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  • 1
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    Cross-species genomics matches driver mutations and cell compartments to model ependymoma (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-20
    Description: Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912966/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Robert A -- Wright, Karen D -- Poppleton, Helen -- Mohankumar, Kumarasamypet M -- Finkelstein, David -- Pounds, Stanley B -- Rand, Vikki -- Leary, Sarah E S -- White, Elsie -- Eden, Christopher -- Hogg, Twala -- Northcott, Paul -- Mack, Stephen -- Neale, Geoffrey -- Wang, Yong-Dong -- Coyle, Beth -- Atkinson, Jennifer -- DeWire, Mariko -- Kranenburg, Tanya A -- Gillespie, Yancey -- Allen, Jeffrey C -- Merchant, Thomas -- Boop, Fredrick A -- Sanford, Robert A -- Gajjar, Amar -- Ellison, David W -- Taylor, Michael D -- Grundy, Richard G -- Gilbertson, Richard J -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-06A18120/CA/NCI NIH HHS/ -- P01 CA096832-078120/CA/NCI NIH HHS/ -- P01CA96832/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA021765-319030/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01 CA129541-01/CA/NCI NIH HHS/ -- R01 CA129541-02/CA/NCI NIH HHS/ -- R01 CA129541-03/CA/NCI NIH HHS/ -- R01 CA129541-04/CA/NCI NIH HHS/ -- R01CA129541/CA/NCI NIH HHS/ -- T32 CA070089/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jul 29;466(7306):632-6. doi: 10.1038/nature09173. Epub 2010 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639864" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Compartmentation ; Central Nervous System/cytology/growth & development ; Central Nervous System Neoplasms/classification/genetics/pathology ; *Disease Models, Animal ; Ependymoma/classification/*genetics/*pathology ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, p16 ; *Genomics ; Humans ; Mice ; Models, Biological ; Mutation/*genetics ; Polymorphism, Single Nucleotide/genetics ; Receptor, EphB2/genetics/metabolism ; Species Specificity ; Stem Cells/cytology/metabolism ; Synapses/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Subtypes of medulloblastoma have distinct developmental origins (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-12-15
    Description: Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059767/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibson, Paul -- Tong, Yiai -- Robinson, Giles -- Thompson, Margaret C -- Currle, D Spencer -- Eden, Christopher -- Kranenburg, Tanya A -- Hogg, Twala -- Poppleton, Helen -- Martin, Julie -- Finkelstein, David -- Pounds, Stanley -- Weiss, Aaron -- Patay, Zoltan -- Scoggins, Matthew -- Ogg, Robert -- Pei, Yanxin -- Yang, Zeng-Jie -- Brun, Sonja -- Lee, Youngsoo -- Zindy, Frederique -- Lindsey, Janet C -- Taketo, Makoto M -- Boop, Frederick A -- Sanford, Robert A -- Gajjar, Amar -- Clifford, Steven C -- Roussel, Martine F -- McKinnon, Peter J -- Gutmann, David H -- Ellison, David W -- Wechsler-Reya, Robert -- Gilbertson, Richard J -- 01CA96832/CA/NCI NIH HHS/ -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-06A18120/CA/NCI NIH HHS/ -- P01 CA096832-078120/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01 CA129541-01/CA/NCI NIH HHS/ -- R01 CA129541-02/CA/NCI NIH HHS/ -- R01 CA129541-03/CA/NCI NIH HHS/ -- R01 CA129541-04/CA/NCI NIH HHS/ -- R01 CA129541-05/CA/NCI NIH HHS/ -- R01 NS037956/NS/NINDS NIH HHS/ -- R01 NS037956-13/NS/NINDS NIH HHS/ -- R01CA129541/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 23;468(7327):1095-9. doi: 10.1038/nature09587. Epub 2010 Dec 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150899" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Stem/*pathology ; Cerebellar Neoplasms/*pathology ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Medulloblastoma/*pathology ; Mice ; Mice, Transgenic ; Mutation ; beta Catenin/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Organometallic Nucleoside Analogues with Ferrocenyl Linker Groups: Synthesis and Cancer Cell Line Studies (2014)
    American Chemical Society (ACS)
    Details
    Publication Date: 2014-06-21
    Description: Journal of Medicinal Chemistry DOI: 10.1021/jm500246h
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 4
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    On evaluating the performance of GSS: furthering the debate,by Paul Finlay [European Journal of Operational Research 107,pp.193-201] (2000)
    Elsevier
    Details
    Publication Date: 2000-01-01
    Print ISSN: 0377-2217
    Electronic ISSN: 1872-6860
    Topics: Mathematics , Economics
    Published by Elsevier
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  • 5
    Electronic Resource
    Electronic Resource
    Natural resistance to urinary tract infection determined by endotoxin-induced inflammation (1988)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 49 (1988), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract Uninary tract infections (UTI) are common, with frequencies ranging from about 1 to 10% in different age groups, Gram-negative bacteria dominate as causative agents. Defects in host resistance to bacteriuria have not been defined at the molecular level. The results of the present study demonstrate that endotoxin-induced inflammation mediates bacterial clearance from the kidneys. Genetic or pharmacologically induced defects in this function drastically impaired the natural resistance to infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.1988.tb02719.x
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  • 6
    Electronic Resource
    Electronic Resource
    Secretor state and renal scarring in girls with recurrent pyelonephritis (1989)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 47 (1989), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract The non-secretor phenotype was significantly associated with the occurrence of renal scarring among patients with recurrent pyelonephritis. Girls (n= 77) with recurrent pyelonephritis were followed from the first known episode of infection for up to twelve years with repeated radiological investigations. They were divided into two categories: those with renal scars (n= 35) and those who did not develop scars (n= 42). There was a significant over-representation of non-secretors among the patients with scarring, (14/35, 40%) compared to the healthy controls (21.8%, P 〈 0.05). The frequency of non-secretors among the girls who did not develop scars in spite of repeated episodes of acute pyelonephritis was not significantly different from the healthy controls (9/42, 21%, n.s.). This study provides a basis for analysis of the influence of secretor state on host-parasite interaction in the urinary tract.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.1989.tb02423.x
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  • 7
    Electronic Resource
    Electronic Resource
    Influence of P blood group phenotype on susceptibility to urinary tract infection (1989)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 47 (1989), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract Bacterial attachment is an important event in the pathogenesis of urinary tract infection (UTI). Increased receptivity on the host cells has been suggested influence proneness to infection. The dual function of the globoseries of glycolipids both as receptors for attaching E. coli and as P blood group antigens lead us to examine the P blood group phenotype distribution in UTI prone patient populations. A correlation between the P1 blood group phenotype and susceptibility to UTI was found. Patients with recurrent pyelonephritis had 74/79 (94%), P1 compared to 75% in healthy controls. In contrast patients with asymptomatic bacteriuria (ABU) had a reduced frequency of P1, 43/74 (58%). P1 and P2 individuals differ in amount and composition of the globoseries of glycolipids on their erythrocytes. A similar difference in other tissues, e.g. uroepithelial cells might explain the association of P1 with UTI. There was, however, no significant difference in bacterial adherence to uroepithelial cells from P1 and P2 individuals. Other mechanisms explaining the increase in P1 individuals in recurrent pyelonephritis are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.1989.tb02422.x
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  • 8
    Electronic Resource
    Electronic Resource
    Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methylcholanthrene-induced sarcoma
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 157 (1988), S. 575-579 
    Details
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0006-291X(88)80288-2
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  • 9
    Electronic Resource
    Electronic Resource
    Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methylcholanthrene-induced sarcoma
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 157 (1988), S. 575-579 
    Details
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0006-291X(88)80288-2
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  • 10
    Electronic Resource
    Electronic Resource
    Break-up of the Atlantic deep western boundary current into eddies at 8° S (2004)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 432 (2004), S. 1018-1020 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The existence in the ocean of deep western boundary currents, which connect the high-latitude regions where deep water is formed with upwelling regions as part of the global ocean circulation, was postulated more than 40 years ago. These ocean currents have been found adjacent to the ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nature03134
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