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  • 1
    Language: English
    In: Clinical cancer research, 2008-01-01, Vol.14 (1), p.123-129
    Description: Purpose: The CD133 antigen has been identified as a putative stem cell marker in normal and malignant brain tissues. In gliomas, it is used to enrich a subpopulation of highly tumorigenic cancer cells. According to the cancer stem cell hypothesis, CD133-positive cells determine long-term tumor growth and, therefore, are suspected to influence clinical outcome. To date, a correlation between CD133 expression in primary tumor tissues and patients' prognosis has not been reported. Experimental Design: To address this question, we analyzed the expression of the CD133 stem cell antigen in a series of 95 gliomas of various grade and histology by immunohistochemistry on cryostat sections. Staining data were correlated with patient outcome. Results: By multivariate survival analysis, we found that both the proportion of CD133-positive cells and their topological organization in clusters were significant ( P 〈 0.001) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. Furthermore, proportion of CD133-positive cells was an independent risk factor for tumor regrowth and time to malignant progression in WHO grade 2 and 3 tumors. Conclusions: These findings constitute the first conclusive evidence that CD133 stem cell antigen expression correlates with patient survival in gliomas, lending support to the current cancer stem cell hypothesis.
    Subject(s): AC133 Antigen ; Adult ; Antigens, CD - biosynthesis ; Antineoplastic agents ; Biological and medical sciences ; Brain Neoplasms - metabolism ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; CD133 ; Disease-Free Survival ; Female ; glioma ; Glioma - metabolism ; Glioma - mortality ; Glioma - pathology ; Glycoproteins - biosynthesis ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Medical sciences ; Middle Aged ; Neurology ; Peptides ; Pharmacology. Drug treatments ; Prognosis ; stem cells ; Stem Cells - metabolism ; Survival Analysis ; Tumors of the nervous system. Phacomatoses
    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: Acta neurochirurgica, 2009-11, Vol.151 (11), p.1359-1365
    Description: The appropriate management of low-grade gliomas is still a matter of debate. So far, there are no randomized studies that analyze the impact of surgical resection on patient outcome. The value of the data obtained from the few retrospective reports available is often limited. In the present study, we performed an analysis on data of 130 adult low-grade glioma patients. Extent of the resection was evaluated in correlation to the overall survival (OS) and progression-free survival (PFS) using Cox regression multivariate analysis. Extended surgery was shown to prolong OS and PFS significantly. Re-surgery in the case of a tumor relapse has a significant impact on OS and PFS, too. In summary, we could retrospectively evaluate a large case series of well-defined low-grade gliomas patients with a long follow-up period showing that extended surgery would be the most effective therapy for low-grade glioma patients even in recurrent diseases.
    Subject(s): Adolescent ; Adult ; Age Factors ; Aged ; Analysis ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Brain Neoplasms - surgery ; Brain tumors ; Cancer ; Care and treatment ; Combined Modality Therapy - methods ; Combined Modality Therapy - statistics & numerical data ; Drug Therapy - methods ; Drug Therapy - statistics & numerical data ; Female ; Glioma - mortality ; Glioma - pathology ; Glioma - surgery ; Gliomas ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Monitoring, Intraoperative ; Neoplasm Invasiveness - physiopathology ; Neoplasm Invasiveness - prevention & control ; Neoplasm Recurrence, Local - epidemiology ; Neoplasm Recurrence, Local - prevention & control ; Neoplasm Recurrence, Local - surgery ; Neuronavigation ; Neurosurgical Procedures - methods ; Neurosurgical Procedures - statistics & numerical data ; Oncology, Experimental ; Patient outcomes ; Preoperative Care ; Prognosis ; Radiotherapy - methods ; Radiotherapy - statistics & numerical data ; Research ; Retrospective Studies ; Stereotaxic Techniques ; Survival Rate ; Treatment Outcome ; Universities and colleges ; Young Adult
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: BMC medicine, 2010-11-18, Vol.8 (1), p.74-74
    Description: An accident or a catastrophic disease may occasionally lead to brain death (BD) during pregnancy. Management of brain-dead pregnant patients needs to follow special strategies to support the mother in a way that she can deliver a viable and healthy child and, whenever possible, also be an organ donor. This review discusses the management of brain-dead mothers and gives an overview of recommendations concerning the organ supporting therapy. To obtain information on brain-dead pregnant women, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included the age of the mother, the cause of brain death, maternal medical complications, gestational age at BD, duration of extended life support, gestational age at delivery, indication of delivery, neonatal outcome, organ donation of the mothers and patient and graft outcome. In our search of the literature, we found 30 cases reported between 1982 and 2010. A nontraumatic brain injury was the cause of BD in 26 of 30 mothers. The maternal mean age at the time of BD was 26.5 years. The mean gestational age at the time of BD and the mean gestational age at delivery were 22 and 29.5 weeks, respectively. Twelve viable infants were born and survived the neonatal period. The management of a brain-dead pregnant woman requires a multidisciplinary team which should follow available standards, guidelines and recommendations both for a nontraumatic therapy of the fetus and for an organ-preserving treatment of the potential donor.
    Subject(s): Brain ; Brain Death ; Brain Injuries - complications ; Brain Injuries - mortality ; Care and treatment ; Coma ; Delivery, Obstetric - methods ; Donation of organs, tissues, etc ; Female ; Health aspects ; Humans ; Injuries ; Life ; Nervous system ; Pregnancy ; Pregnancy Complications ; Pregnant women ; Surgery ; Tissue and Organ Procurement ; Usage
    ISSN: 1741-7015
    E-ISSN: 1741-7015
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 4
    Language: English
    In: Journal of neuro-oncology, 2012-08, Vol.109 (1), p.15-22
    Description: Mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) have been identified in approximately 70–80 % of astrocytomas and oligodendrogliomas of WHO grades II and III, and in secondary glioblastomas. In addition, a low incidence of IDH2 mutations has been detected in these tumors, and the occurence of IDH1 and IDH2 mutations is mutually exclusive. For patients with anaplastic gliomas and glioblastomas with IDH1 mutations, overall survival was significantly longer than for patients with wild-type tumours. However, the prognostic value of IDH1 in low-grade gliomas remains ambiguous. IDH1 codon 132 and IDH2 codon 172 mutation status were determined by direct sequencing for a retrospective series of 100 patients with histologically diagnosed Astrocytomas WHO Grad II (A II), and investigated for association with patient outcome. For the patient cohort analysed, median progression-free survival (PFS) was 44.6 months (95 %-CI 1.0–267.0), time to progression (median time to malignant progression (TtMP) was 74.9 months (95 %-CI 1.6–236.2), and median overall survival (OS) was 81.4 months (95 %-CI 5.5–274.8). IDH1 mutations were identified in 79 % of the patients. IDH2 mutations were not observed. Univariate and multivariate analysis revealed no association between IDH1 mutation status and PFS, TtMP, and OS. Furthermore, there were no significant differences regarding PFS, TtMP, and OS between patients with and without IDH1 mutations who did not receive adjuvant treatment. The prognostic value of IDH1 mutations in low-grade astrocytomas is rather low compared with that in high-grade gliomas.
    Subject(s): Adult ; Aged ; Aged, 80 and over ; Astrocytoma - genetics ; Astrocytoma - mortality ; Astrocytoma - pathology ; Astrocytoma WHO grade II ; Brain Neoplasms - genetics ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Female ; Follow-Up Studies ; Humans ; IDH1 ; IDH2 ; Isocitrate Dehydrogenase - genetics ; Male ; Medicine & Public Health ; Middle Aged ; Mutation - genetics ; Neoplasm Grading ; Neurology ; Oncology ; Overall survival ; Prognosis ; Progression-free survival ; Retrospective Studies ; Survival Rate ; World Health Organization
    ISSN: 0167-594X
    E-ISSN: 1573-7373
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: TheScientificWorld, 2012-08-02, Vol.2012, p.697313-697313
    Description: Aberrant wnt pathway activation through cytoplasmic stabilization of β-catenin is crucial for the development of various human malignancies. In gliomagenesis, the role of canonical (i.e., β-catenin-dependent) signalling is largely unknown. Here, we studied canonical wnt pathway activation in 15 short-term cultures from high-grade gliomas and potential pathomechanisms leading to cytoplasmic β-catenin accumulation. Furthermore, we assessed the prognostic relevance of β-catenin expression in a tissue microarray comprising 283 astrocytomas. Expression of β-catenin, its transcriptional cofactors TCF-1 and TCF-4 as well as GSK-3β and APC, constituents of the β-catenin degradation complex was confirmed by RT-PCR in all cultures. A cytoplasmic β-catenin pool was detectable in 13/15 cultures leading to some transcriptional activity assessed by luciferase reporter gene assay in 8/13. Unlike other malignancies, characteristic mutations of β-catenin and APC leading to cytoplasmic stabilization of β-catenin were excluded by direct sequencing or protein truncation test. In patient tissues, β-catenin expression was directly and its degradation product's (β-catenin-P654) expression was inversely correlated with WHO grade. Increased β-catenin expression and low β-catenin-P654 expression were associated with shorter survival. Altogether, we report on potential canonical wnt pathway activation in high-grade gliomas and demonstrate that β-catenin expression in astrocytomas is associated with increased malignancy and adverse outcome.
    Subject(s): Astrocytoma - metabolism ; Astrocytoma - pathology ; Base Sequence ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; DNA Primers ; Humans ; Polymerase Chain Reaction ; Prognosis ; Wnt Proteins - metabolism
    ISSN: 2356-6140
    E-ISSN: 1537-744X
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 6
    Language: English
    In: Clinical cancer research, 2011, Vol.17 (13), p.4296-4308
    Description: In glioma-in contrast to various other cancers-the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in glioma. T-cell subpopulations from entire sections of 93 WHO°II-IV gliomas were computationally identified using markers CD3, CD8, and Foxp3; survival analysis was then done on primary glioblastomas (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same glioma tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO°II-IV glioma lysates) on CAM-expression in GBM-isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using GBM-derived endothelial cells and autologous T-cells. Infiltration of all T-cell subsets increased in high-grade tumors. Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (T(eff), cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with GBM patient outcome. Interestingly, increased infiltration of T(eff) cells was related to the expression of ICAM-1 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that TGF-β molecules impeded transmigration and downregulated CAM-expression on GBM-isolated endothelial cells; blocking TGF-β receptor signaling increased transmigration. This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in glioma. Specifically, targeting TGF-β1 and TGF-β2 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches.
    Subject(s): Angiogenesis Inducing Agents - metabolism ; Antineoplastic agents ; Biological and medical sciences ; Cell Adhesion Molecules - metabolism ; Cell Movement - drug effects ; Disease Progression ; Down-Regulation - genetics ; Endothelial Cells - immunology ; Endothelial Cells - metabolism ; Gene Expression Regulation, Neoplastic ; Glioblastoma - immunology ; Glioblastoma - metabolism ; Glioblastoma - mortality ; Humans ; Immunologic Factors - immunology ; Immunologic Factors - pharmacology ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Medical sciences ; Neurology ; Pharmacology. Drug treatments ; Protein Kinase Inhibitors - pharmacology ; Receptors, Transforming Growth Factor beta - antagonists & inhibitors ; Signal Transduction - drug effects ; Survival Analysis ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Transforming Growth Factor beta - immunology ; Transforming Growth Factor beta - pharmacology ; Tumors of the nervous system. Phacomatoses
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 7
    Language: English
    In: Acta neurochirurgica, 2009-11, Vol.151 (11), p.1367-1367
    Description: Byline: Rezvan Ahmadi (1), Christine Dictus (1), Christian Hartmann (2), Olga Zurn (1), Lutz Edler (3), Marius Hartmann (4), Stephanie Combs (5), Christel Herold-Mende (1), Christian Rainer Wirtz (1), Andreas Unterberg (1) Author Affiliation: (1) Department of Neurosurgery, University of Heidelberg, INF 400, 69120, Heidelberg, Germany (2) Clinical cooperation unit of Neuropathology, German Cancer Research Center, 69120, Heidelberg, Germany (3) Institute of Biostatistics, German Cancer Research Center, 69120, Heidelberg, Germany (4) Department of Neuroradiology, University of Heidelberg, 69120, Heidelberg, Germany (5) Department of Radiation Oncology, University of Heidelberg, 69120, Heidelberg, Germany Article History: Registration Date: 16/07/2009 Online Date: 04/09/2009 Article note: The online version of the original article can be found at
    Subject(s): Brain tumors ; Cancer ; Care and treatment ; Gliomas ; Oncology, Experimental ; Patient outcomes ; Research ; Universities and colleges
    ISSN: 0001-6268
    E-ISSN: 0942-0940
    Source: Alma/SFX Local Collection
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  • 8
    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): Animals ; Antineoplastic Agents - pharmacology ; Blotting, Western ; Brain Neoplasms - drug therapy ; Brain Neoplasms - pathology ; Cell Differentiation - drug effects ; Cell Separation ; Flow Cytometry ; Glioma - drug therapy ; Glioma - pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mice ; Mice, Inbred NOD ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - pathology ; Polymerase Chain Reaction ; Tretinoin - pharmacology ; Xenograft Model Antitumor Assays
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 9
    Language: English
    In: Critical care medicine, 2009-10, Vol.37 (10), p.2853-2854
    Subject(s): Abridged Index Medicus
    ISSN: 0090-3493
    E-ISSN: 1530-0293
    Source: Hellenic Academic Libraries Link
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  • 10
    Language: English
    In: Critical care medicine, 2009-10, Vol.37 (10), p.2853-2854
    Subject(s): Analgesics, Opioid - administration & dosage ; Analgesics, Opioid - pharmacokinetics ; ATP-Binding Cassette Transporters - physiology ; Blood-Brain Barrier - physiology ; Brain - metabolism ; Cerebral Hemorrhage - cerebrospinal fluid ; Conscious Sedation ; Critical Care ; Dose-Response Relationship, Drug ; Head Injuries, Closed - cerebrospinal fluid ; Humans ; Interleukin-6 - cerebrospinal fluid ; Metabolic Clearance Rate - physiology ; Morphine - administration & dosage ; Morphine - pharmacokinetics ; Morphine Derivatives - cerebrospinal fluid ; Subarachnoid Hemorrhage - cerebrospinal fluid
    ISSN: 0090-3493
    E-ISSN: 1530-0293
    Source: Hellenic Academic Libraries Link
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