Masayoshi Kage

Kurume University, Куруме, Fukuoka, Japan

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Publications (259)733.28 Total impact

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    ABSTRACT: Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.
    Breast cancer research: BCR 07/2014; 16(4):R70. · 5.87 Impact Factor
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    ABSTRACT: Background:It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV.Methods and Results:Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV.Conclusions:Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV.
    Circulation journal : official journal of the Japanese Circulation Society. 06/2014;
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    ABSTRACT: Objective Endometrial cancer is one of the leading causes of malignancy in females. Nuclear findings are important for patients with cancer, and can provide valuable information to treating oncologists. We investigated whether nuclear findings were a useful prognostic factor in patients with endometrial cancer.Method We investigated 71 cases of endometrial carcinoma with paired histology and cytology at Kurume University Hospital. We classified endometrial endometrioid adenocarcinoma (EEC) G1 and G2 as type I carcinomas, and uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CC) and EEC G3 as type II carcinomas. For the establishment of the cytological nuclear atypia classification, we examined the following nuclear factors on the cytological smears: mitotic figures, prominent nucleoli, nuclear area and anisonucleosis.ResultsThere was a significant difference in mitotic figures (P < 0.001) and anisonucleosis (P = 0.026) in cytological smears between type I and type II carcinomas. Based on these findings, we categorized cytological nuclear atypia into three groups, nuclear atypia-1 (57.7%), nuclear atypia-2 (19.7%) and nuclear atypia-3 (22.5%), and this classification system correlated well with prognosis in patients with endometrial cancer (P < 0.001). Furthermore, this classification system was able to extract patients with a good prognosis from those with high-grade carcinomas, such as UPSC+CC+EEC G3, and patients with a poor prognosis from those with EEC G1.Conclusions Our system of cytological nuclear atypia classification based on endometrial cytology can predict patient prognosis. Cytological nuclear atypia classification and histological typing may be useful for the treatment and follow-up of patients with endometrial cancer, and should be routinely incorporated into cytological reports.
    Cytopathology 05/2014; · 1.71 Impact Factor
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    ABSTRACT: Y-box binding protein-1 (YB-1) is a member of the cold shock protein family and functions in transcription and translation. Many studies indicate that YB-1 is strongly expressed in tumor cells and is considered a marker of tumor aggressiveness and clinical prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been associated with poor outcomes in cervical cancer. Clinical trials of EGFR family-base therapy are currently being initiated in cervical cancer. Nuclear YB-1 expression correlates with EGFR expression in various types of cancer. However, the clinical significance of nuclear YB-1 expression in different settings, the correlation with EGFR, and the prognostic implications of YB-1 expression in cervical cancer remain elusive. Nuclear YB-1 expression was immunohistochemically analyzed in tissue specimens obtained from 204 patients with cervical cancer who underwent surgery. Associations of nuclear YB-1 expression with clinicopathological factors such as survival, EGFR expression, and human epidermal growth factor receptor 2 (HER2) expression were investigated. Nuclear YB-1 expression was found in 41 (20.2%) of 204 cases of cervical cancer and correlated with disease stage, tumor diameter, stromal invasion, and lymph-node metastasis. Nuclear YB-1 expression also correlated with EGFR expression (P=0.0114) as well as HER2 expression (P=0.0053). Kaplan-Meier survival analysis showed that nuclear YB-1 expression was significantly associated with poor progression-free survival (P=0.0033) and overall survival (P=0.0003), respectively. Nuclear YB-1 expression is a prognostic marker and correlates with EGFR expression in cervical cancer.
    Gynecologic Oncology 01/2014; · 3.93 Impact Factor
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    ABSTRACT: Flat epithelial lesions of the biliary tract cannot be detected by the image analysis, and the diagnosis entirely depends on pathological examination. The biliary tract is often affected by inflammatory conditions, and the resultant changes of the biliary epithelium make it difficult to differentiate them from neoplasia. Thus, the pathological diagnosis of biliary flat epithelial lesions can be challenging. In the biliary tract, there are several forms of intraepithelial neoplasia of the flat type, and biliary intraepithelial neoplasia (BilIN) is known as one of such lesions that represent the multistep cholangiocarcinogenesis. In this article, the diagnostic criteria and the differential diagnosis of biliary flat epithelial lesions, particularly focusing on BilIN, were presented and discussed to provide help to advance clinical and research applications of the BilIN system.
    Journal of Gastroenterology 01/2014; · 3.79 Impact Factor
  • The American journal of surgical pathology 01/2014; 38(1):144-145. · 4.06 Impact Factor
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    ABSTRACT: To examine the effects of 4-phenylbutyrate (4PB) therapy in a patient with progressive familial intrahepatic cholestasis type 2. A homozygous c.3692G>A (p.R1231Q) mutation was identified in ABCB11. In vitro studies showed that this mutation decreased the cell-surface expression of bile salt export pump (BSEP), but not its transport activity, and that 4PB treatment partially restored the decreased expression of BSEP. Therapy with 4PB had no beneficial effect for 1 month at 200 mg/kg/day and the next month at 350 mg/kg/day but partially restored BSEP expression at the canalicular membrane and significantly improved liver tests and pruritus at a dosage of 500 mg/kg/day. We conclude that 4PB therapy would have a therapeutic effect in patients with progressive familial intrahepatic cholestasis type 2 who retain transport activity of BSEP per se.
    The Journal of pediatrics 01/2014; · 4.02 Impact Factor
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    ABSTRACT: The aim of this study was to investigate correlations between the standardized uptake value of the biopsy site (BSUVmax) and levels of glucose transporter (GLUT)-1, GLUT-3 and hexokinase-II (HK-II), between BSUVmax and the Ki-67 proliferation index (MIB-1), and between BSUVmax and clinicopathological factors. Sixty-eight patients with diffuse large B-cell lymphoma (DLBCL) were included in this study. BSUVmax was significantly correlated with GLUT-1, GLUT-3 and the International Prognostic Index (IPI) (GLUT-1: r = 0.584, IPI: r = 0.363, p r = 0.369, p = 0.009; IPI: r = 0.363, p = 0.004), but not with MIB-1 and HK-II. A statistically significant correlation was observed between GLUT-3 expression and each of IPI and gene expression profiling (GEP) (IPI: p = 0.0186; GEP: p = 0.0179). 2-Deoxy-2-[18F]-fluoro-d-glucose (FDG) uptake was significantly correlated with the levels of GLUT-1 and GLUT-3 and with IPI. The results indicated that GLUT-3 expression is related to GEP and IPI, and that BSUVmax and GLUT-3 may have a relationship with the prognosis of DLBCL.
    Leukemia and Lymphoma 01/2014; 55(3). · 2.30 Impact Factor
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    ABSTRACT: Tumors formed by a highly metastatic human lung cancer cell line are characterized by activated signaling via vascular endothelial growth factor (VEGF)-C through its receptor (VEGFR-3) and aggressive lymph node metastasis. In this study, we examined how these highly metastatic cancers acquired aggressive lymph node metastasis. Compared with their lower metastatic counterparts, the highly metastatic tumors formed by this cell line expressed higher amounts of interleukin (IL)-1α, with similarly augmented expression of IL-1α and IL-1β by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated macrophages. These tumor-associated macrophages were mainly of the M2 type. Administration of a macrophage-targeting drug suppressed the production of these potent angiogenic and lymphangiogenic factors, resulting in decreased tumor growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel plug assays, the highly metastatic cells formed tumors that were extensively infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor (IL-1R) antagonist anakinra. Thus, the IL-1α-driven inflammatory activation of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor microenvironment favorable for lymph node metastasis through cross-talk with macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good therapeutic target for patients with this form of lung cancer.
    PLoS ONE 01/2014; 9(6):e99568. · 3.73 Impact Factor
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    ABSTRACT: Cytological diagnosis of respiratory disease has become important, not only for histological typing using immunocytochemistry (ICC) but also for molecular DNA analysis of cytological material. The aim of this study was to investigate the fixation effect of SurePath preservative fluids. Human lung cancer PC9 and 11-18 cell lines, and lung adenocarcinoma cells in pleural effusion, were fixed in CytoRich Blue, CytoRich Red, 15% neutral-buffered formalin, and 95% ethanol, respectively. PC9 and 11-18 cell lines were examined by ICC with epidermal growth factor receptor (EGFR) mutation-specific antibodies, the EGFR mutation DNA assay, and fluorescence in situ hybridization. The effect of antigenic storage time was investigated in lung adenocarcinoma cells in pleural effusion by ICC using the lung cancer detection markers. PC9 and 11-18 cell lines in formalin-based fixatives showed strong staining of EGFR mutation-specific antibodies and lung cancer detection markers by ICC as compared with ethanol-based fixatives. DNA preservation with CytoRich Blue and CytoRich Red was superior to that achieved with 95% ethanol and 15% neutral-buffered formalin fixatives, whereas EGFR mutations by DNA assay and EGFR gene amplification by fluorescence in situ hybridization were successfully identified in all fixative samples. Although cytoplasmic antigens maintained high expression levels, expression levels in nuclear antigens fell as storage time increased. These results indicate that CytoRich Red is not only suitable for ICC with EGFR mutation-specific antibodies, but also for DNA analysis of cytological material, and is useful in molecular testing of lung cancer, for which various types of analyses will be needed in future. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
    Cancer Cytopathology 10/2013; · 4.43 Impact Factor
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    ABSTRACT: The aim of this study was to reveal the differences in clinicopathological factors affecting maximum standardized uptake value (SUVmax) between esophageal squamous cell carcinoma (ESCC), non-small-cell lung cancer (NSCLC), and papillary thyroid cancer (PTC). This study consisted of 119 patients with ESCC (n=43), PTC (n=40), or NSCLC (n=36). We investigated the correlations between SUVmax and clinicopathological factors by using Spearman's correlation coefficient and the Kruskal-Wallis test. Multiple regression analysis was used to investigate which clinicopathological factors significantly affected SUVmax in each cancer type. The SUVmax correlated with glucose transporter-1 (GLUT-1) expression in NSCLC (r=0.536, P=0.007) and ESCC (r=0.597, P<0.001) but not in PTC. The SUVmax correlated with Ki-67 expression in NSCLC (r=0.381, P=0.022) and PTC (r=0.374, P=0.017) but not in ESCC. A high SUVmax was correlated with a higher pathological T stage (p-T stage) in NSCLC (r=0.536) and ESCC (r=0.597, both P<0.001) but not in PTC. An elevated SUVmax was significantly associated with pathological lymph node status (p-N) in NSCLC, but not in ESCC and PTC. In multiple regression analysis, p-T stage and GLUT-1 expression were statistically significant factors in ESCC, and p-T stage was a statistically significant factor in NSCLC. In PTC, Ki-67 showed a statistically significant association with SUVmax. SUVmax in NSCLC depended on the tumor invasion area; SUVmax in ESCC depended on tumor depth and GLUT-1 expression; and SUVmax in PTC might be associated with cell proliferation. The biological factors affecting SUVmax differ according to tumor type.
    Nuclear Medicine Communications 10/2013; · 1.38 Impact Factor
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    ABSTRACT: Infantile hemangioma (IH), a representative vascular liver tumor, usually occurs in infancy or early childhood but rarely in adults. In this study, we describe a case of IH in a 47-year-old female and we also review the literature. A plain computed tomography (CT) image revealed five hypoattenuating masses in the liver. A dynamic study revealed the masses appeared to be well-enhanced in the arterial phase, and were considered to be high-flow hemangiomas. The tumors appeared as hypointense tumors on the T1-weighted images and as hyperintensities on fat-suppression T2-weighted images. Following the administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), tumors appeared to be well-enhanced in the arterial phase. In the portal phase, tumors demonstrated isointensity compared with the surrounding liver parenchyma, and hypointensity in the equilibrium and hepatobiliary phases. The apparent diffusion coefficient (ADC) values ranged from 2.0 to 2.4x10-3 mm2/sec. Microscopically, the tumors were composed of numerous capillary-like small vessels lined with plump endothelial cells, arranged in a single layer without mitoses, and small bile ducts were trapped and scattered within the tumor. These findings were considered to be characteristic of IH. To the best of our knowledge, this case is the third report on IH in adults.
    Molecular Medicine Reports 10/2013; · 1.17 Impact Factor
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    ABSTRACT: Splenectomy may be a treatment option in hepatocellular carcinoma (HCC) and cirrhosis when there is no potential donor for liver transplantation. We retrospectively investigated the long-term outcome of splenectomy on survival in advanced cirrhotic patients with HCC and thrombocytopenia. Between 1999 and 2009, 46 cirrhotic patients with thrombocytopenia (Child-Pugh class B or C) who underwent splenectomy for the simultaneous or secondary treatment of HCC at our institute were evaluated. The 1-, 3-, and 5-year survival rates were 93.5, 76.0, and 37.9%, respectively. Splenectomy resulted in a significant reduction in mean portal venous pressure from 21.2 to 16.8 mmHg and improvements in liver function tests such as total bilirubin, prothrombin time, platelet count, Child-Pugh score for 3 years, and albumin for 2 years. The mean frequency of treatment for HCC recurrence after surgery was 3.0 times (range: 1-11). Seven patients out of 16 scheduled for Interferon (IFN) therapy after surgery achieved a sustained virological response (SVR). Multivariate analysis identified SVR after IFN therapy as an independent significant prognostic factor (Hazard ratio 0.18, 95%CI 0.03-0.65, P=0.006). Postoperative complications including liver failure (n=1), portal thrombosis (n=7), ascites (n=5), and bacterial infections (n=4) were observed in 14 patients (30%). Splenectomy can be a feasible supportive therapy for the continuation of anticancer therapy and completion of IFN therapy based on improvements in liver function and thrombocytopenia with minimum complications in patients with HCC and advanced cirrhosis with no potential donor.
    The Kurume Medical Journal 09/2013;
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    ABSTRACT: We classified resected intraductal papillary mucinous neoplasms (IPMNs) into four subtypes (gastric, intestinal, pancreatobiliary and oncocytic) according to their morphological features and mucin expression, determined their clinicopathological characteristics and investigated the possibility of preoperatively diagnosing these subtypes. Sixty resected tumors, 4 preoperative tumor biopsies and 10 preoperative pancreatic juice cytology specimens were analyzed. The gastric and intestinal types accounted for the majority of IPMNs. Non-gastric type IPMNs were of high-grade malignancy. Many of the pancreatobiliary-type IPMNs were in an advanced stage and were associated with a poor prognosis. The results of mucin immunohistochemical staining of preoperative biopsy and surgically resected specimens were in agreement with each other, and in close agreement with those for pancreatic juice cytology specimens obtained from 10 patients during endoscopic retrograde cholangiopancreatography (ERCP). The immunostaining of preoperative biopsy specimens and ERCP-obtained pancreatic juice cytology specimens may be useful in the differential diagnosis of gastric and intestinal types of IPMN. If such techniques enable the preoperative diagnosis of IPMN subtypes, their use in combination with conventional preoperative imaging modalities may lead to surgical treatment best suited for the biological characteristics of the four subtypes.
    Oncology Reports 09/2013; · 2.30 Impact Factor
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    ABSTRACT: Splenectomy improves hypersplenic thrombocytopenia in cirrhotic patietnts with hypersplenism. However, the long term influence of splenectomy has not been calrified. We examined whether splenectomy improved liver fibrosis and casused immunological changes. We collected liver and spleen specimens and peripheral blood (PB) from 26 patients with hepatitis C virus (HCV)-related liver cirrhosis. An immunohistochemical examination of CD4, CD8, forkhead box P3 (FOXP3), granzyme B, and transforming growth factor (TGF)-β1, and Masson's Trichrome stain were performed in spleen and liver tissues and in 7 cases of follow-up liver biopsy sections obtained after splenectomy. We obtained PB before and at various intervals after splenectomy. We also examined the ratio of CD4(+) and CD8(+) lymphocytes in PB using flow cytometry. We observed improvements in liver fibrosis in 4 biopsy specimens obtained after splenectomy, in which fibrotic areas significantly decreased from 19.5% to 8.2% (p<0.05). Increases were also observed in the ratio of CD8(+) cells in PB after splenectomy, which resulted in a significant decrease in the CD4(+) /CD8(+) ratio (p<0.001). The carcinogenic rate in patients with a CD4(+) /CD8(+) ratio that decreased by more than 0.5 one month after splenectomy was significantly lower than that in patients with a ratio that decreased by less than 0.5 (p<0.05). Splenectomy may improve liver fibrosis and cause beneficial immunological changes in cirrhotic patients with hepatitis. Improvements in anti-tumor mechanisms can be also expected.
    Hepatology Research 09/2013; · 2.07 Impact Factor
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    ABSTRACT: We tried to characterize the pathological features of patients who developed hepatocellular carcinoma (HCC) with the negative results of both serous hepatitis B surface antigen and hepatitis C virus antibody (non-B non-C). In a multicenter study in Kyushu, Japan, we studied the histopathological characteristics of non-cancerous liver tissues in 129 patients (103 men and 26 women) with non-B non-C HCC. The histological liver damage was evaluated for fibrosis (stage) and inflammation (grade) according to the Ludwig classification of chronic hepatitis. In addition, we examined the hepatitis B virus (HBV) genome in serum samples and liver tissues of 20 patients with non-B non-C HCC. Positivity of serum hepatitis B core (HBc) antibody, alcohol abuse, diabetes, and nonalcoholic steatohepatitis were present in 61 (47%), 76 (59%), 57 (44%), and 8 (6%) patients, respectively. The degree of fibrosis was mild (Stage: 1.6±1.2). The stage of patients with neither serum HBc antibody nor alcohol abuse was significantly lower than the stage of patients with HBc antibody and no alcohol abuse (p < 0.05). HBV genome was detected in 15 cancerous tissues (75%) and 16 non-cancerous liver tissues (80%) in 20 patients with non-B non-C HCC. Only 3 of the 20 patients were positive for serum HBc antibody. Non-B non-C patients appear to develop HCC at a low stage of fibrosis. Occult hepatitis B virus infection is the major risk factor for HCC of non-B non-C patients in Kyushu, Japan.
    Hepatology Research 08/2013; · 2.07 Impact Factor
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    ABSTRACT: Primary biliary cirrhosis (PBC) is a cholestatic liver disease with an elevated serum immunoglobulin M (IgM) level. Patients with PBC may develop extrahepatic manifestations, including hypogammaglobulinemia. However, hypogammaglobulinemia seldom occurs, and the associated changes of lymphocytes remain unknown. Furthermore, the impact of immunoglobulins on the progression of PBC is still unclear. Here, we describe a case of hypogammaglobulinemia developed in a female patient with PBC. The patient was diagnosed with PBC at the age of 46 years and treated with ursodeoxycholic acid and bezafibrate. At the age of 50 years, the patient developed bronchitis, and laboratory test results indicated a marked decrease in serum levels of IgA, IgM, and IgG. Then, the patient was diagnosed as idiopathic hypogammaglobulinemia and treated with immunoglobulin replacement therapy; however, respiratory infections recurred frequently, leading to the patient's death at the age of 53 years. An autopsy revealed hyperplastic bone marrow with CD3-, CD20-, and IgG-positive lymphocytes. However, no CD79a-, CD138-, IgA-, and IgM-positive lymphocytes were observed. Moreover, the severity of PBC progressed even after the onset of hypogammaglobulinemia. In addition, CD3-positive cells were seen around chronic non-suppurative destructive cholangitis in the autopsy specimen of the liver. Thus, the present case demonstrated changes of lymphocytes in hypogammaglobulinemia developmed in patients with PBC. Furthermore, the clinical course of the present case of PBC may indicate that the immunoglobulin-mediated mechanisms may be nonessential for the progression of PBC.
    Hepatology Research 07/2013; · 2.07 Impact Factor
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    ABSTRACT: EGFR kinase inhibitors including gefitinib and erlotinib exert potent therapeutic efficacy in non-small cell lung cancers harboring EGFR activating mutations. However, most patients ultimately develop resistance to these drugs. Here we report a novel mechanism of acquired resistance the reversal of which could clinical outcomes. In erlotinib-resistant lung cancer cells harboring activating EGFR mutations that we established, there was increased expression of Src, integrinβ1, α2, and α5 along with enhanced cell adhesion activity. Interestingly, RNAi-mediated silencing of integrinβ1 restored erlotinib sensitivity and reduced activation of Src and Akt after erlotinib treatment. Further, Src silencing inhibited Akt phosphorylation and cell growth, with this inhibitory effect further augmented by erlotinib treatment. Increased expression of integrinβ1, α5, and/or α2 was also observed in refractory tumor samples from lung cancer patients treated with erlotinib and/or gefitinib. Together, our findings identify the integrinβ1/Src/Akt signaling pathway as a key mediator of acquired resistance to EGFR-targeted anticancer drugs.
    Cancer Research 07/2013; · 8.65 Impact Factor
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    ABSTRACT: Refractory bone and soft tissue sarcomas are challenging diseases to treat because of their robustness to chemotherapy. Although cancer vaccines have the potential to become an attractive treatment modality, their progress has been hampered by the presence of many subtypes of sarcomas and different HLA-types. We investigated whether personalized peptide vaccination (PPV) would be feasible for the vast majority of sarcoma patients. Twenty refractory bone and soft tissue sarcoma patients with 9 different subtypes and 11 different HLA-class IA phenotypes were enrolled in this study. A maximum of four HLA-matched peptides showing higher peptide-specific IgG responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the HLA-A2, -A3, -A11, -A24, -A26, -A31, and -A33 types, and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific CTL and IgG responses along with other laboratory analyses were conducted before and after vaccination. No patients were excluded by either sarcoma subtypes or different HLA-types. No severe adverse events associated with PPV were observed in any patients. Peptide-specific immunological boosting was observed in the post-vaccination samples from the majority of patients. Tumor reduction of the lung metastasis and a long stable disease was observed in each one case, and the median overall survival time of the 20 cases was 9.6 months. Taken together, PPV could be feasible for the vast majority of refractory sarcoma patients because of the safety and higher rates of immunological responses regardless of the presence of different sarcoma subtypes and various HLA-types. This article is protected by copyright. All rights reserved.
    Cancer Science 07/2013; · 3.48 Impact Factor

Publication Stats

2k Citations
733.28 Total Impact Points

Institutions

  • 1986–2014
    • Kurume University
      • • Department of Diagnostic Pathology
      • • School of Medicine
      • • Department of Internal Medicine
      Куруме, Fukuoka, Japan
  • 2009–2012
    • Kyushu University
      • Faculty of Pharmaceutical Sciences
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2011
    • Kumamoto University
      • Department of Pediatric Surgery and Transplantation
      Kumamoto, Kumamoto Prefecture, Japan
  • 2010
    • Kyushu Medical Center
      Hukuoka, Fukuoka, Japan
  • 2008–2009
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
    • Kinki University
      • Department of Gastroenterology and Hepatology
      Ōsaka-shi, Osaka-fu, Japan
  • 2006–2007
    • Tokyo Medical University
      • Division of Pediatrics
      Edo, Tōkyō, Japan
  • 2004
    • Numazu City Hospital
      Sizuoka, Shizuoka, Japan
  • 2003
    • NHO Nagasaki Medical Center
      Nagasaki, Nagasaki, Japan
  • 1999–2000
    • Nagoya City University
      Nagoya, Aichi, Japan