Growth characteristics of intracerebral L5178Y lymphoma cells.

(A-F) Histologic section stained with hematoxylin-eosin. (A-C) Tumor cell growth in untreated animals. (A) Section obtained from mice killed 2 days after tumor challenge, demonstrates early neoplastic infiltration of the brain. Arrow points to lymphoma cells surrounding a capillary vessel (original magnification, 40 ×). (B) Extensive infiltration, associated with small hemorrhages, is observed in mice killed 4 days after challenge (original magnification, 25 ×). (C) Massive neoplastic infiltration, with brain damage (inset), is detected in mice killed 6 days after challenge (original magnification, 10 ×, inset 40 ×). (D-F) Effects of drug treatment on tumor cell growth. Histologic analysis of untreated or drug-treated mice was performed on day 15 after tumor challenge in additional mice that were not considered for the evaluation of survival (original magnification, 4 ×). Arrows point to hemorrhage and necrosis. (D) Untreated control: massive neoplastic infiltration of the brain. (E) 100 mg/kg TZM on days 2 and 3: diffuse brain infiltration. (F) 100 mg/kg NU1025 + TZM on days 2 and 3: focal collections of neoplastic cells, localized mostly under the leptomeninges, with initial infiltration of the brain tissue. There is no evidence of hemorrhage or necrosis. Tumor cell growth was analyzed by quantitative morphometry of histologic sections (n = 15, 5 animals/group). Results, expressed as mean area (mm²± SE) of tumor infiltration, were as follows: untreated control, 6.82 ± 2; TZM, 5.52 ± 1; NU1025 + TZM, 0.058 ± 0.05. Statistical analysis according to unpaired Student's ttest: NU1025 + TZM versus untreated controls,P = .00104; NU1025 + TZM versus TZM,P = .000108; TZM versus untreated controls,P = .115. Tumor growth inhibition induced by NU1025 + TZM or by TZM was 99% (range, 98%-99.9%) and 20% (range, 12%-49%), respectively.