17 research outputs found
A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin
Modification of the Radiation Sensitivity of Human Tumour Cells by a Bis-benzimidazole Derivative
Cell Kinetic Characteristics In Different Parts of Multicellular Spheroids of Human Origin
Influence of endogenous glutathione level on X-ray induced cell cycle delay in human lymphocytes
Enhanced Cell Killing, Inhibition of Recovery from Potentially Lethal Damage and Increased Mutation Frequency by 3-aminobenzamide in Chinese Hamster V79 Cells Exposed to X-rays
Identification of a UV-induced trans-acting protein that stimulates polyomavirus DNA replication
Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin
Combining gene therapy with radiotherapy and chemotherapy holds potential to increase the efficacy of cancer treatment, while minimizing side effects. We tested the responsiveness of synthetic gene promoters containing CArG elements from the Early Growth Response 1 (Egr1) gene after neutron irradiation, doxorubicin and cisplatin. Human MCF-7 breast adenocarcinoma and U373-MG glioblastoma cells were transfected with plasmids containing CArG promoters controlling the expression of the green fluorescent protein (GFP). Exposing the cells to neutrons, doxorubicin or cisplatin resulted in a significant induction of transgene expression. Therapeutic advantage was demonstrated by replacing the reporter with the herpes simplex virus thymidine kinase (HSVtk), able to convert the prodrug ganciclovir (GCV) into a cytotoxin. A 1.3 Gy neutron dose caused 49% growth inhibition in MCF-7 cells, which increased to 63% in irradiated CArG-HSVtk-transfectants treated with GCV. Exposure to 0.5 mM cisplatin or 0.01 mM doxorubicin induced a growth inhibition of 25 - 30% in MCF-7 cells. In the presence of GCV, this value increased to 65 - 70% in cells transfected with the CArG promoter constructs driving the expression of HSVtk. These data indicate that combining CArG-mediated HSVtk/ GCV suicide gene therapy with radio- and chemotherapy can enhance antitumor toxicity, and validates future in vivo investigations