Article Figures & Data
Figures
- Figure 1.
Histopathology of medulloblastomas induced by Shh + HGF. A and B, coronal brain sections showing tumor in the cerebellum and fourth ventricle (A) and obstructive hydrocephalus in the forebrain (B; H&E). C, classic medulloblastoma pattern showing homogeneous sheets of undifferentiated tumor cells (H&E). D, MBEN pattern in which round, neurocytic-appearing tumor cells are arrayed in a linear pattern (top left and inset) adjacent to an area of disorganized cytoarchitecture characteristic of the classic pattern (right; H&E). E, immunoperoxidase staining showing that MBEN areas (left) have abundant immunoreactivity for neuronal differentiation marker NeuN compared with classic-appearing areas (right). F, immunoperoxidase staining showing that Ki67 staining is absent in the MBEN area (left) compared with the actively proliferating cells in the classic-appearing area (right). Scale bars, 500 μm (A and B), 25 μm (C and D, inset), and 50 μm (D–F).
- Figure 2.
Response to Shh- and HGF-targeted therapy in mice with medulloblastomas. Kaplan-Meier survival analysis of mice injected with RCAS-Shh and RCAS-HGF on day 0 and then treated with the indicated therapeutic agents starting on day 14 (arrow). A and B, results from two independent experiments.
- Figure 3.
Analysis of proliferation and apoptosis in Shh + HGF–induced medulloblastomas. Bar graphs and representative photomicrographs showing the percentage (mean ± SEM) of tumor cells with positive immunoreactive staining for Ki67 (proliferation index; A) and cleaved caspase-3 (apoptotic index; B) in Shh + HGF–induced medulloblastomas from mice treated with the indicated therapeutic agents. Scale bars, 25 μm.
- Figure 4.
Analysis of Shh and HGF signaling in response to molecular-targeted therapy. Bar graphs and representative photomicrographs showing the percentage (mean ± SEM) of tumor cells with positive immunoreactive staining for Gli2 in the nucleus (Gli2 index; A) and phosphorylated c-Met in the cytoplasm (pc-Met index; B) in medulloblastomas from mice treated with the indicated therapeutic agents. Phototmicrographs in B show pc-Met+ tumor cells (right) adjacent to cerebellar cortex (left). Scale bars, 25 μm (A) and 50 μm (B).
Tables
- Table 1.
Four-month survival analysis of Ntv-a mice with Shh + HGF–induced medulloblastomas
Therapeutic agent Dosing regimen No. of mice analyzed Median survival (d) P 5G8 2.5 mg/kg i.p. twice weekly 60 23 — L2G7 2.5 mg/kg i.p. twice weekly 58 111 0.03 Cyclopamine + 5G8 10 mg/kg i.p. every other day + 5G8 60 62 0.04 L2G7 + cyclopamine See above regimens 59 47 0.8 5E1 5.0 mg/kg i.p. twice weekly 34 >102 0.04 NOTE: P values were derived from log-rank tests comparing cumulative survival of each test group with 5G8 control. The P value for the cyclopamine group was calculated over a 90-d observation period.
Volume 9, Issue 9
