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Antitumor Effect of Sugar-Modified Cytosine Nucleosides on Growth of Adult T-Cell Leukemia Cells in Mice
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| Title: | Antitumor Effect of Sugar-Modified Cytosine Nucleosides on Growth of Adult T-Cell Leukemia Cells in Mice |
| Authors: | Maeda, Naoyoshi Browse this author →KAKEN DB | | Matsuda, Akira Browse this author →KAKEN DB | | Otsuguro, Satoko Browse this author | | Takahashi, Masahiko Browse this author | | Fujii, Masahiro Browse this author | | Maenaka, Katsumi Browse this author →KAKEN DB |
| Keywords: | adult T-cell leukemia | | cytarazid | | DMDC | | FDMDC | | NOG mice |
| Issue Date: | 5-Nov-2020 |
| Publisher: | MDPI |
| Journal Title: | Vaccines |
| Volume: | 8 |
| Issue: | 4 |
| Start Page: | 658 |
| Publisher DOI: | 10.3390/vaccines8040658 |
| Abstract: | Adult T-cell leukemia (ATL) is a CD4(+) T-cell neoplasm caused by human T-cell leukemia virus type I. As the prognosis for patients with ATL remains extremely poor due to resistance to conventional chemotherapy regimens, introduction of novel therapeutic agents is needed. Previous studies have reported that nucleosides 2 '-deoxy-2 '-methylidenecytidine (DMDC) and its derivative 2 '-deoxy-2 '-methylidene-5-fluorocytidine (FDMDC) exhibit antitumor activities in T-cell acute lymphoblastic leukemia (T-ALL) and solid tumor cell lines. Another nucleoside, 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)cytosine (cytarazid), is considered a therapeutic drug with antitumor activity in human solid tumors. In this study, we investigated the effects of these nucleosides on cell growth in vitro and in vivo using relevant leukemia cell lines and NOD/Shi-scid, IL-2Rg(null) (NOG) mice, respectively. The nucleosides demonstrated significant cytotoxic effects in ATL and T-ALL cell lines. Intraperitoneal administration of FDMDC and DMDC into tumor-bearing NOG mice resulted in significant suppression of tumor growth without lethal side effects. Our findings support a therapeutic application of these nucleosides against tumor progression by targeting DNA polymerase-dependent DNA synthesis in patients with ATL. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/80253 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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