Figure 2
From: Maximizing the potential of aggressive mouse tumor models in preclinical drug testing
Ispinesib is a promising therapy for atypical teratoid rhabdoid tumor. (a) Coronal section of magnetic resonance imaging (MRI) of an infant with atypical teratoid rhabdoid tumor (ATRT). (b) Top view of cranial cavity of different mice implanted with CHLA-06 tumor cells into the right cerebrum (yellow arrows highlight the bulging right brain with tumor growth beneath). (c) Treatment timeline in Batch A animals (Treatment Group = 5, Control Group = 4). Ispinesib in-vivo dosing was 10 mg/kg administered intraperitoneally every 4 days for three doses, with the treatment course repeated on day 21. (d) Top view of cranial cavity of mice brains in Batch B animals (Treatment Group = 4, Control Group = 3). Brains from ispinesib-treated animals (lower panel) were structurally more normal in appearance, in contrast to untreated control animals (upper panel) which were distorted by tumor growth and more necrotic in appearance. Similar findings were observed in Batch A animals (Fig. S5). (e) Progression-free survival of animals in both Batch A and Batch B demonstrating significantly improved survival outcome among ispinesib-treated mice (Log-rank test, Mantel-Cox method). Solubility of ispinesib was increased using different diluent for reconstitution (“Materials and methods”, Batch A: Less soluble. Batch B: More soluble). (f) Overall survival of animals in both Batch A and Batch B similarly demonstrating significantly improved survival outcome among ispinesib-treated mice (Log-rank test, Mantel-Cox method). (g) Hematoxylin and eosin (H&E) staining of formalin-fixed mouse brains (ispinesib-treated versus untreated control, Batch A animals). Coronal sections of mouse brains from ispinesib-treated versus untreated mice showing a tumor mass (black arrows) in the center compressing against normal brain tissue. Magnification (×40 and ×100) photomicrographs showing tumor core interfacing with normal brain parenchyma in mice brains. Magnification (×600) photomicrographs showing ispinesib-treated tumors demonstrating frequent apoptotic bodies (green arrows) but no mitoses (red arrows). In contrast, untreated control xenograft tumors demonstrated numerous mitoses (red arrows) and a small number of apoptotic bodies (green arrows). (h) H&E Coronal sections of ispinesib-treated versus untreated control (Batch B animals). Black arrows indicate tumor. Absence of a visible tumor in mouse which received 7-cycles of ispinesib. Effects were tumor-specific; surrounding mouse brain parenchyma remained healthy with normal appearance, after 7 cycles of ispinesib.
