1-2-dielaidoylphosphatidylethanolamine and Brain-Neoplasms

To aim at demonstrating whether cationic liposome-mediated antisense c-myb oligonucleotide(LipoAON) can inhibit the growth of C6 glioma by intravenous injection.. Intracerebral C6 glioma cells were implanted into the left caudal nucleus of forty-eight male Wistar rats. There were four groups: LipoAON(n = 12), antisense c-myb oligonucleotide (AON; n = 12), cationic liposome (Lipo; n = 12), and normal saline (NS; n = 12). Six days after tumor implantation, the above-mentioned drugs were injected into the right femoral veins of the rats respectively. Two days later, the same drugs were injected into the left femoral veins. The appetite, motor and weight of every animal were closely observed during the whole experiment. Six rats of each group were respectively killed 4 days and 10 days after the end of administration. The weight change, pathologic examination and immunohistochemical analysis of c-myb expression of the tumor were completed.. In LipoAON group, the growth of the tumors was significantly inhibited in a short time after treatment and c-myb expression was down-regulated. But in the AON group and Lipo group, the growth of the tumors was not inhibited and c-myb expression was not down-regulated, compared with that in NS group. The inhibitory effect of LipoAON on the tumors rapidly declined with time and c-myb expression was again up-regulated.. 1. Cationic liposome (LipofectAMINE) as transfection vehicle makes c-myb easily penetrate BBTB and enter the tumor. The technique is simple, safe, highly effective for the transfection of c-mybAON; 2. LipoAON has marked inhibitory effect on the growth of C6 glioma. The AON technical method for inhibiting the expression of c-myb oncogene has a research perspective in the treatment of glioma; 3. The inhibitory effect of LipoAON on the growth of glioma declines with time. The question about how to make c-myb AON have highly effective, sustained and stable expression in the tumor still requires further research.

Topics: Animals; Brain Neoplasms; Cations; Cell Division; Genes, myb; Glioma; Liposomes; Male; Oligonucleotides, Antisense; Phosphatidylethanolamines; Proto-Oncogene Proteins c-myb; Rats; Rats, Wistar; Tumor Cells, Cultured

Topics: Animals; Base Sequence; Brain Neoplasms; Cell Division; Cell Nucleus; Drug Carriers; Glioma; Indicators and Reagents; Liposomes; Microtubule-Associated Proteins; Oligodeoxyribonucleotides, Antisense; Phosphatidylethanolamines; Rats; RNA-Binding Proteins; RNA, Messenger; Thionucleotides; Tumor Cells, Cultured

Epidermal growth factor receptor (EGFR) plays an important role in the progression of malignancy in gliomas. We studied the growth inhibition of the malignant glioma cell lines using an antisense EGFR oligodeoxynucleotide enveloped with Lipofectin. At a concentration of 5 microM of the antisense EGFR oligodeoxynucleotide enveloped with Lipofectin, the proliferation of three malignant glioma cell lines was significantly inhibited (p < 0.05) compared with that of the cells exposed to 5 microM sense EGFR oligodeoxynucleotide. The activity of the tyrosine kinase and the DNA synthesis was also significantly suppressed (p < 0.05). These findings show that the antisense EGFR oligodeoxynucleotide enveloped with Lipofectin has a possibility to become a useful gene therapy against malignant gliomas.

Topics: Brain Neoplasms; Cell Division; DNA, Neoplasm; Drug Carriers; ErbB Receptors; Genetic Therapy; Glioma; Humans; Liposomes; Oligodeoxyribonucleotides, Antisense; Phosphatidylethanolamines; Transfection; Tumor Cells, Cultured

A cavitary glioblastoma model was created by injection of RT-2 cells, which express endogenous wild type p53, into the peritoneal cavity of nude mice. This model developed multiple layers of tumor cells invading the peritoneal surface and was used to mimic the postoperative surgical cavity remaining after glioblastoma (GBM) excision in patients. Rhodamine labeled DMRIE/DOPE + DNA complexes were found to penetrate at least 20 tumor cell layers. Injection of p53 gene/liposome complexes into the intraperitoneal cavity after the tumor was established resulted in massive tumor necrosis. Prominent staining of human p53 protein using the DO-1 antibody was found in tumor cells near the necrotic lesions. Tumor explants expressed human p53 protein and showed a 54% growth reduction in an in vitro growth assay. Further, DMRIE/DOPE mediated p53 gene transfection significantly increased the mean survival time of tumor bearing mice compared to vector control. These results demonstrate the efficiency of using exogenous wild type p53 to suppress glioblastoma cell with endogenous wild type p53 in vivo through liposome mediated transfection method.

Topics: Animals; Brain Neoplasms; Drug Delivery Systems; Gene Transfer Techniques; Genetic Therapy; Glioblastoma; Humans; Lipids; Liposomes; Mice; Mice, Nude; Phosphatidylethanolamines; Quaternary Ammonium Compounds; Rats; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Using a minipump combined with stereotaxic techniques allows continuous delivery of therapeutic genetic materials into the brain. We investigated the therapeutic efficacy of liposome-mediated HSVtk gene transfer of experimental brain F98 glioma followed by treatment with ganciclovir. A single injection of DNA-liposome complexes showed a therapeutically significant decrease in the tumor volume. Continuous intracerebral delivery of DNA-liposome complexes using an osmotic minipump led to complete tumor regression in 36.4% of the treated animals. The safety and toxicity of this gene delivery system were also assessed. No organ pathology was observed in the experimental animals. The continuous gene delivery system could be a useful means of achieving higher doses with less toxicity and without the need for frequent injections.

Topics: Animals; Antiviral Agents; Brain Neoplasms; Cell Survival; DNA, Viral; Ganciclovir; Gene Transfer Techniques; Genes, Reporter; Genetic Therapy; Glioma; Humans; Lac Operon; Lipids; Liposomes; Phosphatidylethanolamines; Quaternary Ammonium Compounds; Rats; Rats, Inbred F344; Simplexvirus; Stereotaxic Techniques; Thymidine Kinase

The Myc family proteins represented by c-Myc are thought to play a crucial role in cellular proliferation, differentiation, transformation, and apoptosis. In this study, we demonstrated the novel role for a Myc family protein in elicitation of immunogenic phenotypes in tumor cells. Injection of rat 9L or C6 glioma cells, together with the s-myc gene linked to the cytomegalovirus promoter, completely prevented formation of both brain tumors and s.c. tumors derived from the parental glioma cells. However, introduction of the s-myc gene had no inhibitory effect on development of B104-derived neuroblastoma. In addition, unlike the s-myc gene, injection of the c-myc or wild type p53 (wt-p53) gene together with glioma cells did not modulate the tumor immunogenicity and resulted in formation of gliomas in the animals. These findings suggest that s-Myc expression may stimulate the presentation of a tumor antigen common to 9L and C6 cells to T lymphocytes and augment the activity of the host immune system, resulting in prevention of glioma formation in vivo. This success in tumor eradication indicates the possibility of application of the s-myc gene for gene therapy of human brain tumors.

Topics: Animals; Brain Neoplasms; Genes, myc; Genes, p53; Genetic Therapy; Glioma; Hindlimb; Male; Neoplasm Transplantation; Neuroblastoma; Phosphatidylethanolamines; Proto-Oncogene Proteins c-myc; Rats; Rats, Inbred F344; Skin Neoplasms; Transfection; Tumor Cells, Cultured