A skin incision was made, the scalp was reflected and a burr hole was drilled 3.5 mm to the right of the bregma. A 4 μL suspension of 1000 F98 glioma cells in serum-free DMEM was injected stereotactically into the right caudate nucleus of syngeneic Fischer rats using a syringe pump (KDS310; Geneq, Inc., Montréal, Quebec, Canada). The cells were injected over 8 min via a 26 gauge needle, which was inserted to a depth of 7 mm from the skull surface

and then withdrawing it to the target depth of 6.5 mm. After tumor cell implantation, the needle was left in place for 2 min and then slowly withdrawn. The burr hole in the calvarium was sealed with bone wax, and the operative field was cleansed with povidone iodine before closure of the scalp incision by sutures. Intracerebral delivery of carboplatin and experimental R788 solubility dmso plan Carboplatin (M.W = 371.25 Da, Faulding Pharmaceuticals, Asnières, France) was diluted in 5% dextrose to obtain a final concentration of 0.5 mg/mL. ALZET osmotic pumps (model #2001, Charles

Rivers Laboratories, L’Abresles, France) and brain infusion kits (Bilaney, Dusseldorf, Germany) were assembled and filled with carboplatin. The pumps were stored in the dark in a sterile solution of 0.9% saline at 37°C for 24 h prior to their use. Seven days after tumor cell implantation the animals were anesthetized and the scalp incision was re-opened. The bone wax was removed with a needle, and the infusion Selleckchem GSK-3 inhibitor cannula was introduced to a depth of 6.5 mm through the hole made at the time of tumor cell implantation. The brain infusion kit was fixed in place with surgical glue, and the pump was implanted in a subcutaneous pocket in the midscapular region, with a sufficient amount of catheter tubing to permit free motion of the animal’s head and neck. The pumps were left in place from days 7 to 13, during which time the animals received an infusion of 144 μL of carboplatin (72 μg, 194 nmol), delivered at a flow rate of 1 μL/h over 6 days, after which the pumps were removed. The rats, were stratified into four groups and treated as follows:

Group 1, Untreated controls; Group 2, Received a 6 days infusion of carboplatin (72 μg/144 μL) beginning on day 7 following tumor implantation; Group 3, Received a single 15 Gy dose of 6 MV X-rays on day 14; Group 4, Received a 6 days infusion Ureohydrolase of carboplatin, beginning on day 7 following tumor implantation in combination with a single 15 Gy dose of 6 MV X-rays administered on day 14. We have compared the survival times of these animals with the experimental groups irradiated with synchrotron X-rays tuned at 78.8 keV, as reported in detail in our previous report [12]. Irradiation with 6 MV photons Irradiations were performed at the University Hospital of Grenoble using a 6 MV LINAC (SLi, Elekta Oncology Systems, Ltd., West Sussex, UK). Rats were placed in a polystyrene box and were irradiated, two at a time.