Juntendo University, Tokyo, established in 1838.

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Department of Molecular Pathogenesis (Department of Pathology and Oncology)

Staff

Professor & Chairman: Okio HINO, M.D., PhD
Professor (Urayasu Hosp): Fujihiko SUZUKI, M.D., PhD
Associate Professor: Sachiko HIROSE, M.D., PhD
Associate Professor: Toshiyuki KOBAYASHI, PhD
Associate Professor: Akira ORIMO, M.D., PhD [Akira Orimo Research Group Introduction | Research Website ]

Inflammation-induced Hepatocarcinogenesis

 Human hetatocellular carcinomas (HCCs) are preceded by chronic hepatitis and cirrhosis. Despite a clear viral etiology (HBV and HCV) of human hepatocarcinogenesis, the mechanism is complex and the distinct molecular pathway or molecules to explain this phenomenon is yet to be determined. Hepatitis viral, "inflammation mediated" hepatocarcinogenesis greatly influences the incidence of somatic genetic events in hepatocytes, by increaseing the number of target cells, or the proliferation of once-hit hepatocytes, eventually leading to HCCs. We propose that hepatitis virus can cause in incidence of HCCs by a combination of two mechanisms; i) cell killing and stimulation of mitosis leading to an accumulation of events necessary for transformation, and ii) an incerase in chromosomal instability mediated by induced recombinogeneic protein(s) during chronic hepatitis. These conditions may be designated as the "hypercarcinogenic state". Our goal is to lead the "hypercarcinogenic state" to the "normo- or hypocarcinogenic" state and to prevent HCC development.
 Previously we reported that DNA binding protein A (dbpA) is a candidate molecule to accelerate the process of the inflammation-induced hepatocarcinogenesis. Recently we reported that the expression of dbpA is associated with the advanced staging of HCC, and that the transversion of the dbpA promoter could be a prognostic marker of HCC. We are currently on the way to analyse the in vivo effect of dbpA for hepatocarcinogenesis by generating the transgenic mouse specifically expressing dbpA in its hepatocyte.

Hereditary Renal carcinogenesis

 Cancer is a heritable disorder of somatic cells. Environment and heredity both operate in the origin of human cancer. The Eker (Tsc 2 mutant) rat model of hereditary renal carcinoma (RC) is an example of Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. To the best of our knowledge, this was the first isolation of a Mendelian dominantly predisposing cancer gene in a naturally occurring animal model. Recently, a new hereditary renal carcinoma in the rat was discovered in Japan, and we named the "Nihon" rat and finally, identified its predisposing (Bhd) gene.
 Products of Tsc1 (hamartin) and Tsc2 (tuberin) form complex and have been reported to negatively regulate the mTOR-S6K1 signal. Some other independent signals are expected to be modulated by hamartin/tuberin. Product of BHD (folliculin) is a novel protein with no known functional information. To elucidate the molecular mechansim of tumor development and to establish therapeutic and chemopreventive treatments of TSC and BHD, functions of gene products should be precisely understood. Now we are trying to elucidate those functions by using in vivo experimental systems, such as transgenic technique, and in vitro cell culture systems.

Human carcinogenesis

 We are also investigating alteration of genes including Bhd, Niban,ERC/mesothelin, and other cancer-related genes in various forms of human neoplasms. With tissue microdissection, and other tissue-based technologies, role of individual genes in multistep carcinogenesis of human tumor samples are investigated. Differences and similarities of these homologous genes between human cancer and animal models will be elucidated.

Asbestos-exposed mesothelioma

 We are also trying to identify new biomarkers and develop new biological testings for the early diagnosis and monitoring of human cancers.
 Recently, we developed a blood-testing kit that may help detect mesothelioma, a cancer believed to be caused by inhaling asbestos.