title: Promising human brain tumors therapy with interference RNA intervention (iRNAi).
abstract: Glioblastoma multiforme (GBM) is the most common type of malignant gliomas, characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fuelled a search for new treatment modalities. Malignant gliomas express preferentially a number of surface markers that may be exploited as therapeutic targets, such as tenascin-C (TN-C), an extracellular matrix glycoprotein that contributes to tumor cell adhesion, invasion, migration and proliferation. In this paper we describe a novel strategy for human brain tumors therapy based on RNA interference (RNAi) and its application after surgery (intervention with RNAi) to inhibit TN-C synthesis. We present data of 46 patients suffering from brain tumors resected and treated with dsRNA with the sequence homology of tenascin-C mRNA (ATN-RNA). The specific effect of ATN-RNA on TN-C downregulation was proved with antibodies against TN-C in glioblastoma multiforme cultured cells. A significant improvement in overall survival (OS) without loosing the quality of life (QOL) of patients was observed. MRI and CT studies showed tumor growth delay or lack of tumor recurrence. This novel therapy based on RNA interference shows a hopeful therapeutical potential. To our knowledge the intervention with RNAi (iRNAi) method is the first protocol of RNAi application in human brain tumor treatment.
authors.affiliation: Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Rolle
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Nowak
authors.forename: Eliza
authors.initials: E
authors.lastname: Wyszko
authors.forename: Monika
authors.initials: M
authors.lastname: Nowak
authors.forename: Ryszard
authors.initials: R
authors.lastname: Zukiel
authors.forename: Rafal
authors.initials: R
authors.lastname: Piestrzeniewicz
authors.forename: Iwona
authors.initials: I
authors.lastname: Gawronska
authors.forename: Miroslawa Z
authors.initials: MZ
authors.lastname: Barciszewska
authors.forename: Jan
authors.initials: J
authors.lastname: Barciszewski
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D015536:Down-Regulation; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D019063:Tenascin / Q000235:genetics / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D019063:Tenascin