Linked Life Data

20132050

Source:http://linkedlifedata.com/resource/pubmed/id/20132050

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-7-8
pubmed:abstractText
Human papillomavirus type 16 (HPV16) is associated with the development of anogenital cancers and their precursor lesions, intraepithelial neoplasia. Treatment strategies against HPV-induced intraepithelial neoplasia are not HPV specific and mostly consist of physical removal or ablation of lesions. We had previously designed an HPV-specific approach to kill HPV-infected cells by the herpes simplex virus type 1 thymidine kinase (TK) gene driven by HPV E2 binding to E2-binding sites (E2BS) in the native HPV16 long control region. E2-induced TK expression renders the cells sensitive to the prodrug ganciclovir. To optimize this therapeutic approach, we modified the native long control region by adding variable numbers of E2BS adjacent to E2BS4, resulting in greatly increased cell death in HPV-positive cell lines with variable levels of E2 protein expression and no reduction in HPV specificity. Our results showed maximum increase in TK expression and cell killing when one additional E2BS was added adjacent to E2BS. As HPV-infected patients also exhibit variable E2 expression across lesions and within a lesion, this approach may potentiate the clinical utility of the herpes simplex virus type 1 TK/ganciclovir therapeutic approach.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1557-7422
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
843-54
pubmed:meshHeading
pubmed-meshheading:20132050-Base Sequence, pubmed-meshheading:20132050-Binding Sites, pubmed-meshheading:20132050-Blotting, Western, pubmed-meshheading:20132050-Cell Line, pubmed-meshheading:20132050-Cell Line, Tumor, pubmed-meshheading:20132050-DNA-Binding Proteins, pubmed-meshheading:20132050-Gene Expression Regulation, pubmed-meshheading:20132050-Gene Therapy, pubmed-meshheading:20132050-Herpesvirus 1, Human, pubmed-meshheading:20132050-Humans, pubmed-meshheading:20132050-Molecular Sequence Data, pubmed-meshheading:20132050-Oncogene Proteins, Viral, pubmed-meshheading:20132050-Plasmids, pubmed-meshheading:20132050-Promoter Regions, Genetic, pubmed-meshheading:20132050-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20132050-Thymidine Kinase, pubmed-meshheading:20132050-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Addition of a single E2 binding site to the human papillomavirus (HPV) type 16 long control region enhances killing of HPV positive cells via HPV E2 protein-regulated herpes simplex virus type 1 thymidine kinase-mediated suicide gene therapy.
pubmed:affiliation
Department of Medicine, University of California-San Francisco , San Francisco, CA 94143, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't