ABSTRACT
OBJECTIVES: As the treatment of human intrinsic brainstem gliomas remains challenging, experimental glioma models are needed. METHODS: We developed a rat model of intrinsic brain stem glioma that uses a stereotactic frame to fix the head for the delivery of C6 glioma cells to target sites via a permanently implanted cannula. We inoculated the rat midbrain, pons or cerebral cortex with 5 x 10(4) cells suspended in 1 microl culture medium over the course of 2 minutes. RESULTS: Three days post-implantation, tumor formation was visible in the periaqueductal gray matter in the midbrain and the tegmentum of the pons. On the tenth day, the tumor diameter exceeded over 2 mm; there was no tumor cell seeding into the cerebrospinal fluid space. The tumor manifested the histological features typical of glioblastoma; Ki-67 labeling index was 32%. DISCUSSION: Because in our model the cannula is permanently implanted, additional inocula can be delivered. Here we detail our rat brainstem glioma model and discuss its usefulness for the investigation of these tumor in humans.
Subject(s)
Brain Stem Neoplasms/physiopathology , Brain Stem/surgery , Brain Tissue Transplantation/methods , Disease Models, Animal , Glioma/physiopathology , Stereotaxic Techniques/instrumentation , Animals , Biomarkers, Tumor/metabolism , Brain Stem/anatomy & histology , Brain Stem Neoplasms/pathology , Brain Tissue Transplantation/instrumentation , Cell Line, Tumor , Glioma/pathology , Graft Survival/physiology , Ki-67 Antigen/metabolism , Male , Mesencephalon/anatomy & histology , Mesencephalon/surgery , Pons/anatomy & histology , Pons/surgery , Rats , Rats, WistarABSTRACT
The in vitro antiproliferative and apoptosis inducing properties of the nonsteroidal anti-inflammatory drugs (NSAIDs) like acetyl salicylic acid (aspirin) and indomethacin were investigated in T98G human glioblastoma cells to explore their potential role in the chemoprevention of human glioma. The biological effects induced by aspirin and indomethacin on T98G cells, in which the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were confirmed by RT-PCR and immunostaining, were investigated by studying cell proliferation and apoptosis assays. The antiproliferative effects occurred in a dose- and time-dependent manner on T98G cells by the treatment with 0.1 -2 mM aspirin and 25-100 microM indomethacin. Moreover, aspirin displayed the greatest growth inhibition within 24 h. Approximately 90% growth inhibition occurred following treatment either with 2 mM aspirin or 100 microM indomethacin by 72 h and induction of apoptosis was confirmed by DNA laddering and TUNEL assay. Our in vitro findings indicate that aspirin and indomethacin have an antiproliferative effect on T98G human glioblastoma cells at toxic concentrations.
