IGF-I: from diagnostic to triple-helix gene therapy of solid tumors
| Autor: | Jerzy Trojan, Ladislas A. Trojan, Ryszard Przewlocki, Alexander Shevelev, Dominique Hénin, Aleksandra Glogowska, Ming X. Wei, Piotr Kopiński, Jolanta Czarny, Adama Ly |
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| Rok vydání: | 2002 |
| Předmět: |
tumors
Genetic enhancement medicine.medical_treatment antisense Apoptosis Biology General Biochemistry Genetics and Molecular Biology Glioma Gene expression medicine Biomarkers Tumor triple-helix Humans Insulin-Like Growth Factor I Gene Growth factor glioblastoma Cancer Transfection DNA Genetic Therapy medicine.disease Molecular biology gene therapy IGF-I Glioblastoma Triple helix |
| Zdroj: | Acta biochimica Polonica. 49(4) |
| ISSN: | 0001-527X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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