| Autor: |
Osamu, Miyazaki, Keiko, Sekine, Naoko, Nakajima, Eiji, Ichimura, Keiko, Ebara, Daichi, Nagai, Takeshi, Onda, Yoshitaka, Miyakawa, Kazuya, Okamoto, Tomio, Morino |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
International journal of cancer. 134(1) |
| ISSN: |
1097-0215 |
| Popis: |
NK012 is a micelle-forming macromolecular prodrug of 7-ethyl-10-hydroxy camptothecin (SN-38), an active metabolite of irinotecan. It is accumulated and retained in tumor tissues and gradually releases SN-38 in an enzyme-independent manner. NK012 was previously demonstrated to have stronger antitumor activity than irinotecan in a broad range of human solid-tumor xenograft models. In our study, we used an orthotopic multiple myeloma (MM) model created by injecting CD138-positive U266B1, a myeloma cell line that produces human IgE lambda light chain (monoclonal protein, M protein), into immunodeficient NOD/Shi-scid, IL-2Rγc (null) mice. This model shows typical bone marrow infiltration by the human myeloma cells. We evaluated the antimyeloma activity of intravenously administered NK012 in this model and showed that it suppressed the M protein concentration in the plasma and proliferation of myeloma cells in the bone marrow in a dose-dependent manner. NK012 suppressed the progression of hind-leg paralysis and prolonged the survival time of the mice compared to the untreated control group. In combination with bortezomib (BTZ), NK012 increased the median survival time compared to that with BTZ alone. In conclusion, these results suggest that NK012 is a potential candidate for use-alone and in combination-in the treatment of MM in humans. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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