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dc.contributor.authorPapaevangelou, E
dc.contributor.authorBoult, JKR
dc.contributor.authorWhitley, GS
dc.contributor.authorRobinson, SP
dc.contributor.authorHowe, FA
dc.date.accessioned2018-09-10T08:35:03Z
dc.date.issued2018-11-01
dc.identifier.citationAngiogenesis, 2018, 21 (4), pp. 737 - 749
dc.identifier.issn0969-6970
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2595
dc.identifier.eissn1573-7209
dc.identifier.doi10.1007/s10456-018-9617-6
dc.description.abstractNitric oxide (NO) has been strongly implicated in glioma progression and angiogenesis. The endogenous inhibitors of NO synthesis, asymmetric dimethylarginine (ADMA) and N-monomethyl-L-arginine (L-NMMA), are metabolized by dimethylarginine dimethylaminohydrolase (DDAH), and hence, DDAH is an intracellular factor that regulates NO. However, DDAH may also have an NO-independent action. We aimed to investigate whether DDAH I has any direct role in tumour vascular development and growth independent of its NO-mediated effects, in order to establish the future potential of DDAH inhibition as an anti-angiogenic treatment strategy. A clone of rat C6 glioma cells deficient in NO production expressing a pTet Off regulatable element was identified and engineered to overexpress DDAH I in the absence of doxycycline. Xenografts derived from these cells were propagated in the presence or absence of doxycycline and susceptibility magnetic resonance imaging used to assess functional vasculature in vivo. Pathological correlates of tumour vascular density, maturation and function were also sought. In the absence of doxycycline, tumours exhibited high DDAH I expression and activity, which was suppressed in its presence. However, overexpression of DDAH I had no measurable effect on tumour growth, vessel density, function or maturation. These data suggest that in C6 gliomas DDAH has no NO-independent effects on tumour growth and angiogenesis, and that the therapeutic potential of targeting DDAH in gliomas should only be considered in the context of NO regulation.
dc.formatPrint-Electronic
dc.format.extent737 - 749
dc.languageeng
dc.language.isoeng
dc.publisherSPRINGER
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectMice
dc.subjectMice, Nude
dc.subjectRats
dc.subjectGlioma
dc.subjectNeovascularization, Pathologic
dc.subjectNitric Oxide
dc.subjectAmidohydrolases
dc.subjectNeoplasm Proteins
dc.subjectNeoplasm Transplantation
dc.subjectFemale
dc.subjectHeterografts
dc.titleAssessment of the direct effects of DDAH I on tumour angiogenesis in vivo.
dc.typeJournal Article
dcterms.dateAccepted2018-04-24
rioxxterms.versionofrecord10.1007/s10456-018-9617-6
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAngiogenesis
pubs.issue4
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume21
pubs.embargo.termsNo embargo
pubs.oa-locationhttps://link.springer.com/content/pdf/10.1007/s10456-018-9617-6.pdf
icr.researchteamPre-Clinical MRI
dc.contributor.icrauthorBoult, Jessica
dc.contributor.icrauthorRobinson, Simon


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