Kaoru Okada

Publications (6)14.93 Total impact

• Article: Overexpression of Forkhead Box M1 Transcription Factor (FOXM1) is a Potential Prognostic Marker and Enhances Chemoresistance for Docetaxel in Gastric Cancer.

  Kaoru Okada, Yoshiyuki Fujiwara, Tsuyoshi Takahashi, Yurika Nakamura, Shuji Takiguchi, Kiyokazu Nakajima, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Masaki Mori, Yuichiro Doki
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  ABSTRACT: BACKGROUND: Mammalian forkhead box transcription factor 1 (FoxM1) has been overexpressed and correlated with pathogenesis in a variety of human malignancies. We investigated the expression status and clinical significance of its overexpression in gastric adenocarcinoma. Furthermore, we demonstrated correlations between FoxM1 overexpression and drug resistance to chemotherapeutic agents in gastric cancer cells and gastric cancer patients treated with chemotherapy. METHODS: Fifty-three (69 %) of 77 tumors were diagnosed as positive for FoxM1 by immunohistochemistry. Multivariate analysis identified FoxM1 expression as a significant independent prognostic predictor for overall and disease-free survival in gastric cancer patients (hazard ratio 3.9 and 3.5, respectively). Furthermore, we investigated associations between FoxM1 overexpression and clinical response of chemotherapy for patients with advanced gastric cancer. RESULTS: Our clinical results showed that FoxM1 overexpression was significantly associated with resistance in chemotherapy of docetaxel in addition to 5-fluorouracil (5-FU) plus S-1 plus cisplatin (CDDP) and was not significant in chemotherapy of 5-FU plus CDDP for patients with advanced gastric cancer. In vitro experiments showed that Mkn7 transfected FoxM1 siRNA significantly reduced chemoresistance to docetaxel over that with parental cell lines and Mkn45 transfected with FoxM1 significantly enhanced chemoresistance to docetaxel over that with parental cell lines. CONCLUSIONS: Our study showed that FoxM1 was an independent prognostic factor in gastric cancer. Furthermore, we showed that FoxM1 was a critical molecule for chemoresistance to a microtubule-stabilizing anticancer agent, docetaxel. Taken together, those results suggest that inhibition of overexpressed FoxM1 will be a promising therapeutic strategy for advanced gastric cancer.
  Annals of Surgical Oncology 10/2012; · 4.17 Impact Factor
• Article: Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer.

  Toru Masuzawa, Yoshiyuki Fujiwara, Kaoru Okada, Ayumu Nakamura, Shuji Takiguchi, Kiyokazu Nakajima, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Ryuji Osawa, Kazuyoshi Takeda, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Masaki Mori, Yuichiro Doki
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  ABSTRACT: The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A*2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.
  International Journal of Oncology 07/2012; · 2.40 Impact Factor
• Article: [Peritoneal lavage cytology under local anesthesia for detection of peritoneal recurrence after surgery].

  Kaoru Okada, Yoshiyuki Fujiwara, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki
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  ABSTRACT: Gastric cancer with positive peritoneal lavage cytology shows a very poor prognosis due to frequent peritoneal recurrence after surgery. Therefore, we have introduced neoadjuvant intra-peritoneal and systemic chemotherapy( NIPS) for gastric cancer with peritoneal microscopic and/or microscopic dissemination before surgery. In patients subjected to the strategy, we have experienced two cases of advanced gastric cancer with CY1, which had been treated with NIPS and curative surgery, had been performed with second peritoneal lavage cytology two years after surgery. In those two cases, S-1 was discontinued due to the negative results of peritoneal lavage cytology. We will present the cases.
  Gan to kagaku ryoho. Cancer & chemotherapy 11/2011; 38(12):2363-5.
• Article: Oncofetal protein, IMP-3, a potential marker for prediction of postoperative peritoneal dissemination in gastric adenocarcinoma.

  Kaoru Okada, Yoshiyuki Fujiwara, Yurika Nakamura, Shuji Takiguchi, Kiyokazu Nakajima, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Tsuyoshi Takahashi, Masaki Mori, Yuichiro Doki
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  ABSTRACT: The aim of this study was to determine the expression of insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP-3) and its clinical significance in gastric cancers, as well the prognostic value of its expression in the peritoneal lavage fluid after surgery. IMP-3 expression was examined by immunohistochemistry in 96 primary gastric tumors. IMP-3 mRNA expression in peritoneal lavage fluid obtained at laparotomy was determine by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Positive staining for IMP-3 was observed in 74% (71/96) of the tumors. IMP-3 expression in gastric tumors correlated significantly with worst overall survival (OS) and recurrence-free survival. Multivariate analyses identified pathological N stage and IMP-3 expression as significant independent prognostic factors for disease-free survival. Eight (28%) of 36 peritoneal lavage samples were cytologically negative but positive for IMP-3 mRNA expression by RT-PCR. The OS of patients with IMP-3-positive peritoneal lavage was significantly worse than of those with negative expression. IMP-3 expression in primary gastric tumors was an independent poor prognostic factor. IMP-3 mRNA expression in peritoneal lavage fluid was a predictor of recurrence after surgery in gastric cancer and a marker of poor prognosis.
  Journal of Surgical Oncology 10/2011; 105(8):780-5. · 2.10 Impact Factor
• Article: REGIV as a potential biomarker for peritoneal dissemination in gastric adenocarcinoma.

  Jeong-Ho Moon, Yoshiyuki Fujiwara, Yurika Nakamura, Kaoru Okada, Hiroyuki Hanada, Chohei Sakakura, Shuji Takiguchi, Kiyokazu Nakajima, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Masaki Mori, Yuichiro Doki
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  ABSTRACT: This study examined the clinical significance of regenerating islet-derived family member 4 (REGIV) in surgically resected gastric tumors. The potential of REGIV as a biomarker in gastric cancer was also assessed including its predictive value for prognosis and recurrence after surgery. Immunohistochemistry was performed to assess the clinical significance of REGIV expression status in surgically resected specimens. The quantitative genetic diagnostic method, transcription-reverse transcription concerted reaction (TRC) that targeted REGIV mRNA was applied for prediction of peritoneal recurrence in gastric cancer. Positive immunostaining for REGIV was observed in 85 cases (52.5%), and correlated significantly with diffuse type histopathology (P = 0.001), advanced T stage (P = 0.022), and frequent peritoneal recurrence (P = 0.009). Multivariate analysis identified advanced T stage (P < 0.001) and REGIV expression (P = 0.034) as independent prognostic factors for peritoneal recurrence-free survival. Overexpression of REGIV protein was evident in the majority of peritoneal tumors (93.8%). REGIV mRNA assessed by TRC could be a predictive marker for peritoneal recurrence after curative operation. REGIV overexpression is common in primary gastric tumors and a potentially suitable marker of diffuse type histopathology and peritoneal dissemination. Overexpression of REGIV mRNA, assessed by the TRC method, is a potentially suitable marker of peritoneal recurrence after curative resection.
  Journal of Surgical Oncology 07/2011; 105(2):189-94. · 2.10 Impact Factor
• Article: Neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer patients with peritoneal dissemination.

  Yoshiyuki Fujiwara, Shuji Takiguchi, Kiyokazu Nakajima, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Kaoru Okada, Masaki Mori, Yuichiro Doki
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  ABSTRACT: The present study was designed to assess the feasibility and efficiency of intraperitoneal and intravenous neoadjuvant chemotherapy in gastric cancer patients with peritoneal dissemination. The study subjects were 25 treatment-naïve patients with gastric cancer. Patients with positive cytology or with peritoneal carcinomatosis received neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), comprising intraperitoneal (i.p.) mitomycin C (MMC) and cisplatin (CDDP), followed by two cycles of intravenous triplet chemotherapy of docetaxel, 5-fluorouracil (5-FU), and CDDP. Gastrectomy with lymph node dissection was performed after NIPS in patients free of peritoneal deposits, confirmed by staging laparoscopy. Seventeen patients had measurable lymph node metastases by the RECIST criteria. CT examination showed response to the treatment in ten (59%, 0 complete response, 10 partial response). Of the 25 patients, 14 (56%) showed negative results on peritoneal cytology with no macroscopic peritoneal metastasis, whereas the remaining 11 were cancer cell-positive on peritoneal cytology or macroscopic peritoneal metastasis even after NIPS. The median survival time for all 25 patients was 16.7 months. Prognosis was better in patients who showed negative cytology and disappearance of peritoneal cancer metastases after NIPS than in those with positive cytology or existing peritoneal deposits (P < 0.0001). The predominant toxicity was myelosuppression and grade 3-4 leukopenia and neutropenia occurred in 20 (80%) patients, which were manageable. No treatment-related mortality was observed during and after NIPS and surgery. The results of this prospective phase II study indicated that the newly designed NIPS was highly effective and well tolerated in patients with advanced gastric cancer and peritoneal dissemination.
  Annals of Surgical Oncology 05/2011; 18(13):3726-31. · 4.17 Impact Factor