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  • 1
    Language: English
    In: Clinical cancer research, 2010-05-15, Vol.16 (10), p.2715-2728
    Description: Stem-like tumor cells comprise a highly tumorigenic and therapy-resistant tumor subpopulation, which is believed to substantially influence tumor initiation and therapy resistance in glioma. Currently, therapeutic, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population; retinoic acid is well known as a potent modulator of differentiation and proliferation in normal stem cells. In glioma, knowledge about the efficacy of retinoic acid-induced differentiation to target the stem-like tumor cell pool could have therapeutic implications. Stem-like glioma cells (SLGC) were differentiated with all-trans retinoic acid-containing medium to study the effect of differentiation on angiogenesis, invasive growth, as well as radioresistance and chemoresistance of SLGCs. In vivo effects were studied using live microscopy in a cranial window model. Our data suggest that in vitro differentiation of SLGCs induces therapy-sensitizing effects, impairs the secretion of angiogenic cytokines, and disrupts SLGCs motility. Further, ex vivo differentiation reduces tumorigenicity of SLGCs. Finally, we show that all-trans retinoic acid treatment alone can induce antitumor effects in vivo. Altogether, these results highlight the potential of differentiation treatment to target the stem-like cell population in glioblastoma.
    Subject(s): Immunohistochemistry ; Cell Separation ; Neoplastic Stem Cells - drug effects ; Humans ; Brain Neoplasms - pathology ; In Situ Hybridization, Fluorescence ; Brain Neoplasms - drug therapy ; Blotting, Western ; Xenograft Model Antitumor Assays ; Animals ; Flow Cytometry ; Cell Differentiation - drug effects ; Glioma - pathology ; Polymerase Chain Reaction ; Neoplastic Stem Cells - pathology ; Mice, Inbred NOD ; Antineoplastic Agents - pharmacology ; Mice ; Glioma - drug therapy ; Tretinoin - pharmacology ; Index Medicus
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 2
    Language: English
    In: Molecular cancer research, 2007-12-01, Vol.5 (12), p.1232-1240
    Description: Glioblastomas, the most malignant of all brain tumors, are characterized by cellular resistance to apoptosis and a highly invasive growth pattern. These factors contribute to the poor response of glioblastomas to radiochemotherapy and prevent their complete neurosurgical resection. However, the driving force behind the distinct motility of glioma cells is only partly understood. Here, we report that in the absence of cellular stress and proapoptotic stimuli, human glioblastoma cells exhibit a constitutive activation of caspases in vivo and in vitro . The inhibition of caspases by various peptide inhibitors decreases the migration of cells in scrape motility assays and the invasiveness of cells in spheroid assays. Similarly, specific small interfering RNA– or antisense-mediated down-regulation of caspase-3 and caspase-8 results in an inhibition of the migratory potential of glioma cells. The constitutive caspase-dependent motility of glioblastoma cells is independent of CD95 activation and it is not mediated by mitogen-activated protein/extracellular signal-regulated kinase kinase signaling. The basal caspase activity is accompanied by a constant cleavage of the motility-associated gelsolin protein, which may contribute to the caspase-mediated promotion of migration and invasiveness in glioblastoma cells. Our results suggest that the administration of low doses of caspase inhibitors that block glioma cell motility without affecting the execution of apoptotic cell death may be exploited as a novel strategy for the treatment of glioblastomas. (Mol Cancer Res 2007;5(12):1232–40)
    Subject(s): migration ; apoptosis ; brain tumors ; invasion ; gliomas ; caspases ; Brain Neoplasms - enzymology ; Glioblastoma - enzymology ; MAP Kinase Signaling System - physiology ; Gelsolin - metabolism ; Neoplasm Invasiveness ; Humans ; Brain Neoplasms - pathology ; Caspase 3 - metabolism ; Caspase 8 - metabolism ; Enzyme Inhibitors - pharmacology ; fas Receptor - metabolism ; Caspase Inhibitors ; Cell Movement - physiology ; Caspase 8 - genetics ; Glioblastoma - pathology ; Caspase 3 - genetics ; Cell Line, Tumor ; RNA, Small Interfering ; Index Medicus
    ISSN: 1541-7786
    E-ISSN: 1557-3125
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 3
    Language: English
    In: IEEE transactions on geoscience and remote sensing, 2016-03, Vol.54 (3), p.1738-1756
    Description: Extended attribute profiles (EAPs) have been widely used for the classification of high-resolution hyperspectral images. EAPs are obtained by computing a sequence of attribute operators. Attribute filters (AFs) are connected operators, so they can modify an image by only merging its flat zones. These filters are effective when dealing with very high resolution images since they preserve the geometrical characteristics of the regions that are not removed from the image. However, AFs, being connected filters, suffer the problem of "leakage" (i.e., regions related to different structures in the image that happen to be connected by spurious links will be considered as a single object). Objects expected to disappear at a certain threshold remain present when they are connected with other objects in the image. The attributes of small objects will be mixed with their larger connected objects. In this paper, we propose a novel framework for morphological AFs with partial reconstruction and extend it to the classification of high-resolution hyperspectral images. The ultimate goal of the proposed framework is to be able to extract spatial features which better model the attributes of different objects in the remote sensed imagery, which enables better performances on classification. An important characteristic of the presented approach is that it is very robust to the ranges of rescaled principal components, as well as the selection of attribute values. Our experimental results, conducted using a variety of hyperspectral images, indicate that the proposed framework for AFs with partial reconstruction provides state-of-the-art classification results. Compared to the methods using only single EAP and stacking all EAPs computed by existing attribute opening and closing together, the proposed framework benefits significant improvements in overall classification accuracy.
    Subject(s): partial reconstruction ; high spatial resolution ; hyperspectral data ; Shape ; Morphology ; Attribute profiles (APs) ; Feature extraction ; classification ; Image reconstruction ; Hyperspectral imaging ; Research ; Image processing ; Remote sensing ; Geographic information systems ; Engineering Sciences ; Signal and Image processing
    ISSN: 0196-2892
    E-ISSN: 1558-0644
    Source: IEEE Electronic Library (IEL)
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  • 4
    Language: English
    In: IEEE geoscience and remote sensing letters, 2015-07, Vol.12 (7), p.1471-1475
    Description: In this letter, we propose a novel approach for improving Random Forest (RF) in hyperspectral image classification. The proposed approach combines the ensemble of features and the semisupervised feature extraction (SSFE) technique. The main contribution of our approach is to construct an ensemble of RF classifiers. In this way, the feature space is divided into several disjoint feature subspaces. Then, the feature subspaces induced by the SSFE technique are used as the input space to an RF classifier. This method is compared with a regular RF and an RF with the reduced features by the SSFE on two real hyperspectral data sets, showing an improved performance in ill-posed, poor-posed, and well-posed conditions. An additional study shows that the proposed method is less sensitive to the parameters.
    Subject(s): Radio frequency ; Training ; ensemble learning ; Accuracy ; semisupervised feature extraction (SSFE) ; Classification ; hyperspectral image ; Feature extraction ; Random Forest (RF) ; Hyperspectral imaging ; Engineering Sciences ; Signal and Image processing
    ISSN: 1545-598X
    E-ISSN: 1558-0571
    Source: IEEE Electronic Library (IEL)
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  • 5
    Language: English
    In: Brain pathology (Zurich, Switzerland), 2007-04, Vol.17 (2), p.146-150
    Description: About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (∼25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.
    Subject(s): Immunohistochemistry ; Microsatellite Instability ; Humans ; Brain Neoplasms - pathology ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Glioma - metabolism ; DNA-Binding Proteins - metabolism ; Glioma - genetics ; Glioma - pathology ; Polymerase Chain Reaction ; Adult ; Child ; Pediatrics ; Genetic aspects ; Measles-mumps-rubella vaccine ; Gliomas ; Cancer ; Index Medicus
    ISSN: 1015-6305
    E-ISSN: 1750-3639
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: Cancer biology & therapy, 2008-12-01, Vol.7 (12), p.1982-1990
    Description: Resistance to apoptosis is one reason for the poor response of malignant brain tumors to therapy. The PPARγ-modulating drug Troglitazone down-regulates the anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis induced by the death ligand TRAIL. To investigate the molecular basis of an experimental combination therapy for malignant gliomas with TRAIL and Troglitazone, we investigated the Troglitazone-induced signaling cascades and the expression of TRAIL receptors and FLIP in malignant gliomas. Troglitazone down-regulated the FLIP protein through accelerated ubiquitin/proteasome-dependent degradation, which might be mediated by a Troglitazone-induced increase in reactive oxygen species. Moreover, Troglitazone induced the phosphorylation of the MAP kinase ERK1/2 as well as of the BAD protein. Inhibition of either PPARγ or MEK1/2 blocked the Troglitazone-mediated phosphorylation of BAD and further increased the synergistic induction of glioma cell death by TRAIL and Troglitazone. Immunohistochemical analysis demonstrated that FLIP and TRAIL-R2 were significantly higher expressed in anaplastic (WHO grade III) than in diffuse (WHO grade II) gliomas. High FLIP and low TRAIL-R2 expression levels were associated with a poor prognosis of patients. Our findings warrant a further pre-clinical evaluation of an experimental anti-glioma therapy with TRAIL and Troglitazone, potentially in conjunction with a MAP kinase inhibitor.
    Subject(s): Cell Line ; Phosphorylation ; Apoptosis - drug effects ; Humans ; Antineoplastic Agents - therapeutic use ; Mitogen-Activated Protein Kinase 1 - drug effects ; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism ; Mitogen-Activated Protein Kinase 3 - drug effects ; Thiazolidinediones - therapeutic use ; Chromans - pharmacology ; Chromans - therapeutic use ; Mitogen-Activated Protein Kinase 3 - metabolism ; Glioma - pathology ; bcl-Associated Death Protein - drug effects ; Cell Line, Tumor ; bcl-Associated Death Protein - metabolism ; Antineoplastic Agents - pharmacology ; Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics ; Proteasome Endopeptidase Complex - metabolism ; Thiazolidinediones - pharmacology ; CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism ; Troglitazone ; Mitogen-Activated Protein Kinase 1 - metabolism ; Index Medicus
    ISSN: 1538-4047
    E-ISSN: 1555-8576
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 7
    Language: English
    In: Clinical cancer research, 2010, Vol.16 (10), p.2715-2728
    Subject(s): Neurology ; Tumors of the nervous system. Phacomatoses ; Pharmacology. Drug treatments ; Biological and medical sciences ; Medical sciences ; Antineoplastic agents
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 8
    Language: English
    In: IEEE transactions on applied superconductivity, 2018-04, Vol.28 (3), p.1-10
    Description: The EuCARD2 collaboration aims at the development of a 10 kA-class superconducting, high current density cable suitable for accelerator magnets, to be tested in small coils and magnets capable to deliver 3-5 T when energized in stand-alone mode, and 15-18 T when inserted in a 12-13 T background magnet. REBCO tape, assembled in a Roebel cable, was selected as conductor. The developed REBCO tape has reached a record engineering critical current density, at 4.2 K and 18 T of 956 A/mm 2 . Roebel cable carried up to 13 kA at 20 K when tested in a small coil (FeatherM0.4). Then a first dipole magnet, wound with two low-grade Roebel cables of 25 m each, was assembled and tested. The dipole reached the short sample critical current of 6 kA generating more than 3 T central field at about 5.7 K, with indications of good current transfer among cable strands and of relatively soft transition. The construction of a costheta dipole is also discussed. Eucard2 is reaching its objective and is continuing with the H2020-ARIES program aiming at doubling the Je at 20 T to obtain 6 T as standalone and 18 T as insert in a high field facility.
    Subject(s): Coils ; High-temperature superconductors ; accelerator magnets ; Critical current density (superconductivity) ; Collaboration ; HTS dipoles ; Superconducting magnets ; Conductors ; HTS conductor ; Condensed Matter Physics ; Electrical and Electronic Engineering ; Electronic, Optical and Magnetic Materials
    ISSN: 1051-8223
    E-ISSN: 1558-2515
    Source: IEEE Electronic Library (IEL)
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  • 9
    Language: English
    In: PloS one, 2016, Vol.11 (3), p.e0150857-e0150857
    Description: In animal studies, extensive data revealed the influence of culture medium on embryonic development, foetal growth and the behaviour of offspring. However, this impact has never been investigated in humans. For the first time, we investigated in depth the effects of embryo culture media on health, growth and development of infants conceived by In Vitro Fertilization until the age of 5 years old. This single-centre cohort study was based on an earlier randomized study. During six months, in vitro fertilization attempts (No. 371) were randomized according to two media (Single Step Medium--SSM group) or Global medium (Global group). This randomized study was stopped prematurely as significantly lower pregnancy and implantation rates were observed in the SSM group. Singletons (No. 73) conceived in the randomized study were included (42 for Global and 31 for SSM). The medical data for gestational, neonatal and early childhood periods were extracted from medical records and parental interviews (256 variables recorded). The developmental profiles of the children in eight domains (social, self-help, gross motor, fine motor, expressive language, language comprehension, letter knowledge and number knowledge--270 items) were compared in relation to the culture medium. The delivery rate was significantly lower in the SSM group than in the Global group (p〈0.05). The culture medium had no significant effect on birthweight, risk of malformation (minor and major), growth and the frequency of medical concerns. However, the children of the Global group were less likely than those of the SSM group to show developmental problems (p = 0.002), irrespective of the different domains. In conclusion, our findings showed that the embryo culture medium may have an impact on further development.
    Subject(s): Fertilization in Vitro ; Culture Media ; Growth ; Humans ; Child, Preschool ; Infant ; Health Status ; Infant, Newborn ; Cohort Studies ; Fertilization in vitro ; Culture media (Biology) ; Embryonic development ; Research ; Child development ; Analysis ; Index Medicus ; Life Sciences ; Human health and pathology ; Gynecology and obstetrics ; Cognitive science ; In vitro fertilization ; Neonates ; Fertilization ; Sperm ; Medical records ; Implantation ; Cardiovascular disease ; Infants ; Gene expression ; Pregnancy ; Embryonic growth stage ; Autism ; Embryogenesis ; Offspring ; Randomization ; Language ; DNA methylation ; Culture media ; Epigenetics ; Birth weight ; Reproductive technologies ; Blood pressure ; Children
    ISSN: 1932-6203
    E-ISSN: 1932-6203
    Source: Academic Search Ultimate
    Source: PubMed Central
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  • 10
    Language: English
    In: International journal of radiation oncology, biology, physics, 2007, Vol.68 (3), p.873-882
    Description: Background: The majority of glioblastoma multiforme (GBM) cells express the epidermal growth factor receptor (EGFR). The present study evaluates the combination of temozolomide (TMZ), EGFR inhibition, and radiotherapy (RT) in GBM cell lines. Methods and Materials: Human GBM cell lines U87, LN229, LN18, NCH 82, and NCH 89 were treated with various combinations of TMZ, RT, and the monoclonal EGFR antibody cetuximab. Responsiveness of glioma cells to the combination treatment was measured by clonogenic survival. Results: Overall, double and triple combinations of RT, TMZ, and cetuximab lead to additive cytotoxic effects (independent toxicity). A notable exception was observed for U87 and LN 18 cell lines, where the combination of TMZ and cetuximab showed substantial antagonism. Interestingly, in these two cell lines, the combination of RT with cetuximab resulted in a substantial increase in cell killing over that expected for independent toxicity. The triple combination with RT, cetuximab, and TMZ was nearly able to overcome the antagonism for the TMZ/cetuximab combination in U87, however only marginally in LN18, GBM cell lines. Conclusion: It appears that EGFR expression is not correlated with cytotoxic effects exerted by cetuximab. Combination treatment with TMZ, cetuximab and radiation resulted in independent toxicity in three out of five cell lines evaluated, the antagonistic effect of the TMZ/cetuximab combination in two cell lines could indicate that TMZ preferentially kills cetuximab-resistant cells, suggesting for some cross-talk between toxicity mechanisms. Expression of EGFR was no surrogate marker for responsiveness to cetuximab, alone or in combination with RT and TMZ.
    Subject(s): Radiology ; Hematology, Oncology and Palliative Medicine ; Human glioma cells ; Temozolomide ; Toxicity ; EGFR ; Radiation ; Cell Survival - drug effects ; Dacarbazine - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Humans ; Epidermal Growth Factor - metabolism ; Antineoplastic Agents - administration & dosage ; Radiation Dosage ; Cell Survival - radiation effects ; Dose-Response Relationship, Drug ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal - administration & dosage ; Chemotherapy, Adjuvant - methods ; Glioblastoma - pathology ; Dacarbazine - analogs & derivatives ; Cell Line, Tumor ; Epidermal Growth Factor - antagonists & inhibitors ; Glioblastoma - metabolism ; Cetuximab ; Dose-Response Relationship, Radiation ; Epidermal growth factor ; Radiotherapy ; Gliomas ; Nuclear radiation ; Cells ; ANTIBODIES ; GLIOMAS ; GROWTH FACTORS ; INHIBITION ; IN VITRO ; CELL KILLING ; RADIOLOGY AND NUCLEAR MEDICINE ; TOXICITY ; RADIOTHERAPY ; RECEPTORS
    ISSN: 0360-3016
    E-ISSN: 1879-355X
    Source: Backfile Package - All of Back Files EBS [ALLOFBCKF]
    Source: Alma/SFX Local Collection
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