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AuthorMeisohle, Dominikdc.contributor.author
Date of accession2016-03-15T06:23:35Zdc.date.accessioned
Available in OPARU since2016-03-15T06:23:35Zdc.date.available
Year of creation2010dc.date.created
AbstractGenetically modified anaerobic clostridia open a new possibility of treatment of solid tumours with promising potential. The immunologically well tolerated spores of these organisms only germinate in hypoxic regions of massive tumours. Proteolytic clostridia in general are able to colonize tumours efficiently. A destructive effect of colonization can be highly increased by the recombinant production of reactive agents directly in the tumour, minimizing possible adverse side effects. CPE is a toxin of Clostridium perfringens and it was shown to target claudin receptors, which are massively overexpressed in pancreatic carcinoma cell lines. CPE thus binds specifically to cancer cells, forms pores, and ultimately causes cell death. A Clostridium acetobutylicum strain was transformed with a shuttle vector carrying the gene for CPE, fused with the amyP signal peptide sequence, and controlled by a constitutive clostridial promoter. This strain is able to produce and secrete up to 500 ng/ml of CPE into the surrounding medium but is not able to colonize in vivo solid tumours efficiently. Therefore, it was the aim of this work to adapt the constitutive expression system to Clostridium sporogenes. Unfortunately, the unwanted expression of this fusion protein in E. coli caused by the used constitutive promoter leads to the death of the host. Thus, attempts were made to use different inducible promoter systems and to silence the expression in E. coli using antisense RNA against the mRNA of the signal peptide. Additionally, new clostridial signal peptides sequences were fused to cpe gene. These constructs were characterized and tested for the further use in C. sporogenes.dc.description.abstract
Languagededc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 01.10.2008)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v2dc.rights.uri
KeywordCancer therapydc.subject
KeywordClostridium perfringens enterotoxindc.subject
KeywordCPEdc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
LCSHCancer. Treatmentdc.subject.lcsh
TitleEntwicklung rekombinanter Clostridium sporogenes-Sporen als neuer Therapieansatz für die Behandlung nekrotisierender Tumoredc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-1881dc.identifier.doi
PPN643739769dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-74710dc.identifier.urn
GNDClostridium sporogenesdc.subject.gnd
FacultyFakultät für Naturwissenschaftenuulm.affiliationGeneral
Date of activation2010-12-13T12:23:12Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 13.864; W: W-H 12.332uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS ID7471uulm.vtsID
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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