Horlad Hasita

Publications (3)8.75 Total impact

• Article: Preoperative portal vein embolization (PVE) for patients with hepatocellular carcinoma can improve resectability and may improve disease-free survival.

  Hirohisa Okabe, Toru Beppu, Takatoshi Ishiko, Toshiro Masuda, Hiromitsu Hayashi, Ryu Otao, Horlad Hasita, Kazutoshi Okabe, Shinichi Sugiyama, Hideo Baba
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  ABSTRACT: The aim of this study is to identify the efficacy of portal vein embolization (PVE) before right hepatectomy in patients with hepatocellular carcinoma (HCC) with regard to hepatic function, surgical stress, and survival benefit. Fifty-five patients with HCC underwent right hepatectomy between 1999 and 2009. Preoperative PVE was performed in 19 patients (PVE group) and was not applied in 36 patients (non-PVE group). Changes in liver function and volume were investigated in PVE group. Short and long clinical outcomes after the surgeries were compared between the two groups. The percentage of future liver remnant (%FLR) before PVE was significantly lower (37.8%) in PVE group than in non-PVE group (58.1%) but increased remarkably after PVE (from 37.8% to 55.0%, P < 0.0001). Cumulative disease-free survival and overall survival rates in PVE group were significantly superior to those in non-PVE group (P = 0.010 and 0.049, respectively). Although surgical stress estimated by E-PASS scores and CRP value was not different between the groups, the postoperative value of PT on postoperative day 3 in PVE group was significantly better than in non-PVE group. Preoperative PVE improves resectability and may improve disease-free survival for patients with HCC requiring right hepatectomy.
  Journal of Surgical Oncology 04/2011; 104(6):641-6. · 2.10 Impact Factor
• Article: Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma.

  Yoshihiro Komohara, Horlad Hasita, Koji Ohnishi, Yukio Fujiwara, Shinya Suzu, Masatoshi Eto, Motohiro Takeya
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  ABSTRACT: Most malignant tumors evidence infiltration of many macrophages. In this study, we investigated an anti-inflammatory macrophage phenotype (M2) in clear cell renal cell carcinoma (RCC) using CD163 and CD204 as markers. Immunostaining showed a correlation between the number of CD163(+) cells and age, sex, nuclear grade, and TNM classification. High infiltration of CD163(+) cells was significantly associated with poor clinical prognosis in univariate analysis but not in multivariate analysis. We also carried out in vitro studies to examine cell-cell interactions between macrophages and cancer cells. Culture supernatants from RCC cell lines induced polarization of macrophages toward the M2 phenotype. Coculture of macrophages with cancer cells significantly induced activation of signal transducers and activators of transcription-3 (Stat3) in the cancer cells. Direct coculture of RCC cells with macrophages led to stronger activation of Stat3 in the cancer cells than did indirect coculture using Transwell chamber dishes. Because RCC cells expressed membrane-type macrophage colony-stimulating factor (mM-CSF) on the cell surface, we suggested that this mM-CSF plays an important role in direct cell-cell interactions. Stat3 activation in cancer cells that was induced by coculture with macrophages was suppressed by downregulation of the M-CSF receptor (M-CSFR) in macrophages and by an inhibitor of M-CSFR. In conclusion, investigation of CD163(+) tumor-associated macrophages would be useful for assessment of the clinical prognosis of patients with ccRCC. Cell-cell interactions mediated by mM-CSF and M-CSFR binding could contribute to cancer cell activation.
  Cancer Science 03/2011; 102(7):1424-31. · 3.33 Impact Factor
• Article: Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma.

  Horlad Hasita, Yoshihiro Komohara, Hirohisa Okabe, Toshiro Masuda, Koji Ohnishi, Xiao F Lei, Toru Beppu, Hideo Baba, Motohiro Takeya
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  ABSTRACT: Many studies have shown that tumor-associated macrophages (TAMs) contribute to tumor development and poor prognosis in various cancers. In this study, we investigated the macrophage populations and phenotypes, and their correlation to angiogenesis, immunosuppression, and clinical prognosis in intrahepatic cholangiocarcinoma (ICC). CD68 (+) and CD163 (+) macrophage infiltration was analyzed in paraffin-embedded tissue samples from 39 patients. CD163 is used as a marker of M2 macrophages. Neovascularization and infiltration of forkhead box P3 (FOXP3) (+) regulatory T cells were also evaluated. The number of CD68 (+) and CD163 (+) macrophages was positively correlated with the numbers of vessels and regulatory T cells. The number of CD163 (+) cells was more closely associated with them. Intrahepatic cholangiocarcinoma (ICC) patients with high counts of CD163 (+) macrophages showed poor disease-free survival (P = 0.0426). The macrophage density was not correlated with overall survival. In an in vitro study using ICC cell lines (HuCCT1, RBE, and MEC) and human macrophages, tumor cell supernatant (TCS) from cell lines induced an activation of signal transducers and activators of transcription-3 (Stat3) and macrophage polarization toward the M2 phenotype. Tumor cell supernatant (TCS) from HuCCT1 most strongly induced Stat3 activation and production of cytokines and other bioactive molecules such as interleukin (IL)-10, vascular endothelial growth factor (VEGF)-A, transforming growth factor (TGF)-beta, and matrix metalloproteinase (MMP)-2. Down-regulation of Stat3 by siRNA significantly suppressed the production of IL-10 and VEGF-A. These results provide suggestive evidence that TAMs contribute to cancer progression via Stat3 activation, and CD163 is useful for evaluating M2 TAMs and predicting the clinical prognosis of ICC patients.
  Cancer Science 08/2010; 101(8):1913-9. · 3.33 Impact Factor