title: IGF-I: from diagnostic to triple-helix gene therapy of solid tumors.
abstract: Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I" therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide--an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors.
authors.affiliation: department of Gene Therapy, Ludwik Rydygier Medical University, Bydgoszcz, Poland.
authors.forename: Ladislas A
authors.initials: LA
authors.lastname: Trojan
authors.forename: Piotr
authors.initials: P
authors.lastname: Kopinski
authors.forename: Ming X
authors.initials: MX
authors.lastname: Wei
authors.forename: Adama
authors.initials: A
authors.lastname: Ly
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Glogowska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Czarny
authors.forename: Alexander
authors.initials: A
authors.lastname: Shevelev
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
authors.forename: Dominique
authors.initials: D
authors.lastname: Henin
authors.forename: Jerzy
authors.initials: J
authors.lastname: Trojan
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C051802:triplex DNA; D007334:Insulin-Like Growth Factor I; D004247:DNA