Member (As of Apr, 2007)
Toyomasa Katagiri, Ph. D. Meng-Lay Lin, Ph. D. Jae-Hyun Park, MSc Sachiko Dobashi, MSc Masahiko Ajiro, MSc Jung-won Kim, MSc Chikako Fukukawa, Ph. D. Tomomi Ueki, M. D., Ph. D. Yosuke Harada, Ph. D. Jun Fujiwara, M. D. Akira Togashi, MSc Ms. Kyoko Kijima Ms. Kie Naito Ms. Yoshiko Fujisawa Ms. Akiko Konuma Ms. Aya Sasaki |
Research Interests
The determination of human genome sequence has been completed as a result
of human genome project. Thus, it is now crucial to clarify the function
of genes in the genome. Particularly functional analysis of genes associated
with human diseases is a matter of great importance. Microarray that enables
to detect expression of thousands of genes with an experiment is a powerful
tool for the research of carcinogenesis in terms of basic research as well
as clinical research.
We fabricated our in-house microarray slides containing 32,256 genes that
correspond almost of all genes in the human genome. We have been performed
expression profile analyses in a breast cancers, renal cell carcinomas,
bladder cancers and soft tissue tumors using the cDNA microarray in combination
with LMM (Laser Microbeam Microdissection). To obtain the precise expression
profile of human cancers, we selectively collected cancer cells by LMM
from clinical tissues that are a mixture of cancer cells, stromal cells,
endothelial cells, and infiltrating lymphocytes (Fig. 1).
We also analyzed expression profiles of 30 normal human tissues. Through
these microarray data, we have identified several candidate genes that
are overexpressed in cancer cells and not expressed in vital organs, as
candidates for novel molecular targets of therapeutic drugs, antibodies,
and peptide vaccine and/or diagnosis of human cancers. Particularly, through
synovial sarcomas (SS) of soft tissues tumors, we focused on Frizzled homologue
10 (FZD10), a member of Frizzled family, is exclusively up-regulated in
SS and its expression is not or hardly detectable in normal organs. Treatment
of two SS cell lines with small interfering RNA (siRNA) decreased the protein
expression of FZD10 specifically and suppressed their cell growth. Moreover,
the specific polyclonal antibody against extracellular domain of FZD10
was markedly effective in mediating antibody-dependent cell cytotoxity
(ADCC) against FZD10-overexpressing SS cells in vitro, and also effective
in vivo, attenuating the growth of SS xenografts in nude mice. Furthermore,
monoclonal antibody (Mab) to FZD10 we established was shown to have specific
binding activity against FZD10 on cell lines expressing FZD10. To further
validate the specific binding activity of those antibodies in vivo, we
injected fluorescent-labeled mAb intraperitoneally or intravenously into
the mice carrying SS xenografts and found that this mAb was bound to the
FZD10-expressing tumors, but not to any other normal mouse tissues by the
use of the in vivo fluorescent imaging system (Fig. 2). Taken together, this specific Mab against FZD10 could be utilized as the novel treatment of SS with minimal or no risk of adverse reactions.
1.Functional analysis of molecular-targets for breast, bladder and kidney cancer therapies
2.Development of prediction system of chemosensitivity to M-VAC neoadjuvant chemotherapy in bladder cancers.
Copyright © 2007 Yusuke Nakamura's Labo., All rights reserved.
Last update: 2007.4.4