Toru Sugiyama

Publications (196) View all

• Article: Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells.

  Ikue Nakayama, Masahiko Shibazaki, Akiko Yashima-Abo, Fumiharu Miura, Toru Sugiyama, Tomoyuki Masuda, Chihaya Maesawa
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  ABSTRACT: Small and large non-coding RNAs (ncRNAs) contribute to the acquisition of aggressive tumor behavior in diverse human malignancies. Two types of ncRNAs, miRNA‑10b (miR-10b) and homemobox (HOX) transcript antisense RNA (HOTAIR), can suppress the translation of the HOXD10 gene, an mRNA encoding a transcriptional repressor that inhibits the expression of cell migration/invasion-associated genes. Using epithelial ovarian cancer cell lines and primary tumors, we investigated whether miR‑10b and/or HOTAIR can regulate the expression of HOXD10, and whether it permits gain of pro‑metastatic gene products, matrix metallopeptidase 14 (MMP14) and ras homolog family member C (RHOC). Overexpression of miR-10b induced a decrease in HOXD10 protein expression, and upregulated the migration and invasion abilities in ovarian cancer cell lines (P<0.05). In these cells, a significant increase of MMP14 and RHOC protein was observed. No significant upregulation of the HOXD10 protein was observed in cells with the treatment of HOTAIR-siRNA. Positive signals for HOXD10 and MMP14 proteins were observed in 47 (69%) and 25 (37%) of 68 patients with epithelial ovarian cancers. An inverse correlation between HOXD10 and MMP14 immunoreactivities was observed (P<0.05), and miR-10b expression was also inversely correlated with HOXD10 protein expression (P<0.05). These results suggested that downregulation of HOXD10 expression by miR-10b overexpression may induce an increase of pro-metastatic gene products, such as MMP14 and RHOC, and contribute to the acquisition of metastatic phenotypes in epithelial ovarian cancer cells.
  International Journal of Oncology 05/2013; · 2.40 Impact Factor
• Article: Investigation of the clinicopathological features of fallopian tube malignancy.

  Yoshihito Yokoyama, Masayuki Futagami, Toshio Fujimoto, Yukihiro Terada, Eriko Takatori, Toru Sugiyama, Takeo Otsuki, Nobuo Yaegashi, Takanobu Kojimahara, Hirohisa Kurachi, Hiroshi Nishiyama, Keiya Fujimori, Toru Tase, Hideki Mizunuma
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  ABSTRACT: The present study investigated the clinico-pathological features of fallopian tube malignancy (FTM) and elucidated the biological behavior of this disorder. Data were compiled concerning FTM from 68 patients from 7 institutes. The patients included 60 cases with fallopian tube carcinoma and 8 cases with fallopian tube carcinosarcoma. The clinical stage was stage III or higher in 72% of the cases. A complete response or partial response was achieved in 56 and 10 of the 68 patients with FTM, respectively, indicating a response rate of 97.1%. The median observation period for FTM was 41 months (3 to 126 months). Three of the 19 patients with stage I/II disease (16%) and 31 of the 49 patients with stage III/IV disease (63%) experienced recurrence, with a median progression-free survival of 17.5 months, and a 3-year overall survival of 77.2%. Regarding the site of recurrence, local intraperitoneal recurrence (26.2%) and solitary recurrences in lymph nodes (19.0%) and in the liver (16.7%) were relatively frequent. Secondary debulking surgery (SDS) was performed in 15 patients (44%) out of the 34 recurrent FTMs. Conversely, recurrence was associated with ascites (carcinomatous peritonitis) in 4 of the 34 recurrent patients, but all 4 patients died. The median survival period after recurrence was 28 months: 7.5 and 30 months with and without ascites, respectively (P<0.001). A univariate analysis showed that prognosis was significantly correlated only with whether SDS could be performed. These results suggest that since FTM frequently results in solitary recurrence, aggressive recurrence treatment including SDS could improve prognosis.
  Oncology Reports 04/2013; · 1.84 Impact Factor
• Article: Towards improved ultrasound-based analysis and 3D visualization of the fetal brain using 3D Slicer.

  Rie Oyama, Marianna Jakab, Miuki Terata, Chizuko Isurugi, Yoshitaka Kaido, Tomonobu Knasugi, Akihiko Kikuchi, Toru Sugiyama, Ron Kikinis, Sonia Pujol
  Ultrasound in Obstetrics and Gynecology 04/2013; · 3.01 Impact Factor
• Article: A pilot study of oxaliplatin with oral S-1 as second-line chemotherapy for patients with recurrent adenocarcimona of the uterine cervix.

  Eriko Takatori, Tadahiro Shoji, Yasuko Suga, Hanae Niinuma, Yuki Miura, Yoshitaka Kaido, Anna Takada, Masahiro Kagabu, Satoshi Takeuchi, Toru Sugiyama
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  ABSTRACT: BACKGROUND: The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent adenocarcinoma of the uterine cervix were examined in a pilot study. PATIENTS AND METHODS: S-1 was orally administered for 14 days at a dose of 80-120 mg/body/day to 7 patients with recurrent adenocarcinoma of the uterine cervix, with oxaliplatin being administered intravenously at a dose of 100 mg/m(2) on day 1. Each therapy cycle was 21 days, and the patients received 6 cycles at most. The antitumor effect, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. RESULTS: The median age of the patients was 49 years. The antitumor effect was rated as a complete response in 2 patients, partial response in 2, and stable disease in 3. The overall response rate was 57.1 %, and the disease control rate was 100 %. Regarding hematological toxicities of grade 3 or more, leukopenia, neutropenia and thrombocytopenia occurred in 42.9, 28.6 and 14.3 %, respectively; regarding non-hematological toxicities, grade 3 rectovaginal fistula occurred in 14.3 %, as well as grade 2 fatigue in 14.3 % of the patients. The median PFS and OS were 5 months (range 3-9 months) and 7 months (range 4-43 months), respectively. CONCLUSIONS: These results suggest that SOX therapy is useful for the treatment of recurrent adenocarcinoma of the uterine cervix, having a promising antitumor effect and minimal adverse effects. It was also suggested that SOX therapy may contribute to improving the prognosis for patients with adenocarcinoma of the uterine cervix.
  International Journal of Clinical Oncology 03/2013; · 1.41 Impact Factor
• Article: Meta-analysis of epoetin beta and darbepoetin alfa treatment for chemotherapy-induced anemia and mortality: individual patient data from Japanese randomized, placebo-controlled trials.

  Yasuo Ohashi, Yukari Uemura, Yasuhito Fujisaka, Toru Sugiyama, Hironobu Ohmatsu, Noriyuki Katsumata, Rumiko Okamoto, Nagahiro Saijo, Tomomitsu Hotta
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  ABSTRACT: Erythropoiesis-stimulating agents (ESAs) reduce the need for transfusions and improve the quality of life in patients receiving chemotherapy, but several clinical trials have suggested that ESAs may have a negative impact on survival. To evaluate the efficacy and safety of the ESAs, epoetin beta and darbepoetin alfa, including their impact on overall survival and thromboembolic events, we conducted an individual data-based meta-analysis of three randomized, placebo-controlled trials studying Japanese patients with chemotherapy-induced anemia. All trials were conducted in compliance with Good Clinical Practice. A total of 511 patients with solid tumor or lymphoma (epoetin beta or darbepoetin alfa n=273, placebo n=238) were included. The ESAs significantly reduced the risk of transfusion (relative risk 0.47, 95% CI 0.29-0.76). No significant effect of the ESAs on overall survival was observed (unadjusted hazard ratio 1.00, 0.75-1.34). A prespecified subgroup analysis showed no strong interaction between the baseline hemoglobin concentration and the effect of ESAs on overall survival. Among the ESA-treated patients, the highest hemoglobin achieved during the treatment period in each patient had no impact on mortality. No increase in thromboembolic events was observed in the ESA-treated patients (0.7% vs. 1.7% placebo). ESAs reduced the risk of transfusion without a negative impact on the survival of patients with chemotherapy-induced anemia.
  Cancer Science 01/2013; · 3.33 Impact Factor