosomal instability. Results Results showed that NG97(ht had an decrease in doubling time through sub cultivation, which was characterized by a converse modulation between the expression of glial fibrillary acidic protein (GFAP and vimentin. In addition, β1 integrins were present in intermediate levels while α5 integrins had a high expression profile as well as fibronectin and laminin. Cytogenetic analysis of NG97(ht revealed several chromosomal abnormalities, 89% of the cells showed to be hyperdiploid and the modal number was assigned to be 63. Several acrocentric chromosomes were visualized and at least 30 figures were attributed to be murine. These findings suggest a possible fusion between the original NG97 cells

Characterization of cells recovered from the xenotransplanted NG97 human-derived glioma cell line subcultured in a long-term in vitro

International Nuclear Information System (INIS)

Machado, Camila ML; Boetcher-Luiz, Fátima; Verinaud, Liana; Ikemori, Rafael Y; Zorzeto, Tatiana Q; Nogueira, Ana CMA; Barbosa, Suse DS; Savino, Wilson; Schenka, André A; Vassallo, José; Heinrich, Juliana K

2008-01-01

In order to elucidate tumoral progression and drug resistance, cultured cell lines are valuable tools applied on tumor related assays provided they are well established and characterized. Our laboratory settled the NG97 cell line derived from a human astrocytoma grade III, which started to develop and express important phenotypical characteristics of an astrocytoma grade IV after injection in the flank of nude mice. Astrocytomas are extremely aggressive malignancies of the Central Nervous System (CNS) and account for 46% of all primary malignant brain tumors. Progression to worse prognosis occurs in 85% of the cases possibly due to changes in cell tumor microenvironment and through biological pathways that are still unclear. This work focused on characterizing the NG97 cell line specifically after being recovered from the xenotransplant, who maintained their undifferentiated characteristics along the following 60 th passages in vitro. These cells were subcultivated to evaluate the possible contribution of these undifferentiated characteristics to the malignant progression phenotype. These characteristics were the expression of molecules involved in the processes of migration, dedifferentiation and chromosomal instability. Results showed that NG97(ht) had an decrease in doubling time through sub cultivation, which was characterized by a converse modulation between the expression of glial fibrillary acidic protein (GFAP) and vimentin. In addition, β1 integrins were present in intermediate levels while α5 integrins had a high expression profile as well as fibronectin and laminin. Cytogenetic analysis of NG97(ht) revealed several chromosomal abnormalities, 89% of the cells showed to be hyperdiploid and the modal number was assigned to be 63. Several acrocentric chromosomes were visualized and at least 30 figures were attributed to be murine. These findings suggest a possible fusion between the original NG97 cells with stromal murine cells in the xenotransplant. In

Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma.

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Jin, Tianbo; Wang, Yuan; Li, Gang; Du, Shuli; Yang, Hua; Geng, Tingting; Hou, Peng; Gong, Yongkuan

2015-01-01

Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ(2) test and genetic model analysis. In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of "GCT" in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively.

MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in A549 lung cancer cells via influencing reactive oxygen species and GSH level.

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Han, Yong Hwan; Park, Woo Hyun

2010-07-01

Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). In the present study, we evaluated the effects of MG132 on the growth of A549 lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels. Treatment with MG132 inhibited the growth of A549 cells with an IC(50) of approximately 20 microM at 24 hours. DNA flow cytometric analysis indicated that 0.5 approximately 30 microM MG132 induced a G1 phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 microM MG132 also induced apoptosis, as evidenced by sub-G1 cells and annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (MMP; Delta psi m). The intracellular ROS levels including O(2) (*-) were strongly increased in 10 or 30 microM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 microM MG132-treated cells. Furthermore, 10 or 30 microM MG132 increased mitochondrial O(2) (*- ) level but 0.1, 0.5 or 1 microM MG132 decreased that. In addition, 10 or 30 microM MG132 induced GSH depletion in A549 cells. In conclusion, MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH.

Effect of CdS/Mg-Doped CdSe Cosensitized Photoanode on Quantum Dot Solar Cells

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Yingxiang Guan

2015-01-01

Full Text Available Quantum dots have emerged as a material platform for low-cost high-performance sensitized solar cells. And doping is an effective method to improve the performance of quantum dot sensitized solar cells (QDSSCs. Since Kwak et al. from South Korea proved the incorporation of Mg in the CdSe quantum dots (QDs in 2007, the Mg-doped CdSe QDs have been thoroughly studied. Here we report a new attempt on CdS/Mg-doped CdSe quantum dot cosensitized solar cells (QDCSSC. We analyzed the performance of CdS/Mg-doped CdSe quantum dot cosensitized solar cells via discussing the different doping concentration of Mg and the different SILAR cycles of CdS. And we studied the mechanism of CdS/Mg-doped CdSe QDs in detail for the reason why the energy conversion efficiency had been promoted. It is a significant instruction on the development of Mg-doped CdSe quantum dot sensitized solar cells (QDSSCs.

[Experimental research in vitro of TK/GCV system for osteosarcoma MG-63 cell damage].

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Zhang, Hua-Dong; Lu, Zhi; Feng, Yi; Liu, Xiao-Li; Hou, Hui-Ming

2014-03-01

To study the killing effects of the liposome-mediated thymidine kinase (TK)/ganciclovir (GCV) system on MG-63 osteosarcoma (OS) cells and its bystander effects. Liposome-mediated TK gene transfected into MG-63 OS cells, the efficiency of transfection was analyzed by flow cytometry and observed under inverted fluorescence microscope. Non-transfected osteosarcoma MG-63 cells were divided into three groups,in the experimental group 1 transfected TK/GCV cells cultured in solutiona liquid mixture by supernatant by 1/10,1/7,1/5,1/2 ratio to original broth; in the experimental group 2 transfected cells cultured in solutiona liquid mixture of supernatant filtered through 0.22 microm filter by 1/10,1/7, 1/5, 1/2 ratio to original broth, in control group the transfection cells cultured in original culture solution. Cell growth inhibition rate and osteosarcoma cell sensitivity to TK/GCV system were measured by MTT assay in each group. The TK gene was transfected into MG-63 OS cells successfully by liposome-mediated, flow cytometry instrument detection TK gene transfection cell transfection efficiency can reach 75.5%. Six days later the MTT assay showed that in the experimental group 1 inhibition rate of all concentration ratio of the mixed culture fluid were statistically significant as compared with the control group (P culture medium was not statistically significant as compared with the control group (P > 0.05). TK gene transfected MG-63 cells increased with the the GCV concentration,the cell apoptosis rate increased. The experiment demonstrated that the MG-63 OS cells are sensitive to the liposome-mediated TK/GCV system and bystander effects are significant.

Aberrant tropoelastin secretion in MG-63 human osteosarcoma cells

International Nuclear Information System (INIS)

Curtiss, S.W.

1989-01-01

The secretion of newly synthesized tropoelastin, the soluble precursor of the extracellular matrix protein elastin, is not well understood. MG-63 human osteosarcoma cells were found by immunoblot analysis to synthesize 62 kD and 64 kD tropoelastins. Media from 63 cells labelled for five hours with [ 3 H]-valine contain no detectable tropoelastin, unlike media from other tropoelastin-synthesizing cells. Immunoblots of conditioned media and 1Ox-concentrated conditioned media left on the cells for six days also show an absence of tropoelastin from the cell media. No insoluble elastin is associated with the cell layer, as determined by amino acid analysis and electron microscopy of 18-21 day cell cultures. The absence of tropoelastin from the cell medium and elastin from the extracellular matrix indicates that MG63 cells do not secrete tropoelastin as expected, but accumulate it intracellularly. This accumulation is transient: immunoblots and immunofluorescence microscopy show that cells three days after passage have the highest steady-state levels of tropoelastin per cell, that day 8 cells contain lower but still significant amounts of tropoelastin, and that by day 22 tropoelastin is no longer present in the cell cultures. Cell density is a critical factor in the observed pattern of tropoelastin expression. Cells seeded at ten fold their usual initial density have high tropoelastin levels at one day after passage, sooner than cells seeded normally. Tropoelastin also disappears from high density-seeded cells more quickly and is no longer detectable at day 10. Lysosome-like vesicles containing membranous structures appear by immunoelectron microscopy to be the primary site of intracellular tropoelastin localization

Quality of life and neuropsychological evaluation for patients with malignant astrocytomas: RTOG 91-14

International Nuclear Information System (INIS)

Choucair, Ali K.; Scott, Charles; Urtasun, Raul; Nelson, Diana; Mousas, Benjamin; Curran, Walter

1997-01-01

Abstract: With increasingly aggressive neurosurgical and radiation therapy modalities (gamma knife, external beam stereotactic radiation and interstitial brachytherapy with or without hyperthermia) offered to patients with malignant astrocytomas (MA), increasing national demand for medical outcome studies and rising health care costs amidst public, business, and governmental debate to cut spending, we as physicians are obligated to continue our research to find effective treatments for malignant astrocytoma (MA) and a cost-effective means to study their impact upon the patient's quality of life (QOL). Purpose: We report data that was collected within the Radiation Therapy Oncology Group (RTOG) on 126 patients with MA who were enrolled in RTOG 91-14. This study was undertaken to prospectively test the feasibility of performing quality of life (QOL) and neuropsychological evaluation (NPE) and collecting this data within the RTOG. Results: The NPE and QOL parameters that were used in this study are cost effective. They are not only much cheaper than formal cognitive and memory testing, but also provide additional information regarding the patients' day to day functional abilities that are not provided by the current routinely used means, such as KPS. The Mini-Mental Status Exam (MMSE) provides greater sensitivity to patients' differences in neurological status and may be preferable to NFS as an eligibility criteria

Pion radiation for high grade astrocytoma: results of a randomized study

International Nuclear Information System (INIS)

Pickles, Tom; Goodman, George B.; Rheaume, Dorianne E.; Duncan, Graeme G.; Fryer, Chris J.; Bhimji, Shamim; Ludgate, Charles; Syndikus, Isabel; Graham, Peter; Dimitrov, Mario; Bowen, Julie

1997-01-01

Purpose: This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas. Methods and Materials: Eighty-four patients were randomized to pion therapy (33-34.5 Gyπ), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS) ≥50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume < 850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms. Results: Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms. Conclusion: In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma

Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain.

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Piotr Bednarczyk

Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

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Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro (Gunma Univ., Maebashi (Japan). School of Medicine)

1992-04-01

A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. {sup 18}F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author).

Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

International Nuclear Information System (INIS)

Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro

1992-01-01

A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. 18 F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author)

The role of radiotherapy in the management of supratentorial low grade astrocytoma

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Song, M. H.; Chang, H. S.; Lee, K. J.

1997-01-01

To evaluate the role of radiotherapy in the management of incompletely resected supratentorial low grade astrocytoma with the analysis of the survival, the pattern of failure, and the prognostic variables affecting survival. Between January 1990 and December 1995, fifty-one patients with supratentorial low grade astrocytoma received radiotherapy after subtotal resection (16 patients) or stereotactic biopsy(35 patients)at Asan Medical Center. External radiotherapy was done by conventional fractionation with the total dose of 4820cGy to 6000cGy(median 5580cGy) and partial brain volume. The follow-up was done from 6 to 79 months(median 48 months). Overall actuarial survival rate at 2 and 5 years were 83.4% and 54.8T, respectively. Progression free survival at 2 and 5 years were 67.4% and 48.7%, respectively. The significant prognostic factors affecting overall survival rate were the performance status, T stage, histologic subtype, radiation field and radiation response. The major pattern of failure was local failure, such as progressive disease and primary site recurrence in 23 patients (45.1%). Progression free survivors excluding 2 patients were physically and intellectually intact without major neurologic deficit. Although the follow-up period of this study was relatively short, overall actuarial and progression free survival rate were encouraging. Patients with good performance status, lower T stage, pilocytic subtype, patients treated with small radiation field and radiation responder showed better survival. As the local failure was the major pattern of failure, the various efforts to decrease the local failure is necessary. (author)

Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration

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Jinyang Wang

2018-05-01

Full Text Available Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR positively correlates with TNM (tumor-node-metastasis stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.

Surface modification of parylene-N films for the culture of osteoblast-like cells (MG-63)

Energy Technology Data Exchange (ETDEWEB)

Liaqat, Usman [Graduate Program of Nano Science and Technology, Yonsei University, 50-Yonsei Ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Ko, Hyuk [Department of Materials Science and Engineering, Yonsei University, 50-Yonsei Ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Suh, Hwal [Graduate Program of Nano Science and Technology, Yonsei University, 50-Yonsei Ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Department of Medical Engineering, College of Medicine, Yonsei University, 50-Yonsei Ro, Seodaemun-gu, Seoul, 120-749 (Korea, Republic of); Lee, Misu [Division of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 406-772 (Korea, Republic of); Pyun, Jae-Chul, E-mail: jcpyun@yonsei.ac.kr [Department of Materials Science and Engineering, Yonsei University, 50-Yonsei Ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

2016-08-15

Highlights: • Osteoblast-like cells (MG-63) was cultured on differently modified surfaces of parylene films. • Proliferation of MG-63 was observed to be far increased on UV-treated parylene-N film. • The influences of UV-treatment were found out on cell viability, proliferation rate and cell cycle. • The influence was estimated to be negligible on the protein synthesis, cell differentiation. • The UV-treated parylene-N was demonstrated to be effectively used for the culture of MG-63. - Abstract: The influence of microenvironments on the culture of osteoblast-like cells (MG-63) has been investigated using parylene films with different surfaces, such as parylene-N film, UV-modified parylene-N film, functional parylene film with amine groups (parylene-A), and UV-modified parylene-A film. In this work, parylene-N film was found to induce dramatic changes in cell adhesion and cell viability before and after UV-treatment with respect to the culture of osteoblast-like cells (MG-63). The influences of such a chemical environment on cell culture were investigated in relation to the cell proliferation (viability and proliferation rate) and the cell physiology (cell cycle, protein synthesis, and differentiation) of cells grown on parylene-N film, UV-modified parylene-N film, parylene-A film, and UV-modified parylene-A film in comparison with cells grown on a polystyrene surface.

Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma

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Arai Hajime

2007-08-01

Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion.

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Park, Woo Hyun; Kim, Suhn Hee

2012-04-01

MG132 as a proteasome inhibitor can induce apoptotic cell death in lung cancer cells. However, little is known about the toxicological cellular effects of MG132 on normal primary lung cells. Here, we investigated the effects of N-acetyl cysteine (NAC) and vitamin C (well known antioxidants) or L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) on MG132-treated human pulmonary fibroblast (HPF) cells in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). MG132 induced growth inhibition and death in HPF cells, accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). MG132 increased ROS levels and GSH-depleted cell numbers in HPF cells. Both antioxidants, NAC and vitamin C, prevented growth inhibition, death and MMP (∆ψm) loss in MG132-treated HPF cells and also attenuated ROS levels in these cells. BSO showed a strong increase in ROS levels in MG132-treated HPF cells and slightly enhanced the growth inhibition, cell death, MMP (∆ψm) loss and GSH depletion. In addition, NAC decreased anonymous ubiquitinated protein levels in MG132-treated HPF cells. Furthermore, superoxide dismutase (SOD) 2, catalase (CTX) and GSH peroxidase (GPX) siRNAs enhanced HPF cell death by MG132, which was not correlated with ROS and GSH level changes. In conclusion, MG132 induced the growth inhibition and death of HPF cells, which were accompanied by increasing ROS levels and GSH depletion. Both NAC and vitamin C attenuated HPF cell death by MG132, whereas BSO slightly enhanced the death.

Characterization of Cancer Stem Cells in Patients with Brain ...

African Journals Online (AJOL)

Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

External Beam Radiotherapy in the Management of Low Grade Astrocytoma of the Brain

International Nuclear Information System (INIS)

Jeon, Ha Jung

2009-01-01

This study was designed to evaluate the effectiveness of postoperative radiotherapy for patients with low-grade astrocytomas and to define an optimal radiotherapeutic regimen and prognostic factors. A total of 69 patients with low-grade astrocytomas underwent surgery and postoperative radiotherapy immediately following surgery at our institution between October 1989 and September 2006. The median patient age was 36 years. Forty-one patients were 40 years or younger and 28 patients were 41 years or older. Fourteen patients underwent a biopsy alone and the remaining 55 patients underwent a subtotal resection. Thirty-nine patients had a Karnofsky performance status of less than 80% and 30 patients had a Karnofsky performance status greater than 80%. Two patients were treated with whole brain irradiation followed by a coned down boost field to the localized area. The remaining 67 patients were treated with a localized field with an appropriate margin. Most of the patients received a dose of 50∼55 Gy and majority of the patients were treated with a dose of 54 Gy. The overall 5-year and 7-year survival rates for all of the 69 patients were 49% and 44%, respectively. Corresponding disease free survival rates were 45% and 40%, respectively. Patients who underwent a subtotal resection showed better survival than patients who underwent a biopsy alone. The overall 5-year survival rates for patients who underwent a subtotal resection and patients who underwent a biopsy alone were 57% and 38%, respectively (p<0.05). Forty-one patients who were 40 years or younger showed a better overall 5-year survival rate as compared with 28 patients who were 41 years or older (56% versus 40%, p<0.05). The overall 5-year survival rates for 30 patients with a Karnofsky performance status greater than 80% and 39 patients with a Karnofsky performance status less than 80% were 51% and 47%, respectively. This finding was not statistically significant. Although one patient was not able to

Optimization of cell adhesion on mg based implant materials by pre-incubation under cell culture conditions.

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Willumeit, Regine; Möhring, Anneke; Feyerabend, Frank

2014-05-05

Magnesium based implants could revolutionize applications where orthopedic implants such as nails, screws or bone plates are used because they are load bearing and degrade over time. This prevents a second surgery to remove conventional implants. To improve the biocompatibility we studied here if and for how long a pre-incubation of the material under cell culture conditions is favorable for cell attachment and proliferation. For two materials, Mg and Mg10Gd1Nd, we could show that 6 h pre-incubation are already enough to form a natural protective layer suitable for cell culture.

Optimization of Cell Adhesion on Mg Based Implant Materials by Pre-Incubation under Cell Culture Conditions

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Regine Willumeit

2014-05-01

Full Text Available Magnesium based implants could revolutionize applications where orthopedic implants such as nails, screws or bone plates are used because they are load bearing and degrade over time. This prevents a second surgery to remove conventional implants. To improve the biocompatibility we studied here if and for how long a pre-incubation of the material under cell culture conditions is favorable for cell attachment and proliferation. For two materials, Mg and Mg10Gd1Nd, we could show that 6 h pre-incubation are already enough to form a natural protective layer suitable for cell culture.

Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features

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Zakrzewski, Krzysztof; Jarząb, Michał; Pfeifer, Aleksandra; Oczko-Wojciechowska, Małgorzata; Jarząb, Barbara; Liberski, Paweł P.; Zakrzewska, Magdalena

2015-01-01

Pilocytic astrocytoma is the most common type of brain tumor in the pediatric population, with a generally favorable prognosis, although recurrences or leptomeningeal dissemination are sometimes also observed. For tumors originating in the supra-or infratentorial location, a different molecular background was suggested, but plausible correlations between the transcriptional profile and radiological features and/or clinical course are still undefined. The purpose of this study was to identify gene expression profiles related to the most frequent locations of this tumor, subtypes based on various radiological features, and the clinical pattern of the disease. Eighty six children (55 males and 31 females) with histologically verified pilocytic astrocytoma were included in this study. Their age at the time of diagnosis ranged from fourteen months to seventeen years, with a mean age of seven years. There were 40 cerebellar, 23 optic tract/hypothalamic, 21 cerebral hemispheric, and two brainstem tumors. According to the radiological features presented on MRI, all cases were divided into four subtypes: cystic tumor with a non-enhancing cyst wall; cystic tumor with an enhancing cyst wall; solid tumor with central necrosis; and solid or mainly solid tumor. In 81 cases primary surgical resection was the only and curative treatment, and in five cases progression of the disease was observed. In 47 cases the analysis was done by using high density oligonucleotide microarrays (Affymetrix HG-U133 Plus 2.0) with subsequent bioinformatic analyses and confirmation of the results by independent RT-qPCR (on 39 samples). Bioinformatic analyses showed that the gene expression profile of pilocytic astrocytoma is highly dependent on the tumor location. The most prominent differences were noted for IRX2, PAX3, CXCL14, LHX2, SIX6, CNTN1 and SIX1 genes expression even within different compartments of the supratentorial region. Analysis of the genes potentially associated with radiological

Classification of astrocyto-mas and meningiomas using statistical discriminant analysis on MRI data

International Nuclear Information System (INIS)

Siromoney, Anna; Prasad, G.N.S.; Raghuram, Lakshminarayan; Korah, Ipeson; Siromoney, Arul; Chandrasekaran, R.

2001-01-01

The objective of this study was to investigate the usefulness of Multivariate Discriminant Analysis for classifying two groups of primary brain tumours, astrocytomas and meningiomas, from Magnetic Resonance Images. Discriminant analysis is a multivariate technique concerned with separating distinct sets of objects and with allocating new objects to previously defined groups. Allocation or classification rules are usually developed from learning examples in a supervised learning environment. Data from signal intensity measurements in the multiple scan performed on each patient in routine clinical scanning was analysed using Fisher's Classification, which is one method of discriminant analysis

Paracrine-mediated osteoclastogenesis by the osteosarcoma MG63 cell line: is RANKL/RANK signalling really important?

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Costa-Rodrigues, J; Teixeira, C A; Fernandes, M H

2011-08-01

Although in the past little attention has been paid to the influence of osteosarcoma cells in osteoclast function, recent studies suggest a close relationship between osteosarcoma aggressiveness and osteoclastic activity. The present study addresses the paracrine effects of MG63 cells, a human osteosarcoma-derived cell line, on the differentiation of peripheral blood osteoclast precursor cells (PBMC). PBMC were cultured for 21 days in the presence of conditioned media from MG63 cell cultures (CM) collected at 48 h (CM_MG1), 7 days (CM_MG2) and 14 days (CM_MG3). MG63 cell cultures displayed the expression of ALP and BMP-2 and, also, the osteoclastogenic genes M-CSF and RANKL, although with a low expression of RANKL. PBMC cultures supplemented with CM presented an evident osteoclastogenic behavior, which was dependent on the culture period of the MG63 cells. The inductive effect appeared to be more relevant for the differentiation and activation genes, c-myc and c-src, and lower for genes associated with osteoclast function. In addition, PBMC cultures displayed increased functional parameters, including calcium phosphate resorbing activity. Assessment of the PBMC cultures in the presence of U0126, PDTC, and indomethacin suggested that in addition to MEK and NFkB pathways, other signaling mechanisms, probably not involving RANKL/RANK interaction, might be activated in the presence of conditioned medium from MG63. In conclusion, MG63 cell line appears to induce a significant paracrine-mediated osteoclastogenic response. Understanding the mechanisms underlying the interaction of osteosarcoma cells and osteoclasts may contribute to the development of new potential approaches in the treatment of such bone metabolic diseases.

Response of MG63 osteoblast-like cells onto polycarbonate membrane surfaces with different micropore sizes.

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Lee, Sang Jin; Choi, Jin San; Park, Ki Suk; Khang, Gilson; Lee, Young Moo; Lee, Hai Bang

2004-08-01

Response of different types of cells on materials is important for the applications of tissue engineering and regenerative medicine. It is recognized that the behavior of the cell adhesion, proliferation, and differentiation on materials depends largely on surface characteristics such as wettability, chemistry, charge, rigidity, and roughness. In this study, we examined the behavior of MG63 osteoblast-like cells cultured on a polycarbonate (PC) membrane surfaces with different micropore sizes (0.2-8.0 microm in diameter). Cell adhesion and proliferation to the PC membrane surfaces were determined by cell counting and MTT assay. The effect of surface micropore on the MG63 cells was evaluated by cell morphology, protein content, and alkaline phosphatase (ALP) specific activity. It seems that the cell adhesion and proliferation were progressively inhibited as the PC membranes had micropores with increasing size, probably due to surface discontinuities produced by track-etched pores. Increasing micropore size of the PC membrane results in improved protein synthesis and ALP specific activity in isolated cells. There was a statistically significant difference (Pmicropore sizes. The MG63 cells also maintained their phenotype under conditions that support a round cell shape. RT-PCR analysis further confirmed the osteogenic phenotype of the MG63 cells onto the PC membranes with different micropore sizes. In results, as micropore size is getting larger, cell number is reduced and cell differentiation and matrix production is increased. This study demonstrated that the surface topography plays an important role for phenotypic expression of the MG63 osteoblast-like cells.

Responses of human normal osteoblast cells and osteoblast-like cell line, MG-63 cells, to pulse electromagnetic field (PEMF

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Suttatip Kamolmatyakul

2008-01-01

Full Text Available The objective of this in vitro study is to investigate the effect of pulsed electromagnetic field (PEMF on cellular proliferation and osteocalcin production of osteoblast-like cell line, MG-63 cells, and human normal osteoblast cells (NHOC obtained from surgical bone specimens. The cells were placed in 24-well culture plates in the amount of 3x104 cell/wells with 2 ml αMEM media supplemented with 10% FBS. The experimental plates were placed between a pair of Helmoltz coils powered by a pulse generator (PEMF, 50 Hz, 1.5 mV/cm in the upper compartment of a dual incubator (Forma. The control plates were placed in the lower compartment of the incubator without Helmotz coils. After three days, the cell proliferation was measured by the method modified from Mossman (J. Immunol Methods 1983; 65: 55-63. Other sets of plates were used for osteocalcin production assessment. Media from these sets were collected after 6 days and assessed for osteocalcin production using ELISA kits. The data were analyzed using a one-way analysis of variance (ANOVA. The results showed that MG-63 cells from the experimental group proliferated significantly more than those from the control group (20% increase, p<0.05. No significant difference in osteocalcin production was detected between the two groups. On the other hand, NHOC from the experimental group produced larger amount of osteocalcin (25% increase, p<0.05 and proliferated significantly more than those from the control group (100% increase, p<0.05. In conclusion, PEMF effect on osteoblasts might depend on their cell type of origin. For osteoblast-like cell line, MG-63 cells, PEMF increased proliferation rate but not osteocalcin production of the cells. However, PEMF stimulation effect on human normal osteoblast cells was most likely associated with enhancement of both osteocalcin production and cell proliferation.

Value of 18F-3,4-dihydroxyphenylalanine PET/MR image fusion in pediatric supratentorial infiltrative astrocytomas: a prospective pilot study.

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Morana, Giovanni; Piccardo, Arnoldo; Milanaccio, Claudia; Puntoni, Matteo; Nozza, Paolo; Cama, Armando; Zefiro, Daniele; Cabria, Massimo; Rossi, Andrea; Garrè, Maria Luisa

2014-05-01

Infiltrative astrocytomas (IAs) represent a group of astrocytic gliomas ranging from low-grade to highly malignant, characterized by diffuse invasion of the brain parenchyma. When compared with their adult counterpart, pediatric IAs may be considered biologically distinct entities; nevertheless, similarly to those in adults they represent a complex oncologic challenge. The aim of this study was to investigate the diagnostic role, clinical contribution, and prognostic value of fused (18)F-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET/MR images in pediatric supratentorial IAs. Pediatric patients with supratentorial IAs involving at least 2 cerebral lobes, either newly diagnosed or with suspected disease progression, prospectively underwent (18)F-DOPA PET and conventional MR imaging, performed within 10 d of each other. (18)F-DOPA PET data were interpreted qualitatively and semiquantitatively, fusing images with MR images. PET scans were classified as positive if tumors identified on MR imaging exhibited tracer uptake above the level of the corresponding contralateral normal brain. Maximum standardized uptake values, tumor-to-normal contralateral tissue ratios, and tumor-to-normal striatum ratios were calculated for all tumors. Correlations between the degree and extent of (18)F-DOPA uptake, MR imaging tumor characteristics, and histologic results were investigated. The contribution of (18)F-DOPA PET/MR image fusion was considered relevant if it enabled one to select the most appropriate biopsy site, discriminate between disease progression and treatment-related changes, or influence treatment strategy. The patient's outcome was finally correlated with (18)F-DOPA uptake. Thirteen patients (8 boys and 5 girls) were included (5 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 gliomatosis cerebri, and 1 glioblastoma multiforme). The (18)F-DOPA uptake pattern was heterogeneous in all positive scans (9/13), revealing metabolic heterogeneities within each tumor. Significant

Comparison of the reaction of bone-derived cells to enhanced MgCl2-salt concentrations.

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Burmester, Anna; Luthringer, Bérengère; Willumeit, Regine; Feyerabend, Frank

2014-01-01

Magnesium-based implants exhibit various advantages such as biodegradability and potential for enhanced in vivo bone formation. However, the cellular mechanisms behind this possible osteoconductivity remain unclear. To determine whether high local magnesium concentrations can be osteoconductive and exclude other environmental factors that occur during the degradation of magnesium implants, magnesium salt (MgCl2) was used as a model system. Because cell lines are preferred targets in studies of non-degradable implant materials, we performed a comparative study of 3 osteosarcoma-derived cell lines (MG63, SaoS2 and U2OS) with primary human osteoblasts. The correlation among cell count, viability, cell size and several MgCl2 concentrations was used to examine the influence of magnesium on proliferation in vitro. Moreover, bone metabolism alterations during proliferation were investigated by analyzing the expression of genes involved in osteogenesis. It was observed that for all cell types, the cell count decreases at concentrations above 10 mM MgCl2. However, detailed analysis showed that MgCl2 has a relevant but very diverse influence on proliferation and bone metabolism, depending on the cell type. Only for primary cells was a clear stimulating effect observed. Therefore, reliable results demonstrating the osteoconductivity of magnesium implants can only be achieved with primary osteoblasts.

Inhibition effect of proteasome inhibitor MG132 combined with X-ray irradiation on cell growth, metastasis and cycle distribution of human lung adenocarcinoma cells

International Nuclear Information System (INIS)

Liu Jing; Tang Yiting; Zhou Jundong; Zhang Shuyu; Cao Han; Wu Jinchang; Luo Judong; Chen Guanglie; Cao Jianping

2014-01-01

Objective: To study the effects of proteasome inhibitor MG132 on the growth, metastasis, and cell cycle distribution of human lung adenocarcinoma cells A549 irradiated by X-rays. Methods: After treatment of MG132 and irradiation,cell proliferation was detected by MTT assay. Survival was measured by clonogenic assay. Cell migration ability was detected by the Scratch migration assay. Cell invasion ability was detected by transwell migration assay. Cell cycle distribution were analyzed by flow cytometry assay. Protein expression was detected by Western blot assay. Results: MG132 alone inhibited cell growth in a dose-and time-dependent manner. MG132 in combination with radiation significantly suppressed the growth, migration and invasion of A549 cells compared to the control (F =554.78, 954.64, P<0.01). MG132 enhanced radiation-induced G 1 -arrest (t =4.44, 12.41, 3.52, 6.72, P<0.05). The G 1 cell cycle distribution rate of MG132 plus RT group was increased to (71.05 ± 4.17)%. The expressions of MMP-2, MMP-9 and Cyclin D1 were significantly suppressed by MG132 in combination with radiation, while the expression of P53 was up-regulated. Conclusions: MG132 inhibits cell growth, migration and invasion ability, and induces G 1 cell cycle arrest of A549 cells treated with MG132 in combination with radiation, in which the down-regulation of MMPs and Cyclin D1 and up-regulation of P53 may be involved. (authors)

miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

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Costello Joseph F

2008-06-01

Full Text Available Abstract Background Glioblastoma multiforme (GBM is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells. Methods We used quantitative RT-PCR to assess microRNA expression in high-grade astrocytomas and adult mouse neural stem cells. To assess the function of candidate microRNAs in high-grade astrocytomas, we transfected miR mimics to cultured-mouse neural stem cells, -mouse oligodendroglioma-derived stem cells, -human glioblastoma multiforme-derived stem cells and -glioblastoma multiforme cell lines. Cellular differentiation was assessed by immunostaining, and cellular proliferation was determined using fluorescence-activated cell sorting. Results Our studies revealed that expression levels of microRNA-124 and microRNA-137 were significantly decreased in anaplastic astrocytomas (World Health Organization grade III and glioblastoma multiforme (World Health Organization grade IV relative to non-neoplastic brain tissue (P erbB tumors and cluster of differentiation 133+ human glioblastoma multiforme-derived stem cells (SF6969. Transfection of microRNA-124 or microRNA-137 also induced G1 cell cycle arrest in U251 and SF6969 glioblastoma multiforme cells, which was associated with decreased expression of cyclin-dependent kinase 6 and phosphorylated retinoblastoma (pSer 807/811 proteins. Conclusion microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse

An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

OpenAIRE

Leis, J F; Kaplan, N O

1982-01-01

The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid pho...

Cuscuta chinensis extract promotes osteoblast differentiation and mineralization in human osteoblast-like MG-63 cells.

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Yang, Hyun Mo; Shin, Hyun-Kyung; Kang, Young-Hee; Kim, Jin-Kyung

2009-02-01

The aim of the present study was to investigate whether the aqueous extract of To-Sa-Za (TSZ-AE), the seed of Cuscuta chinensis Lam., which is a traditional medicinal herb commonly used in Korea and other oriental countries, could induce osteogenic activity in human osteoblast-like MG-63 cells. TSZ-AE treatment mildly promoted the proliferation of MG-63 cells at doses of 500 and 1,000 microg/mL in the 24-hour culture period. Dose-dependent increases in alkaline phosphatase (ALP) activity and collagen synthesis were shown at 48 and 72 hours of incubation. The release of bone morphogenetic protein (BMP)-2 but not osteocalcin in the MG-63 cells was induced by TSZ-AE at 72 hours (100-1,000 microg/mL). In addition, TSZ-AE markedly increased mRNA expression of ALP, collagen, and BMP-2 in the MG-63 cells in a dose-dependent manner. Mineralization in the culture of MG-63 cells was significantly induced at 500 and 1,000 microg/mL TSZ-AE treatment. In conclusion, this study shows that TSZ-AE enhanced ALP activity, collagen synthesis, BMP-2 expression, and mineralization in MG-63 cells. These results strongly suggest that C. chinensis can play an important role in osteoblastic bone formation and may possibly lead to the development of bone-forming drugs.

Journal of Chemical Sciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Compounds 3 and 4 were screened for selective antiproliferative activity in three cancer cell lines of different tissue types (COLO 205 (human colorectal adenocarcinoma),U87 MG (glioblastoma astrocytoma) and MIAPaCa-2 (human pancreatic carcinoma). Geometry-optimized structures for tautomers 3 and 4 (3′ and 4′ ...

Periostin inhibits mechanical stretch-induced apoptosis in osteoblast-like MG-63 cells.

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Yu, Kai-Wen; Yao, Chung-Chen; Jeng, Jiiang-Huei; Shieh, Hao-Ying; Chen, Yi-Jane

2018-04-01

Appropriate mechanical stress plays an important role in regulating the proliferation and differentiation of osteoblasts, whereas high-level mechanical stress may be harmful and compromise cell survival. Periostin, a matricellular protein, is essential in maintaining functional integrity of bone and collagen-rich connective tissue in response to mechanical stress. This study investigated whether or not high-level mechanical stretch induces cell apoptosis and the regulatory role of periostin in mechanical stretch-induced apoptosis in osteoblastic cells. Osteoblast-like MG-63 cells were seeded onto Bio-Flex I culture plates and subjected to cyclic mechanical stretching (15% elongation, 0.1 Hz) in a Flexercell tension plus system-5000. The same process was applied to cells pre-treated with exogenous human recombinant periostin before mechanical stretching. We used a chromatin condensation and membrane permeability dead cell apoptosis kit to evaluate the stretch-induced cell responses. Expression of caspase-3 and cPARP was examined by immunofluorescent stain and flow cytometry. The expression of periostin in MG-63 cells is involved in the TGF-β signaling pathway. High-level cyclic mechanical stretch induced apoptotic responses in MG-63 osteoblastic cells. The percentages of apoptotic cells and cells expressing cPARP protein increased in the groups of cells subjected to mechanical stretch, but these responses were absent in the presence of exogenous periostin. Our study revealed that high-level mechanical stretch induces apoptotic cell death, and that periostin plays a protective role against mechanical stretch-induced apoptosis in osteoblastic cells. Copyright © 2017. Published by Elsevier B.V.

Cloning the Gravity and Shear Stress Related Genes from MG-63 Cells by Subtracting Hybridization

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Zhang, Shu; Dai, Zhong-quan; Wang, Bing; Cao, Xin-sheng; Li, Ying-hui; Sun, Xi-qing

2008-06-01

Background The purpose of the present study was to clone the gravity and shear stress related genes from osteoblast-like human osteosarcoma MG-63 cells by subtractive hybridization. Method MG-63 cells were divided into two groups (1G group and simulated microgravity group). After cultured for 60 h in two different gravitational environments, two groups of MG-63 cells were treated with 1.5Pa fluid shear stress (FSS) for 60 min, respectively. The total RNA in cells was isolated. The gravity and shear stress related genes were cloned by subtractive hybridization. Result 200 clones were gained. 30 positive clones were selected using PCR method based on the primers of vector and sequenced. The obtained sequences were analyzed by blast. changes of 17 sequences were confirmed by RT-PCR and these genes are related to cell proliferation, cell differentiation, protein synthesis, signal transduction and apoptosis. 5 unknown genes related to gravity and shear stress were found. Conclusion In this part of our study, our result indicates that simulated microgravity may change the activities of MG-63 cells by inducing the functional alterations of specific genes.

Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells.

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Chen, Hai-ying; Ren, Xiao-yan; Wang, Wei-hua; Zhang, Ying-xin; Chen, Shuang-feng; Zhang, Bin; Wang, Le-xin

2014-07-01

Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c-jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time-PCR, TRAF2, ASK1 and c-jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c-jun were elevated in MG-132 treated cells. Giving ROS scavenger N-acetyl-L-cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma

International Nuclear Information System (INIS)

Kleinberg, Lawrence; Grossman, Stuart A.; Piantadosi, Steven; Zeltzman, Michel; Wharam, Moody

1999-01-01

Purpose: To determine the effects of sequential versus concurrent administration of cranial radiotherapy and cisplatin/carmustine (BCNU) chemotherapy on survival and toxicity in newly diagnosed high-grade astrocytomas. Methods and Materials: From 1988 to 1996, 101 patients were treated on 2 therapeutic protocols for malignant glioma that used the identical chemotherapy regimen but differed in the timing of cranial radiotherapy. The eligibility criteria for the 2 protocols were identical. In the first protocol (1988-1991, 52 patients), cisplatin 120 mg/BCNU 120 mg i.v. over 72 h, was given for 3 monthly cycles prior to cranial radiotherapy. After a response rate of 42%, with a median survival of 13 months was achieved with this sequential regimen, a successor protocol (1992-1996, 49 patients) was developed in which cranial radiotherapy began concurrently with the start of the identical chemotherapy regimen. Chemotherapy was delayed but not discontinued if prolonged grade III/IV hematologic toxicity was experienced, but protocol therapy was discontinued if disease progression or thromboembolic events occurred. Survival outcome and hematologic toxicity were compared for the patients treated on these protocols. Results: Seventy-seven percent of sequentially-treated patients and 68% of concurrently-treated patients completed all planned therapy. Kaplan-Meier survival was similar to concurrent or sequential administration of chemotherapy and radiotherapy (median 12.8 months vs. 13.8 months, respectively). Hematologic toxicity was significantly less in sequentially- versus concurrently-treated patients, with median nadir per cycle (2.9 vs. 1.8 x 10 3 /mm 3 ) (p < 0.001), and incidence of grade 3/4 leukopenia 40% versus 77% (p = 0.002). There was also an increase in platelet transfusion requirements in concurrently-treated patients, but no significant worsening of anemia. We postulate that the worsened leukopenia results from the effects of concurrent radiotherapy on

Modulation of Wound Healing and Scar Formation by MG53 Protein-mediated Cell Membrane Repair*

Science.gov (United States)

Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M.; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

2015-01-01

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53−/− mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. PMID:26306047

An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

Science.gov (United States)

Leis, J F; Kaplan, N O

1982-11-01

The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid phosphatases tested from potato, wheat germ, milk, and bovine prostate did not show this degree of specificity. The plasma membrane activity also dephosphorylated phosphotyrosine histone at a much greater rate than did the other acid phosphatases. pH profiles for free O-phosphotyrosine and phosphotyrosine histone showed a shift toward physiological pH, indicating possible physiological significance. Phosphotyrosine histone dephosphorylation activity was nearly 10 times greater than that seen for phosphoserine histone dephosphorylation, and Km values were much lower for phosphotyrosine histone dephosphorylation (0.5 microM vs. 10 microM). Fluoride and zinc significantly inhibited phosphoserine histone dephosphorylation. Vanadate, on the other hand, was a potent inhibitor of phosphotyrosine histone dephosphorylation (50% inhibition at 0.5 microM) but not of phosphoserine histone. ATP stimulated phosphotyrosine histone dephosphorylation (160-250%) but inhibited phosphoserine histone dephosphorylation (95%). These results suggest the existence of a highly specific phosphotyrosine protein phosphatase activity associated with the plasma membrane of human astrocytoma.

Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

Science.gov (United States)

Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

2018-05-01

The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(＜4, ≥4 and, ＜8, ≥8 and, ＜12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p ＜0.05). The categorical variables of VDE (＜4 mm/y, ≥4 mm/y and, ＜8 mm/y, ≥8 mm/y and, ＜12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

Bufalin inhibits the differentiation and proliferation of human osteosarcoma cell line hMG63-derived cancer stem cells.

Science.gov (United States)

Chang, Yuewen; Zhao, Yongfang; Zhan, Hongsheng; Wei, Xiaoen; Liu, Tianjin; Zheng, Bo

2014-02-01

Cancer stem cells (CSCs) play an important role in drug resistance of tumor and are responsible for high recurrence rates. Agents that can suppress the proliferation and differentiation of CSCs would provide new opportunity to fight against tumor recurrence. In this study, we developed a new strategy to enrich CSCs in human osteosarcoma cell line hMG63. Using these CSCs as model, we tested the effect of bufalin, a traditional Chinese medicine, on the proliferation and differentiation of CSCs. hMG63 cells were cultured in poly-HEMA-treated dish and cancer stem cell-specific medium. In this nonadhesive culture system, hMG63 formed spheres, which were then collected and injected into the immunodeficient mice. Cisplatin was administered every 3 days for five times. The enriched xenograft tumors were cultured in cancer stem cell-specific medium again to form tumor spheres. Expression of cancer stem cell markers of these cells was measured by flow cytometry. These cells were then treated with bufalin, and the proliferation and differentiation ability were indicated by the expression level of molecular markers and the formation of sphere again in vitro. We obtained a low CD133+/CD44 cell population with high-level stem cell marker. When treated with bufalin, the sphere could not get attached to the flask and failed to differentiate, which was indicated by the stable expression of stem cell marker CD133 and OCT-4 in the condition permissive to differentiation. Treatment of bufalin also suppressed the single cells isolated from the sphere to form sphere again in the nonadhesive culture system, and a decreased expression of proliferation marker Ki67 was also detected in these cells. Sphere-formed and chemoresistant colon xenograft tumors in immunodeficient mice could enrich cancer stem cell population. Bufalin could inhibit proliferation and differentiation of CSCs.

Apoptosis and autophagy induced by pyropheophorbide-α methyl ester-mediated photodynamic therapy in human osteosarcoma MG-63 cells.

Science.gov (United States)

Huang, Qiu; Ou, Yun-Sheng; Tao, Yong; Yin, Hang; Tu, Ping-Hua

2016-06-01

Pyropheophorbide-α methyl ester (MPPa) was a second-generation photosensitizer with many potential applications. Here, we explored the impact of MPPa-mediated photodynamic therapy (MPPa-PDT) on the apoptosis and autophagy of human osteosarcoma (MG-63) cells as well as the relationships between apoptosis and autophagy of the cells, and investigated the related molecular mechanisms. We found that MPPa-PDT demonstrated the ability to inhibit MG-63 cell viability in an MPPa concentration- and light dose-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, MPPa-PDT could also induce autophagy of MG-63 cell. Meanwhile, the ROS scavenger N-acetyl-L-cysteine (NAC) and the Jnk inhibitor SP600125 were found to inhibit the MPPa-PDT-induced autophagy, and NAC could also inhibit Jnk phosphorylation. Furthermore, pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine showed the potential in reducing the apoptosis rate induced by MPPa-PDT in MG-63 cells. Our results indicated that the mitochondrial pathway was involved in MPPa-PDT-induced apoptosis of MG-63 cells. Meanwhile the ROS-Jnk signaling pathway was involved in MPPa-PDT-induced autophagy, which further promoted the apoptosis in MG-63 cells.

Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

Science.gov (United States)

Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

2015-10-02

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53(-/-) mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A case of paraventricular anaplastic astrocytoma following radiation therapy for craniopharyngioma

Energy Technology Data Exchange (ETDEWEB)

Shimizu, Hiroaki; Fujiwara, Kazunori; Kobayashi, Shin-ichi; Kitahara, Masakazu (Ishinomaki Red Cross Hospital, Miyagi (Japan))

1994-04-01

A 20-year-old man received 60 Gy of radiation therapy after partial removal of craniopharyngioma. The patient had been well and follow-up CT scans did not show any aggravation for 16 years. Since his activity gradually diminished, he underwent an MRI at the age of 36 which revealed and abnormal mass on the corpus callosum. The mass lesion progressively enlarged thereafter, and was diagnosed as anaplastic astrocytoma by a stereotactic biopsy. He was treated with interferon, however, died at the age of 37. Review of the literature disclosed 19 other cases of glioma following radiation therapy for sellar/parasellar tumors. Characteristic features of these cases included (1) lowness of age compared to common glioma cases, (2) tendency to be malignant, (3) tendency to occur in areas where significant doses of radiation had been received previously. (author).

Astrocytoma in the medulla oblongata diagnosed by magnetic resonance imaging

International Nuclear Information System (INIS)

Suga, Toshihiro; Takahashi, Shin-ichiro; Sonobe, Makoto; Koshu, Keiji; Hirota, Shigeru; Kawakami, Hiroshi; Fujii, Kyoichi; Namiki, Tsuneo.

1987-01-01

A 22-year-old male was admitted to Mito National Hospital with complaints of persistent, progressive dysphagia, hoarseness, and numbness over his entire body. Neurological examination showed bilateral 7th, 9th, and 10th nerve paralysis, tetraparesis, sensory disturbance of the whole body, and hyper-reflexia of all extremities. Pale, low-density areas in the medulla oblongata and upper cervical spinal cord were detected by conventional computed tomography. Magnetic resonance imaging (MRI) disclosed low-signal masses involving those areas and in the lower cervical cord. Suboccipital craniotomy exposed a solid, firm, well demarcated intramedullary tumor in the medulla oblongata. The tumor was removed en bloc and was histologically diagnosed as a pilocytic astrocytoma. The postoperative course was uneventful and the patient's symptoms improved dramatically. Postoperative MRI revealed no residual tumor in the medulla oblongata or upper cervical cord. This case illustrates the value of preoperative MRI, which precisely delineates the location and extent of the tumor and greatly facilitates direct surgery of the medulla oblongata. (author)

Fast neutron boost for the treatment of grade IV astrocytomas

International Nuclear Information System (INIS)

Breteau, N.; Destembert, B.; Favre, A.; Pheline, C.; Schlienger, M.

1989-01-01

A previous study, on grade IV astrocytomas, compared a combination of photons and fast neutron boost to photons only, both treatments being delivered following a concentrated irradiation schedule. A slight improvement in survival was observed after neutron boost for non operated patients, but not for operated patients. Since death was always related to local recurrence and since no complication occurred after neutron boost, the neutron dose was increased from 6 to 7 Gy in January 1985. No improvement in survival was observed for patients treated with neutron boost after complete resection. After subtotal resection, the group that was treated with the higher neutron boost (7 Gy) showed a significant benefit in survival at twelve months. When patients had only a biopsy before irradiation, there was a benefit in survival after neutron boost, but no additional benefit was gained when the size of the neutron boost was increased from 6 to 7 Gy. (orig.) [de

Dipeptidyl peptidase-IV inhibits glioma cell growth independent of its enzymatic activity

Czech Academy of Sciences Publication Activity Database

Busek, P.; Stremeňová, J.; Sromová, L.; Hilser, M.; Balaziová, E.; Kosek, D.; Trylcová, J.; Strnad, Hynek; Křepela, E.; Šedo, A.

2012-01-01

Roč. 44, č. 5 (2012), s. 738-747 ISSN 1357-2725 Institutional support: RVO:68378050 Keywords : protease * tumour suppression * primary cell cultures * astrocytoma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.152, year: 2012

[Effect of M007 mediated photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro].

Science.gov (United States)

Zhou, Yu-Kai; Wu, Wen-Zhi; Zhang, Lan; Yang, Chun-Hui; Wang, Yan-Ping

2012-01-01

To investigate the effect of a new photosensitizer, M007 mediated photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro. Human osteosarcoma MG63 cells were prepared as 1 x 10(6) /mL single-cell suspension, and 1 mL cells were transferred into 60 mL culture dish, then treated with 5 different gradient dosages (0, 2, 4, 8, 16 micromol/L) of M007 followed by photodynamic therapy or dark reaction for 10 min. The survival rate of the cells and the mode of cell death were detected by flow cytometry with the stain of Annexin V-FITC/PI. The effect on proliferation of survival cells was observed by MTT assay and colony-forming assay. M007 mediated photodynamic therapy induced the inactivation of MG63 human osteosarcoma cells in the way of late apoptosis/necrosis or becoming naked nucleus predominately. More than 90% MG63 cells in M007-PDT group were dead under the treatment of 2-16 micromol/L M007. The survival rates of 4-16 micromol/L M007-PDT group were steadily less than 1%. The optical densities did not increase with extension of culture time in 2-8 micromol/L M007-PDT group (P > 0.05). There were 16 survival alive cells found occasionally in 2 micromol/L M007-PDT group, but no colonies found in other groups. M007 mediated photodynamic therapy totally inactivated human osteosarcoma MG63 cells in vitro with the dosage more than 4 micromol/L.

Cytotoxic effects of chemotherapeutic drugs and heterocyclic compounds at application on the cells of primary culture of neuroepithelium tumors.

Science.gov (United States)

Kulchitsky, Vladimir A; Potkin, Vladimir I; Zubenko, Yuri S; Chernov, Alexander N; Talabaev, Michael V; Demidchik, Yuri E; Petkevich, Sergei K; Kazbanov, Vladimir V; Gurinovich, Tatiana A; Roeva, Margarita O; Grigoriev, Dmitry G; Kletskov, Alexei V; Kalunov, Vladimir N

2012-01-01

Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the brain tumors during neurosurgical operations. The individual features of the cells sensitivity of primary cultures in respect to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6) level in the culture medium after the application of chemotherapy were established. The initial level of Il-6 exceeded 600.0 pg/ml in the cultural medium with histologically verified pilomyxoid astrocytoma cells, and ranged from 100.0 to 200.0 pg/ml in the medium at cultivation of ganglioneuroblastoma and pilocytic astrocytoma. A decrease in the Il-6 level in the medium culture of primary tumors cells was observed after the application of chemotherapeutic agents on the cells of pilomyxoid astrocytoma, astrocytomas, and pilocytic desmoplastic/nodular medulloblastoma. The production of Il-6 increased after application of cytostatic drugs on the cells of oligoastrocytomas. A decrease in Il-6 level after application of Cisplatin and Methotrexate and a 5-10 fold increase in the level of Il-6 after application of Etoposide, Carboplatin, Cytarabine, and Gemcitabine were registered in the medium with ganglioneuroblastoma. To improve the cytotoxic action of chemotherapeutic agents, the combined application of cytostatics with heterocyclic compounds was carried out. A computer modeling of ligand-protein complexes of carbamide using the Dock 6.4 and USF Chimera program packages was performed with molecular mechanics method. Special attention was drawn to the ability of several isoxazole heterocycles and isothiazolyl to inhibit the tyrosine kinase. It was proved in vitro that the joint application of chemotherapeutic agents and heterocyclic compounds could reduce the concentration of the cytostatic factor by 10 or more times, having maintained the maximum cytotoxic effect. It was assumed that the target amplification of cytotoxic action of chemotherapeutic

Different effects of a novel CaO-MgO-SiO₂-based multiphase glass-ceramic on cell behaviors of normal and cancer cells in vitro.

Science.gov (United States)

Zhang, Mengjiao; Chen, Xianchun; Pu, Ximing; Liao, Xiaoming; Huang, Zhongbing; Yin, Guangfu

2014-04-01

The effects in vitro of a novel multiphase glass-ceramic (with nominal composition of 43.19% CaO, 7.68% MgO, and 49.13% SiO2 in weight percent) on cell adhesion, proliferation, differentiation and ultrastructure of human osteosarcoma cell line MG63, mouse fibroblasts L929, and human lung adenocarcinoma epithelial cell line A549 were investigated in this research. Scanning electron microscopy (SEM) micrographs revealed that the surface morphology of this glass-ceramic was beneficial to cell adhesion. The glass-ceramic extracts at certain concentrations could stimulate the proliferation and differentiation of MG63 and L929 cells, whereas inhibit A549 proliferation, which might be resulted from the released Si ions. In addition, when cultured with 0.1mg/mL glass-ceramic powder suspension, the cell ultrastructure of MG63 showed abundant organelles and L929 displayed the phenomena of cellular stress response. While more interestingly, A549 exhibited chromatin condensation, mitochondria swell and RER expansion, which was presumed to be early signs of apoptosis. These results suggest that this novel CaO-MgO-SiO2-based multiphase glass-ceramic has potential for bone regeneration and tissue engineering applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Middle Temporal Gyrus Versus Inferior Temporal Gyrus Transcortical Approaches to High-Grade Astrocytomas in the Mediobasal Temporal Lobe: A Comparison of Outcomes, Functional Restoration, and Surgical Considerations.

Science.gov (United States)

Quinones-Hinojosa, Alfredo; Raza, Shaan M; Ahmed, Ishrat; Rincon-Torroella, Jordina; Chaichana, Kaisorn; Olivi, Alessandro

2017-01-01

High-grade astrocytomas of the mesial temporal lobe may pose surgical challenges. Several approaches (trans-sylvian, subtemporal, and transcortical) have been designed to circumnavigate the critical neurovascular structures and white fiber tracts that surround this area. Considering the paucity of literature on the transcortical approach for these lesions, we describe our institutional experience with transcortical approaches to Grade III/IV astrocytomas in the mesial temporal lobe. Between 1999 and 2009, 23 patients underwent surgery at the Johns Hopkins Medical Institutions for Grade III/IV astrocytomas involving the mesial temporal lobe (without involvement of the temporal neocortex). Clinical notes, operative records, and imaging were reviewed. Thirteen patients had tumors in the dominant hemisphere. All patients underwent surgery via a transcortical approach (14 via the inferior temporal gyrus and 9 via the middle temporal gyrus). Gross total resection was obtained in 92 % of the cohort. Neurological outcomes were: clinically significant stroke (2 patients), new visual deficits (2 patients), new speech deficit (1 patient); seizure control (53 %). In comparison to reported results in the literature for the transylvian and subtemporal approaches, the transcortical approach may provide the access necessary for a gross total resection with minimal neurological consequences. In our series of patients, there was no statistically significant difference in outcomes between the middle temporal gyrus versus the inferior temporal gyrus trajectories.

Neuronavigation-guided intubated wake-up craniotomy for a patient with a brain astrocytoma

Directory of Open Access Journals (Sweden)

Wen-Kuei Fang

2013-08-01

Full Text Available Computer-assisted neuronavigation (an image-guided technique that facilitates brain tumor surgery reduces the risk of neurological morbidity. Postoperative neurological dysfunction is also minimized by performing intraoperative neurological testing during awake craniotomy with proper surgical resection of a brain tumor. However, when the patient's airway is not secured, an awake craniotomy can be hazardous if emergent intubation is necessary. The present report describes a young man with a brain tumor who underwent neuronavigation-guided wake-up craniotomy and surgical resection of an astrocytoma. The patient was intubated throughout the course of the procedure, during which modified intraoperative neurological tests were performed for cortical mapping. The patient recovered well after the operation and without any neurological deficits.

High accuracy of arterial spin labeling perfusion imaging in differentiation of pilomyxoid from pilocytic astrocytoma

Energy Technology Data Exchange (ETDEWEB)

Nabavizadeh, S.A.; Assadsangabi, R.; Hajmomenian, M.; Vossough, A. [Perelman School of Medicine of the University of Pennsylvania, Department of Radiology, Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Santi, M. [Perelman School of Medicine of the University of Pennsylvania, Department of Pathology, Children' s Hospital of Philadelphia, Philadelphia, PA (United States)

2015-05-01

Pilomyxoid astrocytoma (PMA) is a relatively new tumor entity which has been added to the 2007 WHO Classification of tumors of the central nervous system. The goal of this study is to utilize arterial spin labeling (ASL) perfusion imaging to differentiate PMA from pilocytic astrocytoma (PA). Pulsed ASL and conventional MRI sequences of patients with PMA and PA in the past 5 years were retrospectively evaluated. Patients with history of radiation or treatment with anti-angiogenic drugs were excluded. A total of 24 patients (9 PMA, 15 PA) were included. There were statistically significant differences between PMA and PA in mean tumor/gray matter (GM) cerebral blood flow (CBF) ratios (1.3 vs 0.4, p < 0.001) and maximum tumor/GM CBF ratio (2.3 vs 1, p < 0.001). Area under the receiver operating characteristic (ROC) curves for differentiation of PMA from PA was 0.91 using mean tumor CBF, 0.95 using mean tumor/GM CBF ratios, and 0.89 using maximum tumor/GM CBF. Using a threshold value of 0.91, the mean tumor/GM CBF ratio was able to diagnose PMA with 77 % sensitivity, 100 % specificity, and a threshold value of 0.7, provided 88 % sensitivity and 86 % specificity. There was no statistically significant difference between the two tumors in enhancement pattern (p = 0.33), internal architecture (p = 0.15), or apparent diffusion coefficient (ADC) values (p = 0.07). ASL imaging has high accuracy in differentiating PMA from PA. The result of this study may have important applications in prognostication and treatment planning especially in patients with less accessible tumors such as hypothalamic-chiasmatic gliomas. (orig.)

Optimization of high grade glioma cell culture from surgical specimens for use in clinically relevant animal models and 3D immunochemistry.

Science.gov (United States)

Hasselbach, Laura A; Irtenkauf, Susan M; Lemke, Nancy W; Nelson, Kevin K; Berezovsky, Artem D; Carlton, Enoch T; Transou, Andrea D; Mikkelsen, Tom; deCarvalho, Ana C

2014-01-07

Glioblastomas, the most common and aggressive form of astrocytoma, are refractory to therapy, and molecularly heterogeneous. The ability to establish cell cultures that preserve the genomic profile of the parental tumors, for use in patient specific in vitro and in vivo models, has the potential to revolutionize the preclinical development of new treatments for glioblastoma tailored to the molecular characteristics of each tumor. Starting with fresh high grade astrocytoma tumors dissociated into single cells, we use the neurosphere assay as an enrichment method for cells presenting cancer stem cell phenotype, including expression of neural stem cell markers, long term self-renewal in vitro, and the ability to form orthotopic xenograft tumors. This method has been previously proposed, and is now in use by several investigators. Based on our experience of dissociating and culturing 125 glioblastoma specimens, we arrived at the detailed protocol we present here, suitable for routine neurosphere culturing of high grade astrocytomas and large scale expansion of tumorigenic cells for preclinical studies. We report on the efficiency of successful long term cultures using this protocol and suggest affordable alternatives for culturing dissociated glioblastoma cells that fail to grow as neurospheres. We also describe in detail a protocol for preserving the neurospheres 3D architecture for immunohistochemistry. Cell cultures enriched in CSCs, capable of generating orthotopic xenograft models that preserve the molecular signatures and heterogeneity of GBMs, are becoming increasingly popular for the study of the biology of GBMs and for the improved design of preclinical testing of potential therapies.

Photovoltaic performance of a Cd{sub 1−x}Mg{sub x}Te/CdS top-cell structure

Energy Technology Data Exchange (ETDEWEB)

Martinez, Omar S. [Instituto de Energías Renovables, Universidad Nacional Autónoma de México, Temixco, Morelos 62580 (Mexico); Centro del Cambio Global y la Sustentabilidad en el Sureste, Villahermosa, Tabasco 86080 (Mexico); Regalado-Pérez, E.; Mathews, N.R. [Instituto de Energías Renovables, Universidad Nacional Autónoma de México, Temixco, Morelos 62580 (Mexico); Morales, Erik R. [División Académica de Ingeniería y Arquitectura, Universidad Juárez Autónoma de Tabasco, Cunduacán, Tabasco 86690 (Mexico); Reyes-Coronado, David [Unidad Académica Playa del Carmen, Universidad de Quintana Roo, Playa del Carmen, Quintana Roo 77710 (Mexico); Galvez, Geovanni Hernández [Centro del Cambio Global y la Sustentabilidad en el Sureste, Villahermosa, Tabasco 86080 (Mexico); Mathew, Xavier, E-mail: xm@ier.unam.mx [Instituto de Energías Renovables, Universidad Nacional Autónoma de México, Temixco, Morelos 62580 (Mexico)

2015-05-01

In this paper we report the progress in developing a wide band gap alloy material based on CdTe to use as the top-cell absorber in tandem solar cells. High photovoltaic performance for a Cd{sub 1−x}Mg{sub x}Te/CdS top-cell was achieved by tuning the composition of the Cd{sub 1−x}Mg{sub x}Te film, and optimizing the device processing. We have carried out studies on the effect of vapor chloride treatment of the Cd{sub 1−x}Mg{sub x}Te/CdS device and the thermal annealing of the Cu/Au contacts on the opto-electronic properties of the device. With improved contact processing and post deposition treatments, we were able to achieve 9.3% efficiency for a 1.6 eV band gap top-cell; Cd{sub 1−x}Mg{sub x}Te/CdS on conductive glass substrate. - Highlights: • Cd{sub 1−x}Mg{sub x}Te films obtained by co-evaporation of CdTe and Mg • Band gap of Cd{sub 1−x}Mg{sub x}Te can be easily tuned by verifying x. • Band gap of Cd{sub 1−x}Mg{sub x}Te is stable only for short annealing durations. • Obtained efficiency of a Cd{sub 1−x}Mg{sub x}Te based device with a band gap of 1.6 eV is 9.3%.

The Oncolytic Virus MG1 Targets and Eliminates Cells Latently Infected With HIV-1: Implications for an HIV Cure.

Science.gov (United States)

Ranganath, Nischal; Sandstrom, Teslin S; Burke Schinkel, Stephanie C; Côté, Sandra C; Angel, Jonathan B

2018-02-14

Cells latently infected with human immunodeficiency virus (HIV) evade immune- and drug-mediated clearance. These cells harbor intracellular signaling defects, including impairment of the antiviral type I interferon response. Such defects have also been observed in several cancers and have been exploited for the development of therapeutic oncolytic viruses, including the recombinant Maraba virus (MG1). We therefore hypothesized that MG1 would infect and eliminate cells latently infected with HIV-1, while sparing healthy uninfected cells. Preferential infection and elimination by MG1 was first demonstrated in cell lines latently infected with HIV-1. Following this, a reduction in HIV-1 DNA and inducible HIV-1 replication was observed following MG1 infection of latently infected, resting CD4+ T cells generated using an in vitro model of latency. Last, MG1 infection resulted in a reduction in HIV-1 DNA and inducible HIV-1 replication in memory CD4+ T cells isolated from effectively treated, HIV-1-infected individuals. Our results therefore highlight a novel approach to eliminate the latent HIV-1 reservoir. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Mg ion implantation on SLA-treated titanium surface and its effects on the behavior of mesenchymal stem cell

International Nuclear Information System (INIS)

Kim, Beom-Su; Kim, Jin Seong; Park, Young Min; Choi, Bo-Young; Lee, Jun

2013-01-01

Magnesium (Mg) is one of the most important ions associated with bone osseointegration. The aim of this study was to evaluate the cellular effects of Mg implantation in titanium (Ti) surfaces treated with sand blast using large grit and acid etching (SLA). Mg ions were implanted into the surface via vacuum arc source ion implantation. The surface morphology, chemical properties, and the amount of Mg ion release were evaluated by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), Rutherford backscattering spectroscopy (RBS), and inductively coupled plasma-optical emission spectrometer (ICP-OES). Human mesenchymal stem cells (hMSCs) were used to evaluate cellular parameters such as proliferation, cytotoxicity, and adhesion morphology by MTS assay, live/dead assay, and SEM. Furthermore, osteoblast differentiation was determined on the basis of alkaline phosphatase (ALP) activity and the degree of calcium accumulation. In the Mg ion-implanted disk, 2.3 × 10 16 ions/cm 2 was retained. However, after Mg ion implantation, the surface morphology did not change. Implanted Mg ions were rapidly released during the first 7 days in vitro. The MTS assay, live/dead assay, and SEM demonstrated increased cell attachment and growth on the Mg ion-implanted surface. In particular, Mg ion implantation increased the initial cell adhesion, and in an osteoblast differentiation assay, ALP activity and calcium accumulation. These findings suggest that Mg ion implantation using the plasma source ion implantation (PSII) technique may be useful for SLA-treated Ti dental implants to improve their osseointegration capacity. - Highlights: ► Mg ion was coated onto surface of SLA treated titanium via vacuum arc source ion implantation method. ► The morphological characteristics did not change after Mg ion implantation. ► Mg ion implanted SLA Ti is highly cytocompatible. ► Initial cell adhesion of MSCs is improved by Mg ion implantation. ► Mg ion implantation improved

Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

Science.gov (United States)

2017-09-27

Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

Science.gov (United States)

Antonow, Michelli B.; Franco, Camila; Prado, Willian; Beckenkamp, Aline; Silveira, Gustavo P.; Buffon, Andréia; Guterres, Sílvia S.

2017-01-01

Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG. PMID:29271920

Plasma deposited composite coatings to control biological response of osteoblast-like MG-63 cells

Science.gov (United States)

Keremidarska, M.; Radeva, E.; Eleršič, K.; Iglič, A.; Pramatarova, L.; Krasteva, N.

2014-12-01

The successful osseointegration of a bone implant is greatly dependent on its ability to support cellular adhesion and functions. Deposition of thin composite coatings onto the implant surface is a promising approach to improve interactions with cells without compromising implant bulk properties. In this work, we have developed composite coatings, based on hexamethyldisiloxane (HMDS) and detonation nanodiamond (DND) particles and have studied adhesion, growth and function of osteoblast-like MG-63 cells. PPHMDS/DND composites are of interest for orthopedics because they combine superior mechanical properties and good biocompatibility of DND with high adherence of HMDS to different substrata including glass, metals and plastics. We have used two approaches of the implementation of DND particles into a polymer matrix: pre-mixture of both components followed by plasma polymerization and layer-by-layer deposition of HMDS and DND particles and found that the deposition approach affects significantly the surface properties of the resulting layers and cell behaviour. The composite, prepared by subsequent deposition of monomer and DND particles was hydrophilic, with a rougher surface and MG-63 cells demonstrated better spreading, growth and function compared to the other composite which was hydrophobic with a smooth surface similarly to unmodified polymer. Thus, by varying the deposition approach, different PPHMDS/DND composite coatings, enhancing or inhibiting osteoblast adhesion and functions, can be obtained. In addition, the effect of fibronectin pre-adsorption was studied and was found to increase greatly MG-63 cell spreading.

Effect of Electrochemically Deposited MgO Coating on Printable Perovskite Solar Cell Performance

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T.A. Nirmal Peiris

2017-02-01

Full Text Available Herein, we studied the effect of MgO coating thickness on the performance of printable perovskite solar cells (PSCs by varying the electrodeposition time of Mg(OH2 on the fluorine-doped tin oxide (FTO/TiO2 electrode. Electrodeposited Mg(OH2 in the electrode was confirmed by energy dispersive X-ray (EDX analysis and scanning electron microscopic (SEM images. The performance of printable PSC structures on different deposition times of Mg(OH2 was evaluated on the basis of their photocurrent density-voltage characteristics. The overall results confirmed that the insulating MgO coating has an adverse effect on the photovoltaic performance of the solid state printable PSCs. However, a marginal improvement in the device efficiency was obtained for the device made with the 30 s electrodeposited TiO2 electrode. We believe that this undesirable effect on the photovoltaic performance of the printable PSCs is due to the higher coverage of TiO2 by the insulating MgO layer attained by the electrodeposition technique.

Conformal proton radiation therapy for pediatric low-grade astrocytomas

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Hug, E.B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pediatrics and Dept. of Pathology; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States). Section of Radiation Oncology; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Liwnicz, B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pathology

2002-01-01

Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

Heat Modeling and Material Development of Mg-Based Nanomaterials Combined with Solid Oxide Fuel Cell for Stationary Energy Storage

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Huaiyu Shao

2017-11-01

Full Text Available Mg-based materials have been investigated as hydrogen storage materials, especially for possible onboard storage in fuel cell vehicles for decades. Recently, with the development of large-scale fuel cell technologies, the development of Mg-based materials as stationary storage to supply hydrogen to fuel-cell components and provide electricity and heat is becoming increasingly promising. In this work, numerical analysis of heat balance management for stationary solid oxide fuel cell (SOFC systems combined with MgH2 materials based on a carbon-neutral design concept was performed. Waste heat from the SOFC is supplied to hydrogen desorption as endothermic heat for the MgH2 materials. The net efficiency of this model achieves 82% lower heating value (LHV, and the efficiency of electrical power output becomes 68.6% in minimizing heat output per total energy output when all available heat of waste gas and system is supplied to warm up the storage. For the development of Mg-based hydrogen storage materials, various nano-processing techniques have been widely applied to synthesize Mg-based materials with small particle and crystallite sizes, resulting in good hydrogen storage kinetics, but poor thermal conductivity. Here, three kinds of Mg-based materials were investigated and compared: 325 mesh Mg powers, 300 nm Mg nanoparticles synthesized by hydrogen plasma metal reaction, and Mg50Co50 metastable alloy with body-centered cubic structure. Based on the overall performances of hydrogen capacity, absorption kinetics and thermal conductivity of the materials, the Mg nanoparticle sample by plasma synthesis is the most promising material for this potential application. The findings in this paper may shed light on a new energy conversion and utilization technology on MgH2-SOFC combined concept.

Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells.

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Chunliu Li

Full Text Available Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. Sulforaphane (SFN was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells.First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2 and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6.The results showed that SFN (20 µM remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion.SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.

Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

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Araceli Gutiérrez-Rodríguez

2017-01-01

Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

Approach to the irradiation of extensive cervical and upper thoracic spinal astrocytoma

International Nuclear Information System (INIS)

Dvorak, E.

1981-01-01

Intramedullary spinal cord tumors are relatively rare, especially to the extent presented in this report. A 31-year-old woman had been diagnosed as having an inoperable astrocytoma, grade I-II, involving the entire cervical spinal cord and two upper thoracic segments. After decompressive laminectomy, she was referred for a radical course of radiation therapy. An irradiation technique was devised which allowed treatment of a single cylindrical volume of tissue encompassing the known tumor. Field fractionation with undesirable gaps and/or excessive dose to overlying normal structures was avoided. To the cervical spinal cord she received 5590 cGy in 29 fractions over 42 days. By this schedule she received at the same time 4820 cGy to the medulla oblongata and 4880 cGy to the upper thoracic cord. Partial neurological improvement occurred at the end of the treatment. The treatment approach is discussed in the background of the literature data. (orig.) [de

The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells

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Fan, J.Z.; Yang, X.; Bi, Z.G. [Department of Orthopedic Surgery, First Affiliated Hospital, Harbin Medicine University, Harbin (China)

2015-04-28

We investigated whether 6-gingerol affects the maturation and proliferation of osteoblast-like MG63 cells in vitro. Osteoblast-like MG63 cells were treated with 6-gingerol under control conditions, and experimental inflammation was induced by tumor necrosis factor-α (TNF-α). Expression of different osteogenic markers and cytokines was analyzed by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. In addition, alkaline phosphatase (ALP) enzyme activity and biomineralization as markers for differentiation were measured. Treatment with 6-gingerol resulted in insignificant effects on the proliferation rate. 6-Gingerol induced the differentiation of osteoblast-like cells with increased transcription levels of osteogenic markers, upregulated ALP enzyme activity, and enhanced mineralized nodule formation. Stimulation with TNF-α led to enhanced interleukin-6 and nuclear factor-κB expression and downregulated markers of osteoblastic differentiation. 6-Gingerol reduced the degree of inflammation in TNF-α-treated MG-63 cells. In conclusion, 6-gingerol stimulated osteoblast differentiation in normal physiological and inflammatory settings, and therefore, 6-gingerol represents a promising agent for treating osteoporosis or bone inflammation.

MCPIP1 contributes to the toxicity of proteasome inhibitor MG-132 in HeLa cells by the inhibition of NF-κB.

Science.gov (United States)

Skalniak, Lukasz; Dziendziel, Monika; Jura, Jolanta

2014-10-01

Recently, we have shown that the treatment of cells with proteasome inhibitor MG-132 results in the induction of expression of monocyte chemotactic protein-1 induced protein 1 (MCPIP1). MCPIP1 is a ribonuclease, responsible for the degradation of transcripts encoding certain pro-inflammatory cytokines. The protein is also known as an inhibitor of NF-κB transcription factor. Thanks to its molecular properties, MCPIP1 is considered as a regulator of inflammation, differentiation, and survival. Using siRNA technology, we show here that MCPIP1 expression contributes to the toxic properties of MG-132 in HeLa cells. The inhibition of proteasome by MG-132 and epoxomicin markedly increased MCPIP1 expression. While MG-132 induces HeLa cell death, down-regulation of MCPIP1 expression by siRNA partially protects HeLa cells from MG-132 toxicity and restores Nuclear factor-κB (NF-κB) activity, inhibited by MG-132 treatment. Inversely, overexpression of MCPIP1 decreased constitutive activity of NF-κB and limited the survival of HeLa cells, as we have shown in the previous study. Interestingly, although MG-132 decreased the expression of IκBα and increased p65 phosphorylation, the inhibition of constitutive NF-κB activity was observed in MG-132-treated cells. Since the elevated constitutive activity of NF-κB is one of the mechanisms providing increased survival of cancer cells, including HeLa cells, we propose that death-promoting properties of MCPIP1 in MG-132-treated HeLa cells may, at least partially, derive from the negative effect on the constitutive NF-κB activity.

Study of the Mg incorporation in CdTe for developing wide band gap Cd{sub 1-x}Mg{sub x}Te thin films for possible use as top-cell absorber in a tandem solar cell

Energy Technology Data Exchange (ETDEWEB)

Martinez, Omar S. [Centro de Investigacion en Energia, Universidad Nacional Autonoma de Mexico, 62580 Temixco, Morelos (Mexico); Universidad Politecnica del Estado de Guerrero, Comunidad de Puente Campuzano, C.P. 40325 Taxco de Alarcon, Guerrero (Mexico); Millan, Aduljay Remolina [Centro de Investigacion en Energia, Universidad Nacional Autonoma de Mexico, 62580 Temixco, Morelos (Mexico); Huerta, L.; Santana, G. [Instituto de Investigaciones en Materiales, Universidad Nacional Autonoma de Mexico. C.P 04510 Mexico D.F. (Mexico); Mathews, N.R.; Ramon-Garcia, M.L.; Morales, Erik R. [Centro de Investigacion en Energia, Universidad Nacional Autonoma de Mexico, 62580 Temixco, Morelos (Mexico); Mathew, X., E-mail: xm@cie.unam.mx [Centro de Investigacion en Energia, Universidad Nacional Autonoma de Mexico, 62580 Temixco, Morelos (Mexico)

2012-02-15

Highlights: Black-Right-Pointing-Pointer Thin films of Cd{sub 1-x}Mg{sub x}Te with high spatial uniformity and band gap in the range of 1.6-1.96 eV were deposited by vacuum co-evaporation of CdTe and Mg. Black-Right-Pointing-Pointer Obtained Cd{sub 1-x}Mg{sub x}Te films have the structural characteristics of the CdTe, evidence of the change in atomic scattering due to incorporation of Mg was observed. Black-Right-Pointing-Pointer XRD and XPS data confirmed the incorporation of Mg in the lattice of CdTe. Black-Right-Pointing-Pointer SEM images revealed the impact of Mg incorporation on the morphology of the films, the changes in grain size and grain morphology are noticeable. - Abstract: Thin films of Cd{sub 1-x}Mg{sub x}Te with band gap in the range of 1.6-1.96 eV were deposited by vacuum co-evaporation of CdTe and Mg on glass substrates heated at 300 Degree-Sign C. Different experimental techniques such as XRD, UV-vis spectroscopy, SEM, and XPS were used to study the effect of Mg incorporation into the lattice of CdTe. The band gap of the films showed a clear tendency to increase as the Mg content in the film is increased. The Cd{sub 1-x}Mg{sub x}Te films maintain all the structural characteristics of the CdTe, however, diminishing of intensity for the XRD patterns is observed due to both change in preferential orientation and change in atomic scattering due to the incorporation of Mg. SEM images showed significant evidences of morphological changes due to the presence of Mg. XRD, UV-vis spectroscopy, and XPS data confirmed the incorporation of Mg in the lattice of CdTe. The significant increase in band gap of CdTe due to incorporation of Mg suggests that the Cd{sub 1-x}Mg{sub x}Te thin film is a candidate material to use as absorber layer in the top-cell of a tandem solar cell.

Porous composite materials ZrO2(MgO)-MgO for osteoimplantology

International Nuclear Information System (INIS)

Buyakov, Ales; Litvinova, Larisa; Shupletsova, Valeria; Kulbakin, Denis; Kulkov, Sergey

2016-01-01

The pore structure and phase composition of ceramic composite material ZrO 2 (Mg)-MgO at different sintering temperatures were studied. The main mechanical characteristics of the material were determined and it was shown that they are close to the characteristics of natural bone tissues. It was shown that material structure has a positive effect on the pre-osteoblast cells proliferation. In-vitro studies of pre-osteoblast cells, cultivation on material surface showed a good cell adhesion, proliferation and differentiation of MMSC by osteogenic type.

Effect of chemoradiotherapy using ACNU, vincristine, and nicardipine with high-dose irradiation on malignant astrocytomas

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Genka, Shigeru; Shitara, Nobuyuki; Nakamura, Hirohiko; Takakura, Kintomo [Tokyo Univ. (Japan). Hospital

1993-05-01

Fifty-two patients with malignant astrocytoma were treated with cellular synchronization radiation therapy at the University of Tokyo Hospital between 1977 and 1989. Twenty-five patients (Group 1) received 1 - (4-amino-2-methyl-5-pyrimidinyl)methyl - 3 - (2-chloroethyl) - 3 - nitrosourea hydrochloride (ACNU), vincristine, and 60 Gy of irradiation, and 27 patients (Group 2) ACNU, vincristine, the Ca-channel blocker nicardipine, and 72 Gy of irradiation. Median survival times for Groups 1 and 2 were 15 and 30 months, respectively. Although there was no significant difference, Group 2 achieved longer survival with 1-, 2-, and 3-year survival rates of 85.2, 65.8, and 46.9% compared to rates of 66.7, 40.0, and 26.7%, respectively, for Group 1. (author).

Effect of chemoradiotherapy using ACNU, vincristine, and nicardipine with high-dose irradiation on malignant astrocytomas

International Nuclear Information System (INIS)

Genka, Shigeru; Shitara, Nobuyuki; Nakamura, Hirohiko; Takakura, Kintomo

1993-01-01

Fifty-two patients with malignant astrocytoma were treated with cellular synchronization radiation therapy at the University of Tokyo Hospital between 1977 and 1989. Twenty-five patients (Group 1) received 1 - (4-amino-2-methyl-5-pyrimidinyl)methyl - 3 - (2-chloroethyl) - 3 - nitrosourea hydrochloride (ACNU), vincristine, and 60 Gy of irradiation, and 27 patients (Group 2) ACNU, vincristine, the Ca-channel blocker nicardipine, and 72 Gy of irradiation. Median survival times for Groups 1 and 2 were 15 and 30 months, respectively. Although there was no significant difference, Group 2 achieved longer survival with 1-, 2-, and 3-year survival rates of 85.2, 65.8, and 46.9% compared to rates of 66.7, 40.0, and 26.7%, respectively, for Group 1. (author)

Biological characteristics of the MG-63 human osteosarcoma cells on composite tantalum carbide/amorphous carbon films.

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Yin-Yu Chang

Full Text Available Tantalum (Ta is a promising metal for biomedical implants or implant coating for orthopedic and dental applications because of its excellent corrosion resistance, fracture toughness, and biocompatibility. This study synthesizes biocompatible tantalum carbide (TaC and TaC/amorphous carbon (a-C coatings with different carbon contents by using a twin-gun magnetron sputtering system to improve their biological properties and explore potential surgical implant or device applications. The carbon content in the deposited coatings was regulated by controlling the magnetron power ratio of the pure graphite and Ta cathodes. The deposited TaC and TaC/a-C coatings exhibited better cell viability of human osteosarcoma cell line MG-63 than the uncoated Ti and Ta-coated samples. Inverted optical and confocal imaging was used to demonstrate the cell adhesion, distribution, and proliferation of each sample at different time points during the whole culture period. The results show that the TaC/a-C coating, which contained two metastable phases (TaC and a-C, was more biocompatible with MG-63 cells compared to the pure Ta coating. This suggests that the TaC/a-C coatings exhibit a better biocompatible performance for MG-63 cells, and they may improve implant osseointegration in clinics.

PHAKOMATOSIS : INTRESTING CASES OF TUBEROUS SCLEROSIS WITH RETINAL ASTROCYTOMA

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Srinivasa Rao

2015-05-01

Full Text Available NTRODUCTION: Tuberous sclerosis complex (TSC or Morbus Bourneville - Pringle disease is an autosomal dominant phakomatosis, first described by Desiree - Magloire Bourneville in 1880. Tuberous sclerosis is a genetic disorder characterized by the growth of numerous benign tumours in many parts of the body caused by mutations on either of two genes, TSC1 and TSC2. This rare genetic disorder is usually associated with a triad of seizures, mental retardation and cutaneous lesions. Approximately one half of all patients affected by TS develop at least one retinal astrocytoma in one eye. PRESENTATION OF CASES: In the department of ophthalmology, G.S.L M edical C ollege, Rajahmundry, we came across 3 cases of tuberous sclerosis involving multi organ systems. Out of 3 cases, 2 cases were reported to be familial and 1case is sporadic, with a history of epilepsy with angiofibromatosis lesions over the face, multiple ash - leaf lesions over the abdomen, renal angiomyolipomas, multiple subependymal nodules in brain and retinal astrocytic hamartomas in the retina. CONCLUSION: It is important to be cognizant of the likely presence of systemic and ocular pathology in a child with mental retardation and skin lesions. Identification of retinal phakomatosis during ocular evaluation in any suspected case of Tuberous sclerosis can aid in the establishment of the diagnosis of the disease

Introducing directly induced microglia-like (iMG cells from fresh human monocytes: A novel translational research tool for psychiatric disorders.

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Masahiro eOhgidani

2015-05-01

Full Text Available Microglia, glial cells with immunological functions, have been implicated in various neurological diseases and psychiatric disorders in rodent studies, and human postmortem and PET studies. However, the deeper molecular implications of living human microglia have not been clarified.Here, we introduce a novel translational research approach focusing on human microglia. We have recently developed a new technique for creating induced microglia-like (iMG cells from human peripheral blood. Two cytokines, GM-CSF and IL-34, converted human monocytes into the iMG cells within 14 days, which show various microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. We have already confirmed the applicability of this　technique by analyzing iMG cells from a patient of Nasu-Hakola disease (Ohgidani et al., Sci Rep 2014. We herein show possible applications of the iMG cells in translational research.We believe that this iMG technique will open the door to explore various unknown dynamic aspects of human microglia in psychiatric disorders. This also opens new routes for psychopharmacological approach such as drug efficacy screening and personalized medicine.

Synergism between arsenite and proteasome inhibitor MG132 over cell death in myeloid leukaemic cells U937 and the induction of low levels of intracellular superoxide anion

International Nuclear Information System (INIS)

Lombardo, Tomás; Cavaliere, Victoria; Costantino, Susana N.; Kornblihtt, Laura; Alvarez, Elida M.; Blanco, Guillermo A.

2012-01-01

Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated the combined effect of sodium arsenite with the proteasome inhibitor MG132, and the anti-leukaemic agent CAPE, on growth-inhibition and cell death effect in acute myeloid leukaemic cells U937 and Burkitt's lymphoma-derived Raji cells, by the Chou–Talalay method. In addition we explored the association of cytotoxic effect of drugs with changes in intracellular superoxide anion (O 2 − ) levels. Our results showed that combined arsenite + MG132 produced low levels of O 2 − at 6 h and 24 h after exposure and were synergic on cell death induction in U937 cells over the whole dose range, although the combination was antagonistic on growth inhibition effect. Exposure to a constant non-cytotoxic dose of 80 μM hydrogen peroxide together with arsenite + MG132 changed synergism on cell death to antagonism at all effect levels while increasing O 2 − levels. Arsenite + hydrogen peroxide also resulted in antagonism with increased O 2 − levels in U937 cells. In Raji cells, arsenite + MG132 also produced low levels of O 2 − at 6 h and 24 h but resulted in antagonism on cell death and growth inhibition. By contrast, the combination arsenite + CAPE showed high levels of O 2 − production at 6 h and 24 h post exposure but resulted in antagonism over cell death and growth inhibition effects in U937 and Raji cells. We conclude that synergism between arsenite and MG132 in U937 cells is negatively associated to O 2 − levels at early time points after exposure. -- Highlights: ► Arsenic combined cytotoxic and anti-proliferative effects by Chou–Talalay method. ► Cytotoxic effect associated with superoxide levels as assessed by flow cytometry. ► Synergism

Discharge behaviour of Mg-Al-Pb and Mg-Al-Pb-In alloys as anodes for Mg-air battery

International Nuclear Information System (INIS)

Wang, Naiguang; Wang, Richu; Peng, Chaoqun; Peng, Bing; Feng, Yan; Hu, Chengwang

2014-01-01

Highlights: • We investigate the effect of indium on the discharge behaviour of Mg-Al-Pb alloy. • We evaluate the performance of Mg-air batteries with Mg-Al-Pb and Mg-Al-Pb-In anodes. • We analyze the activation mechanism of Mg-Al-Pb-In alloy in the discharge process. - Abstract: The discharge behaviour of Mg-Al-Pb and Mg-Al-Pb-In alloys in 3.5 wt.% NaCl solution is investigated by electrochemical techniques, and compared with that of pure magnesium. The results show that Mg-Al-Pb-In alloy provides a more negative potential and exhibits a higher utilization efficiency in contrast with Mg-Al-Pb alloy and pure magnesium during the half-cell test at a large current density, and gives desirable discharge performance when used as anode for Mg- air battery. The peak power density of the Mg-air battery with Mg-Al-Pb-In anode is 94.5 mW cm −2 , which is comparable with those of Mg-H 2 O 2 semi-fuel batteries. Moreover, the activation mechanism of Mg-Al-Pb-In alloy during the discharge process is also analyzed

Response of the MG-63 human osteosarcoma cell line grown as multicellular spheroids to neutron irradiation

International Nuclear Information System (INIS)

Kubota, Nobuo; Kakehi, Masae; Matsubara, Shou; Koike, Sachiko; Ando, Koichi.

1993-01-01

Multicellular tumor spheroids are composed of the mixed populations of cells with regard to cell proliferation, nutrition, oxygenation and radiosensitivity. Human osteogenic sarcoma is generally considered clinically radioresistant. However, the in vitro cell survival curves for human osteogenic sarcoma cell lines do not differ from those of other tumor cell lines. In this study, the responses of human osteogenic sarcoma cell line to gamma ray and neutrons were investigated by using spheroid system. The spheroids of the osteogenic sarcoma cell line are considered to be a good in vitro model of radioresistant tumors. The purpose of this study is to measure the response of the spheroids to fast neutron irradiation. MG-63 human osteogenic sarcoma cell line was used for this study. The cell line was cultured in alpha-MEM with supplement. Cell survival was estimated after the trypsinization of spheroids 24 hours after irradiation. The method of measuring spheroid cure is explained. The mean number of surviving cells per spheroid can be obtained from the mean clonogenic number and cell survival curve. The cell survival of MG-63 spheroids exposed to gamma ray and neutrons and the dose effect curves for spheroid cure after irradiation are shown. (K.I.)

Porous composite materials ZrO{sub 2}(MgO)-MgO for osteoimplantology

Energy Technology Data Exchange (ETDEWEB)

Buyakov, Ales, E-mail: alesbuyakov@gmail.com [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation); Litvinova, Larisa, E-mail: larisalitvinova@yandex.ru; Shupletsova, Valeria, E-mail: vshupletsova@mail.ru [Immanuel Kant Baltic Federal University, Kaliningrad (Russian Federation); Kulbakin, Denis, E-mail: kulbakin2012@gmail.com [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Kulkov, Sergey, E-mail: kulkov@ispms.ru [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

2016-08-02

The pore structure and phase composition of ceramic composite material ZrO{sub 2}(Mg)-MgO at different sintering temperatures were studied. The main mechanical characteristics of the material were determined and it was shown that they are close to the characteristics of natural bone tissues. It was shown that material structure has a positive effect on the pre-osteoblast cells proliferation. In-vitro studies of pre-osteoblast cells, cultivation on material surface showed a good cell adhesion, proliferation and differentiation of MMSC by osteogenic type.

The in vitro biocompatibility and macrophage phagocytosis of Mg17Al12 phase in Mg-Al-Zn alloys.

Science.gov (United States)

Liu, Chen; He, Peng; Wan, Peng; Li, Mei; Wang, Kehong; Tan, Lili; Zhang, Yu; Yang, Ke

2015-07-01

Mg alloys are gaining interest for applications as biodegradable medical implant, including Mg-Al-Zn series alloys with good combination of mechanical properties and reasonable corrosion resistance. However, whether the existence of second phase particles in the alloys exerts influence on the biocompatibility is still not clear. A deeper understanding of how the particles regulate specific biological responses is becoming a crucial requirement for their subsequent biomedical application. In this work, the in vitro biocompatibility of Mg17Al12 as a common second phase in biodegradable Mg-Al-Zn alloys was investigated via hemolysis, cytotoxicity, cell proliferation, and cell adhesion tests. Moreover, osteogenic differentiation was evaluated by the extracellular matrix mineralization assay. The Mg17Al12 particles were also prepared to simulate the real situation of second phase in the in vivo environment in order to estimate the cellular response in macrophages to the Mg17Al12 particles. The experimental results indicated that no hemolysis was found and an excellent cytocompatibility was also proved for the Mg17Al12 second phase when co-cultured with L929 cells, MC3T3-E1 cells and BMSCs. Macrophage phagocytosis co-culture test revealed that Mg17Al12 particles exerted no harmful effect on RAW264.7 macrophages and could be phagocytized by the RAW264.7 cells. Furthermore, the possible inflammatory reaction and metabolic way for Mg17Al12 phase were also discussed in detail. © 2014 Wiley Periodicals, Inc.

α-MnO2 Nanowires/Graphene Composites with High Electrocatalytic Activity for Mg-Air Fuel Cell

International Nuclear Information System (INIS)

Jiang, Min; He, Hao; Huang, Chen; Liu, Bo; Yi, Wen-Jun; Chao, Zi-Sheng

2016-01-01

Highlights: • α-MnO 2 NWs/graphene was synthesized and studied in Mg-air fuel cell. • The performance of α-MnO 2 NWs/graphene is close to the Pt/C. • The ORR mechanism involves a one-step, quasi-4-electron pathway. • A large area (5 cm*5 cm) cathode was prepared and tested in a full cell. - Abstract: This paper reports the preparation of α-MnO 2 NWs/graphene composites as the cathode catalyst for magnesium-air fuel cell and its excellent electrochemistry performance. The composites are synthesized by self-assembly of α-MnO 2 nan α-MnO 2 NWs/graphene was synthesized and studied in Mg-air fuel cell. α-MnO 2 NWs/graphene was synthesized and studied in Mg-air fuel cell. owires (NWs) on the surface of graphene via a simple hydrothermal method. The α-MnO 2 NWs/graphene composites showed a higher electrochemical activity than the commercial MnO 2 . The oxygen reduction peak of the α-MnO 2 NWs/graphene composites catalyst is tested in a 0.1 M KOH solution at −0.252 V, which is more positive than the commercial MnO 2 (−0.287 V). The ORR limit current density for 28% α-MnO2 NWs/graphene composite is approximately 2.74 mA/cm 2 , which is similar to that of the 20% Pt/C(2.79 mA/cm 2 ) in the same conditions. Based on the Koutecky–Levich plot, the ORR mechanism of the composite involves a one-step, quasi-4-electron pathway. In addition, magnesium-air fuel cell with α-MnO 2 NWs/graphene as catalyst possesses higher current density (140 mA/cm 2 ) and power density (96 mW/cm 2 ) compared to the commercial MnO 2 . This study proves that the cost-effective α-MnO 2 NWs/graphene with higher power generation ability make it possible for the substitute of the noble metals catalyst in the Mg-air fuel cell.

Study on the Mg-Li-Zn ternary alloy system with improved mechanical properties, good degradation performance and different responses to cells.

Science.gov (United States)

Liu, Yang; Wu, Yuanhao; Bian, Dong; Gao, Shuang; Leeflang, Sander; Guo, Hui; Zheng, Yufeng; Zhou, Jie

2017-10-15

Novel Mg-(3.5, 6.5wt%)Li-(0.5, 2, 4wt%)Zn ternary alloys were developed as new kinds of biodegradable metallic materials with potential for stent application. Their mechanical properties, degradation behavior, cytocompatibility and hemocompatibility were studied. These potential biomaterials showed higher ultimate tensile strength than previously reported binary Mg-Li alloys and ternary Mg-Li-X (X=Al, Y, Ce, Sc, Mn and Ag) alloys. Among the alloys studied, the Mg-3.5Li-2Zn and Mg-6.5Li-2Zn alloys exhibited comparable corrosion resistance in Hank's solution to pure magnesium and better corrosion resistance in a cell culture medium than pure magnesium. Corrosion products observed on the corroded surface were composed of Mg(OH) 2 , MgCO 3 and Ca-free Mg/P inorganics and Ca/P inorganics. In vitro cytotoxicity assay revealed different behaviors of Human Umbilical Vein Endothelial Cells (HUVECs) and Human Aorta Vascular Smooth Muscle Cells (VSMCs) to material extracts. HUVECs showed increasing nitric oxide (NO) release and tolerable toxicity, whereas VSMCs exhibited limited decreasing viability with time. Platelet adhesion, hemolysis and coagulation tests of these Mg-Li-Zn alloys showed different degrees of activation behavior, in which the hemolysis of the Mg-3.5Li-2Zn alloy was lower than 5%. These results indicated the potential of the Mg-Li-Zn alloys as good candidate materials for cardiovascular stent applications. Mg-Li alloys are promising as absorbable metallic biomaterials, which however have not received significant attention since the low strength, controversial corrosion performance and the doubts in Li toxicity. The Mg-Li-Zn alloy in the present study revealed much improved mechanical properties higher than most reported binary Mg-Li and ternary Mg-Li-X alloys, with superior corrosion resistance in cell culture media. Surprisingly, the addition of Li and Zn showed increased nitric oxide release. The present study indicates good potential of Mg-Li-Zn alloy as

Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

Directory of Open Access Journals (Sweden)

André de Macedo Bianco

2013-01-01

Full Text Available A retrospective study of 81 patients with low-grade astrocytoma (LGA comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS and progression- free survival (PFS. Degree of tumor resection was classified as gross total resection (GTR, subtotal resection (STR or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013, whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33. Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

Synergism between arsenite and proteasome inhibitor MG132 over cell death in myeloid leukaemic cells U937 and the induction of low levels of intracellular superoxide anion

Energy Technology Data Exchange (ETDEWEB)

Lombardo, Tomás [Laboratorio de Immunotoxicologia (LaITO), IDEHU-CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires (UBA), Buenos Aires (Argentina); Cavaliere, Victoria; Costantino, Susana N. [Laboratorio de Inmunología Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires (Argentina); Kornblihtt, Laura [Servicio de Hematología, Hospital de Clínicas, José de San Martín (UBA), Buenos Aires (Argentina); Alvarez, Elida M. [Laboratorio de Inmunología Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires (Argentina); Blanco, Guillermo A., E-mail: gblanco@ffyb.uba.ar [Laboratorio de Immunotoxicologia (LaITO), IDEHU-CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires (UBA), Buenos Aires (Argentina)

2012-02-01

Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated the combined effect of sodium arsenite with the proteasome inhibitor MG132, and the anti-leukaemic agent CAPE, on growth-inhibition and cell death effect in acute myeloid leukaemic cells U937 and Burkitt's lymphoma-derived Raji cells, by the Chou–Talalay method. In addition we explored the association of cytotoxic effect of drugs with changes in intracellular superoxide anion (O{sub 2}{sup −}) levels. Our results showed that combined arsenite + MG132 produced low levels of O{sub 2}{sup −} at 6 h and 24 h after exposure and were synergic on cell death induction in U937 cells over the whole dose range, although the combination was antagonistic on growth inhibition effect. Exposure to a constant non-cytotoxic dose of 80 μM hydrogen peroxide together with arsenite + MG132 changed synergism on cell death to antagonism at all effect levels while increasing O{sub 2}{sup −} levels. Arsenite + hydrogen peroxide also resulted in antagonism with increased O{sub 2}{sup −} levels in U937 cells. In Raji cells, arsenite + MG132 also produced low levels of O{sub 2}{sup −} at 6 h and 24 h but resulted in antagonism on cell death and growth inhibition. By contrast, the combination arsenite + CAPE showed high levels of O{sub 2}{sup −} production at 6 h and 24 h post exposure but resulted in antagonism over cell death and growth inhibition effects in U937 and Raji cells. We conclude that synergism between arsenite and MG132 in U937 cells is negatively associated to O{sub 2}{sup −} levels at early time points after exposure. -- Highlights: ► Arsenic combined cytotoxic and anti-proliferative effects by Chou–Talalay method. ► Cytotoxic effect

Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats.

Science.gov (United States)

Dodd, Darol; Willson, Gabrielle; Parkinson, Horace; Bermudez, Edilberto

2013-07-01

Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE. Copyright © 2011 John Wiley & Sons, Ltd.

Imaging findings of anaplastic astrocytoma in a child with maple syrup urine disease: a case report.

Science.gov (United States)

Aw-Zoretic, Jessie; Wadhwani, Nitin R; Lulla, Rishi R; Rishi, Lulla R; Ryan, Maura E

2015-09-01

Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism, which usually presents in childhood with encephalopathy due to cerebral edema and dysmyelination. Even with treatment, metabolic stressors may precipitate later episodes of acute decompensation. Changes related to cerebral and white matter edema have been described by magnetic resonance imaging (MRI), and imaging can aid in both initial diagnosis and evaluation of decompensation. To date, there are no published known reports of cancer in patients with MSUD. Here, we present the first case report of an anaplastic astrocytoma in a teenager with MSUD, with a discussion of imaging findings and the use of magnetic resonance spectroscopy (MRS) to help distinguish between tumor and metabolic changes.

Mutant p53 transfection of astrocytic cells results in altered cell cycle control, radiation sensitivity, and tumorigenicity

International Nuclear Information System (INIS)

Kanady, Kirk E.; Mei Su; Proulx, Gary; Malkin, David M.; Pardo, Francisco S.

1995-01-01

Introduction: Alterations in the p53 tumor suppressor gene are one of the most frequent genetic alterations in malignant gliomas. An understanding of the molecular genetic events leading to glial tumor progression would aid in designing therapeutic vectors for controlling these challenging tumor types. We investigated whether mutations in coding exons of the p53 gene result in functional changes altering cell cycle 'checkpoint' control and the intrinsic radiation sensitivity of glial cells. Methods: An astrocytic cell line was derived from a low grade astrocytoma and characterized to be of human karyotype and GFAP positivity. Additionally, the cellular population has never formed tumors in immune-deficient mice. At early passage ( 2 as parameters. Cell kinetic analyses after 2, 5, and 10 Gy of ionizing radiation were conducted using propidium iodide FACS analyses. Results: Overall levels of p53 expression were increased 5-10 fold in the transfected cellular populations. Astrocytic cellular populations transfected with mutant p53 revealed a statistically significant increase in levels of resistance to ionizing radiation in vitro (2-tailed test, SF2, MID). Astrocytic cellular populations transfected with mutant p53, unlike the parental cells, were tumorigenic in SCID mice. Cell kinetic analyses indicated that the untransfected cell line demonstrated dose dependent G1 and G2 arrests. Following transfection, however, the resultant cellular population demonstrated a predominant G2 arrest. Conclusions: Astrocytic cellular populations derived from low grade astrocytomas, are relatively radiation sensitive, non-tumorigenic, and have intact cell cycle ''checkpoints.'' Cellular populations resulting upon transfection of parental cells with a dominant negative p53 mutation, are relatively radiation resistant, when compared to both parental and mock-transfected cells. Transfected cells demonstrate abnormalities of cell cycle control at the G1/S checkpoint, increases in levels

Comparison study of different coatings on degradation performance and cell response of Mg-Sr alloy

International Nuclear Information System (INIS)

Shangguan, Yongming; Sun, Lina; Wan, Peng; Tan, Lili; Wang, Chengyue; Fan, Xinmin; Qin, Ling; Yang, Ke

2016-01-01

To solve the problem of rapid degradation for magnesium-based implants, surface modification especially coating method is widely studied and showed the great potential for clinical application. However, as concerned to the further application and medical translation for biodegradable magnesium alloys, there are still lack of data and comparisons among different coatings on their degradation and biological properties. This work studied three commonly used coatings on Mg-Sr alloy, including micro-arc oxidation coating, electrodeposition coating and chemical conversion coating, and compared these coatings for requirements of favorable degradation and biological performances, how each of these coating systems has performed. Finally the mechanism for the discrepancy between these coatings is proposed. The results indicate that the micro-arc oxidation coating on Mg-Sr alloy exhibited the best corrosion resistance and cell response among these coatings, and is proved to be more suitable for the orthopedic application. - Highlights: • The MAO, PED and Sr-P coating were fabricated on Mg-Sr alloy to evaluate the degradation. • The MAO coating showed the greatest degradation performance among these three coatings. • The PED coating exhibited worse corrosion resistance even than Mg-Sr substrate. • The value of cell proliferation and ALP activity were ranked in the following order: MAO > Sr-P > PED.

Comparison study of different coatings on degradation performance and cell response of Mg-Sr alloy

Energy Technology Data Exchange (ETDEWEB)

Shangguan, Yongming [Department of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); Sun, Lina [Jinzhou Medical University, Jinzhou 121000 (China); Wan, Peng, E-mail: pwan@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR (China); Tan, Lili [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); Wang, Chengyue [Jinzhou Medical University, Jinzhou 121000 (China); Fan, Xinmin [Department of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Qin, Ling [Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR (China); Yang, Ke, E-mail: kyang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China)

2016-12-01

To solve the problem of rapid degradation for magnesium-based implants, surface modification especially coating method is widely studied and showed the great potential for clinical application. However, as concerned to the further application and medical translation for biodegradable magnesium alloys, there are still lack of data and comparisons among different coatings on their degradation and biological properties. This work studied three commonly used coatings on Mg-Sr alloy, including micro-arc oxidation coating, electrodeposition coating and chemical conversion coating, and compared these coatings for requirements of favorable degradation and biological performances, how each of these coating systems has performed. Finally the mechanism for the discrepancy between these coatings is proposed. The results indicate that the micro-arc oxidation coating on Mg-Sr alloy exhibited the best corrosion resistance and cell response among these coatings, and is proved to be more suitable for the orthopedic application. - Highlights: • The MAO, PED and Sr-P coating were fabricated on Mg-Sr alloy to evaluate the degradation. • The MAO coating showed the greatest degradation performance among these three coatings. • The PED coating exhibited worse corrosion resistance even than Mg-Sr substrate. • The value of cell proliferation and ALP activity were ranked in the following order: MAO > Sr-P > PED.

The angiogenic behaviors of human umbilical vein endothelial cells (HUVEC) in co-culture with osteoblast-like cells (MG-63) on different titanium surfaces.

Science.gov (United States)

Shi, Bin; Andrukhov, Oleh; Berner, Simon; Schedle, Andreas; Rausch-Fan, Xiaohui

2014-08-01

Interaction between osteogenesis and angiogenesis plays an important role in implant osseointegration. In the present study we investigated the influence of titanium surface properties on the angiogenic behaviors of endothelial cells grown in direct contact co-culture with osteoblasts. Human umbilical vein endothelial cells (HUVECs) and osteoblast-like cells (MG-63 cells) were grown in direct co-culture on the following titanium surfaces: acid-etched (A), hydrophilic A (modA), coarse-gritblasted and acid-etched (SLA) and hydrophilic SLA (SLActive). Cell proliferation was evaluated by cell counting combined with flow cytometry. The expression of von Willebrand Factor (vWF), thrombomodulin (TM), endothelial cell protein C receptor (EPCR), E-Selectin, as well as vascular endothelial growth factor (VEGF) receptors Flt-1 and KDR in HUVECs and VEGF in MG-63 were measured by qPCR. The dynamic behavior of endothelial cells was recorded by time-lapse microscopy. Proliferation of HUVECs was highest on A, followed by SLA, modA and SLActive surfaces. The expression of vWF, TM, EPCR, E-Selectin and Flt-1 in HUVECs was significantly higher on A than on all other surfaces. The expression of KDR in HUVECs grown on A surface was below detection limit. VEGF expression in MG-63 cells was significantly higher on SLActive vs SLA and modA vs A surfaces. Time-lapse microscopy revealed that HUVECs moved quickest and formed cell clusters earlier on A surface, followed by SLA, modA and SLActive surface. In co-culture conditions, proliferation and expression of angiogenesis associated genes in HUVECs are promoted by smooth hydrophobic Ti surface, which is in contrast to previous mono-culture studies. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Differentiation and cytokine synthesis of human alveolar osteoblasts compared to osteoblast-like cells (MG63) in response to titanium surfaces.

Science.gov (United States)

Rausch-fan, Xiaohui; Qu, Zhe; Wieland, Marco; Matejka, Michael; Schedle, Andreas

2008-01-01

The aim of this study was to investigate the influence of different implant surface topographies and chemistries on the expression of differentiation/proliferation markers on MG63 cells and primary human alveolar osteoblasts. Hydrophobic acid-etched (A) and hydrophobic coarse-grit-blasted, acid-etched (SLA) surfaces and hydrophilic acid-etched (modA) and hydrophilic coarse-grit-blasted (modSLA) surfaces were produced. Thereby, modA and modSLA surfaces were rinsed under nitrogen protection and stored in a sealed glass tube containing isotonic NaCl solution at pH 4-6. Tissue culture plates without specimens served as controls. The behavior of MG63 cells and primary human alveolar osteoblasts (AOB) grown on all surfaces was compared through determination of alkaline phosphatase (ALP) activity, cell proliferation ((3)H-thymidin incorporation, MTT colorimetric assay) and expression of osteocalcin (OC), osteoprotegerin (OPG), transforming growth factor-beta1 (TGF-beta(1)) and vascular endothelial growth factor (VEGF), detected with commercial available test kits. Proliferation of MG63 and primary cells was highest on controls, followed by A surfaces, modA and SLA surfaces being almost on the same level and lowest on modSLA surfaces. modSLA surfaces exhibited highest ALP and OC production, followed by SLA, modA and A surfaces. Proliferation and OC production were comparable for MG63 cells and AOB. OPG, TGF-beta(1) and VEGF produced on primary cells showed a slightly different rank order on different surfaces compared to MG63 cells. modSLA still showed the highest production of OPG, TGF-beta(1) and VEGF, but was followed by modA, SLA and A. Statistical significance was checked by ANOVA (pmodA surfaces showed enhanced expression of OPG, TGF-beta(1) and VEGF on MG63 cells compared to primary human alveolar osteoblasts. Overall, the lowest proliferation rates and the highest expressions of differentiation markers and growth factor productions were observed on modSLA.

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

Energy Technology Data Exchange (ETDEWEB)

Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Schomberg, Paula J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Link, Michael J. [Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Stafford, Scott L., E-mail: Stafford.scott@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)

2012-05-01

Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm{sup 3} (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

International Nuclear Information System (INIS)

Hallemeier, Christopher L.; Pollock, Bruce E.; Schomberg, Paula J.; Link, Michael J.; Brown, Paul D.; Stafford, Scott L.

2012-01-01

Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4–56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm 3 (range, 0.7–26.7). The median tumor margin dose was 15 Gy (range, 12–20). The median follow-up was 8.0 years (range, 0.5–15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

Science.gov (United States)

2017-12-11

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

[Mg2+, ATP-dependent plasma membrane calcium pump of smooth muscle cells. I. Structural organization and properties].

Science.gov (United States)

Veklich, T O; Mazur, Iu Iu; Kosterin, S O

2015-01-01

Tight control of cytoplasm Ca2+ concentration is essential in cell functioning. Changing of Ca2+ concentration is thorough in smooth muscle cells, because it determines relaxation/constraint process. One of key proteins which control Ca2+ concentration in cytoplasm is Mg2+, ATP-dependent plasma membrane calcium pump. Thus, it is important to find compoumds which allowed one to change Mg2+, ATP-dependent plasma membrane calcium pump activity, as long as this topic is of current interest in biochemical research which regards energy and pharmacomechanical coupling mechanism of muscle excitation and contraction. In this article we generalized literatute and own data about properties of smooth muscle cell plasma membrane Ca(2+)-pump. Stuctural oganization, kinetical properties and molecular biology are considered.

Lipoprotein internalisation induced by oncogenic AMPK activation is essential to maintain glioblastoma cell growth.

Science.gov (United States)

Ríos, M; Foretz, M; Viollet, B; Prieto, A; Fraga, M; García-Caballero, T; Costoya, J A; Señarís, R

2014-12-01

Metabolic adaptations are essential during tumour growth to maintain the high proliferation levels exhibited by cancer cells. In this study, we examined the transformations that occurred in the lipid metabolism in astrocytic tumours, and the possible role of the fuel-sensing enzyme AMPK. Metabolic targets might help design new and effective drugs for cancer. To accomplish this objective, we studied both mice and human astrocytic tumours. We first used a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We then confirmed the results in human glioblastoma cell lines and in glioblastoma tissue samples from patients. We show that the high levels of activated AMPK, observed in astrocytic tumours, increase extracellular lipid internalisation and reduce energy expenditure by inhibiting 'de novo' fatty acid (FA) synthesis, which allows tumour cells to obtain building blocks and energy to be able to create new organelles and new cells. Our findings demonstrate that AMPK plays a crucial role in glioblastoma cell growth and suggest that blocking lipoprotein receptors could potentially be used as a plausible therapeutic approach for these and other type of tumours with high levels of AMPK. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synergistic effects of arsenic trioxide combined with ascorbic acid in human osteosarcoma MG-63 cells: a systems biology analysis.

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Huang, X C; Maimaiti, X Y M; Huang, C W; Zhang, L; Li, Z B; Chen, Z G; Gao, X; Chen, T Y

2014-01-01

To further understand the synergistic mechanism of As2O3 and asscorbic acid (AA) in human osteosarcoma MG-63 cells by systems biology analysis. Human osteosarcoma MG-63 cells were treated by As2O3 (1 µmol/L), AA (62.5 µmol/L) and combined drugs (1 µmol/L As2O3 plus 62.5 µmol/L AA). Dynamic morphological characteristics were recorded by Cell-IQ system, and growth rate was calculated. Illumina beadchip assay was used to analyze the differential expression genes in different groups. Synergic effects on differential expression genes (DEGs) were analyzed by mixture linear model and singular value decomposition model. KEGG pathway annotations and GO enrichment analysis were performed to figure out the pathways involved in the synergic effects. We captured 1987 differential expression genes in combined therapy MG-63 cells. FAT1 gene was significantly upregulated in all three groups, which is a promising drug target as an important tumor suppressor analogue; meanwhile, HIST1H2BD gene was markedly downregulated in the As2O3 monotherapy group and the combined therapy group, which was found to be upregulated in prostatic cancer. These two genes might play critical roles in synergetic effects of AA and As2O3, although the exact mechanism needs further investigation. KEGG pathway analysis showed many DEGs were related with tight junction, and GO analysis also indicated that DEGs in the combined therapy cells gathered in occluding junction, apical junction complex, cell junction, and tight junction. AA potentiates the efficacy of As2O3 in MG-63 cells. Systems biology analysis showed the synergic effect on the DEGs.

A case of late presentation of precocious puberty due to pituitary astrocytoma

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Fahimeh Soheilipour

2015-08-01

Full Text Available The importance of assessing precocious puberty, especially in boys, is not only due to the great complications it has for the affected patients, but also to the fatal underlying diseases. Therefore, children with central precocious puberty should first undergo neuroimaging. In this case study, we present a 9.5-year-old boy who was referred to Rasoul-e-Akram Medical Center with increased intracranial pressure, nausea/vomiting, and severe headache having begun three months earlier. The development of secondary sexual changes had started two years earlier, and had been neglected. His testes, penis, and pubic hair were at the fourth Tanner stage. He had elevated luteinizing and follicle stimulating hormones. Microscopic evaluation confirmed low-grade pilocytic astrocytoma WHO grade 1. Emergency brain surgery was conducted in which the brain was decompressed, and chemotherapy was started postoperatively. Two years after the surgery, he remains under chemotherapy, with obvious sexual maturation and a height of 154 cm. Training families and medical staff efficiently can help prevent the late diagnosis and treatment of precocious puberty and, as a result, help patients in their social life.

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)

2017-11-07

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

Biocompatibility Assessment of Novel Bioresorbable Alloys Mg-Zn-Se and Mg-Zn-Cu for Endovascular Applications: In- Vitro Studies.

Science.gov (United States)

Persaud-Sharma, Dharam; Budiansky, Noah; McGoron, Anthony J

2013-01-01

Previous studies have shown that using biodegradable magnesium alloys such as Mg-Zn and Mg-Zn-Al possess the appropriate mechanical properties and biocompatibility to serve in a multitude of biological applications ranging from endovascular to orthopedic and fixation devices. The objective of this study was to evaluate the biocompatibility of novel as-cast magnesium alloys Mg-1Zn-1Cu wt.% and Mg-1Zn-1Se wt.% as potential implantable biomedical materials, and compare their biologically effective properties to a binary Mg-Zn alloy. The cytotoxicity of these experimental alloys was evaluated using a tetrazolium based- MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and a lactate dehydrogenase membrane integrity assay (LDH). The MTS assay was performed on extract solutions obtained from a 30-day period of alloy immersion and agitation in simulated body fluid to evaluate the major degradation products eluted from the alloy materials. Human foreskin fibroblast cell growth on the experimental magnesium alloys was evaluated for a 72 hour period, and cell death was quantified by measuring lactate dehydrogenase concentrations. Both Mg-Zn-Se and Mg-Zn-Cu alloys exhibit low cytotoxicity levels which are suitable for biomaterial applications. The Mg-Zn-Cu alloy was found to completely degrade within 72 hours, resulting in lower human foreskin fibroblast cell viability. The Mg-Zn-Se alloy was shown to be less cytotoxic than both the Mg-Zn-Cu and Mg-Zn alloys.

Enhancement in dye-sensitized solar cells based on MgO-coated TiO2 electrodes by reactive DC magnetron sputtering

International Nuclear Information System (INIS)

Wu Sujuan; Han Hongwei; Tai Qidong; Zhang Jing; Xu Sheng; Zhou Conghua; Yang Ying; Hu Hao; Chen Bolei; Sebo, Bobby; Zhao Xingzhong

2008-01-01

A surface modification method was carried out by reactive DC magnetron sputtering to fabricate TiO 2 electrodes coated with insulating MgO for dye-sensitized solar cells. The MgO-coated TiO 2 electrode had been characterized by x-ray photoelectron spectroscopy (XPS), energy-dispersive x-ray spectroscopy (EDX), scanning electron microscopy (SEM), UV-vis spectrophotometer, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The study results revealed that the TiO 2 modification increases dye adsorption, decreases trap states and suppresses interfacial recombination. The effects of sputtering MgO for different times on the performance of DSSCs were investigated. It indicated that sputtering MgO for 3 min on TiO 2 increases all cell parameters, resulting in increasing efficiency from 6.45% to 7.57%

Influence of SaOS-2 cells on corrosion behavior of cast Mg-2.0Zn0.98Mn magnesium alloy.

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Witecka, Agnieszka; Yamamoto, Akiko; Święszkowski, Wojciech

2017-02-01

In this research, the effect of the presence of living cells (SaOS-2) on in vitro degradation of Mg-2.0Zn-0.98Mn (ZM21) magnesium alloy was examined by two methods simple immersion/cell culture tests and electrochemical measurements (electrochemical impedance spectroscopy and potentiodynamic polarization) under cell culture conditions. In immersion/cell culture tests, when SaOS-2 cells were cultured on ZM21 samples, pH of cell culture medium decreased, therefore weight loss and Mg 2+ ion release from the samples increased. Electrochemical measurements revealed the presence of living cells increased corrosion rate (I corr ) and decreased polarization resistance (R p ) after 48h of incubation. This acceleration of ZM21 corrosion can mainly be attributed to the decrease of medium pH due to cellular metabolic activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Yoga Therapy in Treating Patients With Malignant Brain Tumors

Science.gov (United States)

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

Caryophyllene oxide exhibits anti-cancer effects in MG-63 human osteosarcoma cells via the inhibition of cell migration, generation of reactive oxygen species and induction of apoptosis

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Zheng Pan

2016-12-01

Full Text Available The main objective of the present study was to evaluate the antitumor and apoptotic effects of caryophyllene oxide in MG-63 human osteosarcoma cells. Cell viability of these cells was evaluated by MTT assay while as in vitro wound healing assay was used to study the effect of caryophyllene oxide on cell migration. Fluorescence microscopy and transmission electron microscopy were used to study the changes in cell morphology once the cells undergo apoptosis. Caryophyllene oxide significantly led to cytotoxicity in MG-63 cells showing dose-dependent as well as time-dependent effects. Caryophyllene oxide led to an inhibition of wound closure significantly. At caryophyllene oxide doses of 20, 80 and 120 µM, the percentage of cell migration was shown to be 94.2, 67.1 and 14.8% respectively. With an increase in the caryophyllene oxide dose, the extent of apoptosis also increased characterized by cellular shrinkage, membrane blebbing, chromatin condensation and apoptotic body formation.

Antibacterial biodegradable Mg-Ag alloys

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D Tie

2013-06-01

Full Text Available The use of magnesium alloys as degradable metals for biomedical applications is a topic of ongoing research and the demand for multifunctional materials is increasing. Hence, binary Mg-Ag alloys were designed as implant materials to combine the favourable properties of magnesium with the well-known antibacterial property of silver. In this study, three Mg-Ag alloys, Mg2Ag, Mg4Ag and Mg6Ag that contain 1.87 %, 3.82 % and 6.00 % silver by weight, respectively, were cast and processed with solution (T4 and aging (T6 heat treatment.The metallurgical analysis and phase identification showed that all alloys contained Mg4Ag as the dominant β phase. After heat treatment, the mechanical properties of all Mg-Ag alloys were significantly improved and the corrosion rate was also significantly reduced, due to presence of silver. Mg(OH2 and MgO present the main magnesium corrosion products, while AgCl was found as the corresponding primary silver corrosion product. Immersion tests, under cell culture conditions, demonstrated that the silver content did not significantly shift the pH and magnesium ion release. In vitro tests, with both primary osteoblasts and cell lines (MG63, RAW 264.7, revealed that Mg-Ag alloys show negligible cytotoxicity and sound cytocompatibility. Antibacterial assays, performed in a dynamic bioreactor system, proved that the alloys reduce the viability of two common pathogenic bacteria, Staphylococcus aureus (DSMZ 20231 and Staphylococcus epidermidis (DSMZ 3269, and the results showed that the killing rate of the alloys against tested bacteria exceeded 90%. In summary, biodegradable Mg-Ag alloys are cytocompatible materials with adjustable mechanical and corrosion properties and show promising antibacterial activity, which indicates their potential as antibacterial biodegradable implant materials.

Performance enhancement of perovskite solar cells with Mg-doped TiO2 compact film as the hole-blocking layer

International Nuclear Information System (INIS)

Wang, Jing; Qin, Minchao; Tao, Hong; Ke, Weijun; Chen, Zhao; Wan, Jiawei; Qin, Pingli; Lei, Hongwei; Fang, Guojia; Xiong, Liangbin; Yu, Huaqing

2015-01-01

In this letter, we report perovskite solar cells with thin dense Mg-doped TiO 2 as hole-blocking layers (HBLs), which outperform cells using TiO 2 HBLs in several ways: higher open-circuit voltage (V oc ) (1.08 V), power conversion efficiency (12.28%), short-circuit current, and fill factor. These properties improvements are attributed to the better properties of Mg-modulated TiO 2 as compared to TiO 2 such as better optical transmission properties, upshifted conduction band minimum (CBM) and downshifted valence band maximum (VBM), better hole-blocking effect, and higher electron life time. The higher-lying CBM due to the modulation with wider band gap MgO and the formation of magnesium oxide and magnesium hydroxides together resulted in an increment of V oc . In addition, the Mg-modulated TiO 2 with lower VBM played a better role in the hole-blocking. The HBL with modulated band position provided better electron transport and hole blocking effects within the device

Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death

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Kim Yong K

2011-04-01

Full Text Available Abstract Background Silibinin, a natural polyphenolic flavonoid, has been reported to induce cell death in various cancer cell types. However, the molecular mechanism is not clearly defined. Our previous study showed that silibinin induces glioma cell death and its effect was effectively prevented by calpain inhibitor. The present study was therefore undertaken to examine the role of calpain in the silibinin-induced glioma cell death. Methods U87MG cells were grown on well tissue culture plates and cell viability was measured by MTT assay. ROS generation and △ψm were estimated using the fluorescence dyes. PKC activation and Bax expression were measured by Western blot analysis. AIF nuclear translocation was determined by Western blot and immunocytochemistry. Results Silibinin induced activation of calpain, which was blocked by EGTA and the calpain inhibitor Z-Leu-Leu-CHO. Silibinin caused ROS generation and its effect was inhibited by calpain inhibitor, the general PKC inhibitor GF 109203X, the specific PKCδ inhibitor rottlerin, and catalase. Silibinin-induce cell death was blocked by calpain inhibitor and PKC inhibitors. Silibinin-induced PKCδ activation and disruption of △ψm were prevented by the calpain inhibitor. Silibinin induced AIF nuclear translocation and its effect was prevented by calpain inhibitor. Transfection of vector expressing microRNA of AIF prevented the silibinin-induced cell death. Conclusions Silibinin induces apoptotic cell death through a calpain-dependent mechanism involving PKC, ROS, and AIF nuclear translocation in U87MG human glioma cells.

Degradation of bioabsorbable Mg-based alloys: Assessment of the effects of insoluble corrosion products and joint effects of alloying components on mammalian cells

International Nuclear Information System (INIS)

Grillo, Claudia A.; Alvarez, Florencia; Fernández Lorenzo de Mele, Mónica A.

2016-01-01

This work is focused on the processes occurring at the bioabsorbable metallic biomaterial/cell interfaces that may lead to toxicity. A critical analysis of the results obtained when degradable metal disks (pure Mg and rare earth-containing alloys (ZEK100 alloys)) are in direct contact with cell culture and those obtained with indirect methods such as the use of metal salts and extracts was made. Viability was assessed by Acridine Orange dye, neutral red and clonogenic assays. The effects of concentration of corrosion products and possible joint effects of the binary and ternary combinations of La, Zn and Mg ions, as constituents of ZEK alloys, were evaluated on a mammalian cell culture. In all cases more detrimental effects were found for pure Mg than for the alloys. Experiments with disks showed that gradual alterations in pH and in the amount of corrosion products were better tolerated by cells and resulted in higher viability than abrupt changes. In addition, viability was dependent on the distance from the source of ions. Experiments with extracts showed that the effect of insoluble degradation products was highly detrimental. Indirect tests with Zn ions revealed that harmful effects may be found at concentrations ≥ 150 μM and at ≥ 100 μM in mixtures with Mg. These mixtures lead to more deleterious effects than single ions. Results highlight the need to develop a battery of tests to evaluate the biocompatibility of bioabsorbable biomaterials. - Highlights: • A metal disk setup is better in simulating in vivo situations than extracts and salts. • The biodegradation process and cell metabolism were interdependent. • Zn (100 μM) and Mg (8.2 × 10"3 μM) mixtures are more toxic than single Zn or Mg. • Insoluble degradation products of Mg showed high negative effect on cell viability.

Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation

International Nuclear Information System (INIS)

Guizzetti, Marina; Pathak, Shantha; Giordano, Gennaro; Costa, Lucio G.

2005-01-01

Though little attention has been given to the possibility that glial cells may represent a target for the developmental neurotoxicity of organophosphorus (OP) insecticides, recent evidence, obtained in particular with chlorpyrifos (CP), suggests that developmental exposure to this compound may indeed target astrocytes. To substantiate and expand these observations, we carried out a series of in vitro studies utilizing fetal rat astrocytes and a human astrocytoma cell line, 1321N1 cells, to investigate the effect of the OPs CP, diazinon (DZ) and parathion (P), their oxygen analogs chlorpyrifos oxon (CPO), diazoxon (DZO) and paraoxon (PO), and their metabolites 3,5,6-trichloro-2-pyridinol (TCP), 2-isopropyl-6-methyl-4-pyrimidol (IMP) and para-nitrophenol (PNP), on cell proliferation. In fetal rat astrocytes and astrocytoma cells maintained in serum, CP, DZ, P, CPO, DZO, and PO induced a concentration-dependent inhibition in [ 3 H]thymidine incorporation with a very similar potency (IC 50 between 45 and 57 μM). Among the other metabolites, PNP was the most potent (IC 50 = 70-80 μM), while TCP and IMP were much less effective (IC 50 > 100 μM). Cytotoxicity appears to account only for a small part of the effect on DNA synthesis. OP insecticides and their oxons were three- to six-fold more potent in inhibiting [ 3 H]thymidine incorporation when cells were synchronized in the G 0 /G 1 phase of the cell cycle and re-stimulated by carbachol or epidermal growth factor. These results suggest that OP insecticides and their oxons affect astroglial cell proliferation and that the transition from the G 0 /G 1 to the S/G 2 phase of the cell cycle may be particularly sensitive to the action of these compounds

Attachment and proliferation of human osteoblast-like cells (MG-63) on laser-ablated titanium implant material

Energy Technology Data Exchange (ETDEWEB)

Györgyey, Ágnes; Ungvári, Krisztina [Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, H-6720 Szeged (Hungary); Kecskeméti, Gabriella; Kopniczky, Judit [Department of Optics and Quantum Electronics, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged (Hungary); Hopp, Béla [Research Group on Laser Physics, Hungarian Academy of Sciences and University of Szeged, H-6720 Szeged (Hungary); Oszkó, Albert [Department of Physical Chemistry and Materials Science, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged (Hungary); Pelsöczi, István; Rakonczay, Zoltán [Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, H-6720 Szeged (Hungary); Nagy, Katalin [Department of Oral Surgery, Faculty of Dentistry, University of Szeged, H-6720 Szeged (Hungary); Turzó, Kinga, E-mail: kturzo@yahoo.com [Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, H-6720 Szeged (Hungary)

2013-10-15

Demand is increasing for shortening the long (3–6 months) osseointegration period to rehabilitate patients' damaged chewing apparatus in as short a time as possible. For dental implants, as for biomaterials in general, the bio- and osseointegration processes can be controlled at molecular and cellular levels by modification of the implant surface. One of the most promising of such surface modifications is laser ablation, as demonstrated by our previous results [46]. Commercially pure (CP4) sand-blasted, acid-etched titanium disks (Denti® System Ltd., Hungary) were irradiated with a KrF excimer laser (248 nm, fluence 0.4 J/cm{sup 2}, FWHM 18 ns, 2000 pulses), or with a Nd:YAG laser (532 nm, 1.3 J/cm{sup 2}, 10 ns, 200 pulses) then examined by SEM, AFM, and XPS. In vitro attachment (24 h) and proliferation (72 h) of MG-63 osteoblast cells were investigated via dimethylthiazol-diphenyl tetrazolium bromide (MTT), alamarBlue (AB) assays alkaline phosphatase quantification (ALP) and SEM. SEM and AFM revealed significant changes in morphology and roughness. XPS confirmed the presence of TiO{sub 2} on each sample; after Nd:YAG treatment a reduced state of Ti (Ti{sup 3+}) was also observed. MTT, AB and ALP measurements detected an increase in the number of cells between the 24- and 72 hour observations; however, laser treatment did not affect cell attachment and proliferation significantly. - Highlights: • CP4 titanium implant surfaces were modified with Nd:YAG and KrF excimer laser. • SEM and AFM revealed significant changes in morphology and roughness. • XPS confirmed the presence of TiO{sub 2} on each sample; after Nd:YAG treatment a reduced state of Ti (Ti{sup 3+}) was found. • Cell proliferation experiments detected an increased number of MG-63 cells between the 24 h and 72 h observations. • Laser treatments neither disturbed, nor enhanced MG-63 cell attachment and proliferation significantly.

Attachment and proliferation of human osteoblast-like cells (MG-63) on laser-ablated titanium implant material

International Nuclear Information System (INIS)

Györgyey, Ágnes; Ungvári, Krisztina; Kecskeméti, Gabriella; Kopniczky, Judit; Hopp, Béla; Oszkó, Albert; Pelsöczi, István; Rakonczay, Zoltán; Nagy, Katalin; Turzó, Kinga

2013-01-01

Demand is increasing for shortening the long (3–6 months) osseointegration period to rehabilitate patients' damaged chewing apparatus in as short a time as possible. For dental implants, as for biomaterials in general, the bio- and osseointegration processes can be controlled at molecular and cellular levels by modification of the implant surface. One of the most promising of such surface modifications is laser ablation, as demonstrated by our previous results [46]. Commercially pure (CP4) sand-blasted, acid-etched titanium disks (Denti® System Ltd., Hungary) were irradiated with a KrF excimer laser (248 nm, fluence 0.4 J/cm 2 , FWHM 18 ns, 2000 pulses), or with a Nd:YAG laser (532 nm, 1.3 J/cm 2 , 10 ns, 200 pulses) then examined by SEM, AFM, and XPS. In vitro attachment (24 h) and proliferation (72 h) of MG-63 osteoblast cells were investigated via dimethylthiazol-diphenyl tetrazolium bromide (MTT), alamarBlue (AB) assays alkaline phosphatase quantification (ALP) and SEM. SEM and AFM revealed significant changes in morphology and roughness. XPS confirmed the presence of TiO 2 on each sample; after Nd:YAG treatment a reduced state of Ti (Ti 3+ ) was also observed. MTT, AB and ALP measurements detected an increase in the number of cells between the 24- and 72 hour observations; however, laser treatment did not affect cell attachment and proliferation significantly. - Highlights: • CP4 titanium implant surfaces were modified with Nd:YAG and KrF excimer laser. • SEM and AFM revealed significant changes in morphology and roughness. • XPS confirmed the presence of TiO 2 on each sample; after Nd:YAG treatment a reduced state of Ti (Ti 3+ ) was found. • Cell proliferation experiments detected an increased number of MG-63 cells between the 24 h and 72 h observations. • Laser treatments neither disturbed, nor enhanced MG-63 cell attachment and proliferation significantly

Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells

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Puri Christina

2007-03-01

Full Text Available Abstract Background Podoplanin is a membrane mucin that, among a series of tissues, is expressed on late osteoblasts and osteocytes. Since recent findings have focussed on podoplanin's potential role as a tumour progression factor, we aimed at identifying regulatory elements conferring PDPN promoter activity. Here, we characterized the molecular mechanism controlling basal PDPN transcription in human osteoblast-like MG63 versus Saos-2 cells. Results We cloned and sequenced 2056 nucleotides from the 5'-flanking region of the PDPN gene and a computational search revealed that the TATA and CAAT box-lacking promoter possesses features of a growth-related gene, such as a GC-rich 5' region and the presence of multiple putative Sp1, AP-4 and NF-1 sites. Reporter gene assays demonstrated a functional promoter in MG63 cells exhibiting 30-fold more activity than in Saos-2 cells. In vitro DNase I footprinting revealed eight protected regions flanked by DNaseI hypersensitive sites within the region bp -728 to -39 present in MG63, but not in Saos-2 cells. Among these regions, mutation and supershift electrophoretic mobility shift assays (EMSA identified four Sp1/Sp3 binding sites and two binding sites for yet unknown transcription factors. Deletion studies demonstrated the functional importance of two Sp1/Sp3 sites for PDPN promoter activity. Overexpression of Sp1 and Sp3 independently increased the stimulatory effect of the promoter and podoplanin mRNA levels in MG63 and Saos-2 cells. In SL2 cells, Sp3 functioned as a repressor, while Sp1 and Sp3 acted positively synergistic. Weak PDPN promoter activity of Saos-2 cells correlated with low Sp1/Sp3 nuclear levels, which was confirmed by Sp1/Sp3 chromatin immunoprecipitations in vivo. Moreover, methylation-sensitive Southern blot analyses and bisulfite sequencing detected strong methylation of CpG sites upstream of bp -464 in MG63 cells, but hypomethylation of these sites in Saos-2 cells. Concomitantly

CdCl2 passivation of polycrystalline CdMgTe and CdZnTe absorbers for tandem photovoltaic cells

Science.gov (United States)

Swanson, Drew E.; Reich, Carey; Abbas, Ali; Shimpi, Tushar; Liu, Hanxiao; Ponce, Fernando A.; Walls, John M.; Zhang, Yong-Hang; Metzger, Wyatt K.; Sampath, W. S.; Holman, Zachary C.

2018-05-01

As single-junction silicon solar cells approach their theoretical limits, tandems provide the primary path to higher efficiencies. CdTe alloys can be tuned with magnesium (CdMgTe) or zinc (CdZnTe) for ideal tandem pairing with silicon. A II-VI/Si tandem holds the greatest promise for inexpensive, high-efficiency top cells that can be quickly deployed in the market using existing polycrystalline CdTe manufacturing lines combined with mature silicon production lines. Currently, all high efficiency polycrystalline CdTe cells require a chloride-based passivation process to passivate grain boundaries and bulk defects. This research examines the rich chemistry and physics that has historically limited performance when extending Cl treatments to polycrystalline 1.7-eV CdMgTe and CdZnTe absorbers. A combination of transmittance, quantum efficiency, photoluminescence, transmission electron microscopy, and energy-dispersive X-ray spectroscopy clearly reveals that during passivation, Mg segregates and out-diffuses, initially at the grain boundaries but eventually throughout the bulk. CdZnTe exhibits similar Zn segregation behavior; however, the onset and progression is localized to the back of the device. After passivation, CdMgTe and CdZnTe can render a layer that is reduced to predominantly CdTe electro-optical behavior. Contact instabilities caused by inter-diffusion between the layers create additional complications. The results outline critical issues and paths for these materials to be successfully implemented in Si-based tandems and other applications.

Effect of sterilization process on surface characteristics and biocompatibility of pure Mg and MgCa alloys

International Nuclear Information System (INIS)

Liu, X.L.; Zhou, W.R.; Wu, Y.H.; Cheng, Y.; Zheng, Y.F.

2013-01-01

The aim of this work was to investigate the effect of various sterilization methods on surface characteristics and biocompatibility of MgCa alloy, with pure Mg as a comparison, including steam autoclave sterilization (SA), ethylene oxide steam sterilization (EO), glutaraldehyde sterilization (GD), dry heat sterilization (DH) and Co60 γ ray radiation sterilization (R) technologies. The surface characterizations were performed by environmental scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, grazing incidence X-ray diffraction, water contact angle and surface free energy measurement, whereas the cytotoxicity and hemocompatibility were evaluated by cellular adhesive experiment, platelet adhesion and hemolysis test. The results showed that the five sterilization processes caused more changes on the surface of MgCa alloy than that on the surface of pure Mg. The GD sterilization caused the most obvious changes on the surface of the pure Mg, and the SA sterilization made the largest alteration on the MgCa alloy surface. The GD and DH sterilization processes could cause increases on surface free energy for both pure Mg and MgCa alloys, while the other three sterilization processes reduced the surface free energy. The DH and GD sterilization processes caused the least alteration on the cell adhesion on pure Mg surface, whereas the EO sterilization performed the greatest impact on the cell adhesion on the Mg–Ca alloy surface. The hemolysis percentage of pure Mg and MgCa alloys were reduced by SA sterilization, meanwhile the other four sterilization processes increased their hemolysis percentages significantly, especially for the EO sterilization. - Highlights: • The effect of sterilization on surface chemistry and biocompatibility was studied. • Sterilization caused more surface changes on MgCa alloy than pure Mg. • Co60 γ ray radiation is the most appropriate sterilization process

Three-dimensional cell organization leads to almost immediate HRE activity as demonstrated by molecular imaging of MG-63 spheroids using two-photon excitation microscopy.

Science.gov (United States)

Indovina, Paola; Collini, Maddalena; Chirico, Giuseppe; Santini, Maria Teresa

2007-02-20

Hypoxia through HRE (hypoxia-responsive element) activity in MG-63 human osteosarcoma cells grown in monolayer and as very small, three-dimensional tumor spheroids was investigated using molecular imaging techniques. MG-63 cells were stably transfected with a vector constructed with multiple copies of the HRE sequence of the human vascular endothelial growth factor (VEGF) gene and with the enhanced green fluorescent protein (EGFP) coding sequence. During hypoxia when HIF-1alpha (hypoxia-inducible factor-1alpha) is stabilized, the binding of HIF-1 to the HRE sequences of the vector allows the transcription of EGFP and the appearance of fluorescence. Transfected monolayer cells were characterized by flow cytometric analysis in response to various hypoxic conditions and HIF-1alpha expression in these cells was assessed by Western blotting. Two-photon excitation (TPE) microscopy was then used to examine both MG-63-transfected monolayer cells and spheroids at 2 and 5 days of growth in normoxic conditions. Monolayer cells reveal almost no fluorescence, whereas even very small spheroids (HRE activation. This activation of the HRE sequences, which control a wide variety of genes, suggests that monolayer cells and spheroids of the MG-63 cell line have different genes activated and thus diverse functional activities.

In vitro cytotoxicity of SiO2 or ZnO nanoparticles with different sizes and surface charges on U373MG human glioblastoma cells

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Kim JE

2014-12-01

Full Text Available Jung-Eun Kim,1,* Hyejin Kim,1,* Seong Soo A An,2 Eun Ho Maeng,3 Meyoung-Kon Kim,4 Yoon-Jae Song1 1Department of Life Science, 2Department of Bionano Technology, Gachon University, Seongnam-Si, South Korea; 3Korea Testing and Research Institute, Seoul, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea *These authors contributed equally to this work Abstract: Silicon dioxide (SiO2 and zinc oxide (ZnO nanoparticles are widely used in various applications, raising issues regarding the possible adverse effects of these metal oxide nanoparticles on human cells. In this study, we determined the cytotoxic effects of differently charged SiO2 and ZnO nanoparticles, with mean sizes of either 100 or 20 nm, on the U373MG human glioblastoma cell line. The overall cytotoxicity of ZnO nanoparticles against U373MG cells was significantly higher than that of SiO2 nanoparticles. Neither the size nor the surface charge of the ZnO nanoparticles affected their cytotoxicity against U373MG cells. The 20 nm SiO2 nanoparticles were more toxic than the 100 nm nanoparticles against U373MG cells, but the surface charge had little or no effect on their cytotoxicity. Both SiO2 and ZnO nanoparticles activated caspase-3 and induced DNA fragmentation in U373MG cells, suggesting the induction of apoptosis. Thus, SiO2 and ZnO nanoparticles appear to exert cytotoxic effects against U373MG cells, possibly via apoptosis. Keyword: apoptosis

Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007.

Science.gov (United States)

Adams, Hadie; Avendaño, Javier; Raza, Shaan M; Gokaslan, Ziya L; Jallo, George I; Quiñones-Hinojosa, Alfredo

2012-05-20

Observational cross-sectional study. Using data from the population-based cancer registries of the Surveillance, Epidemiology and End Results (SEER) program, we analyzed demographic features, tumor and treatment characteristics, as well as survival rates in patients with primary malignant astrocytomas of the spinal cord (PMASC). PMASC is a rare neoplasm and is considered to carry the same dismal outcome as their cerebral counterparts. Our current knowledge is incomplete, and understanding the epidemiology, diagnosis, and optimal treatment still poses challenges. The SEER data from 1973 to 2007 were reviewed for pathologically confirmed primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord (C72.0). We compared the clinical features and outcomes of the cohort in uni- and multivariate fashion. Survival was calculated and compared using Kaplan-Meier curves and log-rank analysis. Our search criteria retrieved 135 patients diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-, and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA had a median survival time of 17 months versus 10 months in patients diagnosed with glioblastomas. Adult patients observed markedly prolonged survival compared with the pediatric group, with a 16-month versus 9-month median survival, respectively. Multivariate analysis revealed age at diagnosis, pediatric and adult age groups, sex, tumor histology, and extent of resection as significant predictors of survival. Interestingly, outcomes did not significantly change throughout the last decades or by receiving radiotherapy. Outcome for patients diagnosed with PMASC remains poor and presents an ongoing challenge for professionals in the field of neurospinal medicine and surgery. In our analyses of AA, adult patients, males, and patients undergoing radical resections were associated with increased survival. However, incidence of these lesions is low; hence, building strong

Multifaceted role of galectin-3 on human glioblastoma cell motility

International Nuclear Information System (INIS)

Debray, Charles; Vereecken, Pierre; Belot, Nathalie; Teillard, Peggy; Brion, Jean-Pierre; Pandolfo, Massimo; Pochet, Roland

2004-01-01

Astrocytic tumors' aggressiveness results from an imbalance between cell proliferation and cell death favoring growth, but also from the propensity of tumor cells to detach from the primary tumor site, migrate, and invade the surrounding parenchyma. Astrocytic tumor progression is known to be associated with an increased expression of galectin-3. We investigated in cell culture how galectin-3 expression affects astrocytoma cell motility. Galectin-3 deficient cells were obtained by stable transfection of the U373 glioblastoma cell line with a specific expression antisense plasmid. Cultured galectin-3 deficient glioblastoma cells showed increased motility potential on laminin and modifications in the cytoskeleton reorganization. In addition, c-DNA microarrays and quantitative immunofluorescence analysis showed that galectin-3 deficient U373 cells have an increased expression of integrins-α6 and -β1, proteins known to be implicated in the regulation of cell adhesion

In vitro investigation of anodization and CaP deposited titanium surface using MG63 osteoblast-like cells

Energy Technology Data Exchange (ETDEWEB)

Lee, J.M. [Department of Prosthodontics and Dental Research Institute, School of Dentistry, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul 110-749 (Korea, Republic of); Lee, J.I. [Department of Oral Pathology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Lim, Y.J., E-mail: limdds@snu.ac.kr [Department of Prosthodontics and Dental Research Institute, School of Dentistry, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul 110-749 (Korea, Republic of)

2010-03-01

The aim of the present study was to investigate surface characteristics in four different titanium surfaces (AN: anodized at 270 V; AN-CaP: anodic oxidation and CaP deposited; SLA: sandblasted and acid etched; MA: machined) and to evaluate biological behaviors such as cell adhesion, cell proliferation, cytoskeletal organization, and osteogenic protein expression of MG63 osteoblast-like cells at the early stage. Surface analysis was performed using scanning electron microscopy, thin-film X-ray diffractometry, and a confocal laser scanning microscope. In order to evaluate cellular responses, MG63 osteoblast-like cells were used. The cell viability was evaluated by MTT assay. Immunofluorescent analyses of actin, type I collagen, osteonectin and osteocalcin were performed. The anodized and CaP deposited specimen showed homogeneously distributed CaP particles around micropores and exhibited anatase type oxides, titanium, and HA crystalline structures. This experiment suggests that CaP particles on the anodic oxidation surface affect cellular attachment and spreading. When designing an in vitro biological study for CaP coated titanium, it must be taken into account that preincubation in medium prior to cell seeding and the cell culture medium may affect the CaP coatings. All these observations illustrate the importance of the experimental conditions and the physicochemical parameters of the CaP coating. It is considered that further evaluations such as long-term in vitro cellular assays and in vivo experiments should be necessary to figure out the effect of CaP deposition to biological responses.

In vitro investigation of anodization and CaP deposited titanium surface using MG63 osteoblast-like cells

International Nuclear Information System (INIS)

Lee, J.M.; Lee, J.I.; Lim, Y.J.

2010-01-01

The aim of the present study was to investigate surface characteristics in four different titanium surfaces (AN: anodized at 270 V; AN-CaP: anodic oxidation and CaP deposited; SLA: sandblasted and acid etched; MA: machined) and to evaluate biological behaviors such as cell adhesion, cell proliferation, cytoskeletal organization, and osteogenic protein expression of MG63 osteoblast-like cells at the early stage. Surface analysis was performed using scanning electron microscopy, thin-film X-ray diffractometry, and a confocal laser scanning microscope. In order to evaluate cellular responses, MG63 osteoblast-like cells were used. The cell viability was evaluated by MTT assay. Immunofluorescent analyses of actin, type I collagen, osteonectin and osteocalcin were performed. The anodized and CaP deposited specimen showed homogeneously distributed CaP particles around micropores and exhibited anatase type oxides, titanium, and HA crystalline structures. This experiment suggests that CaP particles on the anodic oxidation surface affect cellular attachment and spreading. When designing an in vitro biological study for CaP coated titanium, it must be taken into account that preincubation in medium prior to cell seeding and the cell culture medium may affect the CaP coatings. All these observations illustrate the importance of the experimental conditions and the physicochemical parameters of the CaP coating. It is considered that further evaluations such as long-term in vitro cellular assays and in vivo experiments should be necessary to figure out the effect of CaP deposition to biological responses.

Influence of Dy in solid solution on the degradation behavior of binary Mg-Dy alloys in cell culture medium.

Science.gov (United States)

Yang, Lei; Ma, Liangong; Huang, Yuanding; Feyerabend, Frank; Blawert, Carsten; Höche, Daniel; Willumeit-Römer, Regine; Zhang, Erlin; Kainer, Karl Ulrich; Hort, Norbert

2017-06-01

Rare earth element Dy is one of the promising alloying elements for magnesium alloy as biodegradable implants. To understand the effect of Dy in solid solution on the degradation of Mg-Dy alloys in simulated physiological conditions, the present work studied the microstructure and degradation behavior of Mg-Dy alloys in cell culture medium. It is found the corrosion resistance enhances with the increase of Dy content in solid solution in Mg. This can be attributed to the formation of a relatively more corrosion resistant Dy-enriched film which decreases the anodic dissolution of Mg. Copyright © 2017 Elsevier B.V. All rights reserved.

Selective antibacterial effects of mixed ZnMgO nanoparticles

International Nuclear Information System (INIS)

Vidic, Jasmina; Stankic, Slavica; Haque, Francia; Ciric, Danica; Le Goffic, Ronan; Vidy, Aurore; Jupille, Jacques; Delmas, Bernard

2013-01-01

Antibiotic resistance has impelled the research for new agents that can inhibit bacterial growth without showing cytotoxic effects on humans and other species. We describe the synthesis and physicochemical characterization of nanostructured ZnMgO whose antibacterial activity was compared to its pure nano-ZnO and nano-MgO counterparts. Among the three oxides, ZnO nanocrystals—with the length of tetrapod legs about 100 nm and the diameter about 10 nm—were found to be the most effective antibacterial agents since both Gram-positive (B. subtilis) and Gram-negative (E. coli) bacteria were completely eradicated at concentration of 1 mg/mL. MgO nanocubes (the mean cube size ∼50 nm) only partially inhibited bacterial growth, whereas ZnMgO nanoparticles (sizes corresponding to pure particles) revealed high specific antibacterial activity to Gram-positive bacteria at this concentration. Transmission electron microscopy analysis showed that B. subtilis cells were damaged after contact with nano-ZnMgO, causing cell contents to leak out. Our preliminary toxicological study pointed out that nano-ZnO is toxic when applied to human HeLa cells, while nano-MgO and the mixed oxide did not induce any cell damage. Overall, our results suggested that nanostructured ZnMgO, may reconcile efficient antibacterial efficiency while being a safe new therapeutic for bacterial infections.

Selective antibacterial effects of mixed ZnMgO nanoparticles

Science.gov (United States)

Vidic, Jasmina; Stankic, Slavica; Haque, Francia; Ciric, Danica; Le Goffic, Ronan; Vidy, Aurore; Jupille, Jacques; Delmas, Bernard

2013-05-01

Antibiotic resistance has impelled the research for new agents that can inhibit bacterial growth without showing cytotoxic effects on humans and other species. We describe the synthesis and physicochemical characterization of nanostructured ZnMgO whose antibacterial activity was compared to its pure nano-ZnO and nano-MgO counterparts. Among the three oxides, ZnO nanocrystals—with the length of tetrapod legs about 100 nm and the diameter about 10 nm—were found to be the most effective antibacterial agents since both Gram-positive ( B. subtilis) and Gram-negative ( E. coli) bacteria were completely eradicated at concentration of 1 mg/mL. MgO nanocubes (the mean cube size 50 nm) only partially inhibited bacterial growth, whereas ZnMgO nanoparticles (sizes corresponding to pure particles) revealed high specific antibacterial activity to Gram-positive bacteria at this concentration. Transmission electron microscopy analysis showed that B. subtilis cells were damaged after contact with nano-ZnMgO, causing cell contents to leak out. Our preliminary toxicological study pointed out that nano-ZnO is toxic when applied to human HeLa cells, while nano-MgO and the mixed oxide did not induce any cell damage. Overall, our results suggested that nanostructured ZnMgO, may reconcile efficient antibacterial efficiency while being a safe new therapeutic for bacterial infections.

Selective antibacterial effects of mixed ZnMgO nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Vidic, Jasmina, E-mail: jasmina.vidic@jouy.inra.fr [VIM, Institut de la Recherche Agronomique (France); Stankic, Slavica, E-mail: slavica.stankic@insp.jussieu.fr; Haque, Francia [CNRS, Institut des Nanosciences de Paris, UMR 7588 (France); Ciric, Danica; Le Goffic, Ronan; Vidy, Aurore [VIM, Institut de la Recherche Agronomique (France); Jupille, Jacques [CNRS, Institut des Nanosciences de Paris, UMR 7588 (France); Delmas, Bernard [VIM, Institut de la Recherche Agronomique (France)

2013-05-15

Antibiotic resistance has impelled the research for new agents that can inhibit bacterial growth without showing cytotoxic effects on humans and other species. We describe the synthesis and physicochemical characterization of nanostructured ZnMgO whose antibacterial activity was compared to its pure nano-ZnO and nano-MgO counterparts. Among the three oxides, ZnO nanocrystals-with the length of tetrapod legs about 100 nm and the diameter about 10 nm-were found to be the most effective antibacterial agents since both Gram-positive (B. subtilis) and Gram-negative (E. coli) bacteria were completely eradicated at concentration of 1 mg/mL. MgO nanocubes (the mean cube size {approx}50 nm) only partially inhibited bacterial growth, whereas ZnMgO nanoparticles (sizes corresponding to pure particles) revealed high specific antibacterial activity to Gram-positive bacteria at this concentration. Transmission electron microscopy analysis showed that B. subtilis cells were damaged after contact with nano-ZnMgO, causing cell contents to leak out. Our preliminary toxicological study pointed out that nano-ZnO is toxic when applied to human HeLa cells, while nano-MgO and the mixed oxide did not induce any cell damage. Overall, our results suggested that nanostructured ZnMgO, may reconcile efficient antibacterial efficiency while being a safe new therapeutic for bacterial infections.

Co-expression of TIMP-1 and its cell surface binding partner CD63 in glioblastomas

DEFF Research Database (Denmark)

Aaberg-Jessen, Charlotte; Sørensen, Mia D.; Matos, Ana L.S.A.

2018-01-01

scoring. CD63 expression in tumor-associated microglia/macrophages was examined by double-immunofluorescence with ionized calcium-binding adapter molecule 1 (Iba1). The association between CD63 and TIMP-1 was investigated using previously obtained TIMP-1 data from our astrocytoma cohort. Cellular co-expression...... of CD63 was widely distributed in astrocytomas with a significantly increased level in glioblastomas. CD63 levels did not significantly correlate with patient survival at a protein level, and CD63 did not augment the prognostic significance of TIMP-1. Up to 38% of the CD63+ cells expressed Iba1; however......, Iba1 did not appear to impact the prognostic value of CD63. A significant correlation was found between TIMP-1 and CD63, and the TIMP-1 and CD63 proteins were co-expressed at the cellular level and located in close molecular proximity, suggesting that TIMP-1 and CD63 could be co...

EG-03EXPRESSION OF PRMT5 CORRELATES WITH MALIGNANT GRADE IN GLIOMAS AND PLAYS A PIVOTAL ROLE IN TUMOR GROWTH

Science.gov (United States)

Han, Xiaosi; Li, Rong; Zhang, Wenbin; Yang, Xiuhua; Fathallah-Shaykh, Hassan; Gillespie, Yancey; Nabors, Burt

2014-01-01

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ω-NG,N′G-symmetric dimethylarginine residues on histones as well as other proteins. The modification play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth.

Prussian Blue Mg-Li Hybrid Batteries.

Science.gov (United States)

Sun, Xiaoqi; Duffort, Victor; Nazar, Linda F

2016-08-01

The major advantage of Mg batteries relies on their promise of employing an Mg metal negative electrode, which offers much higher energy density compared to graphitic carbon. However, the strong coulombic interaction of Mg 2+ ions with anions leads to their sluggish diffusion in the solid state, which along with a high desolvation energy, hinders the development of positive electrode materials. To circumvent this limitation, Mg metal negative electrodes can be used in hybrid systems by coupling an Li + insertion cathode through a dual salt electrolyte. Two "high voltage" Prussian blue analogues (average 2.3 V vs Mg/Mg 2+ ; 3.0 V vs Li/Li + ) are investigated as cathode materials and the influence of structural water is shown. Their electrochemical profiles, presenting two voltage plateaus, are explained based on the two unique Fe bonding environments. Structural water has a beneficial impact on the cell voltage. Capacities of 125 mAh g -1 are obtained at a current density of 10 mA g -1 (≈C/10), while stable performance up to 300 cycles is demonstrated at 200 mA g -1 (≈2C). The hybrid cell design is a step toward building a safe and high density energy storage system.

Videography supported adhesion, and proliferation behavior of MG-63 osteoblastic cells on 2.5D titania nanotube matrices.

Science.gov (United States)

Manurung, Robeth Viktoria; Fu, Pei-Wen; Chu, Yeh-Shiu; Lo, Chun-Min; Chattopadhyay, Surojit

2016-04-01

Human osteosarcoma cells MG-63 were cultured on anodically etched titania nanotubes (TiO2 NT), with diameters ranging from 40-100 nm, to study the correlations between cell proliferation and adhesion on the 2.5 dimensional (2.5D) extracellular matrix (ECM). Unlike other reports, mostly based on mouse stem cells, and 2D cell culture, our studies indicate that the 2.5D NT promote higher proliferation and activity, but less 2D adhesion. Proliferation of the MG-63 cells was significantly higher in the NTs, the best being the 70 nm diameter sample, compared to planar titania (control). This is consistent with previous studies. However, cellular adhesion was stronger on TiO2 NT with increasing diameter, and highest on the control as obtained from shear stress measurement, paxilin imaging, and western blot measurements probing focal adhesion kinase, p130 CAS, and extracellular-regulated kinase, in addition to cell morphology imaging by fluorescence microscopy. We provide direct videography of cell migration, and cell speed data indicating faster filopodial activity on the TiO2 NT surfaces having lower adhesion. This evidence was not available previously. The NT matrices promote cells with smaller surface area, because of less 2D stretching. In contrast, on comparatively planar 2D-like surfaces uniaxial stretching of the cell body with strong anchoring of the filopodia, resulted in larger cell surface area, and demonstrated stronger adhesion. The difference in the results, with those previously published, may be generally attributed to, among others, the use of mouse stem cells (human osteosarcoma used here), and unannealed as-grown TiO2 NTs used previously (annealed ECMs used here). © 2015 Wiley Periodicals, Inc.

Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in children

International Nuclear Information System (INIS)

Gunny, Roxana S.; Saunders, Dawn E.; Hayward, Richard D.; Phipps, Kim P.; Harding, Brian N.

2005-01-01

Cerebellar low-grade astrocytomas (CLGAs) of childhood are benign tumours and are usually curable by surgical resection alone or combined with adjuvant radiotherapy. To undertake a retrospective study of our children with CLGA to determine the optimum schedule for surveillance imaging following initial surgery. In this report we describe the phenomenon of spontaneous regression of residual tumour and discuss its prognostic significance regarding future imaging. A retrospective review was conducted of children treated for histologically proven CLGA at Great Ormond Street Hospital from 1988 to 1998. Of 83 children with CLGA identified, 13 (15.7%) had incomplete resections. Two children with large residual tumours associated with persistent symptoms underwent additional treatment. Eleven children were followed by surveillance imaging alone for a mean of 6.83 years (range 2-13.25 years). Spontaneous tumour regression was seen in 5 (45.5%) of the 11 children. There were no differences in age, gender, symptomatology, histological grade or Ki-67 fractions between those with spontaneous tumour regression and those with progression. There was a non-significant trend that larger volume residual tumours progressed. Residual tumour followed by surveillance imaging may either regress or progress. For children with residual disease we recommend surveillance imaging every 6 months for the first 2 years, every year for years 3, 4 and 5, then every second year if residual tumour is still present 5 years after initial surgery. This would detect not only progressive or recurrent disease, but also spontaneous regression which can occur later than disease progression. (orig.)

MgO Nanoparticle Modified Anode for Highly Efficient SnO2-Based Planar Perovskite Solar Cells.

Science.gov (United States)

Ma, Junjie; Yang, Guang; Qin, Minchao; Zheng, Xiaolu; Lei, Hongwei; Chen, Cong; Chen, Zhiliang; Guo, Yaxiong; Han, Hongwei; Zhao, Xingzhong; Fang, Guojia

2017-09-01

Reducing the energy loss and retarding the carrier recombination at the interface are crucial to improve the performance of the perovskite solar cell (PSCs). However, little is known about the recombination mechanism at the interface of anode and SnO 2 electron transfer layer (ETL). In this work, an ultrathin wide bandgap dielectric MgO nanolayer is incorporated between SnO 2 :F (FTO) electrode and SnO 2 ETL of planar PSCs, realizing enhanced electron transporting and hole blocking properties. With the use of this electrode modifier, a power conversion efficiency of 18.23% is demonstrated, an 11% increment compared with that without MgO modifier. These improvements are attributed to the better properties of MgO-modified FTO/SnO 2 as compared to FTO/SnO 2 , such as smoother surface, less FTO surface defects due to MgO passivation, and suppressed electron-hole recombinations. Also, MgO nanolayer with lower valance band minimum level played a better role in hole blocking. When FTO is replaced with Sn-doped In 2 O 3 (ITO), a higher power conversion efficiency of 18.82% is demonstrated. As a result, the device with the MgO hole-blocking layer exhibits a remarkable improvement of all J-V parameters. This work presents a new direction to improve the performance of the PSCs based on SnO 2 ETL by transparent conductive electrode surface modification.

Combination of Proteasomal Inhibitors Lactacystin and MG132 Induced Synergistic Apoptosis in Prostate Cancer Cells

Directory of Open Access Journals (Sweden)

Robert B. Shirley

2005-12-01

Full Text Available The proteasome inhibitor Velcade (bortezomib/PS-341 has been shown to block the targeted proteolytic degradation of short-lived proteins that are involved in cell maintenance, growth, division, and death, advocating the use of proteasomal inhibitors as therapeutic agents. Although many studies focused on the use of one proteasomal inhibitor for therapy, we hypothesized that the combination of proteasome inhibitors Lactacystin (AG Scientific, Inc., San Diego, CA and MG132 (Biomol International, Plymouth Meeting, PA may be more effective in inducing apoptosis. Additionally, this regimen would enable the use of sublethal doses of individual drugs, thus reducing adverse effects. Results indicate a significant increase in apoptosis when LNCaP prostate cancer cells were treated with increasing levels of Lactacystin, MG132, or a combination of sublethal doses of these two inhibitors. Furthermore, induction in apoptosis coincided with a significant loss of IKKα, IKKβ, and IKKγ proteins and NFκB activity. In addition to describing effective therapeutic agents, we provide a model system to facilitate the investigation of the mechanism of action of these drugs and their effects on the IKK-NFκB axis.

Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas.

Science.gov (United States)

Muñoz, Jorge; Inda, María Del Mar; Lázcoz, Paula; Zazpe, Idoya; Fan, Xing; Alfaro, Jorge; Tuñón, Teresa; Rey, Juan A; Castresana, Javier S

2012-01-01

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14(ARF), and p16(INK4A)), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14(ARF) and p16(INK4A) did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14(ARF) and p16(INK4A), in which other alterations (mutations, homozygous deletions) are prevalent.

Nestin expression in neuroepithelial tumors.

Science.gov (United States)

Schiffer, Davide; Manazza, Andrea; Tamagno, Ilaria

2006-05-29

Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.

Strength of FePd/MgO and FePt/MgO interfaces from first principles

Science.gov (United States)

Černý, M.

2018-04-01

Cleavage characteristics such as the cleavage energy and the cleavage stress of FePd/MgO and FePt/MgO interfaces are computed from first principles. Considering several possible cleavage planes, the weakest link in these systems is found as the plane with the lowest cleavage stress. This weakest plane is identified in both systems with the interface plane, where the cohesion is reduced by 30% compared to the MgO bulk. Two distinct models of tensile test are employed to verify the results and convergence of computed values with respect to size of the simulation cell is discussed.

Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors.

Science.gov (United States)

Camacho, Luis H; Olson, Jon; Tong, William P; Young, Charles W; Spriggs, David R; Malkin, Mark G

2007-04-01

Phenylbutyrate (PBA), and its metabolite phenylacetate (PAA), induce growth inhibition and cellular differentiation in multiple tumor models. However, despite their potential anti-cancer properties, several pharmacodynamic aspects remain unknown. We conducted a dose escalating trial to evaluate twice-daily intravenous PBA infusions for two consecutive weeks (Monday through Friday) every month at five dose levels (60-360 mg/kg/day). Twenty-one patients with the following malignancies were treated: colon carcinoma 4, non-small cell lung carcinoma 4; anaplastic astrocytoma 3, glioblastoma multiforme 3, bladder carcinoma 2, sarcoma 2, and ovarian carcinoma, rectal hemangiopericytoma, and pancreatic carcinoma 1 each. Conversion of PBA to PAA and phenylacetylglutamine (PAG) was documented without catabolic saturation. Plasma content of PBA > or =1 mM was documented for only 3 h following each dose at the top two dosages. The therapy was well tolerated overall. Common adverse effects included grade 1 nausea/vomiting, fatigue, and lightheadedness. Dose limiting toxicities were short-term memory loss, sedation, confusion, nausea, and vomiting. Two patients with anaplastic astrocytoma and a patient with glioblastoma remained stable without tumor progression for 5, 7, and 4 months respectively. Administration of PBA in a twice-daily infusion schedule is safe. The maximum tolerated dose is 300 mg/kg/day. Study designs with more convenient treatment schedules and specific molecular correlates may help to further delineate the mechanism of action of this compound. Future studies evaluating PBA's ability to induce histone acetylation and cell differentiation alone or in combination with other anti-neoplastics are recommended.

Morphology and Differentiation of MG63 Osteoblast Cells on Saliva Contaminated Implant Surfaces

Directory of Open Access Journals (Sweden)

Neda Shams

2015-11-01

Full Text Available Objectives: Osteoblasts are the most important cells in the osseointegration process. Despite years of study on dental Implants, limited studies have discussed the effect of saliva on the adhesion process of osteoblasts to implant surfaces. The aim of this in vitro study was to evaluate the effect of saliva on morphology and differentiation of osteoblasts attached to implant surfaces.Materials and Methods: Twelve Axiom dental implants were divided into two groups. Implants of the case group were placed in containers, containing saliva, for 40 minutes. Then, all the implants were separately stored in a medium containing MG63 human osteoblasts for a week. Cell morphology and differentiation were assessed using a scanning electron microscope and their alkaline phosphatase (ALP activity was determined. The t-test was used to compare the two groups.Results: Scanning electron microscopic observation of osteoblasts revealed round or square cells with fewer and shorter cellular processes in saliva contaminated samples, whereas elongated, fusiform and well-defined cell processes were seen in the control group. ALP level was significantly lower in case compared to control group (P<0.05.Conclusion: Saliva contamination alters osteoblast morphology and differentiation and may subsequently interfere with successful osseointegration. Thus, saliva contamination of bone and implant must be prevented or minimized.

Highly Efficient Flexible Quantum Dot Solar Cells with Improved Electron Extraction Using MgZnO Nanocrystals.

Science.gov (United States)

Zhang, Xiaoliang; Santra, Pralay Kanti; Tian, Lei; Johansson, Malin B; Rensmo, Håkan; Johansson, Erik M J

2017-08-22

Colloidal quantum dot (CQD) solar cells have high potential for realizing an efficient and lightweight energy supply for flexible or wearable electronic devices. To achieve highly efficient and flexible CQD solar cells, the electron transport layer (ETL), extracting electrons from the CQD solid layer, needs to be processed at a low-temperature and should also suppress interfacial recombination. Herein, a highly stable MgZnO nanocrystal (MZO-NC) layer is reported for efficient flexible PbS CQD solar cells. Solar cells fabricated with MZO-NC ETL give a high power conversion efficiency (PCE) of 10.4% and 9.4%, on glass and flexible plastic substrates, respectively. The reported flexible CQD solar cell has the record efficiency to date of flexible CQD solar cells. Detailed theoretical simulations and extensive characterizations reveal that the MZO-NCs significantly enhance charge extraction from CQD solids and diminish the charge accumulation at the ETL/CQD interface, suppressing charge interfacial recombination. These important results suggest that the low-temperature processed MZO-NCs are very promising for use in efficient flexible solar cells or other flexible optoelectronic devices.

Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

Directory of Open Access Journals (Sweden)

Vik-Mo Audun O

2006-10-01

Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

Cerebellar giant cell glioblastoma multiforme in an adult

Directory of Open Access Journals (Sweden)

Sudhansu Sekhar Mishra

2014-01-01

Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

TREATMENT OF PROGRESSION OF DIFFUSE ASTROCYTOMA BY HERBAL MEDICINE: CASE REPORT.

Science.gov (United States)

Trogrlić, Ivo; Trogrlić, Dragan; Trogrlić, Zoran

2016-01-01

The paper presents the results of the use of phytotherapy in a 33-year-old woman who, after finishing the oncological treatment of diffuse astrocytoma, had tumour progression. Phytotherapy was introduced after the tumour had progressed. It consisted of 4 types of herbal medicine which the subject was taking in form of tea once a day at regular intervals. The patient started phytotherapy along with temozolomide, which was the only oncological treatment she was under after the tumour had progressed. Following the finished chemotherapy, the patient continued the treatment with herbal medicine only. She regularly took phytotherapy without interruption and to the fullest extent for 30 months, and the results of treatment were monitored by periodic scanning using nuclear magnetic resonance technique. The control scanning that was conducted after the end of combined treatment with temozolomide and phytotherapy showed tumour regression. The patient continued with phytotherapy after finishing chemotherapy and, during the following 24 months, it was the sole treatment option. In that period, the regression of the tumour continued, until a control examination 30 months after the introduction of phytotherapy showed no clinical and radiological signs of tumour. The results presented in this research paper clearly indicate the potential of phytotherapy in the treatment of some types of brain tumours. A complete regression of tumour following the treatment with nothing but herbal medicine offers support for such claim. Future research should demonstrate the effectiveness of phytotherapy, as a supplementary form of brain tumour treatment, and the results of this research should be compared with the existing information on the effectiveness of the protocols currently used in the treatment of these types of tumour.

MgO-hybridized TiO{sub 2} interfacial layers assisting efficiency enhancement of solid-state dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Sakai, Nobuya; Ikegami, Masashi; Miyasaka, Tsutomu, E-mail: miyasaka@toin.ac.jp [Graduate School of Engineering, Toin University of Yokohama, 1614 Kurogane-cho, Aoba, Yokohama, Kanagawa 225-8502 (Japan)

2014-02-10

Interfacial modification of a thin TiO{sub 2} compact layer (T-CL) by hybridization with MgO enhanced the quantum conversion efficiency of solid-state dye-sensitized solar cells (ssDSSCs) comprising a multilayer structure of transparent electrode/T-CL/dye-sensitized mesoporous TiO{sub 2}/hole conductor/metal counter electrode. The Mg(CH{sub 3}COO){sub 2} treatment was employed to introduce a MgO-TiO{sub 2} CL (T/M-CL), which enhanced the physical connection and conduction between the CL and mesoporous semiconductor layer as a consecutive interface, owing to the dehydration reaction of Mg(CH{sub 3}COO){sub 2}. The photocurrent density of ssDSSC was increased 33% by the T/M-CL compared with the T-CL, using an equivalent amount of adsorbed dye. The ssDSSC with the T/M-CL yielded the highest efficiency of 4.02% under irradiation at 100 mW cm{sup −2}. The electrical impedance spectroscopy showed that the charge-transfer resistance (R{sub ct}) of the photoelectrode with T/M-CL was reduced by 300 Ω from the reference non-treated T-CL electrode. Characterized by the intrinsically low R{sub ct} of the compact layer, the T/M-CL is capable of improving the photovoltaic performance of solid-state sensitized mesoscopic solar cells.

Difference in 201TlCl accumulation mechanism in brain tumors. A comparison of their Na+-K+ ATPase activities

International Nuclear Information System (INIS)

Sugo, Nobuo; Kuroki, Takao; Nemoto, Masaaki; Mito, Toshiaki; Seiki, Yoshikatsu; Shibata, Iekado

2000-01-01

The accumulation levels of 201 TlCl and Na + -K + ATPase activity in tumor tissue were compared among glioblastoma, benign glioma and meningioma to study the difference in the mechanism of 201 TlCl accumulation. The subjects were 19 cases comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1 pilocytic astrocytoma and 9 meningioma. Preoperative 201 TlCl SPECT was performed in all the cases, and Thallium Index (TL index) was calculated by a ratio of 201 TlCl in the tumor area and the contralateral area. In addition, cell membrane was extracted from the tumor tissue collected intraoperatively to determine Na + -K + ATPase activity. No statistically significant difference in TL index was noted between the glioblastoma group (6.97±2.67) and the meningioma group (5.87±1.99). This fact showed that there was no difference in the accumulation level of 201 TlCl between the two groups. On the other hand, the glioblastoma group indicated a higher value of Na + -K + ATPase activity (49.13±43.76 μmole/hour/mg protein) than the meningioma group (7.73±13.84 μmol/hour/mg protein) (p + -K + ATPase activity in 201 TlCl accumulation in glioblastoma and the influences of other accumulation mechanism than Na + -K + ATPase activity such as the volume of intratumoral vascular bed in meningioma. (author)

Post-fusion treatment with MG132 increases transcription factor expression in somatic cell nuclear transfer embryos in pigs.

Science.gov (United States)

You, Jinyoung; Lee, Joohyeong; Kim, Jinyoung; Park, Junhong; Lee, Eunsong

2010-02-01

The objective of this study was to examine the effect of post-fusion treatment of somatic cell nuclear transfer (SCNT) oocytes with the proteasomal inhibitor MG132 on maturation promoting factor (MPF) activity, nuclear remodeling, embryonic development, and gene expression of cloned pig embryos. Immediately after electrofusion, SCNT oocytes were treated with MG132 and/or caffeine for 2 hr, vanadate for 0.5 hr, or vanadate for 0.5 hr followed by MG132 for 1.5 hr. Of the MG132 concentrations tested (0-5 microM), the 1 microM concentration showed a higher rate of blastocyst formation (25.9%) than 0 (14.2%), 0.5 (16.9%), and 5 microM (16.9%). Post-fusion treatment with MG132, caffeine, and both MG132 and caffeine improved blastocyst formation (22.1%, 21.4%, and 24.4%, respectively), whereas vanadate treatment inhibited blastocyst formation (6.5%) compared to the control (11.1%). When examined 2 hr after fusion and 1 hr after activation, MPF activity remained at a higher (P fusion with caffeine and/or MG132, but it was decreased by vanadate. The rate of oocytes showing premature chromosome condensation was not altered by MG132 but was decreased by vanadate treatment. In addition, formation of single pronuclei was increased by MG132 compared to control and vanadate treatment. MG132-treated embryos showed increased expression of POU5F1, DPPA2, DPPA3, DPPA5, and NDP52l1 genes compared to control embryos. Our results demonstrate that post-fusion treatment of SCNT oocytes with MG132 prevents MPF degradation and increases expression of transcription factors in SCNT embryos, which are necessary for normal development of SCNT embryos. (c) 2009 Wiley-Liss, Inc.

Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

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Justyna Moskwa

Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

The cytotoxicity of a 2-chloroethylnitrosourea analog of sarcosinamide in the SK-MG-1 human glioma cell line as a possible indicator for transport

Energy Technology Data Exchange (ETDEWEB)

Skalski, V.; Feindel, W.; Panasci, L.C. (Lady Davis Institute for Medical Research, Montreal, Quebec (Canada))

1989-07-01

The cytotoxicities of a new sarcosinamide analog of chloroethylnitrosourea (SarCNU) and of BCNU were examined in the glioma cell line SK-MG-1 in the presence or absence of excess concentrations of amino acids and sarcosinamide. The cytotoxicity of SarCNU, but not of BCNU, was significantly reduced in the presence of excess sarcosinamide. The stability of SarCNU was not significantly altered by increasing concentrations of sarcosinamide. In order to investigate the possibility that sarcosinamide inhibits the uptake of SarCNU, the transport of tritiated sarcosinamide was examined in SK-MG-1 cells. The uptake of 3H-sarcosinamide was inhibited by excess, unlabelled sarcosinamide and SarCNU but not by BCNU, glycine or sarcosine. These results suggest the existence of a carrier-mediated transport for sarcosinamide which can accomodate SarCNU in SK-MG-1 cells.

Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

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James C K Lai

2008-12-01

Full Text Available James C K Lai1, Maria B Lai1, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Christopher K Daniels1, Solomon W Leung21Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, and Biomedical Research Institute; 2Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USAAbstract: The use of titanium dioxide (TiO2 in various industrial applications (eg, production of paper, plastics, cosmetics, and paints has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO2 nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO2 micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO nanoparticles were the most effective, TiO2 nanoparticles the second most effective, and magnesium oxide (MgO nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO2 micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.Keywords: cytotoxicity of titanium dioxide micro- and nanoparticles, cytotoxicity of zinc oxide and magnesium oxide nanoparticles, human neural cells

Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloys

Science.gov (United States)

Cipriano, Aaron F.; Sallee, Amy; Tayoba, Myla; Cortez Alcaraz, Mayra C.; Lin, Alan; Guan, Ren-Guo; Zhao, Zhan-Yong; Liu, Huinan

2018-01-01

Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x = 0.15, 0.5, 1.0, 1.5 wt%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-h in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at% ratio ~1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at% ~1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24 h was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6 mM Mg2+ ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn2+ ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications. PMID:27746360

Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea [Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz (Austria); DeVaney, Trevor [Institute of Biophysics, Medical University of Graz (Austria); Zimmer, Andreas [Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University, Graz (Austria); Raynham, Tony; Ireson, Christopher [Cancer Research Technology Ltd, London (United Kingdom); Sattler, Wolfgang, E-mail: wolfgang.sattler@medunigraz.at [Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz (Austria)

2013-08-01

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen. Time-lapse microscopy demonstrated that random cell migration was significantly diminished in response to PRKD2 silencing. The pharmacological PRKD family inhibitor CRT0066101 decreased chemotactic migration and invasion across uncoated or matrigel-coated Transwell inserts. Silencing of PRKD2 attenuated migration and invasion of U87MG cells even more effectively. In terms of downstream signaling, CRT0066101 prevented PRKD2 autophosphorylation and inhibited p44/42 MAPK and to a smaller extent p54/46 JNK and p38 MAPK activation. PRKD2 silencing impaired activation of p44/42 MAPK and p54/46 JNK, downregulated nuclear c-Jun protein levels and decreased c-Jun{sup S73} phosphorylation without affecting the NFκB pathway. Finally, qPCR array analyses revealed that silencing of PRKD2 downregulates mRNA levels of integrin alpha-2 and -4 (ITGA2 and -4), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and matrix metallopeptidase 1 (MMP1). Findings of the present study identify PRKD2 as a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. Highlights: • Sphingosine-1-phosphate induces glioma cell migration and invasion. • Part of the effects is mediated by protein kinase D2 (PRKD2) activation. • Inactivation of PRKD2 attenuates glioblastoma cell migration and invasion. • Both, RNAi and pharmacological inhibition of PRKD2 inhibits MAPK

Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro

International Nuclear Information System (INIS)

Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea; DeVaney, Trevor; Zimmer, Andreas; Raynham, Tony; Ireson, Christopher; Sattler, Wolfgang

2013-01-01

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen. Time-lapse microscopy demonstrated that random cell migration was significantly diminished in response to PRKD2 silencing. The pharmacological PRKD family inhibitor CRT0066101 decreased chemotactic migration and invasion across uncoated or matrigel-coated Transwell inserts. Silencing of PRKD2 attenuated migration and invasion of U87MG cells even more effectively. In terms of downstream signaling, CRT0066101 prevented PRKD2 autophosphorylation and inhibited p44/42 MAPK and to a smaller extent p54/46 JNK and p38 MAPK activation. PRKD2 silencing impaired activation of p44/42 MAPK and p54/46 JNK, downregulated nuclear c-Jun protein levels and decreased c-Jun S73 phosphorylation without affecting the NFκB pathway. Finally, qPCR array analyses revealed that silencing of PRKD2 downregulates mRNA levels of integrin alpha-2 and -4 (ITGA2 and -4), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and matrix metallopeptidase 1 (MMP1). Findings of the present study identify PRKD2 as a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. Highlights: • Sphingosine-1-phosphate induces glioma cell migration and invasion. • Part of the effects is mediated by protein kinase D2 (PRKD2) activation. • Inactivation of PRKD2 attenuates glioblastoma cell migration and invasion. • Both, RNAi and pharmacological inhibition of PRKD2 inhibits MAPK

20% Efficient Zn0.9Mg0.1O:Al/Zn0.8Mg0.2O/Cu(In,Ga)(S,Se)2 Solar Cell Prepared by All-Dry Process through a Combination of Heat-Light-Soaking and Light-Soaking Processes.

Science.gov (United States)

Chantana, Jakapan; Kato, Takuya; Sugimoto, Hiroki; Minemoto, Takashi

2018-04-04

Development of Cd-free Cu(In,Ga)(S,Se) 2 (CIGSSe)-based thin-film solar cells fabricated by an all-dry process is intriguing to minimize optical loss at a wavelength shorter than 520 nm owing to absorption of the CdS buffer layer and to be easily integrated into an in-line process for cost reduction. Cd-free CIGSSe solar cells are therefore prepared by the all-dry process with a structure of Zn 0.9 Mg 0.1 O:Al/Zn 0.8 Mg 0.2 O/CIGSSe/Mo/glass. It is demonstrated that Zn 0.8 Mg 0.2 O and Zn 0.9 Mg 0.1 O:Al are appropriate as buffer and transparent conductive oxide layers with large optical band gap energy values of 3.75 and 3.80 eV, respectively. The conversion efficiency (η) of the Cd-free CIGSSe solar cell without K-treatment is consequently increased to 18.1%. To further increase the η, the Cd-free CIGSSe solar cell with K-treatment is next fabricated and followed by posttreatment called the heat-light-soaking (HLS) + light-soaking (LS) process, including HLS at 110 °C followed by LS under AM 1.5G illumination. It is disclosed that the HLS + LS process gives rise to not only the enhancement of carrier density but also the decrease in the carrier recombination rate at the buffer/absorber interface. Ultimately, the η of the Cd-free CIGSSe solar cell with K-treatment prepared by the all-dry process is enhanced to the level of 20.0%.

Melting relations in the MgO-MgSiO3 system up to 70 GPa

Science.gov (United States)

Ohnishi, Satoka; Kuwayama, Yasuhiro; Inoue, Toru

2017-06-01

Melting experiments in a binary system MgO-MgSiO3 were performed up to 70 GPa using a CO2 laser heated diamond anvil cell. The quenched samples were polished and analyzed by a dualbeam focused ion beam (FIB) and a field emission scanning electron microscope (FE-SEM), respectively. The liquidus phase and the eutectic composition were determined on the basis of textual and chemical analyses of sample cross sections. Our experimental results show that the eutectic composition is the Si/Mg molar ratio of 0.76 at 35 GPa and it decreases with increasing pressure. Above 45 GPa, it becomes relatively constant at about 0.64-0.65 Si/Mg molar ratio. Using our experimental data collected at a wide pressure range up to 70 GPa together with previous experimental data, we have constructed a thermodynamic model of the eutectic composition of the MgO-MgSiO3 system. The eutectic composition extrapolated to the pressure and temperature conditions at the base of the mantle is about 0.64 Si/Mg molar ratio. The modeled eutectic composition is quite consistent with a previous prediction from ab initio calculations (de Koker et al. in Earth Planet Sci Lett 361:58-63, 2013), suggesting that the simple assumption of a non-ideal regular solution model can well describe the melting relation of the MgO-MgSiO3 system at high pressure. Our results show that the liquidus phase changes from MgO-periclase to MgSiO3-bridgmanite at 35 GPa for the simplified pyrolite composition ( 0.7 Si/Mg molar ratio), while MgSiO3-bridgmanite is the liquidus phase at the entire lower mantle conditions for the chondritic composition ( 0.84 Si/Mg molar ratio).

Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Dae-Hee, E-mail: leedneo@gmail.com [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Dong-Wook [Department of Microbiology, Immunology, and Cancer Biology, University of VA (United States); Jung, Chang-Hwa [Division of Metabolism and Functionality Research, Korea Food Research Institute (Korea, Republic of); Lee, Yong J. [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Park, Daeho, E-mail: daehopark@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

2014-09-15

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.

Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

International Nuclear Information System (INIS)

Lee, Dae-Hee; Kim, Dong-Wook; Jung, Chang-Hwa; Lee, Yong J.; Park, Daeho

2014-01-01

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway

Structural and electronic properties of Mg and Mg-Nb co-doped TiO2 (101) anatase surface

International Nuclear Information System (INIS)

Sasani, Alireza; Baktash, Ardeshir; Mirabbaszadeh, Kavoos; Khoshnevisan, Bahram

2016-01-01

Highlights: • Formation energy of Mg and Mg-Nb co-doped TiO_2 anatase surface (101) is studied. • Effect of Mg defect to the TiO_2 anatase (101) surface and bond length distribution of the surface is studied and it is shown that Mg defects tend to stay far from each other. • Effect of Mg and Nb to the bond length distribution of the surface studied and it is shown that these defects tend to stay close to each other. • Effects of Mg and Mg-Nb defects on DSSCs using TiO_2 anatase hosting these defects are studied. - Abstract: In this paper, by using density functional theory, Mg and Nb-Mg co-doping of TiO_2 anatase (101) surfaces are studied. By studying the formation energy of the defects and the bond length distribution of the surface, it is shown that Mg defects tend to stay as far as possible to induce least possible lattice distortion while Nb and Mg defects stay close to each other to cause less stress to the surface. By investigating band structure of the surface and changes stemmed from the defects, potential effects of Mg and Mg-Nb co-doping of TiO_2 surface on dye-sensitized solar cells are investigated. In this study, it is shown that the Nb-Mg co-doping could increase J_S_C of the surface while slightly decreasing V_O_C compared to Mg doped surface, which might result in an increase in efficiency of the DSSCs compared to Nb or Mg doped surfaces.

Surgical resection of grade II astrocytomas in the superior frontal gyrus.

Science.gov (United States)

Peraud, Aurelia; Meschede, Magnus; Eisner, Wilhelm; Ilmberger, Josef; Reulen, Hans-Jürgen

2002-05-01

Surgery in the superior frontal gyrus partially involving the supplementary motor area (SMA) may be followed by contralateral transient weakness and aphasia initially indistinguishable from damage to the primary motor cortex. However, recovery is different, and SMA deficits may resolve completely within days to weeks. No study has assessed the distinct postoperative deficits after tumor resection in the SMA on a homogeneous patient group. Twenty-four patients with World Health Organization Grade II astrocytomas in the superior frontal gyrus consecutively treated by surgery were studied. Degree and duration of postoperative deficits were evaluated according to tumor location and boundaries via magnetic resonance imaging scans, intraoperative neuromonitoring results, and extent of tumor resection. Postoperatively, motor deficits were evident in 21 of 24 and speech deficits in 9 of 12 patients. Motor function quickly recovered in 11 and speech function in 3 patients. None of the 12 patients in whom the posterior tumor resection line was at a distance of more than 0.5 cm from the precentral sulcus experienced persistent motor deficits. Eight of these patients developed typical SMA syndrome with transient initiation difficulties. Seven of 12 patients in whom the tumor extended to the precentral sulcus still had motor deficits at the 12-month follow-up assessment. Surgery for Grade II gliomas in the superior frontal gyrus is more likely to result in permanent morbidity when the resection is performed at a distance of less than 0.5 cm from the precentral gyrus or positive stimulation points. Therefore, cortical mapping of motor and speech function, in critical cases under local anesthesia with the patient as his or her own monitor, is recommended; resection should be tailored to obtain good functional outcome and maintain quality of life.

Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

Science.gov (United States)

2018-05-15

Ewing's Sarcoma; Osteosarcoma; Astrocytoma; Atypical Teratoid/Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Glioma; Medulloblastoma; Rhabdoid Tumor; Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Rhabdomyosarcoma

A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Coexpressing Neuronal and Glial Markers

Directory of Open Access Journals (Sweden)

Anjali Shiras

2003-11-01

Full Text Available The molecular mechanisms involved in tumor progression from a low-grade astrocytoma to the most malignant glioblastoma multiforme (GBM have been hampered due to lack of suitable experimental models. We have established a model of tumor progression comprising of two cell lines derived from the same astrocytoma tumor with a set of features corresponding to low-grade glioma (as in HNGC-1 and high-grade GBM (as in HNGC-2. The HNGC-1 cell line is slowgrowing, contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly proliferating, anchorage-independent, highly tumorigenic, and invasive cell line. The proliferation of cell lines is independent of the addition of exogenous growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid karyotype except for a disomy of chromosome 2. The two cell lines express the neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as well as glial differentiation protein S100μ. The HNGC-1 cell line also expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic differentiation marker, hence contributing toward a more morphologically differentiated phenotype with a propensity for neural differentiation in vitro. Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and loss of fibronectin were observed only in the HNGC-2 cell line, implicating the significance of these pathways in tumor progression. This in vitro model system assumes importance in unraveling the cellular and molecular mechanisms in differentiation, transformation, and gliomagenesis.

Biocompatible nanogel derived from functionalized dextrin for targeted delivery of doxorubicin hydrochloride to MG 63 cancer cells.

Science.gov (United States)

Das, Dipankar; Rameshbabu, Arun Prabhu; Ghosh, Paulomi; Patra, Priyapratim; Dhara, Santanu; Pal, Sagar

2017-09-01

The present article demonstrates the targeted delivery of doxorubicin hydrochloride to human osteosarcoma cancer cell lines (MG 63) using functionalized dextrin based crosslinked, pH responsive and biocompatible nanogel. The nanogel has been prepared through Michael-type addition reaction using dextrin (Dxt), N, N'-methylene bisacrylamide (MBA, as crosslinker), acrylic acid (AA, as monomer) and potassium persulfate (KPS, as initiator). The structure, composition, morphology of the nanogel have been explored using FTIR and 1 H NMR spectroscopy, XRD, TGA, DSC, CHN and AFM analyses. The TEM analysis confirmed that the size of nanogel appeared within 100nm, while DLS study indicates that the diameter of the nanogel remained between 113 and 126nm. The AFM study implied the porous morphology of the synthesized nanogel. The rheological study suggests the gel behaviour of the synthesized nanogel at 37±0.1°C. Difference in% swelling at pH 5.5 and 7.4 indicates pH-responsiveness of the nanogel. The in vitro cytocompatibility results ascertained that the nanogel is non-toxic to human mesenchymal stem cells (hMSCs). In vitro cellular uptake study confirmed that FITC-loaded nanogel can cross the cellular membrane and be well uptake by the cell cytoplasm. The nanogel could efficiently encapsulate doxorubicin hydrochloride (Dox) with the loading efficiency of 27±0.2% after 72h. The Dox-loaded nanogel demonstrates anti-cancer activity towards MG 63 cancer cells and release the encapsulated drug in a controlled way. Copyright © 2017 Elsevier Ltd. All rights reserved.

The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism

International Nuclear Information System (INIS)

Pajonk, Frank; Ophoven, Arndt van; Weissenberger, Christian; McBride, William H

2005-01-01

By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay. Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity. We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132

Ionic conductivity and fuel cell properties of apatite-type lanthanum silicates doped with Mg and containing excess oxide ions

Energy Technology Data Exchange (ETDEWEB)

Yoshioka, Hideki [Hyogo Prefectural Institute of Technology, 3-1-12 Yukihira-cho, Suma-ku, Kobe 654-0037 (Japan); Nojiri, Yoshihiro [Kyushu University, Department of Mechanical Engineering Science, Faculty of Engineering, Motooka 744, Nishi-ku, Fukuoka 819-0935 (Japan); Tanase, Shigeo [National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577 (Japan)

2008-11-30

Enhancement of the ionic conductivity of lanthanum silicate-based apatites is examined with emphasis on optimizing the La composition and the Mg doping level at the same time. La{sub 10}Si{sub 5.8}Mg{sub 0.2}O{sub 26.8} and La{sub 9.8}Si{sub 5.7}Mg{sub 0.3}O{sub 26.4} show the highest level of the ionic conductivities among apatite silicates, 8.8 and 7.4 x 10{sup -} {sup 2} S cm{sup -} {sup 1} at 800 C, respectively, with a very low level of activation energy (0.42-0.43 eV). Their conductivities are higher than yttria stabilized zirconia (YSZ) below 900 C and even comparable to Sr and Mg doped lanthanum gallate (LSGM) below 550 C. A solid oxide fuel cell using La{sub 9.8}Si{sub 5.7}Mg{sub 0.3}O{sub 26.4} as an electrolyte with Ni-ceria cermet anode and Sr doped lanthanum cobaltite cathode exhibits a remarkable improvement in power generation compared to previous data using Pt electrodes. Structural investigation by the Rietveld analysis on the powder X-ray diffraction pattern shows significant enlargement of the bottleneck triangle sizes of the conduction channel with the Mg doping. (author)

Study of the Mg incorporation in CdTe for developing wide band gap Cd1−xMgxTe thin films for possible use as top-cell absorber in a tandem solar cell

International Nuclear Information System (INIS)

Martínez, Omar S.; Millán, Aduljay Remolina; Huerta, L.; Santana, G.; Mathews, N.R.; Ramon-Garcia, M.L.; Morales, Erik R.; Mathew, X.

2012-01-01

Highlights: ► Thin films of Cd 1−x Mg x Te with high spatial uniformity and band gap in the range of 1.6–1.96 eV were deposited by vacuum co-evaporation of CdTe and Mg. ► Obtained Cd 1−x Mg x Te films have the structural characteristics of the CdTe, evidence of the change in atomic scattering due to incorporation of Mg was observed. ► XRD and XPS data confirmed the incorporation of Mg in the lattice of CdTe. ► SEM images revealed the impact of Mg incorporation on the morphology of the films, the changes in grain size and grain morphology are noticeable. - Abstract: Thin films of Cd 1−x Mg x Te with band gap in the range of 1.6–1.96 eV were deposited by vacuum co-evaporation of CdTe and Mg on glass substrates heated at 300 °C. Different experimental techniques such as XRD, UV–vis spectroscopy, SEM, and XPS were used to study the effect of Mg incorporation into the lattice of CdTe. The band gap of the films showed a clear tendency to increase as the Mg content in the film is increased. The Cd 1−x Mg x Te films maintain all the structural characteristics of the CdTe, however, diminishing of intensity for the XRD patterns is observed due to both change in preferential orientation and change in atomic scattering due to the incorporation of Mg. SEM images showed significant evidences of morphological changes due to the presence of Mg. XRD, UV–vis spectroscopy, and XPS data confirmed the incorporation of Mg in the lattice of CdTe. The significant increase in band gap of CdTe due to incorporation of Mg suggests that the Cd 1−x Mg x Te thin film is a candidate material to use as absorber layer in the top-cell of a tandem solar cell.

Performance of intermediate temperature (600-800 °C) solid oxide fuel cell based on Sr and Mg doped lanthanum-gallate electrolyte

Science.gov (United States)

Gong, Wenquan; Gopalan, Srikanth; Pal, Uday B.

The solid electrolyte chosen for this investigation was La 0.9Sr 0.1Ga 0.8Mg 0.2O 3 (LSGM). To select appropriate electrode materials from a group of possible candidate materials, AC complex impedance spectroscopy studies were conducted between 600 and 800 °C on symmetrical cells that employed the LSGM electrolyte. Based on the results of the investigation, LSGM electrolyte supported solid oxide fuel cells (SOFCs) were fabricated with La 0.6Sr 0.4Co 0.8Fe 0.2O 3-La 0.9Sr 0.1Ga 0.8Mg 0.2O 3 (LSCF-LSGM) composite cathode and nickel-Ce 0.6La 0.4O 2 (Ni-LDC) composite anode having a barrier layer of Ce 0.6La 0.4O 2 (LDC) between the LSGM electrolyte and the Ni-LDC anode. Electrical performances of these cells were determined and the electrode polarization behavior as a function of cell current was modeled between 600 and 800 °C.

The effect of gallic acid on cytotoxicity, Ca(2+) homeostasis and ROS production in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes.

Science.gov (United States)

Hsu, Shu-Shong; Chou, Chiang-Ting; Liao, Wei-Chuan; Shieh, Pochuen; Kuo, Daih-Huang; Kuo, Chun-Chi; Jan, Chung-Ren; Liang, Wei-Zhe

2016-05-25

Gallic acid, a polyhydroxylphenolic compound, is widely distributed in various plants, fruits and foods. It has been shown that gallic acid passes into blood brain barrier and reaches the brain tissue of middle cerebral artery occlusion rats. However, the effect of gallic acid on Ca(2+) signaling in glia cells is unknown. This study explored whether gallic acid affected Ca(2+) homeostasis and induced Ca(2+)-associated cytotoxicity in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes. Gallic acid (20-40 μM) concentration-dependently induced cytotoxicity and intracellular Ca(2+) level ([Ca(2+)]i) increases in DBTRG-05MG cells but not in CTX TNA2 cells. In DBTRG-05MG cells, the Ca(2+) response was decreased by half by removal of extracellular Ca(2+). In Ca(2+)-containing medium, gallic acid-induced Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (2-APB, econazole and SKF96365). In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin abolished gallic acid-induced [Ca(2+)]i increases. Conversely, incubation with gallic acid also abolished thapsigargin-induced [Ca(2+)]i increases. Inhibition of phospholipase C with U73122 abolished gallic acid-induced [Ca(2+)]i increases. Gallic acid significantly caused cytotoxicity in DBTRG-05MG cells, which was partially prevented by prechelating cytosolic Ca(2+) with BAPTA-AM. Moreover, gallic acid activated mitochondrial apoptotic pathways that involved ROS production. Together, in DBTRG-05MG cells but not in CTX TNA2 cells, gallic acid induced [Ca(2+)]i increases by causing Ca(2+) entry via 2-APB, econazole and SKF96365-sensitive store-operated Ca(2+) entry, and phospholipase C-dependent release from the endoplasmic reticulum. This Ca(2+) signal subsequently evoked mitochondrial pathways of apoptosis that involved ROS production. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic Properties

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Bartłomiej Augustynek

2018-01-01

Full Text Available Potassium channel openers (KCOs have been shown to play a role in cytoprotection through the activation of mitochondrial potassium channels. Recently, in several reports, a number of data has been described as off-target actions for KCOs. In the present study, we investigated the effects of BKCa channel openers CGS7181, CGS7184, NS1619, and NS004 in neuronal cells. For the purpose of this research, we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma U-87 MG cell line. We showed that CGS7184 activated the mitochondrial BKCa (mitoBKCa channel in single-channel recordings performed on astrocytoma mitoplasts. Moreover, when applied to the rat brain homogenate or isolated rat brain mitochondria, CGS7184 increased the oxygen consumption rate, and can thus be considered a potentially cytoprotective agent. However, experiments on intact neuronal HT22 cells revealed that both CGS7181 and CGS7184 induced HT22 cell death in a concentration- and time-dependent manner. By contrast, we did not observe cell death when NS1619 or NS004 was applied. CGS7184 toxicity was not abolished by BKCa channel inhibitors, suggesting that the observed effects were independent of a BKCa-type channel activity. CGS7184 treatment resulted in an increase of cytoplasmic Ca2+ concentration that likely involved efflux from internal calcium stores and the activation of calpains (calcium-dependent proteases. The cytotoxic effect of the channel opener was partially reversed by a calpain inhibitor. Our data show that KCOs under study not only activate mitoBKCa channels from brain tissue, but also induce cell death when used in cellular models.

Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

International Nuclear Information System (INIS)

Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song

2015-01-01

To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces

Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

Energy Technology Data Exchange (ETDEWEB)

Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song, E-mail: song_li59@126.com

2015-08-21

To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces.

Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

Science.gov (United States)

Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

2013-03-21

HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

Increased Inhibitor of Differentiation 4 (Id4 Expression in Glioblastoma: A Tissue Microarray Study

Directory of Open Access Journals (Sweden)

Weifin Zeng, Elisabeth J. Rushing, Daniel P. Hartmann, Norio Azumi

2010-01-01

Full Text Available Background: The inhibitor of differentiation/DNA binding protein family (Id1-4 is involved in cell cycle control, tumorigenesis and angiogenesis through the negative regulation of helix-loop-helix transcription factors. Of these proteins, Id4 is known to play an important role in neural stem cell differentiation, and deregulation has been implicated in glial neoplasia. However, the expression and significance of Id4 in astrocytomas has not been fully addressed. Herein we report the differential expression of Id4 in astrocytomas of various grades using tissue microarrays (TMA and immunohistochemistry (IHC. Design: The GBM TMA was constructed from 53 archival cases at Georgetown University Hospital and a TMA with normal brain controls and grades II-III astrocytoma was obtained from Cybrdi (Rockville, MD. TMA sections were stained with Id4 antibody and the slides were scored according to the percentage of staining astrocytic nuclei (<9% -, 10-50% +, >51% ++. The Fisher Exact test was used to test for statistical significance. Results: Nuclear staining for Id4 was seen in 73.58% GBMs, 25% grade III, and 12.5% grade II astrocytomas; staining was absent in normal brain tissue. There was a statistically significant difference between GBM and grades II, III astrocytoma (p <0.01. Significant Id4 expression was not detected in normal brain. Conclusions: Our study confirms the frequent upregulation of Id4 expression in GBM, which lends support to its role in tumorigenesis, possibly in the transformation of low to high-grade astrocytoma (i.e. GBM. Further studies are warranted to determine the precise role of Id4 in glial neoplasia and its potential use in targeted therapy for GBM.

Structural and electronic properties of Mg and Mg-Nb co-doped TiO2 (101) anatase surface

Energy Technology Data Exchange (ETDEWEB)

Sasani, Alireza [Department of Science, Karaj Islamic Azad University, Karaj, Alborz, P.O. Box 31485-313 (Iran, Islamic Republic of); Baktash, Ardeshir [Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box 87317-51167 (Iran, Islamic Republic of); Mirabbaszadeh, Kavoos, E-mail: mirabbas@aut.ac.ir [Department of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, P. O. Box 15875-4413 (Iran, Islamic Republic of); Khoshnevisan, Bahram [Institute of Nano Science and Nano Technology, University of Kashan, Kashan, P.O. Box 87317-51167 (Iran, Islamic Republic of)

2016-10-30

Highlights: • Formation energy of Mg and Mg-Nb co-doped TiO{sub 2} anatase surface (101) is studied. • Effect of Mg defect to the TiO{sub 2} anatase (101) surface and bond length distribution of the surface is studied and it is shown that Mg defects tend to stay far from each other. • Effect of Mg and Nb to the bond length distribution of the surface studied and it is shown that these defects tend to stay close to each other. • Effects of Mg and Mg-Nb defects on DSSCs using TiO{sub 2} anatase hosting these defects are studied. - Abstract: In this paper, by using density functional theory, Mg and Nb-Mg co-doping of TiO{sub 2} anatase (101) surfaces are studied. By studying the formation energy of the defects and the bond length distribution of the surface, it is shown that Mg defects tend to stay as far as possible to induce least possible lattice distortion while Nb and Mg defects stay close to each other to cause less stress to the surface. By investigating band structure of the surface and changes stemmed from the defects, potential effects of Mg and Mg-Nb co-doping of TiO{sub 2} surface on dye-sensitized solar cells are investigated. In this study, it is shown that the Nb-Mg co-doping could increase J{sub SC} of the surface while slightly decreasing V{sub OC} compared to Mg doped surface, which might result in an increase in efficiency of the DSSCs compared to Nb or Mg doped surfaces.

Degradation of bioabsorbable Mg-based alloys: Assessment of the effects of insoluble corrosion products and joint effects of alloying components on mammalian cells.

Science.gov (United States)

Grillo, Claudia A; Alvarez, Florencia; Fernández Lorenzo de Mele, Mónica A

2016-01-01

This work is focused on the processes occurring at the bioabsorbable metallic biomaterial/cell interfaces that may lead to toxicity. A critical analysis of the results obtained when degradable metal disks (pure Mg and rare earth-containing alloys (ZEK100 alloys)) are in direct contact with cell culture and those obtained with indirect methods such as the use of metal salts and extracts was made. Viability was assessed by Acridine Orange dye, neutral red and clonogenic assays. The effects of concentration of corrosion products and possible joint effects of the binary and ternary combinations of La, Zn and Mg ions, as constituents of ZEK alloys, were evaluated on a mammalian cell culture. In all cases more detrimental effects were found for pure Mg than for the alloys. Experiments with disks showed that gradual alterations in pH and in the amount of corrosion products were better tolerated by cells and resulted in higher viability than abrupt changes. In addition, viability was dependent on the distance from the source of ions. Experiments with extracts showed that the effect of insoluble degradation products was highly detrimental. Indirect tests with Zn ions revealed that harmful effects may be found at concentrations ≥ 150 μM and at ≥ 100 μM in mixtures with Mg. These mixtures lead to more deleterious effects than single ions. Results highlight the need to develop a battery of tests to evaluate the biocompatibility of bioabsorbable biomaterials. Copyright © 2015 Elsevier B.V. All rights reserved.

Properties of thymidylate synthetase from Ehrlich ascites carcinoma cells. Effect of Mg2/ and MgATP2-.

Science.gov (United States)

Jastreboff, M; Kedzierska, B; Rode, W

1982-01-15

Ehrlich ascites carcinoma thymidylate synthetase was purified to electrophoretic homogeneity by affinity chromatography on 10-formyl-5,8-dideazofolate-ethyl-Sepharose. Electrophoretic analysis of the formation of the enzyme-5-fluorodeoxyuridylate-5,10-methylenetetrahydrofolate complexes showed the presence of two binding sites for 5-fluorodeoxyuridylate on the enzyme molecule. Molecular weight of the native enzyme was found to be 78,5000, whereas that of its monomer was 38, 500. The apparent Michaelis constants for dUMP and (+/-)-L-5,10-methylenetetrahydrofolate were 1.3 +/- 0.4 and 32.2 +/- 0.7 micrometers respectively. Phosphate acted as a weak inhibitor, competitive toward dUMP. The enzyme reaction exhibited a temperature-dependent change of activation energy, reflected in the binding affinity of dUMP, with a transitional temperature of 35.8 degrees. Both Mg2+ and MgATP2- were strong activators of the enzyme, MgATP2- being more effective.

In vivo and in vitro degradation comparison of pure Mg, Mg-10Gd and Mg-2Ag: a short term study

Directory of Open Access Journals (Sweden)

I Marco

2017-02-01

Full Text Available The purpose of this study was to compare short term in vitro and in vivo biodegradation studies with low purity Mg (> 99.94 %, Mg-10Gd and Mg-2Ag designed for biodegradable implant applications. Three in vitro testing conditions were applied, using (i phosphate buffered saline (PBS, (ii Hank’s balanced salt solution (HBSS and (iii Dulbecco’s modified eagle medium (DMEM in 5 % CO2 under sterile conditions. Gas evolution and mass loss (ML were assessed, as well as the degradation layer, by elemental mapping and scanning electron microscopy (SEM. In vivo, implantations were performed on male Sprague-Dawley rats evaluating both, gas cavity volume and implant volume reduction by micro-computed tomography (µCT, 7 d after implantation. Samples were produced by casting, solution heat treatment and extrusion in disc and pin shape for the in vitro and in vivo experiments, respectively. Results showed that when the processing of the Mg sample varied, differences were found not only in the alloy impurity content and the grain size, but also in the corrosion behaviour. An increase of Fe and Ni or a large grain size seemed to play a major role in the degradation process, while the influence of alloying elements, such as Gd and Ag, played a secondary role. Results also indicated that cell culture conditions induced degradation rates and degradation layer elemental composition comparable to in vivo conditions. These in vitro and in vivo degradation layers consisted of Mg hydroxide, Mg-Ca carbonate and Ca phosphate.

Enhanced voltage-controlled magnetic anisotropy in magnetic tunnel junctions with an MgO/PZT/MgO tunnel barrier

Science.gov (United States)

Chien, Diana; Li, Xiang; Wong, Kin; Zurbuchen, Mark A.; Robbennolt, Shauna; Yu, Guoqiang; Tolbert, Sarah; Kioussis, Nicholas; Khalili Amiri, Pedram; Wang, Kang L.; Chang, Jane P.

2016-03-01

Compared with current-controlled magnetization switching in a perpendicular magnetic tunnel junction (MTJ), electric field- or voltage-induced magnetization switching reduces the writing energy of the memory cell, which also results in increased memory density. In this work, an ultra-thin PZT film with high dielectric constant was integrated into the tunneling oxide layer to enhance the voltage-controlled magnetic anisotropy (VCMA) effect. The growth of MTJ stacks with an MgO/PZT/MgO tunnel barrier was performed using a combination of sputtering and atomic layer deposition techniques. The fabricated MTJs with the MgO/PZT/MgO barrier demonstrate a VCMA coefficient, which is ˜40% higher (19.8 ± 1.3 fJ/V m) than the control sample MTJs with an MgO barrier (14.3 ± 2.7 fJ/V m). The MTJs with the MgO/PZT/MgO barrier also possess a sizeable tunneling magnetoresistance (TMR) of more than 50% at room temperature, comparable to the control MTJs with an MgO barrier. The TMR and enhanced VCMA effect demonstrated simultaneously in this work make the MgO/PZT/MgO barrier-based MTJs potential candidates for future voltage-controlled, ultralow-power, and high-density magnetic random access memory devices.

Effective internalization of U251-MG-secreted exosomes into cancer cells and characterization of their lipid components.

Science.gov (United States)

Toda, Yuki; Takata, Kazuyuki; Nakagawa, Yuko; Kawakami, Hikaru; Fujioka, Shusuke; Kobayashi, Kazuya; Hattori, Yasunao; Kitamura, Yoshihisa; Akaji, Kenichi; Ashihara, Eishi

2015-01-16

Exosomes, the natural vehicles of various biological molecules, have been examined in several research fields including drug delivery. Although understanding of the biological functions of exosomes has increased, how exosomes are transported between cells remains unclear. We hypothesized that cell tropism is important for effective exosomal intercellular communication and that parental cells regulate exosome movement by modulating constituent exosomal molecules. Herein, we demonstrated the strong translocation of glioblastoma-derived exosomes (U251exo) into their parental (U251) cells, breast cancer (MDA-MB-231) cells, and fibrosarcoma (HT-1080). Furthermore, disruption of proteins of U251exo by enzymatic treatment did not affect their uptake. Therefore, we focused on lipid molecules of U251exo with the expectation that they are crucial for effective incorporation of U251exo by cancer cells. Phosphatidylethanolamine was identified as a unique lipid component of U251-MG cell-derived extracellular vesicles. From these results, valuable insight is provided into the targeting of U251exo to cancer cells, which will help to develop a cancer-targeted drug delivery system. Copyright © 2014 Elsevier Inc. All rights reserved.

The influence of surface chemistry and topography on the contact guidance of MG63 osteoblast cells.

Science.gov (United States)

Ismail, F S Magdon; Rohanizadeh, R; Atwa, S; Mason, R S; Ruys, A J; Martin, P J; Bendavid, A

2007-05-01

The purpose of the present study was to determine in vitro the effects of different surface topographies and chemistries of commercially pure titanium (cpTi) and diamond-like carbon (DLC) surfaces on osteoblast growth and attachment. Microgrooves (widths of 2, 4, 8 and 10 microm and a depth of 1.5-2 microm) were patterned onto silicon (Si) substrates using microlithography and reactive ion etching. The Si substrates were subsequently vapor coated with either cpTi or DLC coatings. All surfaces were characterized using atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Using the MG63 Osteoblast-Like cell line, we determined cell viability, adhesion, and morphology on different substrates over a 3 day culture period. The results showed cpTi surfaces to be significantly more hydrophilic than DLC for groove sizes larger than 2 microm. Cell contact guidance was observed for all grooved samples in comparison to the unpatterned controls. The cell viability tests indicated a significantly greater cell number for 8 and 10 microm grooves on cpTi surfaces compared to other groove sizes. The cell adhesion study showed that the smaller groove sizes, as well as the unpatterned control groups, displayed better cell adhesion to the substrate.

Csk-Induced Phosphorylation of Src at Tyrosine 530 is Essential for H2O2-Mediated Suppression of ERK1/2 in Human Umbilical Vein Endothelial Cells

Science.gov (United States)

Jeon, Bo Kyung; Kwon, Kihwan; Kang, Jihee Lee; Choi, Youn-Hee

2015-01-01

Mitogen-activated protein kinases (MAPKs) are key signal transducers involved in various cellular events such as growth, proliferation, and differentiation. Previous studies have reported that H2O2 leads to phosphorylation of extracellular signal-regulated kinase (ERK), one of the MAPKs in endothelial cells. The current study shows that H2O2 suppressed ERK1/2 activation and phosphorylation at specific concentrations and times in human umbilical vein endothelial cells but not in immortalized mouse aortic endothelial cells or human astrocytoma cell line CRT-MG. Phosphorylation of other MAPK family members (i.e., p38 and JNK) was not suppressed by H2O2. The decrease in ERK1/2 phosphorylation induced by H2O2 was inversely correlated with the level of phosphorylation of Src tyrosine 530. Using siRNA, it was found that H2O2-induced suppression of ERK1/2 was dependent on Csk. Physiological laminar flow abrogated, but oscillatory flow did not affect, the H2O2-induced suppression of ERK1/2 phosphorylation. In conclusion, H2O2-induced Csk translocation to the plasma membrane leads to phosphorylation of Src at the tyrosine 530 residue resulting in a reduction of ERK1/2 phosphorylation. Physiological laminar flow abrogates this effect of H2O2 by inducing phosphorylation of Src tyrosine 419. These findings broaden our understanding of signal transduction mechanisms in the endothelial cells against oxidative stress. PMID:26234813

STAT6 expression in glioblastoma promotes invasive growth

International Nuclear Information System (INIS)

Merk, Barbara C; Owens, Jennifer L; Lopes, Maria-Beatriz S; Silva, Corinne M; Hussaini, Isa M

2011-01-01

Glioblastoma (GBM) is a highly aggressive malignant primary brain tumor, characterized by rapid growth, diffuse infiltration of cells into both adjacent and remote brain regions, and a generalized resistance to currently available treatment modalities. Recent reports in the literature suggest that Signal Transducers and Activators of Transcription (STATs) play important roles in the regulation of GBM pathophysiology. STAT6 protein expression was analyzed by Western blotting in GBM cell lines and by immunohistochemistry in a tissue microarray (TMA) of glioma patient tissues. We utilized shRNA against STAT6 to investigate the effects of prolonged STAT6 depletion on the growth and invasion of two STAT6-positive GBM cell lines. Cell proliferation was assessed by measuring 3 H-Thymidine uptake over time. Invasion was measured using an in vitro transwell assay in which cells invade through a type IV collagen matrix toward a chemoattractant (Fetal Bovine Serum). Cells were then stained and counted. Kaplan-Meyer survival curves were generated to show the correlation between STAT6 gene expression and patient survival in 343 glioma patients and in a subset of patients with only GBM. Gene expression microarray and clinical data were acquired from the Rembrandt [1] public data depository (https://caintegrator.nci.nih.gov/rembrandt/). Lastly, a genome-wide expression microarray analysis was performed to compare gene expression in wild-type GBM cells to expression in stable STAT6 knockdown clones. STAT6 was expressed in 2 GBM cell lines, U-1242MG and U-87MG, and in normal astrocytes (NHA) but not in the U-251MG GBM cell line. In our TMA study, STAT6 immunostaining was visible in the majority of astrocytomas of all grades (I-IV) but not in normal brain tissue. In positive cells, STAT6 was localized exclusively in the nuclei over 95% of the time. STAT6-deficient GBM cells showed a reduction in 3 H-Thymidine uptake compared to the wild-type. There was some variation among the

Mg/O2 Battery Based on the Magnesium-Aluminum Chloride Complex (MACC) Electrolyte

DEFF Research Database (Denmark)

Vardar, Galin; Smith, Jeffrey G.; Thomson, Travis

2016-01-01

Mg/O2 cells employing a MgCl2/AlCl3/DME (MACC/DME) electrolyte are cycled and compared to cells with modified Grignard electrolytes, showing that performance of magnesium/oxygen batteries depends strongly on electrolyte composition. Discharge capacity is far greater for MACC/DME-based cells, whil...

Obtention of Al-Mg alloys of porous morphology; Obtencion de aleaciones Al-Mg de morfologia porosa

Energy Technology Data Exchange (ETDEWEB)

Barragan V, J.; Zamora R, L.; Sandoval J, A.R.; Iturbe G, J.L. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2006-07-01

With the objective of using it as fuel cell, a Mg{sub 25}AI alloy of porous morphology was obtained. The material it was hydrogenates at 200 C by different time. It was analyzed by Scanning Electron Microscopy SEM and X-ray diffion, XRD. Those XRD diffractographs present peaks run toward the origin, that which indicates a volume increase of the unitary cell by effect of the hydrogen absorption. (Author)

Effects of fluoridation of porcine hydroxyapatite on osteoblastic activity of human MG63 cells

International Nuclear Information System (INIS)

Li, Zhipeng; Huang, Baoxin; Mai, Sui; Wu, Xiayi; Zhang, Hanqing; Qiao, Wei; Luo, Xin; Chen, Zhuofan

2015-01-01

Biological hydroxyapatite, derived from animal bones, is the most widely used bone substitute in orthopedic and dental treatments. Fluorine is the trace element involved in bone remodeling and has been confirmed to promote osteogenesis when administered at the appropriate dose. To take advantage of this knowledge, fluorinated porcine hydroxyapatite (FPHA) incorporating increasing levels of fluoride was derived from cancellous porcine bone through straightforward chemical and thermal treatments. Physiochemical characteristics, including crystalline phases, functional groups and dissolution behavior, were investigated on this novel FPHA. Human osteoblast-like MG63 cells were cultured on the FPHA to examine cell attachment, cytoskeleton, proliferation and osteoblastic differentiation for in vitro cellular evaluation. Results suggest that fluoride ions released from the FPHA play a significant role in stimulating osteoblastic activity in vitro, and appropriate level of fluoridation (1.5 to 3.1 atomic percents of fluorine) for the FPHA could be selected with high potential for use as a bone substitute. (paper)

Effect of biomimetic 3D environment of an injectable polymeric scaffold on MG-63 osteoblastic-cell response

International Nuclear Information System (INIS)

Verma, Shalini; Kumar, Neeraj

2010-01-01

Solid PLGA microspheres were fabricated and characterized in terms of their in vitro degradation behaviour. Microsphere scaffolds were then modified covalently by P-15 (GTPGPQGIAGQRGVV) to obtain a 3D bioactive collagen surrogate matrix for bone filling applications. These scaffolds were characterized for surface topography, hydrophilicity and evaluated for their effect on osteoblastic activity of MG-63 cell line vis-a-vis 2D monolayer culture. AFM and contact angle experiments indicated enhanced nano-level roughness and hydrophilicity on P-15 modification. Modified scaffolds showed enhanced cell attachment, proliferation, extracellular matrix formation, mineralization and collagen type-I expression when compared to unmodified microspheres, prerequisite for bone filling applications. On long term in vitro cell culture, however, decreased cell viability was observed which may be attributed to the acidic microenvironment generated due to polymer degradation and reduction in nutrient diffusion through the copious ECM formed in 3D scaffolds. Though a higher cell count could be obtained in 2D monolayer cell culture, it was overshadowed by weak cell attachment, poor phenotypic characteristics, decreased cell viability and low mineralization levels, over 28 day cell culture studies. Results indicate that P-15 modified microsphere scaffolds may provide a natural, biomimetic 3D environment and may be successfully exploited for non-invasive bone filling applications.

Effect of different surface nanoroughness of titanium dioxide films on the growth of human osteoblast-like MG63 cells

Czech Academy of Sciences Publication Activity Database

Vandrovcová, Marta; Hanuš, J.; Drábik, M.; Kylián, O.; Biederman, H.; Lisá, Věra; Bačáková, Lucie

100A, č. 4 (2012), s. 1016-1032 ISSN 1549-3296 R&D Projects: GA AV ČR(CZ) KAN101120701 Institutional research plan: CEZ:AV0Z50110509 Keywords : titanium dioxide * nanoscale surface roughness * MG63 cells Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.834, year: 2012

Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

Energy Technology Data Exchange (ETDEWEB)

Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

2004-07-01

We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

International Nuclear Information System (INIS)

Yousry, Indra; Yousry, Tarek A.; Muacevic, Alexander; Olteanu-Nerbe, Vlad; Naidich, Thomas P.

2004-01-01

We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

Preparation of the fast setting and degrading Ca–Si–Mg cement with both odontogenesis and angiogenesis differentiation of human periodontal ligament cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Yi-Wen [Graduate Institute of Clinical Medical Science, China Medical University, Taichung City, Taiwan (China); 3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China); Hsu, Tuan-Ti [Institute of Oral Science, Chung Shan Medical University, Taichung City, Taiwan (China); Wang, Kan [H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Georgia Tech Manufacturing Institute, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Shie, Ming-You, E-mail: eviltacasi@gmail.com [3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China)

2016-03-01

Develop a fast setting and controllable degrading magnesium–calcium silicate cement (Mg–CS) by sol–gel, and establish a mechanism using Mg ions to stimulate human periodontal ligament cells (hPDLs) are two purposes of this study. We have used the diametral tensile strength measurement to obtain the mechanical strength and stability of Mg–CS cement; in addition, the cement degradation properties is realized by measuring the releasing amount of Si and Mg ions in the simulated body fluid. The other cell characteristics of hPDLs, such as proliferation, differentiation and mineralization were examined while hPDLs were cultured on specimen surfaces. This study found out the degradation rate of Mg–CS cements depends on the Mg content in CS. Regarding in vitro bioactivity; the CS cements were covered with abundant clusters of apatite spherulites after immersion of 24 h, while less apatite spherulites were formatted on the Mg-rich cement surfaces. In addition, the authors also explored the effects of Mg ions on the odontogenesis and angiogenesis differentiation of hPDLs in comparison with CS cement. The proliferation, alkaline phosphatase, odontogenesis-related genes (DSPP and DMP-1), and angiogenesis-related protein (vWF and ang-1) secretion of hPDLs were significantly stimulated when the Mg content of the specimen was increased. The results in this study suggest that Mg–CS materials with this modified composition could stimulate hPDLs behavior and can be good bioceramics for bone substitutes and hard tissue regeneration applications as they stimulate odontogenesis/angiogenesis. - Highlights: • The fast setting and degrading Mg–CS cement was synthesized by sol–gel. • Promoted proliferation of hPDLs on Mg–CS specimens • Mg–CS can degrade and release Si and Mg ions into SBF. • Up-regulation of odontogenic and angiogenic of hPDLs • Mg–CS may be good bone substitutes for hard tissue regeneration applications.

Preparation of the fast setting and degrading Ca–Si–Mg cement with both odontogenesis and angiogenesis differentiation of human periodontal ligament cells

International Nuclear Information System (INIS)

Chen, Yi-Wen; Hsu, Tuan-Ti; Wang, Kan; Shie, Ming-You

2016-01-01

Develop a fast setting and controllable degrading magnesium–calcium silicate cement (Mg–CS) by sol–gel, and establish a mechanism using Mg ions to stimulate human periodontal ligament cells (hPDLs) are two purposes of this study. We have used the diametral tensile strength measurement to obtain the mechanical strength and stability of Mg–CS cement; in addition, the cement degradation properties is realized by measuring the releasing amount of Si and Mg ions in the simulated body fluid. The other cell characteristics of hPDLs, such as proliferation, differentiation and mineralization were examined while hPDLs were cultured on specimen surfaces. This study found out the degradation rate of Mg–CS cements depends on the Mg content in CS. Regarding in vitro bioactivity; the CS cements were covered with abundant clusters of apatite spherulites after immersion of 24 h, while less apatite spherulites were formatted on the Mg-rich cement surfaces. In addition, the authors also explored the effects of Mg ions on the odontogenesis and angiogenesis differentiation of hPDLs in comparison with CS cement. The proliferation, alkaline phosphatase, odontogenesis-related genes (DSPP and DMP-1), and angiogenesis-related protein (vWF and ang-1) secretion of hPDLs were significantly stimulated when the Mg content of the specimen was increased. The results in this study suggest that Mg–CS materials with this modified composition could stimulate hPDLs behavior and can be good bioceramics for bone substitutes and hard tissue regeneration applications as they stimulate odontogenesis/angiogenesis. - Highlights: • The fast setting and degrading Mg–CS cement was synthesized by sol–gel. • Promoted proliferation of hPDLs on Mg–CS specimens • Mg–CS can degrade and release Si and Mg ions into SBF. • Up-regulation of odontogenic and angiogenic of hPDLs • Mg–CS may be good bone substitutes for hard tissue regeneration applications.

Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model

International Nuclear Information System (INIS)

Pei, Jian; Park, In-Ho; Ryu, Hyang-Hwa; Li, Song-Yuan; Li, Chun-Hao; Lim, Sa-Hoe; Wen, Min; Jang, Woo-Youl; Jung, Shin

2015-01-01

Glioblastoma is a highly lethal neoplasm that frequently recurs locally after radiotherapy, and most of these recurrences originate from near the irradiated target field. In the present study, we identified the effects of radiation on glioma invasion and p53, TIMP-2, and MMP-2 expression through in vitro and in vivo experiments. The U87MG (wt p53) and U251 (mt p53) human malignant glioma cell lines were prepared, and the U2OS (wt 53) and Saos2 (del p53) osteosarcoma cell lines were used as p53 positive and negative controls. The four cell lines and p53 knock-downed U87MG cells received radiation (2–6 Gy) and were analyzed for expression of p53 and TIMP-2 by Western blot, and MMP-2 activity was detected by zymography. In addition, the effects of irradiation on directional invasion of malignant glioma were evaluated by implanting nude mice with bioluminescent u87-Fluc in vivo followed by MMP-2, p53, and TIMP-2 immunohisto-chemistry and in situ zymography. MMP-2 activity and p53 expression increased in proportional to the radiation dose in cell lines with wt p53, but not in the cell lines with del or mt p53. TIMP-2 expression did not increase in U87MG cells. MMP-2 activity decreased in p53 knock-downed U87MG cells but increased in the control group. Furthermore, radiation enhanced MMP-2 activity and increased tumor margin invasiveness in vivo. Tumor cells invaded by radiation overexpressed MMP-2 and p53 and revealed high gelatinolytic activity compared with those of non-radiated tumor cells. Radiation-induced upregulation of p53 modulated MMP-2 activity, and the imbalance between MMP-2 and TIMP-2 may have an important role in glioblastoma invasion by degrading the extracellular matrix. Bioluminescent “U87-Fluc”was useful for observing tumor formation without sacrifice after implanting tumor cells in the mouse brain. These findings suggest that the radiotherapy involved field for malignant glioma needs to be reconsidered, and that future trials should investigate

Synthetic nanocomposite MgH2/5 wt. % TiMn2 powders for solid-hydrogen storage tank integrated with PEM fuel cell.

Science.gov (United States)

El-Eskandarany, M Sherif; Shaban, Ehab; Aldakheel, Fahad; Alkandary, Abdullah; Behbehani, Montaha; Al-Saidi, M

2017-10-16

Storing hydrogen gas into cylinders under high pressure of 350 bar is not safe and still needs many intensive studies dedic ated for tank's manufacturing. Liquid hydrogen faces also severe practical difficulties due to its very low density, leading to larger fuel tanks three times larger than traditional gasoline tank. Moreover, converting hydrogen gas into liquid phase is not an economic process since it consumes high energy needed to cool down the gas temperature to -252.8 °C. One practical solution is storing hydrogen gas in metal lattice such as Mg powder and its nanocomposites in the form of MgH 2 . There are two major issues should be solved first. One related to MgH 2 in which its inherent poor hydrogenation/dehydrogenation kinetics and high thermal stability must be improved. Secondly, related to providing a safe tank. Here we have succeeded to prepare a new binary system of MgH 2 /5 wt. % TiMn 2 nanocomposite powder that show excellent hydrogenation/dehydrogenation behavior at relatively low temperature (250 °C) with long cycle-life-time (1400 h). Moreover, a simple hydrogen storage tank filled with our synthetic nanocomposite powders was designed and tested in electrical charging a battery of a cell phone device at 180 °C through a commercial fuel cell.

Alterations of Mg2+ After Hemorrhagic Shock.

Science.gov (United States)

Lee, Mun-Young; Yang, Dong Kwon; Kim, Shang-Jin

2017-11-01

Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg 2+ levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg 2+ as the physiologically active form. The aim of this study was to determine changes in blood Mg 2+ and tMg after hemorrhage in rats identifying mechanism and origin of the changes in blood Mg 2+ . Hemorrhagic shock produced significant increases in blood Mg 2+ , plasma tMg, Na + , K + , Cl - , anion gap, partial pressures of oxygen, glucose, and blood urea nitrogen but significant decreases in RBC tMg, blood Ca 2+ , HCO 3 - , pH, partial pressures of carbon dioxide, hematocrit, hemoglobin, total cholesterol, and plasma/RBC ATP. During hemorrhagic shock, K + , anion gap, and BUN showed significant positive correlations with changes in blood Mg 2+ level, while Ca 2+ , pH, and T-CHO correlated to Mg 2+ in a negative manner. In conclusion, hemorrhagic shock induced an increase in both blood-free Mg 2+ and tMg, resulted from Mg 2+ efflux from metabolic damaged cell with acidosis and ATP depletion.

The influence of fluid shear stress on the expression of Cbfa1 in MG-63 cells cultured under different gravitational conditions

Science.gov (United States)

Zhang, S.; Wang, B.; Cao, X. S.; Yang, Z.; Sun, X. Q.

2008-12-01

AuthorPurposeThis study was aimed to explore the effect of flow shear stress on the expression of Cbfa1 in human osteosarcoma cells and to survey its functional alteration in simulated microgravity. After culture for 48 h in two different gravitational environments, i.e. 1 G terrestrial gravitational condition and simulated microgravity condition, human osteosarcoma cells (MG-63) were treated with 0.5 or 1.5 Pa fluid shear stress (FSS) in a flow chamber for 15, 30, and 60 min, respectively. The total RNA in cells was isolated. RT-PCR analysis was made to examine the gene expression of Cbfa1. The total protein of cells was extracted and the expression of Cbfa1 protein was detected by means of Western blotting. ResultsMG-63 cells cultured in 1 G condition reacted to FSS treatment with an enhanced expression of Cbfa1. Compared with no-FSS control group, Cbfa1 mRNA expression increased significantly at 30 and 60 min with the treatment of FSS ( P cells cultured in simulated microgravity by using clinostat, the expression of Cbfa1 was significantly different between 1 G and simulated microgravity conditions at each test time ( P cultured in simulated microgravity, Cbfa1 mRNA expression increased significantly at 30 and 60 min with the treatment of FSS ( P osteosarcoma cells. And this inducible function of FSS was adversely affected by simulated microgravity.

MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility

Directory of Open Access Journals (Sweden)

Daniel Luxen

2017-02-01

Full Text Available Epigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH. Fifty-nine glioma tissue samples and seven glioma cell lines were examined for hypermethylation of the MTSS1 promotor, MTSS1 expression levels and gene dosage. GBM cell lines were treated with demethylating agents and interrogated for functional consequences of MTSS1 expression after transient transfection. Hypermethylation was significantly associated with IDH1/2 mutation. Comparative SNP analysis indicates higher incidence of loss of heterozygosity of MTSS1 in anaplastic astrocytomas and secondary glioblastomas as well as hypermethylation of the remaining allele. Reversal of promoter hypermethylation results in an increased MTSS1 expression. Cell motility was significantly inhibited by MTSS1 overexpression without influencing cell growth or apoptosis. Immunofluorescence analysis of MTSS1 in human astrocytes indicates co-localization with actin filaments. MTSS1 is down-regulated by DNA methylation in glioblastoma cell lines and is part of the G-CIMP phenotype in primary glioma tissues. Our data on normal astrocytes suggest a function of MTSS1 at focal contact structures with an impact on migratory capacity but no influence on apoptosis or cellular proliferation.

Nanocrystalline diamond: In vitro biocompatibility assessment by MG63 and human bone marrow cells cultures.

Science.gov (United States)

Amaral, M; Dias, A G; Gomes, P S; Lopes, M A; Silva, R F; Santos, J D; Fernandes, M H

2008-10-01

Nanocrystalline diamond (NCD) has a great potential for prosthetic implants coating. Nevertheless, its biocompatibility still has to be better understood. To do so, we employed several materials characterization techniques (SEM, AFM, micro-Raman spectroscopy) and cell culture assays using MG63 osteoblast-like and human bone marrow cells. Biochemical routines (MTT assays, Lowry's method, ALP activity) supported by SEM and confocal microscopy characterization were carried out. We used silicon nitride (Si3N4) substrates for NCD coatings based on a previous demonstration of the superior adhesion and tribological performance of these NCD coated ceramics. Results demonstrate an improved human osteoblast proliferation and the stimulation of differentiated markers, like ALP activity and matrix mineralization, compared with standard polystyrene tissue culture plates. The nanometric featuring of NCD, associated to its chemical affinity are key points for bone regeneration purposes.

Support for the initial attachment, growth and differentiation of MG-63 cells: a comparison between nano-size hydroxyapatite and micro-size hydroxyapatite in composites

Directory of Open Access Journals (Sweden)

Filová E

2014-08-01

Full Text Available Elena Filová,1 Tomáš Suchý,2,3 Zbynek Sucharda,2 Monika Šupová,2 Margit Žaloudková,2 Karel Balík,2 Vera Lisá,1 Miroslav Šlouf,4 Lucie Bacáková11Department of Biomaterials and Tissue Engineering, Institute of Physiology, 2Department of Composite and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, 3Laboratory of Biomechanics, Department of Mechanics, Biomechanics and Mechatronics, Faculty of Mechanical Engineering, CTU in Prague, 4Department of Morphology and Rheology of Polymer Materials, Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech RepublicAbstract: Hydroxyapatite (HA is considered to be a bioactive material that favorably influences the adhesion, growth, and osteogenic differentiation of osteoblasts. To optimize the cell response on the hydroxyapatite composite, it is desirable to assess the optimum concentration and also the optimum particle size. The aim of our study was to prepare composite materials made of polydimethylsiloxane, polyamide, and nano-sized (N or micro-sized (M HA, with an HA content of 0%, 2%, 5%, 10%, 15%, 20%, 25% (v/v (referred to as N0–N25 or M0–M25, and to evaluate them in vitro in cultures with human osteoblast-like MG-63 cells. For clinical applications, fast osseointegration of the implant into the bone is essential. We observed the greatest initial cell adhesion on composites M10 and N5. Nano-sized HA supported cell growth, especially during the first 3 days of culture. On composites with micro-size HA (2%–15%, MG-63 cells reached the highest densities on day 7. Samples M20 and M25, however, were toxic for MG-63 cells, although these composites supported the production of osteocalcin in these cells. On N2, a higher concentration of osteopontin was found in MG-63 cells. For biomedical applications, the concentration range of 5%–15% (v/v nano-size or micro-size HA seems to be optimum

Differential effects of inhibitors and detergents on the Ca2+-ATPase and Mg2+-ATPase activities of the plasma membrane of a human oat cell carcinoma

International Nuclear Information System (INIS)

Knowles, A.F.; Lawrence, C.M.

1986-01-01

Plasma membranes of human oat cell carcinoma possess Mg 2+ - and Ca 2+ -dependent ATPase activities of similar magnitude. These activities exhibit the unusual characteristic of being inactiviated by prolonged incubation of the membrane with 1-2 mM dithiothreitol (DTT). Inactivation by DTT was prevented by lowering the incubation temperature, elevation of the membrane protein concentration, and addition of ATP. Fluorosulfonylbenzoyl adenosine (FSBA), an affinity ATP analog, also inactivates these activities. The Ca 2+ -ATPase activity appears to be more sensitive to both DTT and FSBA. The Ca 2+ -ATPase activity is more easily inactivated by Triton X-100, while the Mg 2+ -ATPase is preferentially activated by digitonin. These differential effects of inhibitors and detergents suggest that the Ca 2+ -ATPase and Mg 2+ -ATPase are separate enzymes. Incubation of oat cell carcinoma plasma membrane with [ 3 H]FSBA resulted in the labeling of several proteins. A labelled 35,000 dalton protein corresponds to the molecular weight of the oat cell carcinoma plasma membrane Ca 2+ -ATPase previously purified in this laboratory. The identity of one or more of the other labelled proteins with the Mg 2+ -ATPase has not been demonstrated, but is presently under investigation

Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

Science.gov (United States)

Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

2016-01-01

Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

In vitro study of nanostructured diopside coating on Mg alloy orthopedic implants

International Nuclear Information System (INIS)

Razavi, Mehdi; Fathi, Mohammadhossein; Savabi, Omid; Vashaee, Daryoosh; Tayebi, Lobat

2014-01-01

The high corrosion rate of Mg alloys has hindered their application in various areas, particularly for orthopedic applications. In order to decrease the corrosion rate and to improve the bioactivity, mechanical stability and cytocompatibility of the Mg alloy, nanostructured diopside (CaMgSi 2 O 6 ) has been coated on AZ91 Mg alloy using a combined micro arc oxidation (MAO) and electrophoretic deposition (EPD) method. The crystalline structure, the morphology and the composition of the samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electrochemical corrosion test, immersion test, and compression test were used to evaluate the corrosion resistance, the in vitro bioactivity and the mechanical stability of the samples, respectively. The cytocompatibility of the samples was tested by the cell viability and the cell attachment of L-929 cells. The results confirmed that the diopside coating not only slows down the corrosion rate, but also enhances the in vitro bioactivity, mechanical stability and cytocompatibility of AZ91 Mg alloy. Therefore, Mg alloy coated with nanostructured diopside offers a promising approach for biodegradable bone implants. - Highlights: • The diopside coating was applied on Mg alloy using the combined MAO and EPD methods. • The corrosion resistance of the diopside coated Mg alloy was noticeably improved. • The in vitro bioactivity of the diopside coated Mg alloy was considerably increased. • The mechanical stability of biodegradable Mg alloy was enhanced by diopside coating. • The cytocompatibility of the Mg alloy was improved employing diopside coating

In vitro study of nanostructured diopside coating on Mg alloy orthopedic implants

Energy Technology Data Exchange (ETDEWEB)

Razavi, Mehdi, E-mail: mehdi.razavi@okstate.edu [Biomaterials Research Group, Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan 81746-73461 (Iran, Islamic Republic of); School of Materials Science and Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK 74106 (United States); School of Electrical and Computer Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK 74106 (United States); Fathi, Mohammadhossein [Biomaterials Research Group, Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Dental Materials Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Savabi, Omid [Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan 81746-73461 (Iran, Islamic Republic of); Vashaee, Daryoosh [School of Electrical and Computer Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK 74106 (United States); Tayebi, Lobat, E-mail: lobat.tayebi@okstate.edu [School of Materials Science and Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK 74106 (United States); School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States)

2014-08-01

The high corrosion rate of Mg alloys has hindered their application in various areas, particularly for orthopedic applications. In order to decrease the corrosion rate and to improve the bioactivity, mechanical stability and cytocompatibility of the Mg alloy, nanostructured diopside (CaMgSi{sub 2}O{sub 6}) has been coated on AZ91 Mg alloy using a combined micro arc oxidation (MAO) and electrophoretic deposition (EPD) method. The crystalline structure, the morphology and the composition of the samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electrochemical corrosion test, immersion test, and compression test were used to evaluate the corrosion resistance, the in vitro bioactivity and the mechanical stability of the samples, respectively. The cytocompatibility of the samples was tested by the cell viability and the cell attachment of L-929 cells. The results confirmed that the diopside coating not only slows down the corrosion rate, but also enhances the in vitro bioactivity, mechanical stability and cytocompatibility of AZ91 Mg alloy. Therefore, Mg alloy coated with nanostructured diopside offers a promising approach for biodegradable bone implants. - Highlights: • The diopside coating was applied on Mg alloy using the combined MAO and EPD methods. • The corrosion resistance of the diopside coated Mg alloy was noticeably improved. • The in vitro bioactivity of the diopside coated Mg alloy was considerably increased. • The mechanical stability of biodegradable Mg alloy was enhanced by diopside coating. • The cytocompatibility of the Mg alloy was improved employing diopside coating.

Characterization of TEM1/endosialin in human and murine brain tumors

International Nuclear Information System (INIS)

Carson-Walter, Eleanor B; Walter, Kevin A; Winans, Bethany N; Whiteman, Melissa C; Liu, Yang; Jarvela, Sally; Haapasalo, Hannu; Tyler, Betty M; Huso, David L; Johnson, Mahlon D

2009-01-01

TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models. In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice. TEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, αSMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts. TEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1

Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH)

Energy Technology Data Exchange (ETDEWEB)

Mueller, K. [Leipzig Univ. (Germany). Dept. of Radiotherapy and Radiation Oncology; Gnekow, A.; Falkenstein, F. [General Hospital of Augsburg (Germany). Hospital for Children and Adolescents] [and others

2013-08-15

Purpose: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. Patients and methods: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. Results: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 {+-} 5 % after EFRT and 65 {+-} 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. Conclusion: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative. (orig.)

Impact of silk fibroin-based scaffold structures on human osteoblast MG63 cell attachment and proliferation

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Varkey A

2015-10-01

Full Text Available Aneesia Varkey,1,2 Elakkiya Venugopal,2 Ponjanani Sugumaran,2 Gopinathan Janarthanan,1 Mamatha M Pillai,2 Selvakumar Rajendran,2 Amitava Bhattacharyya1 1Advanced Textile and Polymer Research Laboratory, 2Tissue Engineering Laboratory, PSG Institute of Advanced Studies, Coimbatore, Tamil Nadu, India Abstract: The present study was carried out to investigate the impact of various types of silk fibroin (SF scaffolds on human osteoblast-like cell (MG63 attachment and proliferation. SF was isolated from Bombyx mori silk worm cocoons after degumming. Protein concentration in the degummed SF solution was estimated using Bradford method. Aqueous SF solution was used to fabricate three different types of scaffolds, viz, electrospun nanofiber mat, sponge, and porous film. The structures of the prepared scaffolds were characterized using optical micro­scopy and field emission scanning electron microscopy. The changes in the secondary structure of the proteins and the thermal behavior of the scaffolds were determined by Fourier transform infrared spectroscopy and thermo-gravimetric analysis, respectively. The biodegradation rate of scaffolds was determined by incubating the scaffolds in simulated body fluid for 4 weeks. MG63 cells were seeded on the scaffolds and their attachment and proliferation onto the scaffolds were studied. The MTT assay was carried out to deduce the toxicity of the developed scaffolds. All the scaffolds were found to be biocompatible. The amount of collagen produced by the osteoblast-like cells growing on different scaffolds was estimated. Keywords: silk fibroin scaffold, electrospun nanofiber, porous film, sponge, osteoblast

Distribution of phospholipase C isozymes in various rat tissues and cultured cells

International Nuclear Information System (INIS)

Suh, P.G.; Ryu, S.H.; Choi, W.C.; Lee, K.Y.; Rhee, S.G.

1987-01-01

Monoclonal antibodies prepared against PLC-I or PLC-II enzyme did not cross-react with the other. Using a pair of antibodies which recognizes 2 different antigenic sites on the same molecule, radioimmunoassays were developed for the quantitation of PLC-I and PLC-II in homogenates of various tissues and cultured cells, prepared by homogenization in a 2 M KCl buffer. The contents of PLC enzymes were measured in 19 rat tissues, in human platelets and in 17 cultured cells. Results indicate that the concentration of PLC-I and PLC-II is very high in brain, PLC-I is localized mainly in brain and partly in seminal vesicles, PLC-II is found in most tissues and cells. PLC-I is highly localized even in brain: 5 different neuroblastoma did not contain PLC-I while 2 glioma and 1 astrocytoma contained significant amounts

Dipeptidyl peptidase IV in two human glioma cell lines

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A Sedo

2009-12-01

Full Text Available There is growing evidence that dipeptidyl peptidase IV [DPP-IV, EC 3.4.14.5] takes part in the metabolism of biologically active peptides participating in the regulation of growth and transformation of glial cells. However, the knowledge on the DPP-IV expression in human glial and glioma cells is still very limited. In this study, using histochemical and biochemical techniques, the DPP-IV activity was demonstrated in two commercially available human glioma cell lines of different transformation degree, as represented by U373 astrocytoma (Grade III and U87 glioblastoma multiforme (Grade IV lines. Higher total activity of the enzyme, as well as its preferential localisation in the plasma membrane, was observed in U87 cells. Compared to U373 population, U87 cells were morphologically more pleiomorphic, they were cycling at lower rate and expressing less Glial Fibrillary Acidic Protein. The data revealed positive correlation between the degree of transformation of cells and activity of DPP-IV. Great difference in expression of this enzyme, together with the phenotypic differences of cells, makes these lines a suitable standard model for further 57 studies of function of this enzyme in human glioma cells.

Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

Science.gov (United States)

Wu, Yuanhao; He, Guanping; Zhang, Yu; Liu, Yang; Li, Mei; Wang, Xiaolan; Li, Nan; Li, Kang; Zheng, Guan; Zheng, Yufeng; Yin, Qingshui

2016-02-01

In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.

Performance of intermediate temperature (600-800{sup o}C) solid oxide fuel cell based on Sr and Mg doped lanthanum-gallate electrolyte

Energy Technology Data Exchange (ETDEWEB)

Gong, Wenquan; Gopalan, Srikanth; Pal, Uday B. [Department of Manufacturing Engineering, Boston University, MA 02215 (United States)

2006-09-29

The solid electrolyte chosen for this investigation was La{sub 0.9}Sr{sub 0.1}Ga{sub 0.8}Mg{sub 0.2}O{sub 3} (LSGM). To select appropriate electrode materials from a group of possible candidate materials, AC complex impedance spectroscopy studies were conducted between 600 and 800{sup o}C on symmetrical cells that employed the LSGM electrolyte. Based on the results of the investigation, LSGM electrolyte supported solid oxide fuel cells (SOFCs) were fabricated with La{sub 0.6}Sr{sub 0.4}Co{sub 0.8}Fe{sub 0.2}O{sub 3}-La{sub 0.9}Sr{sub 0.1}Ga{sub 0.8}Mg{sub 0.2}O{sub 3} (LSCF-LSGM) composite cathode and nickel-Ce{sub 0.6}La{sub 0.4}O{sub 2} (Ni-LDC) composite anode having a barrier layer of Ce{sub 0.6}La{sub 0.4}O{sub 2} (LDC) between the LSGM electrolyte and the Ni-LDC anode. Electrical performances of these cells were determined and the electrode polarization behavior as a function of cell current was modeled between 600 and 800{sup o}C. (author)

Common pediatric cerebellar tumors: correlation between cell densities and apparent diffusion coefficient metrics.

Science.gov (United States)

Koral, Korgün; Mathis, Derek; Gimi, Barjor; Gargan, Lynn; Weprin, Bradley; Bowers, Daniel C; Margraf, Linda

2013-08-01

To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are useful in the preoperative diagnosis of common pediatric cerebellar tumors and this utility is generally attributed to differences in cellularity of tumors

Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

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Tahmasebi Mirgani M

2014-01-01

Full Text Available Maryam Tahmasebi Mirgani,1 Benedetta Isacchi,2 Majid Sadeghizadeh,1,* Fabio Marra,3 Anna Rita Bilia,2,* Seyed Javad Mowla,1 Farhood Najafi,4 Esmael Babaei51Department of Genetics, Tarbiat Modares University, Tehran, Iran; 2Department of Chemistry, University of Florence, Sesto Fiorentino, Italy; 3Department of Experimental and Clinical Medicine, University of Florence, Italy; 4Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran; 5Department of Biology, University of Tabriz, Tabriz, Iran*These authors contributed equally to this workAbstract: Glioblastoma is an invasive tumor of the central nervous system. Tumor recurrence resulting from ineffective current treatments, mainly due to the blood–brain barrier, highlights the need for innovative therapeutic alternatives. The recent availability of nanotechnology represents a novel targeted strategy in cancer therapy. Natural products have received considerable attention for cancer therapy because of general lower side effects. Curcumin is a new candidate for anticancer treatment, but its low bioavailability and water solubility represent the main disadvantages of its use. Here, curcumin was efficiently encapsulated in a nontoxic nanocarrier, termed dendrosome, to overcome these problems. Dendrosomal curcumin was prepared as 142 nm spherical structures with constant physical and chemical stability. The inhibitory role of dendrosomal curcumin on the proliferation of U87MG cells, a cellular model of glioblastoma, was evaluated by considering master genes of pluripotency and regulatory miRNA (microribonucleic acid. Methylthiazol tetrazolium assay and flow cytometry were used to detect the antiproliferative effects of dendrosomal curcumin. Annexin-V-FLUOS and caspase assay were used to quantify apoptosis. Real-time polymerase chain reaction was used to analyze the expression of OCT4 (octamer binding protein 4 gene variants (OCT4A, OCT4B, and OCT4B1, SOX-2 (SRY

Theoretical Limiting Potentials in Mg/O2 Batteries

DEFF Research Database (Denmark)

Smith, Jeffrey G.; Naruse, Junichi; Hiramatsu, Hidehiko

2016-01-01

A rechargeable battery based on a multivalent Mg/O2 couple is an attractive chemistry due to its high theoretical energy density and potential for low cost. Nevertheless, metal-air batteries based on alkaline earth anodes have received limited attention and generally exhibit modest performance....... In addition, many fundamental aspects of this system remain poorly understood, such as the reaction mechanisms associated with discharge and charging. The present study aims to close this knowledge gap and thereby accelerate the development of Mg/O2 batteries by employing first-principles calculations...... by the presence of large thermodynamic overvoltages. In contrast, MgO2-based cells are predicted to be much more efficient: superoxide-terminated facets on MgO2 crystallites enable low overvoltages and round-trip efficiencies approaching 90%. These data suggest that the performance of Mg/O2 batteries can...

Nanostructured Layered Cathode for Rechargeable Mg-Ion Batteries.

Science.gov (United States)

Tepavcevic, Sanja; Liu, Yuzi; Zhou, Dehua; Lai, Barry; Maser, Jorg; Zuo, Xiaobing; Chan, Henry; Král, Petr; Johnson, Christopher S; Stamenkovic, Vojislav; Markovic, Nenad M; Rajh, Tijana

2015-08-25

Nanostructured bilayered V2O5 was electrochemically deposited within a carbon nanofoam conductive support. As-prepared electrochemically synthesized bilayered V2O5 incorporates structural water and hydroxyl groups, which effectively stabilizes the interlayers and provides coordinative preference to the Mg(2+) cation in reversible cycling. This open-framework electrode shows reversible intercalation/deintercalation of Mg(2+) ions in common electrolytes such as acetonitrile. Using a scanning transmission electron microscope we demonstrate that Mg(2+) ions can be effectively intercalated into the interlayer spacing of nanostructured V2O5, enabling electrochemical magnesiation against a Mg anode with a specific capacity of 240 mAh/g. We employ HRTEM and X-ray fluorescence (XRF) imaging to understand the role of environment in the intercalation processes. A rebuilt full cell was tested by employing a high-energy ball-milled Sn alloy anode in acetonitrile with Mg(ClO4)2 salt. XRF microscopy reveals effective insertion of Mg ions throughout the V2O5 structure during discharge and removal of Mg ions during electrode charging, in agreement with the electrode capacity. We show using XANES and XRF microscopy that reversible Mg intercalation is limited by the anode capacity.

Proteome of Salmonella enterica serotype Tyhimurium Grown in Low Mg2+/pH Medium

Energy Technology Data Exchange (ETDEWEB)

Shi, Liang; Ansong, Charles; Smallwood, Heather S.; Rommereim, Leah M.; McDermott, Jason E.; Brewer, Heather M.; Norbeck, Angela D.; Taylor, Ronald C.; Gustin, Jean K.; Heffron, Fred; Smith, Richard D.; Adkins, Joshua N.

2009-09-04

To determine the impact of a low Mg2+/pH defined growth medium (MgM) on the proteome of Salmonella enterica serotype Typhimurium, we cultured S. Typhimurium cells in the medium under two different conditions termed MgM Shock and MgM Dilution and then comparatively analyzed the bacterial cells harvested from these conditions by a global proteomic approach. Proteomic results showed that MgM Shock and MgM Dilution differentially affected the S. Typhimurium proteome. MgM Shock induced a group of proteins whose induction usually occurred at low O2 level, while MgM Dilution induced those related to the type III secretion system (T3SS) of Salmonella Pathogenicity Island 2 (SPI2) and those involved in thiamine or biotin biosynthesis. The metabolic state of the S. Typhimurium cells grown under MgM Shock condition also differed significantly from that under MgM Dilution condition. Western blot analysis not only confirmed the proteomic results, but also showed that the abundances of SPI2-T3SS proteins SsaQ and SseE and biotin biosynthesis proteins BioB and BioD increased after S. Typhimurium infection of RAW 264.7 macrophages. Deletion of the gene encoding BioB reduced the bacterial ability to replicate inside the macrophages, suggesting a biotin-limited environment encountered by S. Typhimurium within RAW 264.7 macrophages.

The Proteasome Inhibitor MG-132 Protects Hypoxic SiHa Cervical Carcinoma Cells after Cyclic Hypoxia/Reoxygenation from Ionizing Radiation

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Frank Pajonk

2006-12-01

Full Text Available INTRODUCTION: Transient hypoxia and subsequent reoxygenation are common phenomena in solid tumors that greatly influence the outcome of radiation therapy. This study was designed to determine how varying cycles of hypoxia/reoxygenation affect the response of cervical carcinoma cells irradiated under oxic and hypoxic conditions and whether this could be modulated by proteasome inhibition. MATERIALS AND METHODS: Plateau-phase SiHa cervical carcinoma cells in culture were exposed to varying numbers of 30-minute cycles of hypoxia/reoxygenation directly before irradiation under oxic or hypoxic conditions. 26S Proteasome activity was blocked by addition of MG-132. Clonogenic survival was measured by a colonyforming assay. RESULTS: Under oxic conditions, repeated cycles of hypoxia/reoxygenation decreased the clonogenic survival of SiHa cells. This effect was even more pronounced after the inhibition of 26S proteasome complex. In contrast, under hypoxic conditions, SiHa cells were radioresistant, as expected, but this was increased by proteasome inhibition. CONCLUSIONS: Proteasome inhibition radiosensitizes oxygenated tumor cells but may also protect tumor cells from ionizing radiation under certain hypoxic conditions.

Synthesis and Cell Seeding Assessment of Novel Biphasic Nano Powder in the CaO–MgO–SiO2 System for Bone Implant Application

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Kazem Marzban

2017-02-01

Full Text Available Objective(s: CaO–MgO–SiO2 system bioceramics possess good characteristics for hard tissue engineering applications. The aim of the study was to synthesize the nano powder by using a sol-gel method and evaluate of bioactivity in the cells culture. Methods: To characterize of powder X-ray diffraction (XRD, transmission electron microscopy (TEM and to evaluate the bioactivity sample cell seeding and methylthiazol tetrazolium (MTT assay were performed. Results: X-ray diffraction (XRD analysis showed that the biphasic powder was obtained at 1300°C for 2 h by using a sol-gel method. Transmission electron microscopy (TEM image showed that powder particle size was about 45 nm. Besides, cell culture results indicated that the percentage of viability values was increased by the extension of period. Conclusions: found that the sample is cytocompatible and has cell proliferation potential in culture medium. The present study demonstrates that, the biphasic CaO–MgO–SiO2 system can be used to achieve novel bioactive materials for bone implant application.

Structural characterization of Mg{sub 3}MnH{sub {approx}}{sub 6}--a new high-pressure phase synthesized in a multi-anvil cell at 6 GPa

Energy Technology Data Exchange (ETDEWEB)

Blomqvist, Helen; Roennebro, Ewa; Kyoi, Daisuke; Sakai, Tetsuo; Noreus, Dag

2003-08-25

With modern X-ray diffraction refinement methods it was shown to be possible to identify a new Mg{sub 3}MnH{sub {approx}}{sub 6} phase from a minute sample volume in spite of poor crystallinity and coexisting impurity phases. The new hydride was synthesized at 6 GPa in a high-pressure multi-anvil cell at 873 K. A monoclinic unit cell was found with a=8.827(2), b=4.657(2), c=4.676(2) A and {beta}=105.74(2) deg., space group P2{sub 1}/m (no. 11), Z=2, V=184.99 A{sup 3}. Manganese is surrounded by a distorted cube of magnesium with average Mn-Mg distances of 2.78(2) A. The cubes share edges in the b and c directions of the unit cell but are separated by a distance of {approx}3.6 A along a, forming a layered structure. The hydrogen positions were not possible to determine, as only a small sample amount could be prepared. If the metal atom structure of the title compound is compared to the already known Mg{sub 3}MnH{sub 7} it can be concluded that Mg{sub 3}MnH{sub {approx}}{sub 6} also consists of manganese hydrido complexes counterbalanced by magnesium ions, but with a different alignment of the magnesium cubes.

Phosphorylated intermediate of (Ca2+ + K+)-stimulated Mg2+-dependent transport ATPase in endoplasmic reticulum from rat pancreatic acinar cells

International Nuclear Information System (INIS)

Imamura, K.; Schulz, I.

1985-01-01

Formation and decomposition of the phosphorylated intermediate of endoplasmic reticulum (Ca 2+ + Mg 2+ )-ATPase from pancreatic acinar cells have been studied using lithium dodecyl sulfate- and tetradecyltrimethylammonium bromide-polyacrylamide gel electrophoresis. Incorporation of 32 P from [gamma- 32 P]ATP is Ca 2+ -dependent (approximate Km for free [Ca 2+ ] = 2-3 x 10(-8) mol/liter). Formation of the 100-kDa phosphoprotein is rapid, reaching maximal 32 P incorporation within 1 s at room temperature. At 4 degrees C, phosphorylation is slower and dephosphorylation is drastically decreased. For dephosphorylation, Mg 2+ and monovalent cations such as K + or Na + are necessary. Vanadate inhibits both 32 P incorporation and 32 P liberation dose dependently (Km = 3 x 10(-6) mol/liter), whereas mitochondrial inhibitors and ouabain have no effect. The phosphoprotein is stable at pH 2 and destabilizes with increasing pH being completely decomposed at pH 9. Reduction of 32 P incorporation in the presence of high concentrations of cold ATP and hydroxylamine suggests formation of acylphosphate present in the ATPase intermediate. The characteristics of Ca 2+ , cation, and pH dependencies of the ATPase activity are similar to those previously described for MgATP-dependent Ca 2+ transport into rough endoplasmic reticulum from pancreatic acinar cells. The data suggest that the 100-kDa phosphoprotein as described in this study is the intermediate of this Ca2+ transport ATPase

Difference in {sup 201}TlCl accumulation mechanism in brain tumors. A comparison of their Na{sup +}-K{sup +} ATPase activities

Energy Technology Data Exchange (ETDEWEB)

Sugo, Nobuo; Kuroki, Takao; Nemoto, Masaaki; Mito, Toshiaki; Seiki, Yoshikatsu; Shibata, Iekado [Toho Univ., Tokyo (Japan). Omori Hospital

2000-07-01

The accumulation levels of {sup 201}TlCl and Na{sup +} -K{sup +} ATPase activity in tumor tissue were compared among glioblastoma, benign glioma and meningioma to study the difference in the mechanism of {sup 201}TlCl accumulation. The subjects were 19 cases comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1 pilocytic astrocytoma and 9 meningioma. Preoperative {sup 201}TlCl SPECT was performed in all the cases, and Thallium Index (TL index) was calculated by a ratio of {sup 201}TlCl in the tumor area and the contralateral area. In addition, cell membrane was extracted from the tumor tissue collected intraoperatively to determine Na{sup +} -K{sup +} ATPase activity. No statistically significant difference in TL index was noted between the glioblastoma group (6.97{+-}2.67) and the meningioma group (5.87{+-}1.99). This fact showed that there was no difference in the accumulation level of {sup 201}TlCl between the two groups. On the other hand, the glioblastoma group indicated a higher value of Na{sup +} -K{sup +} ATPase activity (49.13{+-}43.76 {mu}mole/hour/mg protein) than the meningioma group (7.73{+-}13.84 {mu}mol/hour/mg protein) (p<0.05, t test). These results suggested the involvement of Na{sup +} -K{sup +} ATPase activity in {sup 201}TlCl accumulation in glioblastoma and the influences of other accumulation mechanism than Na{sup +} -K{sup +} ATPase activity such as the volume of intratumoral vascular bed in meningioma. (author)

Sequel of MgO nanoparticles in PLACL nanofibers for anti-cancer therapy in synergy with curcumin/β-cyclodextrin

International Nuclear Information System (INIS)

Sudakaran, Shruthi Vathaluru; Venugopal, Jayarama Reddy; Vijayakumar, Gnaneshwar Puvala; Abisegapriyan, Sivasubramanian; Grace, Andrews Nirmala; Ramakrishna, Seeram

2017-01-01

Pharmaceutical industries spend more money in developing new and efficient methods for delivering successful drugs for anticancer therapy. Electrospun nanofibers and nanoparticles loaded with drugs have versatile biomedical applications ranging from wound healing to anticancer therapy. We aimed to attempt for fabricating elastomeric poly (L-lactic acid-co-ε-caprolactone) (PLACL) with Aloe Vera (AV), magnesium oxide (MgO) nanoparticles, curcumin (CUR) and β-cyclodextrin (β-CD) composite nanofibers to control the growth of MCF-7 cells for breast cancer therapy. The study focused on the interaction of MgO nanoparticle with CUR and β-CD inhibiting the proliferation of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. FESEM micrographs of fabricated electrospun PLACL, PLACL/AV, PLACL/AV/MgO, PLACL/AV/MgO/CUR and PLACL/AV/MgO/β-CD nanofibrous scaffolds achieved bead free, random and uniform nanofibers with fiber diameter in the range of 786 ± 286, 507 ± 171, 334 ± 95, 360 ± 94 and 326 ± 80 nm respectively. Proliferation of MCF-7 cells was decreased by 65.92% in PLACL/AV/MgO/CUR with respect to PLACL/AV/MgO nanofibrous scaffolds on day 9. The obtained results proved that 1% CUR interacting with MgO nanoparticles showed higher inhibition of MCF-7 cells among all other nanofibrous scaffolds thus serving as a promising biocomposite material system for the breast cancer therapy. - Highlights: • Biocomposite nanofibrous scaffolds fabricated bead free, uniform and possess rough fiber surface • Aloe Vera and MgO nanoparticles initiates cell adhesion and proliferation • CUR (1%)/MgO nanoparticle showed higher level of cell inhibition of MCF-7 cells compared to all other nanofibrous scaffolds • PLACL/AV/MgO/CUR nanofibrous scaffolds proved to be a potential material system for cancer therapy

Sequel of MgO nanoparticles in PLACL nanofibers for anti-cancer therapy in synergy with curcumin/β-cyclodextrin

Energy Technology Data Exchange (ETDEWEB)

Sudakaran, Shruthi Vathaluru [Centre for Nanofibers & Nanotechnology, Mechanical Engineering, Faculty of Engineering, National University of Singapore (Singapore); The Centre for Nanotechnology Research, VIT University, Vellore (India); Venugopal, Jayarama Reddy, E-mail: mpejrv@nus.edu.sg [Centre for Nanofibers & Nanotechnology, Mechanical Engineering, Faculty of Engineering, National University of Singapore (Singapore); Vijayakumar, Gnaneshwar Puvala [Centre for Nanofibers & Nanotechnology, Mechanical Engineering, Faculty of Engineering, National University of Singapore (Singapore); Abisegapriyan, Sivasubramanian [Centre for Nanofibers & Nanotechnology, Mechanical Engineering, Faculty of Engineering, National University of Singapore (Singapore); The Centre for Nanotechnology Research, VIT University, Vellore (India); Grace, Andrews Nirmala [The Centre for Nanotechnology Research, VIT University, Vellore (India); Ramakrishna, Seeram [Centre for Nanofibers & Nanotechnology, Mechanical Engineering, Faculty of Engineering, National University of Singapore (Singapore)

2017-02-01

Pharmaceutical industries spend more money in developing new and efficient methods for delivering successful drugs for anticancer therapy. Electrospun nanofibers and nanoparticles loaded with drugs have versatile biomedical applications ranging from wound healing to anticancer therapy. We aimed to attempt for fabricating elastomeric poly (L-lactic acid-co-ε-caprolactone) (PLACL) with Aloe Vera (AV), magnesium oxide (MgO) nanoparticles, curcumin (CUR) and β-cyclodextrin (β-CD) composite nanofibers to control the growth of MCF-7 cells for breast cancer therapy. The study focused on the interaction of MgO nanoparticle with CUR and β-CD inhibiting the proliferation of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. FESEM micrographs of fabricated electrospun PLACL, PLACL/AV, PLACL/AV/MgO, PLACL/AV/MgO/CUR and PLACL/AV/MgO/β-CD nanofibrous scaffolds achieved bead free, random and uniform nanofibers with fiber diameter in the range of 786 ± 286, 507 ± 171, 334 ± 95, 360 ± 94 and 326 ± 80 nm respectively. Proliferation of MCF-7 cells was decreased by 65.92% in PLACL/AV/MgO/CUR with respect to PLACL/AV/MgO nanofibrous scaffolds on day 9. The obtained results proved that 1% CUR interacting with MgO nanoparticles showed higher inhibition of MCF-7 cells among all other nanofibrous scaffolds thus serving as a promising biocomposite material system for the breast cancer therapy. - Highlights: • Biocomposite nanofibrous scaffolds fabricated bead free, uniform and possess rough fiber surface • Aloe Vera and MgO nanoparticles initiates cell adhesion and proliferation • CUR (1%)/MgO nanoparticle showed higher level of cell inhibition of MCF-7 cells compared to all other nanofibrous scaffolds • PLACL/AV/MgO/CUR nanofibrous scaffolds proved to be a potential material system for cancer therapy.

Investigation of Mg(OH)2 nanoparticles as an antibacterial agent

International Nuclear Information System (INIS)

Dong Chunxu; Cairney, John; Sun Qunhui; Maddan, Orville Lee; He Gaohong; Deng Yulin

2010-01-01

Our experimental results of using Mg(OH) 2 nanoparticles as an antibacterial agent are reported in this study. The antibacterial behavior of Mg(OH) 2 nanoparticles in liquid culture and in paper sheets was investigated. The colony forming units (CFU) counting and the headspace gas chromatography (HS-GC) measurement were used to determine the cell viability. Results indicate that Mg(OH) 2 nanoparticles are effective antibacterial agent against Escherichia coli (E. coli) and Burkholderia phytofirmans, and the OH - and Mg 2+ ions in Mg(OH) 2 water suspension were found not to be the reason for killing the bacteria. Mg(OH) 2 nanoparticles could be added directly to wood pulp to make paper sheets, whose antibacterial efficiency increased with the increase of the nanoparticle amount. The possible mechanism of antibacterial effect of Mg(OH) 2 nanoparticles is discussed.

Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors.

Science.gov (United States)

Sameshima, Tetsuro; Nabeshima, Kazuki; Toole, Bryan P; Inoue, Teruhiko; Yokogami, Kiyotaka; Nakano, Shinichi; Ohi, Takekazu; Wakisaka, Shinichiro

2003-06-01

In a previous study, we demonstrated that the expression levels in tumor cells of emmprin (CD147) correlated with the grade of astrocytic tumors. Also, we found that emmprin was expressed in vascular endothelial cells of the non-neoplastic brain and hypothesized that emmprin expression could be associated with normal blood-brain-barrier (BBB) function of vascular endothelial cells. In this study, this possibility was examined in non-neoplastic brain, glioma and metastatic carcinoma tissues by comparing emmprin immunohistochemistry with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement of magnetic resonance imaging (MRI), which is a clinical indicator of the BBB function. This study included 10 cases of non-neoplastic brain tissues, 7 of metastatic carcinoma, 7 of diffuse astrocytoma, 4 of anaplastic astrocytoma and 13 of glioblastoma multiforme. In all the cases, MRI with administration of Gd-DTPA was performed. The lesions were resected using the microdissection method with the help of ultrasonography and a neuronavigator. The tissues from Gd-DTPA-enhanced or non-enhanced areas were processed into frozen sections and subjected to immunohistochemistry with anti-emmprin antibody. The expression of emmprin in brain vascular endothelial cells inversely correlated with Gd-DTPA-enhancement of MRI: emmprin was positive in tissues not enhanced by Gd-DTPA and was negative in DTPA-enhanced tissues. Since BBB function presumably remains unimpaired in regions in which MR images are not Gd-DTPA-enhanced, emmprin expression appears to be associated with unimpaired BBB function. This is the first report to demonstrate a possible correlation between emmprin expression and BBB function in humans.

Biphasic Response to Luteolin in MG-63 Osteoblast-Like Cells under High Glucose‑Induced Oxidative Stress

Directory of Open Access Journals (Sweden)

Naser Abbasi

2016-03-01

Full Text Available Background: Clinical evidence indicates the diabetes-induced impairment of osteogenesis caused by a decrease in osteoblast activity. Flavonoids can increase the differentiation and mineralization of osteoblasts in a high-glucose state. However, some flavonoids such as luteolin may have the potential to induce cytotoxicity in osteoblast-like cells. This study was performed to investigate whether a cytoprotective concentration range of luteolin could be separated from a cytotoxic concentration range in human MG-63 osteoblast-like cells in high-glucose condition. Methods: Cells were cultured in a normal- or high-glucose medium. Cell viability was determined with the MTT assay. The formation of intracellular reactive oxygen species (ROS was measured using probe 2’,7’ -dichlorofluorescein diacetate, and osteogenic differentiation was evaluated with an alkaline phosphatase bioassay. Results: ROS generation, reduction in alkaline phosphatase activity, and cell death induced by high glucose were inhibited by lower concentrations of luteolin (EC50, 1.29±0.23 µM. Oxidative stress mediated by high glucose was also overcome by N-acetyl-L-cysteine. At high concentrations, luteolin caused osteoblast cell death in normal- and high-glucose states (IC50, 34±2.33 and 27±2.42 µM, respectively, as represented by increased ROS and decreased alkaline phosphatase activity. Conclusion: Our results indicated that the cytoprotective action of luteolin in glucotoxic condition was manifested in much lower concentrations, by a factor of approximately 26 and 20, than was its cytotoxic activity, which occurred under normal or glucotoxic condition, respectively.

Sorption of selenium on Mg-Al and Mg-Al-Eu layered double hydroxides

International Nuclear Information System (INIS)

Curtius, H.; Paparigas, Z.; Kaiser, G.

2008-01-01

Salt domes represent deep geological formations which are under consideration as final repositories for irradiated research reactor fuel elements. For long-term safety aspects the mobilisation of the radionuclides due to a water ingress is intensively investigated. At the Institute of Energy Research (IEF-6), leaching experiments were performed in a hot cell facility with UAl x -Al and U 3 Si 2 -Al dispersed research reactor fuel elements in repository-relevant MgCl 2 -rich salt brines under anaerobic conditions. The fuel plates corroded completely within one year and a Mg-Al-layered double hydroxide (LDH) with chloride as interlayer anion was identified as one crystalline phase component of the corrosion products (secondary phases). This Mg-Al-LDH was synthesized, characterized, and the ability to retard europium by an incorporation process was investigated. Europium, as a representative for lanthanides, was identified to be one of the radionuclides which were found in the corrosion products. We could show that europium was incorporated in the lattice structure. LDHs have high anion exchange capacities that enhance their potential to remove anionic contaminants from aqueous systems. In this work the sorption behaviour of selenium in the chemical form as selenite (SeO 3 2- ) on Mg-Al-LDH and on Mg-Al-Eu-LDH was investigated. Especially the influence of the larger europium-III ion was of interest. It represents in the Mg-Al-Eu-LDH about 10% of the molar aluminium amount. The sorption has been experimentally studied in a wide range of pH, ionic strength, radionuclide and sorbent concentration. Both LDHs with chloride as interlayer anion were synthesized by a coprecipitation method under controlled conditions, and their main physico-chemical properties were analyzed prior to the sorption experiments. The sorption kinetics of selenite on the LDHs in water and in MgCl 2 -rich brine were rapid using a LDH concentration of 10 g/L. Equilibrium, indicated by stable p

Glioblastoma: Molecular Pathways, Stem Cells and Therapeutic Targets

International Nuclear Information System (INIS)

Jhanwar-Uniyal, Meena; Labagnara, Michael; Friedman, Marissa; Kwasnicki, Amanda; Murali, Raj

2015-01-01

Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM

Glioblastoma: Molecular Pathways, Stem Cells and Therapeutic Targets

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Jhanwar-Uniyal, Meena, E-mail: meena_jhanwar@nymc.edu; Labagnara, Michael; Friedman, Marissa; Kwasnicki, Amanda; Murali, Raj [Department of Neurosurgery, New York Medical College, Valhalla, NY 10595 (United States)

2015-03-25

Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM.

MgB sub 2 superconductor: a review

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Mollah, S; Chaudhuri, B K

2003-01-01

Synthesis, structure and properties of the most intensively studied newly discovered intermetallic binary superconductor MgB sub 2 have been reviewed up to October, 2002. It has a hexagonal unit cell with cell parameters a approx 3.1432 A and c approx 3.5193 A. MgB sub 2 bulk samples synthesized under high pressure (approx 3.5 GPa) and high temperature (approx 1000 degC) has density approx 2.63 g/cm sup 3. The normal state carriers of MgB sub 2 are holes which have been established from the positive thermoelectric power and Hall coefficient measurements. The external pressure decreases the critical temperature (T sub c) with dT sub c /dP in the range of -1 to -2 K/GPa. The T sub c decreases rapidly by the doping of Mn, Li, Co, C, Al, Ni and Fe but increases slightly by Zn doping. However, no significant change of T sub c is observed by the doping of Si and Be. It is further noticed that the anisotropic ratio gamma(= H sub c sub 2 sup a sup b /H sub c sub 2 sup c) approx 1-5 with lower critical field (H sub c ...

Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages

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Perno Carlo

2002-09-01

Full Text Available Abstract Background Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occuring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M. Results Flow cytometric analysis (FACS of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite and by abnormal formation of malondialdehyde (MDA. Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining. Conclusions Taken together, our results suggest that inibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders.

Long-term results of postoperative radiotherapy in adult patients with incompletely excised infratentorial low grade astrocytoma

International Nuclear Information System (INIS)

Pluta, E.; Glinski, B.; Szpytma, T.; Nowak-Sadzikowska, J.

2002-01-01

lnfratentorial low grade astrocytoma (ILGA) occurs rarely in adult patients and accounts for about 3% of all intracranial tumors.The basic method of treatment for ILGA is surgery. Complete resection results in high local control rate and the role of postoperative irradiation in management of partially resected tumors is not clearly determined. The aim of this study was to evaluate the efficacy of postoperative irradiation in adult patients with incompletely excised ILGA. Between 1975 and 1995, thirty one adult patients with incompletely excised ILGA received postoperative irradiation with curative intent. All patients were treated with megavoltage gamma rays ( 60C o). The total dose ranged from 50 to 60 Gy (mean; 54 Gy) and was delivered with daily fraction of 1.8-2 Gy. The treatment volume covered the tumor being area with a margin of 1-2 cm. Tolerance to treatment has been found to be good in 30 patients (97%). The overall 15-year actuarial survival rate was 62% in the entire group. Young patients, up to twenty years of age achieved a 15-year overall actuarial survival rate of 85%, older patients - 46%. This difference was statistically significant (p =0. 0205). Conventionally fractionated postoperative radiotherapy with doses of 50 to 60 Gy may improve long term results of adult patients with ILGA after uncomplete resection. Age is a significant prognostic factor - young patients, up to twenty years of age, show best survival. (author)

Boron neutron capture therapy for children with malignant brain tumor

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Komatsu, Hisao; Kageji, Teruyoshi; Tsuji, Fumio; Matsumoto, Keizo; Kitamura, Katsuji; Hatanaka, Hiroshi; Minobe, Takashi.

1993-01-01

Among the 131 cases with brain tumors treated by boron-neutron capture therapy (BNCT), seventeen were children. Eight supratentorial tumors included five astrocytomas(grade 2-4), two primitive neuroectodermal tumors (PNET) and one rhabdomyosarcoma. Seven pontine tumors included one astrocytoma, one PNET and 5 unverified gliomas. Two cerebellar tumors (PNET and astrocytoma) were also treated. All pontine tumors showed remarkable decrease in size after BNCT. However, most of them showed regrowth of the tumors because the neutrons were insufficient due to the depth. Four cases with cerebral tumor died of remote cell dissemination, although they all responded to BNCT. One of them survived 7 years after repeated BNCTs. An 11 years old girl with a large astrocytoma in the right frontal lobe has lived more than 11 years and is now a draftswoman at a civil engineering company after graduating from a technical college. An 8 years old girl with an astrocytoma in the left occipital lobe has no recurrence of the tumor for 2 years and attends on elementary school without mental and physical problems. Two children (one year old girl and four years old boy) with cerebellar tumors have shown showed an excellent growth after BNCT and had no neurological deficits. Mental and physical development in patients treated by BNCT is usually better than that in patients treated by conventional radiotherapy. (author)

Structural and transport properties of Sn-Mg alloys

International Nuclear Information System (INIS)

Meydaneri, F.; Saatci, E.; Oezdemir, M.; Ari, M.; Durmus, S.

2010-01-01

The structural and temperature dependence transport of Sn-Mg alloys have been investigated for five different samples (Pure Sn, Sn-1.0 wt % Mg , Sn-2.0 wt % Mg , Sn-6.0 wt.% Mg and Pure Mg). Scanning Electron Microscopy (SEM), x-ray diffraction (XRD) and Energy Dispersive x-ray Analysis (EDX) measurements were carried out in order to clarify the structural properties of the samples. It has been found that, the samples have tetragonal crystal symmetry except the pure Mg which has hexagonal crystal symmetry. The cell parameters decrease slightly with addition of Mg element. The SEM micrographs of the samples show that, the samples have smooth surfaces with clear grain boundary. There is no crack, porosity or defects on the surfaces. The electrical resistivity of the samples increases almost linearly with the increasing temperature, which were measured by four-point probe technique. The thermal conductivity values are in between 0.60-1.00 W/Km, which are decrease slightly with temperature and increase with composition of Mg. The thermal conductivity values of the alloys are in between the values of the pure samples. Thermal conductivity results of the alloys have been compared with available other studies and a good agreement has been seen between the results. In addition, the temperature coefficients of electrical resistivity and thermal conductivity have been determined, which are independent with the compositions of alloying elements

Phenolic content of Sicilian virgin olive oils and their effect on MG-63 human osteoblastic cell proliferation

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García-Martínez, O.

2014-09-01

Full Text Available The aim of this study was, first, to investigate the influence of olive variety and elevation of orchards on the phenolic compound content of Sicilian virgin olive oils (VOOs and, second, to investigate the effects of VOO phenolic extracts on osteoblast cell growth using the human MG-63 osteosarcoma cell line. Olive oil phenolic content and its effect on human osteosarcoma cell proliferation varied according to the type of cultivar and the grove altitude. This variation was also observed within the same type of cultivar. This observation demonstrates that the cultivar and the grove location can significantly affect the chemical composition and bioactivity of virgin olive oil. Although this study supports the hypothesis that virgin olive oil phenolic fractions exert a beneficial effect on bone health, further studies assessing the in vivo accessibility of virgin olive oil phenolic compounds to osteoblast cells should be carried out.El objetivo del presente trabajo es investigar la influencia de la variedad y la altitud del cultivo en el contenido fenólico de aceites de oliva virgen Sicilianos. Asimismo, se ha investigado el efecto de los extractos fenólicos de los aceites en el crecimiento de osteoblastos usando la línea celular de osteosarcoma humano MG-63. El contenido fenólico y el efecto de los extractos analizados en la proliferación de la línea celular osteoblástica muestra una variabilidad consistente de acuerdo con el tipo y la altitud del cultivo. Estos datos demuestran que estas características pueden afectar significativamente la composición química y los efectos en salud del aceite de oliva virgen. Los resultados de este trabajo soportan la hipótesis de que las fracciones fenólicas de los aceites de oliva vírgenes ejercen un efecto beneficioso en la salud ósea. Asimismo, se deben realizar más estudios que establezcan la accesibilidad in vivo de los compuestos fenólicos del aceite de oliva virgen a las células osteoblásticas.

The effect of the MgO buffer layer thickness on magnetic anisotropy in MgO/Fe/Cr/MgO buffer/MgO(001)

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Kozioł-Rachwał, Anna, E-mail: a.koziolrachwal@aist.go.jp [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, al. Mickiewicza 30, 30-059 Kraków (Poland); Nozaki, Takayuki; Zayets, Vadym; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); Suzuki, Yoshishige [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)

2016-08-28

The relationship between the magnetic properties and MgO buffer layer thickness d was studied in epitaxial MgO/Fe(t)/Cr/MgO(d) layers grown on MgO(001) substrate in which the Fe thickness t ranged from 0.4 nm to 1.1 nm. For 0.4 nm ≤ t ≤ 0.7 nm, a non-monotonic coercivity dependence on the MgO buffer thickness was shown by perpendicular magneto-optic Kerr effect magnetometry. For thicker Fe films, an increase in the buffer layer thickness resulted in a spin reorientation transition from perpendicular to the in-plane magnetization direction. Possible origins of these unusual behaviors were discussed in terms of the suppression of carbon contamination at the Fe surface and changes in the magnetoelastic anisotropy in the system. These results illustrate a method to control magnetic anisotropy in MgO/Fe/Cr/MgO(d) via an appropriate choice of MgO buffer layer thickness d.

Surface treatments for controlling corrosion rate of biodegradable Mg and Mg-based alloy implants

International Nuclear Information System (INIS)

Uddin, M S; Hall, Colin; Murphy, Peter

2015-01-01

Due to their excellent biodegradability characteristics, Mg and Mg-based alloys have become an emerging material in biomedical implants, notably for repair of bone as well as coronary arterial stents. However, the main problem with Mg-based alloys is their rapid corrosion in aggressive environments such as human bodily fluids. Previously, many approaches such as control of alloying materials, composition and surface treatments, have been attempted to regulate the corrosion rate. This article presents a comprehensive review of recent research focusing on surface treatment techniques utilised to control the corrosion rate and surface integrity of Mg-based alloys in both in vitro and in vivo environments. Surface treatments generally involve the controlled deposition of thin film coatings using various coating processes, and mechanical surfacing such as machining, deep rolling or low plasticity burnishing. The aim is to either make a protective thin layer of a material or to change the micro-structure and mechanical properties at the surface and sub-surface levels, which will prevent rapid corrosion and thus delay the degradation of the alloys. We have organised the review of past works on coatings by categorising the coatings into two classes—conversion and deposition coatings—while works on mechanical treatments are reviewed based on the tool-based processes which affect the sub-surface microstructure and mechanical properties of the material. Various types of coatings and their processing techniques under two classes of coating and mechanical treatment approaches have been analysed and discussed to investigate their impact on the corrosion performance, biomechanical integrity, biocompatibility and cell viability. Potential challenges and future directions in designing and developing the improved biodegradable Mg/Mg-based alloy implants were addressed and discussed. The literature reveals that no solutions are yet complete and hence new and innovative approaches

Surface treatments for controlling corrosion rate of biodegradable Mg and Mg-based alloy implants

Science.gov (United States)

Uddin, M S; Hall, Colin; Murphy, Peter

2015-01-01

Due to their excellent biodegradability characteristics, Mg and Mg-based alloys have become an emerging material in biomedical implants, notably for repair of bone as well as coronary arterial stents. However, the main problem with Mg-based alloys is their rapid corrosion in aggressive environments such as human bodily fluids. Previously, many approaches such as control of alloying materials, composition and surface treatments, have been attempted to regulate the corrosion rate. This article presents a comprehensive review of recent research focusing on surface treatment techniques utilised to control the corrosion rate and surface integrity of Mg-based alloys in both in vitro and in vivo environments. Surface treatments generally involve the controlled deposition of thin film coatings using various coating processes, and mechanical surfacing such as machining, deep rolling or low plasticity burnishing. The aim is to either make a protective thin layer of a material or to change the micro-structure and mechanical properties at the surface and sub-surface levels, which will prevent rapid corrosion and thus delay the degradation of the alloys. We have organised the review of past works on coatings by categorising the coatings into two classes—conversion and deposition coatings—while works on mechanical treatments are reviewed based on the tool-based processes which affect the sub-surface microstructure and mechanical properties of the material. Various types of coatings and their processing techniques under two classes of coating and mechanical treatment approaches have been analysed and discussed to investigate their impact on the corrosion performance, biomechanical integrity, biocompatibility and cell viability. Potential challenges and future directions in designing and developing the improved biodegradable Mg/Mg-based alloy implants were addressed and discussed. The literature reveals that no solutions are yet complete and hence new and innovative approaches

Single Cell Oncogenesis

Science.gov (United States)

Lu, Xin

It is believed that cancer originates from a single cell that has gone through generations of evolution of genetic and epigenetic changes that associate with the hallmarks of cancer. In some cancers such as various types of leukemia, cancer is clonal. Yet in other cancers like glioblastoma (GBM), there is tremendous tumor heterogeneity that is likely to be caused by simultaneous evolution of multiple subclones within the same tissue. It is obvious that understanding how a single cell develops into a clonal tumor upon genetic alterations, at molecular and cellular levels, holds the key to the real appreciation of tumor etiology and ultimate solution for therapeutics. Surprisingly very little is known about the process of spontaneous tumorigenesis from single cells in human or vertebrate animal models. The main reason is the lack of technology to track the natural process of single cell changes from a homeostatic state to a progressively cancerous state. Recently, we developed a patented compound, photoactivatable (''caged'') tamoxifen analogue 4-OHC and associated technique called optochemogenetic switch (OCG switch), which we believe opens the opportunity to address this urgent biological as well as clinical question about cancer. We propose to combine OCG switch with genetically engineered mouse models of head and neck squamous cell carcinoma and high grade astrocytoma (including GBM) to study how single cells, when transformed through acute loss of tumor suppressor genes PTEN and TP53 and gain of oncogenic KRAS, can develop into tumor colonies with cellular and molecular heterogeneity in these tissues. The abstract is for my invited talk in session ``Beyond Darwin: Evolution in Single Cells'' 3/18/2016 11:15 AM.

Microstructural evolution in Mg-rich Mg-Zn-Y alloys

International Nuclear Information System (INIS)

Biswas, T.; Ranganathan, S.; Nair, S.; Bajargan, G.

2005-01-01

Mg-rich Mg-Zn-Y alloys with nominal compositions Mg 97 Zn 1 Y 2 , Mg 97 Zn 2 Y 1 , Mg 92 Zn 6.5 Y 1.5 and Mg 97-x Zn 1 Y 2 Zr x have been chosen for the present study. These alloys are prepared by using sand casting mold. The sand cast alloys are remelted and subjected to copper mold casting and melt spinning techniques. The effect of cooling rate on microstructures was studied. It is observed that the size of the precipitates decreases with an increase of cooling rate. The formation of nano precipitates results in higher strength of the alloy as compared to the conventional alloys. The microstructures of melt spun ribbons are compared with RS/PM (rapidly solidified power metallurgy) Mg 97 Zn 1 Y 2 alloy, obtained from a different source. (author)

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

Science.gov (United States)

Estlin, E. J.; Lashford, L.; Ablett, S.; Price, L.; Gowing, R.; Gholkar, A.; Kohler, J.; Lewis, I. J.; Morland, B.; Pinkerton, C. R.; Stevens, M. C.; Mott, M.; Stevens, R.; Newell, D. R.; Walker, D.; Dicks-Mireaux, C.; McDowell, H.; Reidenberg, P.; Statkevich, P.; Marco, A.; Batra, V.; Dugan, M.; Pearson, A. D.

1998-01-01

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted. Images Figure 5 p658-b Figure 6 p659-b PMID:9744506

In vitro degradation and cytotoxicity of Mg/Ca composites produced by powder metallurgy.

Science.gov (United States)

Zheng, Y F; Gu, X N; Xi, Y L; Chai, D L

2010-05-01

Mg/Ca (1 wt.%, 5 wt.%, 10 wt.% Ca) composites were prepared from pure magnesium and calcium powders using the powder metallurgy method, aiming to enlarge the addition of Ca content without the formation of Mg(2)Ca. The microstructures, mechanical properties and cytotoxicities of Mg/Ca composite samples were investigated. The corrosion of Mg/Ca composites in Dulbecco's modified Eagle's medium (DMEM) for various immersion intervals was studied by electrochemical impedance spectroscopy measurements and environmental scanning electron microscope, with the concentrations of released Mg and Ca ions in DMEM for various immersion time intervals being measured. It was shown that the main constitutional phases were Mg and Ca, which were uniformly distributed in the Mg matrix. The ultimate tensile strength (UTS) and elongation of experimental composites decreased with increasing Ca content, and the UTS of Mg/1Ca composite was comparable with that of as-extruded Mg-1Ca alloy. The corrosion potential increased with increasing Ca content, whereas the current density and the impedance decreased. It was found that the protective surface film formed quickly at the initial immersion stage. With increasing immersion time, the surface film became compact, and the corrosion rate of Mg/Ca composites slowed down. The surface film consisted mainly of CaCO(3), MgCO(3)x3H(2)O, HA and Mg(OH)(2) after 72 h immersion in DMEM. Mg/1Ca and Mg/5Ca composite extracts had no significant toxicity (p>0.05) to L-929 cells, whereas Mg/10Ca composite extract induced approximately 40% reduced cell viability. Copyright (c) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Powder metallurgical low-modulus Ti-Mg alloys for biomedical applications.

Science.gov (United States)

Liu, Yong; Li, Kaiyang; Luo, Tao; Song, Min; Wu, Hong; Xiao, Jian; Tan, Yanni; Cheng, Ming; Chen, Bing; Niu, Xinrui; Hu, Rong; Li, Xiaohui; Tang, Huiping

2015-11-01

In this work, powder metallurgical (PM) Ti-Mg alloys were prepared using combined techniques of mechanical alloying and spark plasma sintering. The alloys mainly consist of super saturations of Mg in Ti matrix, and some laminar structured Ti- and Mg-rich phases. The PM Ti-Mg alloys contain a homogeneous mixtures of nanocrystalline Mg and Ti phases. The novel microstructures result in unconventional mechanical and biological properties. It has been shown that the PM Ti-Mg alloys have a much lower compression modulus (36-50GPa) compared to other Ti alloys, but still remain a very high compressive strength (1500-1800MPa). In addition, the PM Ti-Mg alloys show good biocompatibility and bioactivity. Mg can dissolve in the simulated body fluids, and induce the formation of the calcium phosphate layer. The compression modulus of PM Ti-Mg alloys decreases with the amount of Mg, while the bioactivity increases. Although the corrosion resistance of Ti-Mg alloys decreases with the content of Mg, the alloys still show good stability in simulated body fluid under electrochemical conditions. The indirect and direct cytotoxicity results show that PM Ti-Mg alloys have a good biocompatibility to NIH-3T3 cells. Therefore, the PM Ti-Mg alloys are promising candidates in biomedical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Obtention of Al-Mg alloys of porous morphology

International Nuclear Information System (INIS)

Barragan V, J.; Zamora R, L.; Sandoval J, A.R.; Iturbe G, J.L.

2006-01-01

With the objective of using it as fuel cell, a Mg 25 AI alloy of porous morphology was obtained. The material it was hydrogenates at 200 C by different time. It was analyzed by Scanning Electron Microscopy SEM and X-ray diffraction, XRD. Those XRD diffractographs present peaks run toward the origin, that which indicates a volume increase of the unitary cell by effect of the hydrogen absorption. (Author)

Particles induced surface nanoroughness of titanium surface and its influence on adhesion of osteoblast-like MG-63 cells

Science.gov (United States)

Solař, P.; Kylián, O.; Marek, A.; Vandrovcová, M.; Bačáková, L.; Hanuš, J.; Vyskočil, J.; Slavínská, D.; Biederman, H.

2015-01-01

Titanium is one of the most common materials employed for production of implants, which is due to its good biocompatibility. However, the colonization of titanium surface by osteoblast cells may be influenced by its roughness and therefore precise control of roughness of titanium surface as well as identification of its optimal value for growth of cells is of high importance. In this study the nanorough titanium surfaces were prepared on polished disks of TiAlV by two step method of deposition. In the first step TiAlV were coated by nanoparticles generated by gas aggregation sources. Such prepared films of nanoparticles were subsequently covered with a titanium overlayer. Different values of surface roughness in the range 1-100 nm were achieved by variation of the size and number of the nanoparticles. Such prepared surfaces were subsequently used for investigation of influence of roughness of titanium surfaces on the adhesion of human osteoblast-like MG-63 cells. It was found out that 7 days after seeding the highest number of adhering cells was observed for samples with root-mean-square roughness of 30 nm.

Expression of iron-related genes in human brain and brain tumors

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Britton Robert S

2009-04-01

Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.