Satoshi Aono

Publications (2)9.14 Total impact

• Article: The combination therapy of α-galactosylceramide and 5-fluorouracil showed antitumor effect synergistically against liver tumor in mice.

  Hiroshi Aketa, Tomohide Tatsumi, Keisuke Kohga, Hinako Tsunematsu, Satoshi Aono, Satoshi Shimizu, Takahiro Kodama, Takatoshi Nawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Atsushi Hosui, Takuya Miyagi, Naoki Hiramatsu, Tatsuya Kanto, Norio Hayashi, Tetsuo Takehara
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  ABSTRACT: α-Galactosylceramide (α-GalCer) has been reported to be therapeutic against metastatic liver tumors in mice. However, little is known regarding the efficacy of combined chemo-immunotherapy using α-GalCer and anti-cancer drugs. In this study, we evaluated the antitumor effect of the combination therapy of α-GalCer and 5-fluorouracil (5-FU) against liver tumors of MC38 colon cancer cells. The liver weights of tumor-bearing mice treated with the combination were significantly lower than those of non-treated mice and of mice treated with 5-FU or α-GalCer alone. No toxic effects on the liver and renal functions were observed in any of the treatment groups. α-GalCer treatment induced significant activation of liver NK cells in vivo, but 5-FU treatment did not. 5-FU treatment resulted in a significant up-regulation of NKG2D activating molecules (Rae-1 and H60) and DNAM-1 ligands (CD112 and CD155) on MC38 cells, but α-GalCer did not. The cytolytic activity of α-GalCer-activated liver mononuclear cells against 5-FU-treated MC38 cells was significantly higher than that against non-treated cells. The increase of the cytolytic activity induced by 5-FU partially depended on NKG2D-Rae-1 or H60 signals. Depletion of NK cells significantly inhibited the antitumor efficacy of 5-FU against MC38 liver tumors, which suggested that the antitumor effect of 5-FU partially depended on the cytolytic activity of NK cells. These results demonstrated that the combination therapy of α-GalCer and 5-FU produced synergistic antitumor effects against liver tumors by increasing the expression of NK activating molecules on cancer cells. The present study suggests a promising new chemo-immunotherapy against metastatic liver cancer. © 2013 Wiley Periodicals, Inc.
  International Journal of Cancer 02/2013; · 5.44 Impact Factor
• Article: Interleukin-1β enhances the production of soluble MICA in human hepatocellular carcinoma.

  Keisuke Kohga, Tomohide Tatsumi, Hinako Tsunematsu, Satoshi Aono, Satoshi Shimizu, Takahiro Kodama, Hayato Hikita, Masashi Yamamoto, Tsugiko Oze, Hiroshi Aketa, Atsushi Hosui, Takuya Miyagi, Hisashi Ishida, Naoki Hiramatsu, Tatsuya Kanto, Norio Hayashi, Tetsuo Takehara
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  ABSTRACT: The production of soluble major histocompatibility complex class I-related chain A (MICA) is thought to antagonize NKG2D-mediated immunosurveillance. Interleukin-1β (IL-1β) is elevated in patients with chronic hepatitis C (CH), and this might contribute to the escape of hepatocellular carcinoma (HCC) cells from innate immunity. In this study, we investigated the immunoregulatory role of IL-1β in the production of soluble MICA of HCC cells. First, we investigated the correlation between the serum IL-1β levels and soluble MICA in CH patients. Serum IL-1β levels were associated with soluble MICA levels in CH patients. The serum IL-1β levels of CH patients with the HCC occurrence were significantly higher than those of CH patients without HCC. We next examined the MICA production of IL-1β-treated HCC cells. Addition of IL-1β resulted in significant increase in the production of soluble MICA in HepG2 and PLC/PRF/5 cells, human HCC cells. But soluble MICA was not detected in both non-treated and IL-1β-treated normal hepatocytes. Addition of IL-1β did not increase the expressions of membrane-bound MICA on HCC cells. These were observed similarly in various cancer cells including a gastric cancer (MKN1), two colon cancers (HCT116 and HT29) and a cervical cancer (HeLa). Addition of IL-1β also increased the expression of a disintegrin and metalloproteinase (ADAM)9 in HCC cells, and the knockdown of ADAM9 in IL-1β-treated HCC cells resulted in the decrease in the production of soluble MICA of HCC cells. These findings indicate that IL-1β might enhance the production of soluble MICA by activating ADAM9 in human HCC.
  Cancer Immunology and Immunotherapy 02/2012; 61(9):1425-32. · 3.70 Impact Factor