Ozone dosage effect on C6 cell growth, in vitro and in vivo tests: double bond index for characterization

Ozone dissolved in a saline solution applied as a medical therapy promoted an 85% decrement in C6 tumor activity.

Cerebral Blood Volume Quantification in a C6 Tumor Model Using Gadolinium per (3,6-Anhydro) α-Cyclodextrin as a New Magnetic Resonance Imaging Preclinical Contrast Agent

In magnetic resonance imaging (MRI), cerebral blood volume (CBV) quantification is dependent on the MRI sequence and on the properties of the contrast agents (CAs). By using the rapid steady-state T1 method, we show the potential of gadolinium per (3,6-anhydro) α-cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd3+ with per (3,6-anhydro)-α-cyclodextrin), for the CBV quantification in the presence of blood—brain barrier lesions. After biocompatibility and relaxivity experiments, in vivo experiments on rats were performed on a C6 tumor model with 0.05 mmol Gd-ACX/kg (<1/10 of the median lethal dose) injected at a 25mmol/L concentration, inducing neither nephrotoxicity nor hemolysis. On T1-weighted images, a signal enhancement of 170% appeared in vessels after injection, but not in the tumor (during the 1 h of observation), in contrast to the 90% signal enhancement obtained with Gd-DOTA (a clinical MRI CA) injected at a T1 isoefficient dose. This result shows the absence of Gd-ACX extravasation into the tumor tissue and its confinement to the vascular space. Fractional CBV values were found similar to Gd-ACX and Gd-DOTA in healthy brain tissue and in the contralateral hemisphere of tumor-bearing rats, whereas only Gd-ACX was appropriate for CBV quantification in tumor regions.

A brain-tumor model utilizing stereotactic implantation of a permanent cannula

✓ A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-µl injection containing 106 C6 glioblastoma cells (five rats), 106 Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(−5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(−5.0) and the same number of rats received a 1-µl injection containing 105 cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acidic protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (± standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 ± 0.2; A(+3.7) 3.5 ≥ 1.1; A(+2.7) 5.7 ± 1.7; A(+1.7) 9.5 ± 2.3; A(+0.7) 7.5 ± 3.2; A(−0.3) 3.7 ± 2.9; and A(−1.3) 0.3 ± 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 106 cells in the 10-µl volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure.