The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
YM155, a Novel Small-Molecule Survivin Suppressant, Induces Regression of Established Human Hormone-Refractory Prostate Tumor Xenografts
Abstract
Various accumulating evidence suggests that survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in drug resistance and cancer cell survival in many types of cancer, including hormone-refractory prostate cancer (HRPC). Here, we characterized YM155, a novel small-molecule survivin suppressant, using a survivin gene promoter activity assay. YM155 suppressed expression of survivin and induced apoptosis in PC-3 and PPC-1 human HRPC cell lines at 10 nmol/L. In contrast, YM155 up to 100 nmol/L showed little effect on expression levels of other IAP- or Bcl-2–related proteins. In a s.c. xenografted PC-3 tumor model in mice, 3-day continuous infusions of YM155 at 3 to 10 mg/kg induced massive tumor regression accompanied by suppression of intratumoral survivin. YM155 also completely inhibited the growth of orthotopically xenografted PC-3 tumors. No significant decreases in body weight were observed in mice treated with YM155 during the experimental period. Pharmacokinetic analyses indicated that YM155 is highly distributed to tumors and at concentrations ∼20-fold higher than those in plasma. Our findings represent the first attempt to show tumor regression and suppression of survivin in p53-deficient human HRPC cells by a single small molecular compound treatment. Further extensive investigation of YM155 in many types of cancer, including HRPC, seems to be worthwhile to develop this novel therapeutic approach. [Cancer Res 2007;67(17):8014–21]
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Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., & Thun, M. J. (2007) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.57.1.43 · Cited by 7,439
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Metadata
- Authors
- Nakahara, T., Takeuchi, M., Kinoyama, I., Minematsu, T., Shirasuna, K., Matsuhisa, A., Kita, A., Tominaga, F., Yamanaka, K., Kudoh, M., & Sasamata, M.
- Venue
- Cancer Research
- Published
- 2007-09-01
- Volume
- 67
- Issue
- 17
- Pages
- 8014-8021
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2172124462
- Cited by
- 497
- References
- 1
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Nakahara, T., Takeuchi, M., Kinoyama, I., Minematsu, T., Shirasuna, K., Matsuhisa, A., Kita, A., Tominaga, F., Yamanaka, K., Kudoh, M., & Sasamata, M. (2007). YM155, a Novel Small-Molecule Survivin Suppressant, Induces Regression of Established Human Hormone-Refractory Prostate Tumor Xenografts. Cancer Research. https://doi.org/10.1158/0008-5472.can-07-1343
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