Figure 2.

Effect of maximal tolerated dose (MTD) of eribulin mesylate, paclitaxel, and ixabepilone on dorsal root ganglion (DRG) morphology. DRG morphology at the light microscopic level showed changes after each chemotherapy (at its MTD). Ixabepilone (D) caused most severe and frequent morphologic changes both in neuronal and glial compartments. Severely injured, degenerating neurons are outlined (red). Dark cytoplasmic inclusions were evident and were often localized in the perinuclear area. Vacuolations (white arrows) and swelling phenomena (red arrowheads) were evident in the cytoplasm of satellite cells (D). DRGs from paclitaxel-treated mice (C) also displayed degenerating nerve cells (outlined by red circle) with dark cytoplasm (red arrows) and clear vacuolations in cytoplasm of satellite cells (white arrow). Alterations in the proximal axons of DRG were also observed (white circle). DRGs from eribulin mesylate-treated mice (B) showed mild pathologic changes evidenced by some cytoplasmic vacuolation (white arrow) and degenerating nerve cells (red arrow), as compared to vehicle-treated mice (A). Scale bar, 20 μm. (Reprinted from Wozniak, K.M., Nomoto, K., Lapidus, R.G., Wu, Y., Carozzi, V., Cavaletti, G., Hayakawa, K., Hosokawa, S., Towle, M.J., Littlefield, B.A. and Slusher, B.S. (2011). Comparison of neuropathy-inducing effects of eribulin mesylate, paclitaxel, and ixabepilone in mice. Cancer Res, 71, 3952–3962. Reproduced with permission from American Association for Cancer Research.)