@article{oai:u-ryukyu.repo.nii.ac.jp:02002365,
 author = {Ishikawa, Chie and Matsuda, Takehiro and Okudaira, Taeko and Tomita, Mariko and Kawakami, Hirochika and Tanaka, Yuetsu and Masuda, Masato and Ohshiro, Kazuiku and Ohta, Takao and Mori, Naoki},
 issue = {3},
 journal = {British journal of haematology},
 note = {Anti-resorptive bisphosphonates are used for the treatment of hypercalcemia and bone complications associated with malignancies and osteoporosis, but have also been shown to have anti-tumour effects in various cancers. Adult T-cell leukaemia (ATL) is a fatal T-cell malignancy caused by infection with human T-cell leukaemia virus type I (HTLV-I), and remains incurable. ATL is associated with osteolytic bone lesions and hypercalcemia, which are major factors in the morbidity of ATL. Thus, the search for anti-ATL agents that have both anti-tumour and anti-resorptive activity is warranted. The bisphosphonate agent, incadronate prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells, but not of non-infected T-cell lines or normal peripheral blood mononuclear cells. Incadronate induced S-phase cell cycle arrest and apoptosis in HTLV-I-infected T-cell lines, and treatment of these cells with substrates of the mevalonate pathway blocked the incadronate-mediated growth suppression. Incadronate also prevented the prenylation of Rap1A protein. These results demonstrated that incadronate-induced growth suppression occurs by interfering with the mevalonate pathway. Importantly, treatment with incadronate reduced tumour formation from an HTLV-I-infected T-cell line, when these cells were inoculated subcutaneously into severe combined immunodeficient mice. These findings suggest that incadronate could be potentially useful for the treatment of ATL., 論文},
 pages = {424--432},
 title = {Bisphosphonate incadronate inhibits growth of human T-cell leukaemia virus type I-infected T-cell lines and primary adult T-cell leukaemia cells by interfering with the mevalonate pathway},
 volume = {136}
}