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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 28 January 2014, Vol.111(4), pp.E501-10
    Description: Phase variation of hypermutable simple sequence repeats (SSRs) is a widespread and stochastic mechanism to generate phenotypic variation within a population and thereby contributes to host adaptation of bacterial pathogens. Although several examples of SSRs that affect transcription or coding potential have been reported, we now show that a SSR also impacts small RNA-mediated posttranscriptional regulation. Based on in vitro and in vivo analyses, we demonstrate that a variable homopolymeric G-repeat in the leader of the TlpB chemotaxis receptor mRNA of the human pathogen Helicobacter pylori is directly targeted by a small RNA (sRNA), RepG (Regulator of polymeric G-repeats). Whereas RepG sRNA is highly conserved, the tlpB G-repeat length varies among diverse H. pylori strains, resulting in strain-specific RepG-mediated tlpB regulation. Based on modification of the G-repeat length within one strain, we demonstrate that the G-repeat length determines posttranscriptional regulation and can mediate both repression and activation of tlpB through RepG. In vitro translation assays show that this regulation occurs at the translational level and that RepG influences tlpB translation dependent on the G-repeat length. In contrast to the digital ON-OFF switches through frame-shift mutations within coding sequences, such modulation of posttranscriptional regulation allows for a gradual control of gene expression. This connection to sRNA-mediated posttranscriptional regulation might also apply to other genes with SSRs, which could be targeting sites of cis- or trans-encoded sRNAs, and thereby could facilitate host adaptation through sRNA-mediated fine-tuning of virulence gene expression.
    Keywords: Homopolymeric Repeat ; Noncoding RNA ; Gene Expression Regulation, Bacterial ; RNA Processing, Post-Transcriptional ; Repetitive Sequences, Nucleic Acid ; Chemotaxis -- Genetics ; Helicobacter Pylori -- Genetics
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Molecular Cancer, Oct 11, 2011, Vol.10, p.128
    Description: Glioblastomas (GBM) are a paradigm for the investigation of cancer stem cells (CSC) in solid malignancies. The susceptibility of GBM CSC to standard chemotherapeutic drugs is controversial as the existing literature presents conflicting experimental data. Here, we summarize the experimental evidence on the resistance of GBM CSC to alkylating chemotherapeutic agents, with a special focus on temozolomide (TMZ). The data suggests that CSC are neither resistant nor susceptible to chemotherapy per se. Detoxifying proteins such as O.sup.6.sup.-methylguanine-DNA-methyltransferase (MGMT) confer a strong intrinsic resistance to CSC in all studies. Extrinsic factors may also contribute to the resistance of CSC to TMZ. These may include TMZ concentrations in the brain parenchyma, TMZ dosing schemes, hypoxic microenvironments, niche factors, and the re-acquisition of stem cell properties by non-stem cells. Thus, the interaction of CSC and chemotherapy is more complex than may be expected and it is necessary to consider these factors in order to overcome chemoresistance in the patient.
    Keywords: Chemotherapy -- Health Aspects ; Glioblastomas -- Development And Progression ; Glioblastomas -- Care And Treatment ; Glioblastomas -- Research ; Stem Cells -- Research
    ISSN: 1476-4598
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Molecular Cancer, Oct 11, 2011, Vol.10, p.128
    Description: Glioblastomas (GBM) are a paradigm for the investigation of cancer stem cells (CSC) in solid malignancies. The susceptibility of GBM CSC to standard chemotherapeutic drugs is controversial as the existing literature presents conflicting experimental data. Here, we summarize the experimental evidence on the resistance of GBM CSC to alkylating chemotherapeutic agents, with a special focus on temozolomide (TMZ). The data suggests that CSC are neither resistant nor susceptible to chemotherapy per se. Detoxifying proteins such as O.sup.6.sup.-methylguanine-DNA-methyltransferase (MGMT) confer a strong intrinsic resistance to CSC in all studies. Extrinsic factors may also contribute to the resistance of CSC to TMZ. These may include TMZ concentrations in the brain parenchyma, TMZ dosing schemes, hypoxic microenvironments, niche factors, and the re-acquisition of stem cell properties by non-stem cells. Thus, the interaction of CSC and chemotherapy is more complex than may be expected and it is necessary to consider these factors in order to overcome chemoresistance in the patient.
    Keywords: Chemotherapy -- Health Aspects ; Glioblastomas -- Development And Progression ; Glioblastomas -- Care And Treatment ; Glioblastomas -- Research ; Stem Cells -- Research
    ISSN: 1476-4598
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Molecular Cancer, 01 October 2011, Vol.10(1), p.128
    Description: Abstract Glioblastomas (GBM) are a paradigm for the investigation of cancer stem cells (CSC) in solid malignancies. The susceptibility of GBM CSC to standard chemotherapeutic drugs is controversial as the existing literature presents conflicting experimental data. Here, we summarize the experimental evidence on the resistance of GBM CSC to alkylating chemotherapeutic agents, with a special focus on temozolomide (TMZ). The data suggests that CSC are neither resistant nor susceptible to chemotherapy per se. Detoxifying proteins such as O6-methylguanine-DNA-methyltransferase (MGMT) confer a strong intrinsic resistance to CSC in all studies. Extrinsic factors may also contribute to the resistance of CSC to TMZ. These may include TMZ concentrations in the brain parenchyma, TMZ dosing schemes, hypoxic microenvironments, niche factors, and the re-acquisition of stem cell properties by non-stem cells. Thus, the interaction of CSC and chemotherapy is more complex than may be expected and it is necessary to consider these factors in order to overcome chemoresistance in the patient.
    Keywords: Glioblastoma ; Cancer Stem Cell ; Temozolomide ; Chemoresistance ; Bcnu ; Medicine ; Biology
    ISSN: 1476-4598
    E-ISSN: 1476-4598
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  • 5
    Language: English
    In: Clinical Neuroradiology, 2018, Vol.28(1), pp.99-107
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00062-016-0517-0 Byline: Dagmar Beier (1,2,3), Selin Kocakaya (3), Peter Hau (4), Christoph Patrick Beier (1,2,3) Keywords: Adult; Medulloblastoma; Magnetic resonance imaging; Computed tomography; Contrast enhancement Abstract: Purpose Current knowledge on the spectrum of the neuroradiological appearance of adult medulloblastoma is sparse. Due to the rarity of the disease, adult patients were generally diagnosed and treated similar to children however, pediatric and adult medulloblastomas display substantial molecular differences that may influence the neuroradiological phenotype. This study therefore aimed at assessment of the neuroradiological spectrum of adult medulloblastoma in comparison to pediatric tumors. Methods All available publications on adult medulloblastoma published until June 2013 were screened for imaging data on single patients. A total of 109 patients were identified and compared to 118 pediatric patients described in 4 cohorts. Results The average age of the adult patients was 34.3 years. Most adult medulloblastomas (57.6%) were localized laterally (vs. 14.4% in pediatric patients). On T1-weighted sequences, only 41.1% of all adult medulloblastomas appeared hypointense (vs. 89.3%) and 69.6% were hyperintense on T2 sequences (vs. 83%). In contrast to pediatric patients only 53.3% showed strong contrast enhancement (pediatric patients 77.1%), while the contrast uptake of the remainder was described as subtle, moderate or lacking. Contrast enhancement was more often described as inhomogeneous in adults (35.5% as compared to 15.2% in children) and 26.4% had cysts. Conclusion Although the neuroradiological spectrum of medulloblastoma in adults was similar to children, an atypical presentation with inhomogeneous contrast enhancement, more hyperintense signal on T1 and a more hypointense signal on T2-weighted sequences was common. Given the rarity of the tumor, awareness of these differences constitutes a prerequisite to avoid delays in diagnostics. Author Affiliation: (1) 0000 0001 0728 0170, grid.10825.3e, Department of Clinical Research, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense, Denmark (2) 0000 0004 0512 5013, grid.7143.1, Department of Neurology, University Hospital of Odense, Sdr. Boulevard 29, 5000, Odense, Denmark (3) 0000 0000 8653 1507, grid.412301.5, Department of Neurology, University Hospital Aachen, Pauwelsstra[sz]e 20, 52074, Aachen, Germany (4) 0000 0000 9194 7179, grid.411941.8, Wilhelm Sander NeuroOncology Unit and Department of Neurology, University Hospital Regensburg, Universitatsstra[sz]e 80, 93053, Regensburg, Germany Article History: Registration Date: 28/04/2016 Received Date: 01/02/2016 Accepted Date: 28/04/2016 Online Date: 22/06/2016 Article note: The authors D. Beier and S. Kocakaya contributed equally to the manuscript.
    Keywords: Adult ; Medulloblastoma ; Magnetic resonance imaging ; Computed tomography ; Contrast enhancement
    ISSN: 1869-1439
    E-ISSN: 1869-1447
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  • 6
    Language: English
    In: Cancer Letters, 10 September 2013, Vol.338(1), pp.32-40
    Description: Ten years after the first description of cancer stem cells (CSCs) in glioblastoma (GBM), the initial concept of CSC has been challenged and our understanding of cellular heterogeneity within malignant brain tumors became more complex. The increasing knowledge on CSC also influences preclinical research and clinical practice. This review therefore describes current concepts and controversies on CSC in GBM and summarizes the recent progress how the CSC hypothesis is about to translate into preclinical and clinical application.
    Keywords: Cancer Stem Cells ; Cd133 ; Glioblastoma ; Radioresistance ; Chemoresistance ; Medicine
    ISSN: 0304-3835
    E-ISSN: 1872-7980
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  • 7
    Language: English
    In: Frontiers in bioscience (Elite edition), 01 January 2011, Vol.3, pp.701-10
    Description: Glioblastomas (GBM) are paradigmatic for the investigation of cancer stem cells (CSC) in solid tumors. Recently, the discovery of CD133- CSC in addition to CD133+ CSC has substantially added to our understanding of the complexity of GBM CSC. This review gives an overview on our current knowledge on CD133-...
    Keywords: Biomarkers, Tumor -- Metabolism ; Cell Differentiation -- Physiology ; Glioblastoma -- Metabolism ; Interleukin Receptor Common Gamma Subunit -- Metabolism ; Neoplastic Stem Cells -- Metabolism
    E-ISSN: 1945-0508
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 8
    In: Journal of Bacteriology, April, 2000, Vol.182(7-8), p.2068(9)
    Description: Results describe four histidine kinases along with their cognate response regulators as bacterial two-component systems model in Helicobacter pylori. Data are presented on chemotaxis and two orphan response regulatory systems.
    Keywords: Helicobacter Pylori -- Genetic Aspects ; Cellular Signal Transduction -- Genetic Aspects ; Protein Kinases -- Research ; Genetic Regulation ; Transcription (Genetics)
    ISSN: 0021-9193
    Source: Cengage Learning, Inc.
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  • 9
    In: Journal of Bacteriology, Jan, 2002, Vol.184(1-2), p.350(13)
    Description: Results show that the two-component signal transduction system of Helicobacter pylori is composed of histidine kinase HP165 and a response regulator HP166, both belonging to the OmpR family of regulators. Data suggest the genes regulate their expression with HP166 acting as a transcriptional activator of gene expression.
    Keywords: Helicobacter Pylori -- Genetic Aspects ; Gene Expression -- Analysis ; Cellular Signal Transduction -- Genetic Aspects ; Bacterial Genetics -- Physiological Aspects
    ISSN: 0021-9193
    Source: Cengage Learning, Inc.
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  • 10
    Language: English
    In: Microbiology (Reading, England), May 2013, Vol.159(Pt 5), pp.880-9
    Description: HP1043 of Helicobacter pylori is an orphan response regulator (RR) with a highly degenerate receiver sequence incapable of phosphorylation, which is essential for cell viability. In contrast, the orthologous RR protein of Helicobacter pullorum, an enterohepatic Helicobacter species mainly isolated from poultry, harbours a consensus receiver sequence and is associated with a cognate histidine kinase (HK). Here, we show that this two-component system of H. pullorum, denoted HPMG439/HPMG440, is involved in the control of nitrogen metabolism by regulating the expression of glutamate dehydrogenase, an AmtB ammonium transporter and a PII protein. However, the role of the RR HPMG439 is not restricted to nitrogen regulation since, in contrast with the HK HPMG440, HPMG439 is essential for growth of H. pullorum under nutrient-rich conditions.
    Keywords: Gene Expression Regulation, Bacterial ; Multigene Family ; Epsilonproteobacteria -- Metabolism ; Transcription Factors -- Metabolism
    ISSN: 13500872
    E-ISSN: 1465-2080
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