Growth inhibition of subcutaneously transplanted human glioma by transfection-induced tumor necrosis factor-alpha and augmentation of the effect by gamma-interferon.
Using subcutaneous solid tumors produced by U251-MG human glioma cells, we studied the in vivo transfection of the cells with the tumor necrosis factor-alpha (TNF-alpha) gene delivered by means of liposomes. When the tumor had become 7 mm in diameter, liposomes with entrapped TNF-alpha gene were injected into the center of the subcutaneous tumor. We found that mRNA of transfection-induced TNF-alpha, which was expressed in the tumor tissue, was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) method and its protein was demonstrated by enzyme-linked immunoassay. Growth of the tumor was inhibited when the injection was carried out five times at every other day. The growth-inhibitory effect by transfection-induced TNF-alpha was much remarkable as compared with exogenous TNF-alpha and the effect was enhanced by the intraperitoneal injection of gamma-interferon (IFN-gamma) 12 h prior to intratumoral injection of the liposomes.
Harada
K
K
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Yoshida
J
J
Mizuno
M
M
Sugita
K
K
Kurisu
K
K
Uozumi
T
T
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D003131:Combined Modality Therapy; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005910:Glioma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D016019:Survival Analysis; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D017931:DNA Primers; D008081:Liposomes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma