Figure 6.

Photomicrographs of RGD or scrambled peptide repeatedly introduced intracranially into cannulated normal rat brain (a-c) or 9L tumor-bearing rat brain (d-i). At 24 hr following the last infusion: (a) Rat brains administered RGD peptide at high doses show signs of stress including congested vessels (black arrows) and capillaries (white arrow). (b) At higher power, brains given RGD peptide at higher doses also showed infiltration of mononuclear cells and polymorphonuclear cells (black arrows), indicative of an acute inflammatory reaction. At 7 or 14 days following the last infusion: (c) Small focal sterile granulomas often formed in cannulated rat brain, whether treated with saline or peptide, as visualized by a necrotic center (Nc) surrounded by a fibrotic wall (Fb). Normal brain (NB) was immediately adjacent to the granuloma. (d) At low power, a representative sized area of necrosis characteristic of scrambled peptide treated brains is shown next to (e) a representative larger sized area of necrosis characteristic of RGD peptide treated brains. The (f) saline-treated tumor has viable cells showing a number of mitotic figures (black arrows) and (g) tumor cells at the periphery of the solid tumor mass are infiltrating into perivascular spaces within normal brain. The (h) RGD peptide treated brain sections show many cells with pyknotic nuclei interspersed within the solid tumor mass adjacent to the instillation site (i) often the palisading areas of growth better show the pyknotic cells that are assumed undergoing apoptosis. Healthy tumor cells are also shown growing in perivascular spaces of the RGD peptide treated brains, however, similar to that shown in g. Magnifications are: d,e = 40X, a,c = 100X, h,i = 200X, f,g = 400X, b = 600X