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  • 1
    Language: English
    In: International journal of cancer, 01 February 2011, Vol.128(3), pp.501-10
    Description: The transmembrane protein CD133 and its extracellular epitope AC133 are controversial cancer markers. In glioma, AC133 demarcates a subpopulation of stem-like tumor cells, so-called cancer stem cells (CSCs), which seem to drive tumor formation and are highly resistant to conventional chemo- and radiotherapy. Lately, experimental evidence for the existence of AC133-independent CSCs has challenged the importance previously attributed to AC133-positive glioma cells. These findings either imply that (i) AC133-positive and AC133-negative glioma cells comprise different, independent CSC populations, (ii) AC133-positive glioma cells are derived from primordial AC133-negative CSCs or (iii) AC133-negative CSCs have lost AC133 expression, while retaining their stem-like features and tumor initiation capacity, and can reacquire AC133 expression in vivo. In our article, we review evidence for and against each of the possible tumor models in glioma and will discuss technical hurdles in the AC133 detection process. In addition, we will outline new insights into CD133 regulation, which suggest certain degree of plasticity between some AC133-positive and AC133-negative CSC populations.
    Keywords: Antigens, CD -- Metabolism ; Glioma -- Pathology ; Glycoproteins -- Metabolism ; Peptides -- Metabolism
    E-ISSN: 1097-0215
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  • 2
    In: Nature Neuroscience, 2017, Vol.20(8), p.1035
    Keywords: Adult ; Erbb Receptors ; Glioblastoma ; Humans ; MAP Kinase Signaling System ; Egfr Protein, Human ; Erbb Receptors;
    ISSN: 1097-6256
    E-ISSN: 1546-1726
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  • 3
    Language: English
    In: Analytica Chimica Acta, May 6, 2012, Vol.725, p.57(10)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.aca.2012.03.003 Byline: Ramadan Ali (a), Benito Campos (b), Gerhard Dyckhoff (c), Walter E. Haefeli (a), Christel Herold-Mende (b), Jurgen Burhenne (a) Keywords: Retinoids; Stability; High performance liquid chromatography; Brain tumors; Serum Abstract: Display Omitted Author Affiliation: (a) Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany (b) Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany (c) Section of Molecular Cell Biology Group, Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Article History: Received 30 December 2011; Revised 29 February 2012; Accepted 4 March 2012
    Keywords: Brain ; Brain Tumors ; Chromatography ; Liquid Chromatography ; Tumors ; Retinoids
    ISSN: 0003-2670
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 11 February 2014, Vol.111(6), pp.E692-701
    Description: A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment. The AC133 epitope of CD133 currently is one of the best-characterized tumor stem cell markers for many intra- and extracranial tumor entities. Here we demonstrate the successful noninvasive detection of AC133(+) tumor stem cells by PET and near-infrared fluorescence molecular tomography in subcutaneous and orthotopic glioma xenografts using antibody-based tracers. Particularly, microPET with (64)Cu-NOTA-AC133 mAb yielded high-quality images with outstanding tumor-to-background contrast, clearly delineating subcutaneous tumor stem cell-derived xenografts from surrounding tissues. Intracerebral tumors as small as 2-3 mm also were clearly discernible, and the microPET images reflected the invasive growth pattern of orthotopic cancer stem cell-derived tumors with low density of AC133(+) cells. These data provide a basis for further preclinical and clinical use of the developed tracers for high-sensitivity and high-resolution monitoring of AC133(+) tumor stem cells.
    Keywords: Cscs ; Cancer Stem Cells ; Glioblastoma ; Antigens, CD -- Immunology ; Glycoproteins -- Immunology ; Neoplastic Stem Cells -- Immunology ; Peptides -- Immunology ; Positron-Emission Tomography -- Methods
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 5
    In: Plastic and Reconstructive Surgery, 2011, Vol.127(5), pp.1830-1837
    Description: BACKGROUND:: Extracorporal shock wave therapy has a significant positive effect on rescuing the ischemic zone of flap tissue if applied immediately after surgical intervention. The purpose of this study was to determine the potential preoperative effect of noninvasive extracorporal shock wave therapy to precondition flap tissue compared with the well-established surgical delay procedure. METHODS:: Thirty-two male Wistar rats were randomized into four groups, and an oversized, random-pattern flap was raised in each animal. In group D7, a surgical delay was carried out 1 week before full flap harvest. In group E7, the whole flap area was treated with extracorporal shock wave therapy to induce mechanical delay. Group E7D7 was treated preoperatively with a combination of surgical delay and extracorporal shock wave therapy. Group C constituted the control group, in which the skin flap was harvested without any prior intervention. Seven days after flap harvest, flap survival, perfusion, microvessel density, and vascular endothelial growth factor concentration were assessed. RESULTS:: Flap survival, perfusion, and microvessel density were significantly increased in the delay group (group D7) and the extracorporal shock wave therapy group (group E7) compared with the control group (group C). Combining both pretreatments (group E7D7) did not have a favorable cumulative effect. Vascular endothelial growth factor expression was not significantly increased in any group. CONCLUSIONS:: Although not superior to surgical delay, the authors see many advantages of extracorporal shock wave therapy; it is noninvasive, easily applicable, less time- consuming, and less expensive. Thus, it may constitute an alternative procedure in clinical situations that warrant a noninvasive, fast, and easily applicable treatment.
    Keywords: Animals–Prevention & Control ; Disease Models, Animal–Therapeutic Use ; Graft Rejection–Methods ; Graft Survival–Methods ; High-Energy Shock Waves–Methods ; Male–Methods ; Preoperative Care–Methods ; Rats–Methods ; Rats, Wistar–Methods ; Skin Transplantation–Methods ; Surgical Flaps–Methods ; Time Factors–Methods ; Ultrasonography, Interventional–Methods ; Abridged;
    ISSN: 0032-1052
    E-ISSN: 15294242
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  • 6
    Language: English
    In: Analytica Chimica Acta, 06 May 2012, Vol.725, pp.57-66
    Description: ► It is the first sensitive assay for the quantification of retinoids in lipid-rich tissue (brain). ► We report the relationship between gender and age for retinoids other than retinol. ► This is the first report assessing the light sensitivity of different retinoids in biological matrix. ► This is the first report analyzing serum:tissue ratios of retinoid concentrations in normal tissue (tonsils). ► We report the relationship of retinoid serum:tissue ratios in tumors and confirm substantial accumulation in tissue. Retinoic acid signaling is essential for central nervous system (CNS) differentiation and appears to be impaired in tumors. Thus far, there are no established methods to quantify relevant retinoids (all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis retinoic acid, and retinol) in human brain tumors. We developed a single step extraction and quantification procedure for polar and apolar retinoids in normal tissue, lipid-rich brain tumor tissues, and serum. This quantification procedure is based on high performance liquid chromatography (HPLC) with diode-array detection (DAD) using all-trans-acitretin as an internal standard and extraction by liquid–liquid partition with ethyl acetate and borate buffer at pH 9. Recovery with this extraction procedure was higher than earlier (two-step) liquid–liquid extraction procedures based on hexane, NaOH, and HCl. The overall quantification procedure was validated according to Food and Drug Administration (FDA) guidelines and fulfilled all criteria of accuracy, precision, selectivity, recovery, and stability. The overall method accuracy varied between −5.6% and +5.4% for serum and −3.8% and +6.2% for tissues, and overall precision ranged from 3.1% to 6.9% for serum and 2.1% to 8.3% for tissues (%CV batch-to-batch). The lower limit of quantification for all compounds in tumor tissue (and serum) was 3.9 ng g (ng mL ). Using this assay, photodegradation of the retinoids was evaluated and endogenous polar and apolar retinoids were quantified in sera and brain tumor tissues of patients and compared with serum and tonsil tissue concentrations of controls. It may thus serve as a suitable method for the characterization of retinoid uptake and metabolism in the respective compartments.
    Keywords: Retinoids ; Stability ; High Performance Liquid Chromatography ; Brain Tumors ; Serum ; Chemistry
    ISSN: 0003-2670
    E-ISSN: 1873-4324
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  • 7
    Language: English
    In: PLoS ONE, 2012, Vol.7(7), p.e41298
    Description: To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas. ; To address intertumoral heterogeneity we investigated non- microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors. To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence, and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components. All tumors and tumor components were analyzed for allelic loss of 1p/19q (LOH 1p/19q), for mutations and for R132 mutations in the gene. The investigation of non- microdissected tumor tissue revealed clonality in 75% (38/51). Aberrant molecular alterations upon recurrence were detected in 25% (13/51). 64% (9/14) of these were novel and associated with tumor progression. Loss of previously detected alterations was observed in 36% (5/14). One tumor pair (1/14; 7%) was significant for both. Intratumoral clonality was detected in 57% (4/7) of the microdissected tumor pairs and in 75% (3/4) of single microdissected tumors. 43% (3/7) of tumor pairs and one single tumor (25%) revealed intratumoral heterogeneity. While intratumoral heterogeneity affected both the - mutational status and the LOH1p/19q status, all tumors with intratumoral heterogeneity shared the R132 mutation as a common feature in both their microdissected components. ; The majority of recurrent gliomas are of monoclonal origin. However, the detection of divertive tumor cell clones in morphological distinct tumor components sharing - mutations as early event may provide insight into the tumorigenesis of true mixed gliomas.
    Keywords: Research Article ; Biology ; Medicine ; Genetics And Genomics ; Oncology
    E-ISSN: 1932-6203
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  • 8
    In: International Journal of Cancer, 01 December 2014, Vol.135(11), pp.2727-2734
    Description: Proteoglycans are often overexpressed in tumors and can be found on several normal and neoplastic stem cells. In this study, we analyzed in‐depth the role of CSPG4 in head and neck squamous cell carcinomas (HNSCC). Analysis of CSPG4 in a homogeneous study sample of HPV‐negative stage IVa HNSCCs revealed overexpression of protein and mRNA levels in a subgroup of HNSCC tumors and a significant association of high CSPG4 protein levels with poor survival. This could be validated in three publicly available microarray datasets. As a potential cause for upregulated CSPG4 expression, we identified DNA hypomethylation in a CpG‐island of the promoter region. Accordingly, we found an inverse correlation of methylation and patient outcome. Finally, CSPG4 re‐expression was achieved by demethylating treatment of highly methylated HNSCC cell lines establishing a direct link between methylation and CSPG4 expression. In conclusion, we identified CSPG4 as a novel biomarker in HNSCC on several biological levels and established a causative link between DNA methylation and CSPG4 protein and mRNA expression. What's New? Head and neck squamous cell carcinoma (HNSCC) is a frequent cancer characterized by clinical and biological heterogeneity and poor disease outcome. Here, the authors examined the expression level of the stem cell‐associated proteoglycan CSPG4 as a potential novel biomarker in HNSCC. Studies were restricted to stage IVa tumors negative for human papilloma virus infection and showed increased expression of CSPG4 mRNA and protein expression accompanied by decreased promoter methylation. Promoter methylation was inversely correlated with disease outcome and could be reversed with demethylating agents, underscoring the therapeutic potential of CSPG4 targeting in the treatment of HNSCC patients.
    Keywords: Cspg4 Methylation And Expression ; Hnscc ; Survival
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 9
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(5), p.e96239
    Description: Glioblastoma is the most common and lethal primary brain tumor. Tumor initiation and recurrence are likely caused by a sub-population of glioblastoma stem cells, which may derive from mutated neural stem and precursor cells. Since CD133 is a stem cell marker for both normal brain and glioblastoma, and to better understand glioblastoma formation and recurrence, we looked for dys-regulated microRNAs in human CD133+ glioblastoma stem cells as opposed to CD133+ neural stem cells isolated from normal human brain. Using FACS sorting of low-passage cell samples followed by microRNA microarray analysis, we found 43 microRNAs that were dys-regulated in common in three separate CD133+ human glioblastomas compared to CD133+ normal neural stem cells. Among these were several microRNAs not previously associated with cancer. We then verified the microRNAs dys-regulated in glioblastoma using quantitative real time PCR and Taqman analysis of the original samples, as well as human GBM stem cell and established cell lines and many human specimens. We show that two candidate oncogenic microRNAs, miR-363 and miR-582-5p, can positively influence glioblastoma survival, as shown by forced expression of the microRNAs and their inhibitors followed by cell number assay, Caspase 3/7 assay, Annexin V apoptosis/fluorescence activated cell sorting, siRNA rescue of microRNA inhibitor treatment, as well as 3'UTR mutagenesis to show luciferase reporter rescue of the most successful targets. miR-582-5p and miR-363 are shown to directly target Caspase 3, Caspase 9, and Bim.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.4032-4032
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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