Dag R. Sørensen
Department of comparative medicine, Rikshospitalet, University of Oslo
Malignant gliomas are very aggressive tumors and are resistant to current therapies including surgery, chemotherapy and radiation. Thus, there is a need for developing novel therapeutic strategies. Notably, this tumor is characterized by rapidly dividing cells and a high degree of vascularity (angiogenesis).
Recombinant endostatin and chemically synthesized DNA enzyme against the protein kinase C a were used in this study. For in vitro experiments, the DNA enzyme was delivered to glioma cells via cationic liposomes. For in vivo experiments, recombinant endostatin was delivered via a mini osmotic pump connected to a brain infusion kit for a period of up to 28 days, whereas the PKCa DNA enzyme was given as a single intracranial injection on day 3 after tumor cell inoculation.
The DNA enzyme inhibited glioma cell proliferation in vitro and PKCa gene expression in a dose dependent manner as compared with its inactive form. Rats treated with both the endostatin and the PKCa DNA enzyme survived longer (P<0.0002) than those treated with either endostatin (P< 0.025) or PKCa (P< 0.047) alone.
Taken together, the data suggest that combined targeting of tumor cell proliferation and tumor vasculature represent an attractive therapeutic strategy against gliosarcoma growth.
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