Bone is one of the most frequent sites for breast and prostate cancers to metastasize. Primary symptoms of metastatic bone disease (MBD) include osteolysis and pain. The long-term goal of Dr. Ichiro Nishimura’s laboratory is to elucidate the mechanism of MBD and to design clinically viable therapeutic modalities to alleviate the MBD symptoms.
His current projects focus on osteoclasts and peripheral sensory neurons. Osteoclasts are myeloid-derived immune cells specialized to resorb bone and have been shown to be highly activated in MBD. Nishimura’s lab investigates the role of osteoclasts in MBD-related pathology as well as tumor promotion. MBD often manifests radiating pain due to cancer-induced neuropathy. His lab uses the sciatic nerve entrapment model in rats to test the effectiveness of cationized gelatin nanoparticles in order to manage painful neuropathy. The hyper-activated voltage-gated sodium channel was significantly attenuated by the nanoparticle delivery of shRNA, resulting in the prolonged pain-free behaviors. Expanding this “proof-of-concept” study, Nishimura’s team is testing more translatable therapy designs.
Selected Cancer-Related Publications:
Armin BB, Hokugo A, Nishimura I, Tamplen M, Beumer J 3rd, Steinberg ML, Abemayor E, Nabili V. Brachytherapy-mediated bone damage in a rat model investigating maxillary osteoradionecrosis. Arch Otolaryngol Head Neck Surg. 2012 Feb;138(2):167-71. doi: 10.1001/archoto.2011.1176.
Hokugo A, Sun S, Park S, McKenna CE, Nishimura I. Equilibrium-dependent bisphosphonate interaction with crystalline bone mineral explains anti-resorptive pharmacokinetics and prevalence of osteonecrosis of the jaw in rats. Bone. 2013 Mar;53(1):59-68. doi: 10.1016/j.bone.2012.11.030. Epub 2012 Dec 4.
Ruangsri S, Lin A, Mulpuri Y, Lee K, Spigelman I, Nishimura I. Relationship of axonal voltage-gated sodium channel 1.8 (NaV1.8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats. J Biol Chem. 2011 Nov 18;286(46):39836-47. doi: 10.1074/jbc.M111.261701. Epub 2011 Sep 30.
Honda Y, Ding X, Mussano F, Wiberg A, Ho CM, Nishimura I. Application of feedback system control (FSC) to identify the optimized osteogenic drug cocktails. IEEE, 10.1109/MHS.2011.6102147, 2011.
Mussano F, Lee KJ, Zuk P, Tran L, Cacalano NA, Jewett A, Carossa S, Nishimura I. Differential effect of ionizing radiation exposure on multipotent and differentiation-restricted bone marrow mesenchymal stem cells. J Cell Biochem. 2010 Oct 1;111(2):322-32. doi: 10.1002/jcb.22699.