Department of Pharmacotherapy

Link for labolatory Homepage

Professor　Shozo Nishida 　nishidaphar.kindai.ac.jp
	Pathology　(2ng grade) Pharmacotherapy 1　(3rd grade) Practice of Clinical Pharmacy　(4th grade) Hospital and Community Rotations　(4th grade) Early Exposure to Pharmacy Profession　(1st grade)

Assistant　Masahiro Tsubaki 　tsubakiphar.kindai.ac.jp
	Practice of Clinical Pharmacy　(4th grade)

Research

1.　 Research on the inhibitors of osteolysis caused by multiple myeloma
2.　 Research on apoptotic inducers
3.　 Research on the inhibitors of cancer metastasis

Introduction

Research on the inhibitors of osteolysis caused by multiple myeloma

Cancer is defined as malignant neoplasm (tumor) formed by the abnormal growth of cells. Among cancers, multiple myeloma is derived from plasma cells that have become malignant. Plasma cells differentiate from lymphocytes, which are a type of leukocyte. Myeloma cells secrete proteins to activate the osteoclasts that absorb the bone. Thus, the myeloma cells destroy the bone when they grow prolifically. Therefore, the patients experience severe pain, and since they tend to have a fractured bone, their quality of life (QOL) declines greatly. If the levels of the proteins secreted from myeloma can be controlled, it is likely that the patients will have an improved QOL and that their prognosis can be improved to a large extent. At present, we have found a few agents that can control the secretion of these proteins and are investigating their mechanisms of action.

Research on apoptotic inducers

Many anticancer drugs have been developed to kill cancerous cells, but there are some cancers for which no anticancer drug is effective. Therefore, we are investigating agents that can induce apoptosis effectively in cancerous cells, as well as their mechanisms of inducing apoptosis and of restoring the actions of anticancer agents. The induction of apoptosis is a type of cell death. In recent years, it was found that this induction is determined the balance between the mechanism of cell deaths (death signal) and that of survival (survival signal). Our laboratory is undertaking a search for agents that weaken the survival signal of cancerous cells and to look for a way to induce apoptosis effectively in cancerous cells. Treatment with anticancer agents produces so many side effects that such treatment is unsuitable for elderly people in many cases. Apoptotic inducers with few side effects seem to be suitable as the treatment for elderly people who cannot withstand treatment with anticancer agents. If we can discover some effective apoptotic inducers, we expect that these inducers will become the mainstream of malignant tumor treatment.

Research on the inhibitors of cancer metastasis

In many cases, malignant tumors show high infiltration into surrounding tissues, and therefore are metastatic. Since the infiltration and metastasis of cancer have a decisive influence on the prognosis of patients, the control of infiltration and metastasis will surely improve the life expectancy of the patients. A few metastatic inhibitors have already been found in our laboratory. We are now investigating their inhibitory mechanism and the clinical applications of these inhibitors.

Publication (2004-2006)

2005
1. Nishida S., Tsubaki M., Hoshino M., Namimatsu A., Uji H., Yoshioka S., Tanimori Y., Yanae M., Iwaki M., and Irimajiri K., Nitrogen-containing bisphosphonate, YM529/ONO-5920 (a novel minodronic acid), inhibits RANKL expression in a cultured bone marrow stromal cell line ST2. Biochem. Biophys. Res. Commun. 328, 91-97 (2005).
2. Nishida S., Matsuoka H., Tsubaki M., Tanimori Y., Yanae M., Fujii Y., and Iwaki M., Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK. Mol Cell Biochem. 269, 109-114 (2005)
2004
1. Matsuda H, Hirata N, Naruto S, Nishida S, Irimajiri K, Samukawa K, Kubo M. Anti-proliferative effect of ginseng radix on human premyelocytic leukemia cells (HL-60). J Traditional Medicenes, 22,4-8(2004)
2. Nishida S, Kinoshita S, Tomura T. Diethyldithiocarbamate can induce two different type of death: apoptosis and necrosis mediating the differential MAP kinase activation and redox regulation in HL60 cells. Mol Cell Biochem, .265, 23-32.(2004)