Shingo Miyamoto

Fukuoka University, Hukuoka, Fukuoka, Japan

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Publications (100)290.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although DNA methylation is considered to play an important role during myogenic differentiation, chronological alterations in DNA methylation and gene expression patterns in this process have been poorly understood. Using the Infinium HumanMethylation450 BeadChip array, we obtained a chronological profile of the genome-wide DNA methylation status in a human myoblast differentiation model, where myoblasts were cultured in low-serum medium to stimulate myogenic differentiation. As the differentiation of the myoblasts proceeded, their global DNA methylation level increased and their methylation patterns became more distinct from those of mesenchymal stem cells and skeletal muscle tissues. Gene ontology analysis revealed that genes whose promoter region was hypermethylated upon myoblast differentiation were highly significantly enriched with muscle-related terms such as "muscle contraction" and "muscle system process." Sequence motif analysis identified 8-bp motifs somewhat similar to the binding motifs of ID4 and ZNF238 to be most significantly enriched in hypermethylated promoter regions. ID4 and ZNF238 have been shown to be critical transcriptional regulators of muscle-related genes during myogenic differentiation. An integrated analysis of DNA methylation and gene expression profiles revealed that de novo DNA methylation of non-CpG island (CGI) promoters was more often associated with transcriptional down-regulation than that of CGI promoters. These results strongly suggest the existence of an epigenetic mechanism in which DNA methylation modulates the functions of key transcriptional factors to coordinately regulate muscle-related genes during myogenic differentiation.
    Human Molecular Genetics 09/2014; · 6.68 Impact Factor
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    ABSTRACT: Objective This retrospective study aimed to determine the predictive factors for the efficacy of pelvic arterial embolization for postpartum hemorrhage. Materials and methods Twenty-one patients who underwent pelvic arterial embolization for postpartum hemorrhage of >1000 mL between September 2006 and September 2011 were enrolled in this study. The patients were divided into two subgroups according to the blood loss and time from the end of pelvic arterial embolization to complete hemostasis: good-response (16 patients) and poor-response groups (5 patients). The following predictive factors were compared between the groups: (1) patient characteristics; (2) blood loss; (3) time between delivery (or onset of bleeding) and pelvic arterial embolization; (4) obstetrical disseminated intravascular coagulation score comprising clinical background, clinical signs, and laboratory data; (5) individual disseminated intravascular coagulation score; (6) shock index; and (7) laboratory data including platelet count, prothrombin time-international normalized ratio, fibrinogen, fibrin degradation products, and antithrombin-III at the time of pelvic arterial embolization. Results In the poor-response group, the obstetrical and individual disseminated intravascular coagulation scores and prothrombin time-international normalized ratio were higher than those in the good-response group (p < 0.05). Platelet count, fibrinogen, and fibrin degradation products were lower than those in the good-response group (p < 0.05). All obstetrical disseminated intravascular coagulation scores in the poor-response group were >9 points. Conclusion The efficacy of pelvic arterial embolization is related to the presence or absence of coagulation disorders. When the obstetrical disseminated intravascular coagulation score is high (>9 points), the efficacy may be poor.
    Taiwanese Journal of Obstetrics and Gynecology 09/2014; 53(3):366–371. · 1.26 Impact Factor
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    ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor family, is a target for ovarian cancer therapy. The present study investigated the administration schedule of BK-UM, an anticancer agent targeting HB-EGF.
    Anticancer research 08/2014; 34(8):4615-20. · 1.87 Impact Factor
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    ABSTRACT: Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells.
    Cancer Medicine 07/2014;
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    ABSTRACT: We report the first case of the successful detection of postpartum unruptured vaginal pseudoaneurysm using power- and pulsed-Doppler ultrasonography after delivery.
    SpringerPlus 01/2014; 3:482.
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    ABSTRACT: Recently developed transcription activator-like effector nuclease (TALEN) technology has enabled the creation of knockout mice, even for genes on the Y chromosome. In this study, we generated a knockout mouse for Sry, a sex-determining gene on the Y chromosome, using microinjection of TALEN RNA into pronuclear stage oocytes. As expected, the knockout mouse had female external and internal genitalia, a female level of blood testosterone and a female sexually dimorphic nucleus in the brain. The knockout mouse exhibited an estrous cycle and performed copulatory behavior as females, although it was infertile or had reduced fertility. A histological analysis showed that the ovary of the knockout mouse displayed a reduced number of oocytes and luteinized unruptured follicles, implying that a reduced number of ovulated oocytes is a possible reason for infertility and/or reduced fertility in the KO mouse.
    Scientific Reports 11/2013; 3:3136. · 5.08 Impact Factor
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    ABSTRACT: The majority of human tumors display a high rate of glycolysis under aerobic conditions. This phenomenon was recognized approximately seven decades ago and is known as the Warburg effect. Several key enzymes required to maintain this high level of glucose metabolism are found in tumor cells. The effects of the glycolytic enzymes are known to be directly or indirectly regulated by various signaling pathways, oncogenes, suppressor genes and transcription factors. Recent molecular biology studies have shown that multiple genetic alterations are related to tumor development. Therefore, these factors may be rational targets for cancer therapy. In this short review, we describe several important molecules that affect aerobic glycolysis and discuss their possible use as therapeutic targets for cancer.
    Anticancer research 07/2013; 33(7):2855-60. · 1.87 Impact Factor
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    ABSTRACT: We report anesthetic management of a 38-year-old woman with pulmonary thromboembolism for total hysterectomy. She had been taking oral contraceptives for adenomyosis of the uterus. She had thrombi in the arteries from pulmonary trunk to bilateral main pulmonary arteries. Thrombolytic and anticoagulant therapies did not decrease the thrombi. Removal of the swollen uterus suspected to be the origin of the thrombi, rather than thromboembolectomy, was scheduled. Cannulation for percutaneous cardiopulmonary support was set up just in case of hemodynamic derangement, before the surgery. Cardiac contraction was evaluated with transesophageal echocardiography during the surgery. There was no untoward perioperative event. Pulmonary thromboembolectomy was not done because the postoperative CT revealed shrinkage of the pulmonary thrombi after anticoagulation treatment.
    Masui. The Japanese journal of anesthesiology 06/2013; 62(6):696-8.
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    ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is one of several pro-angiogenic factors, and represents a possible therapeutic target for patients with triple-negative breast cancer (TNBC). However, the role of HB-EGF in promoting tumor aggressiveness in TNBC remains unclear. In order to investigate specific genes and pathways involved in TNBC tumorigenesis, we profiled gene expression changes in two TNBC cell lines under two-dimensional culture (2DC) and three-dimensional culture (3DC) and in a tumor xenograft model. We identified simultaneous upregulation of HB-EGF, vascular endothelial growth factor A (VEGFA) and angiopoietin-like 4 (ANGPTL4) in 3DC and tumor xenografts, compared with 2DC. We show that HB-EGF regulates the expression of VEGFA or ANGPTL4 via transcriptional regulation of hypoxia inducible factor-1 alpha and nuclear factor kappa B. Furthermore, suppression of VEGFA or ANGPTL4 expression enhanced HB-EGF expression, highlighting a unique regulatory loop underlying this angiogenesis network. Targeted knockdown of HB-EGF significantly suppressed tumor formation in a TNBC xenograft model, compared with individual knockdown of either VEGFA or ANGPTL4, by reducing the expression of both VEGFA and ANGPTL4. In patients with TNBC, VEGFA or ANGPTL4 expression was also significantly correlated with HB-EGF expression. Low concentrations of exogenously added HB-EGF strongly activated the proliferation of endothelial cells, tube formation and vascular permeability in blood vessels, in a similar fashion to high doses of VEGFA and ANGPTL4. Taken together, these results suggest that HB-EGF plays a pivotal role in the acquisition of tumor aggressiveness in TNBC by orchestrating a molecular hierarchy regulating tumor angiogenesis.
    Molecular Cancer Research 02/2013; · 4.35 Impact Factor
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    ABSTRACT: Acute pulmonary thromboembolism (PTE) is a common illness that causes death and disability. Deep vein thrombosis (DVT) is often found in patients with a large myomatous uterus, and can occasionally result in acute PTE. Here, we describe the achievement of a favorable outcome in a case of acute PTE. The patient presented with acute PTE caused by a large uterine leiomyoma, without DVT of the lower extremities. Percutaneous cardiopulmonary support (PCPS) was used as an adjunct to thrombolytic therapy to treat the right ventricular thrombus with acute PTE. According to emergency practice, PCPS was initiated, and the patient was successfully treated with thrombolytic and anticoagulant therapy associated with total abdominal hysterectomy. This case suggests that PCPS can lead to favorable clinical outcomes in patients with large uterine leiomyomata and severe PTE.
    Taiwanese journal of obstetrics & gynecology 12/2012; 51(4):639-42.
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    ABSTRACT: Emmprin is a transmembrane glycoprotein known as a matrix metalloproteinase inducer and is highly up-regulated in malignant cancer cells. The monocarboxylate transporters (MCTs) are responsible for H(+)-linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of emmprin as a chaperone and that MCT-1 also acts as chaperone for emmprin. The objectives of this study were to clarify emmprin and MCT-1 expression patterns in ovarian epithelial tumors and to elucidate the clinicopathological significance of co-localization of the two molecules. Immunohistochemical analysis of 205 epithelial tumors indicated that emmprin is always localized in cell membranes but its distribution differs according to tumor type: in lateral membranes in 89 % of adenomas, in lateral and basal membranes in 76 % of borderline tumors, and in membranes surrounding the entire cell in 98 % of carcinomas. Most carcinomas in situ also showed a lateral and basal expression pattern. In only 21 % of the carcinomas, the cells expressing membranous MCT-1 showed co-localized emmprin expression. Poor co-localization of the two molecules was more frequently found in serous carcinomas. However, the overall survival was not significantly different for the good and poor co-localization carcinoma groups. These findings indicate that the emmprin expression pattern might discriminate between invasive carcinomas and borderline tumors including carcinoma in situ. Moreover, there may be an as yet unidentified regulatory mechanism(s), for localization of MCT-1 and emmprin in cell membranes in vivo.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2012; 461(4):457-66. · 2.56 Impact Factor
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    ABSTRACT: We previously established a three-dimensional (3-D) colonic crypt model using HKe3 cells which are human colorectal cancer (CRC) HCT116 cells with a disruption in oncogenic KRAS, and revealed the crucial roles of oncogenic KRAS both in inhibition of apoptosis and in disruption of cell polarity; however, the molecular mechanism of KRAS-induced these 3-D specific biological changes remains to be elucidated. Among the genes that were upregulated by oncogenic KRAS in this model, we focused on the phosphodiesterase 4B (PDE4B) of which expression levels were found to be higher in clinical tumor samples from CRC patients in comparison to those from healthy control in the public datasets of gene expression analysis. PDE4B2 was specifically overexpressed among other PDE4 isoforms, and re-expression of oncogenic KRAS in HKe3 cells resulted in PDE4B overexpression. Furthermore, the inhibition of PDE4 catalytic activity using rolipram reverted the disorganization of HCT116 cells into the normal physiologic state of the epithelial cell polarity by inducing the apical assembly of ZO-1 (a tight junction marker) and E-cadherin (an adherens junction marker) and by increasing the activity of caspase-3 (an apoptosis marker) in luminal cavities. Notably, rolipram reduced the AKT phosphorylation, which is known to be associated with the disruption of luminal cavity formation and CRC development. Similar results were also obtained using PDE4B2-shRNAs. In addition, increased expression of PDE4B mRNA was found to be correlated with relapsed CRC in a public datasets of gene expression analysis. These results collectively suggested that PDE4B is upregulated by oncogenic KRAS, and also that the inhibition of PDE4 catalytic activity can induce both epithelial cell polarity and luminal apoptosis in CRC, thus highlighting the utility of our 3-D culture (3 DC) model for the KRAS-induced development of CRC in 3-D microenvironment. Indeed, using this model, we found that PDE4B is a promising candidate for a therapeutic target as well as prognostic molecular marker in CRC. Further elucidation of the signaling network of PDE4B2 in 3 DC would provide a better understanding of CRC in vivo.
    Molecular Cancer 07/2012; 11:46. · 5.40 Impact Factor
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    ABSTRACT: Biotherapy is a form of treatment that uses the natural immune system to protect the body against infection, cancer, and other diseases, and can fortify the body against some side-effects of other treatments. Biotherapy employs substances called biological response modifiers (BRMs), which include vaccines, monoclonal antibodies, cytokines, and adjuvants. BRMs are used alone or in combination with each other. Several BRMs are widely accepted in the treatment of certain types of cancer, while others are being tried in research studies. Side-effects of biotherapy vary among agents and patients. However, these side-effects usually disappear after the end of treatment.
    Anticancer research 06/2012; 32(6):2229-33. · 1.87 Impact Factor
  • Article: Preface.
    Anticancer research 06/2012; 32(6):2225. · 1.87 Impact Factor
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    ABSTRACT: We previously found that oncogenic KRAS induces increased expression of microRNAs (miRNAs), such as miR-200c and miR-221/222, in human colorectal cancer (CRC) HCT116 cells in a three-dimensional (3D)-specific manner, however, the regulation of miRNA expression through oncogenic KRAS in other types of CRC remains unclear. The differential expression of 94 cancer-related miRNAs was examined in DLD-1 and DKO-4 cells (DLD-1 cells with a disrupted oncogenic KRAS) in 3D cultures. Increased miR-15b, miR-16, miR-23a, miR-24, miR-103 and miR-222 expression was observed in 3D and in 2D cultures. Of note, increased miR-181a, miR-200c and miR-210 expression was only observed in 3D cultures. Furthermore, miR-181a and miR-210 were significantly overexpressed in DLD-1 cells in 3D culture compared with those in HCT116 cells, and were significantly overexpressed in human CRC specimens. Oncogenic KRAS regulates 3D-specific miRNAs that are possibly associated with CRC development in vivo.
    Anticancer research 06/2012; 32(6):2271-5. · 1.87 Impact Factor
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    ABSTRACT: Heparin binding epidermal growth factor-like growth factor (HB-EGF) is involved in development and homeostasis as well as in pathological processing of chronic diseases, especially cancer. Enhancement of HB-EGF expression is directly or indirectly regulated by transcriptional factors, including activator protein-1 (AP-1), specificity protein (SP)1, SP3, nuclear factor kappa B (NF-κB), hypoxia inducible factor 1, alpha subunit (HIF-1α, myogenic differentiation 1 (MyoD), Wilms tumor 1 (WT-1) and snail homolog 1 (Snail), and also by microRNAs. These transcription or post-transcription factors may communicate to form an autocrine HB-EGF amplification loop. Emerging evidence has indicated that HB-EGF is a rational target for the therapy of cancer and atherosclerosis. In this review, we discuss the relationship between the HB-EGF autocrine loop and HB-EGF transcriptional factors, and we highlight HB-EGF as a therapeutic target in diverse diseases.
    Anticancer research 06/2012; 32(6):2347-52. · 1.87 Impact Factor
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    ABSTRACT: The management of malignant ascites is critical for the treatment of patients with advanced gynecological cancer. The purpose of this study was to assess the clinical significance of cell-free and concentrated ascites re-infusion therapy (CART). Adverse events, alterations in Eastern Cooperative Oncology Group performance status, serum albumin, body weight and abdominal circumference, and overall survival were examined in 22 patients with advanced gynecological cancer which were treated with CART. Most of the adverse events were grade 1 or 2 fever. CART treatment had little effect on ECOG performance status and on levels of serum albumin. There was a significant decrease in body weight and in abdominal circumference post-treatment with CART, relative to pre-treatment (p<0.01). The overall survival rate was significantly prolonged in 14 patients after CART plus chemotherapy, as compared with eight patients after CART alone (p<0.01). CART may contribute to the improvement of quality of life and of survival in patients with advanced gynecological cancer.
    Anticancer research 06/2012; 32(6):2353-7. · 1.87 Impact Factor
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    ABSTRACT: Colostrum contains a wide variety of crucial nutritional elements including growth factors for newborn infants to adapt to the extrauterine environment. To investigate the clinical significance of epidermal growth factor receptor ligands in milk during the first month of lactation. The concentrations of epidermal growth factor (EGF), amphiregulin (AR) and transforming growth factor-α (TGF-α) in milk sampled from a total of 31 normal mothers at days 1-3, 5, and 30 postpartum were examined using ELISA. At days 1-3, the concentration of EGF was extremely high [131.6 ± 20.4 (mean ± SEM) ng/ml] compared to that of AR (4,197.2 ± 1,055.2 pg/ml) or TGF-α (261.7 ± 33.6 pg/ml), while the concentration of AR was significantly elevated compared to that of TGF-α. At days 5 and 30, the concentration of EGF was significantly elevated compared to that of AR or TGF-α. In 16 mothers among the same 31 subjects, samples were longitudinally obtained on days 1, 2, 5, and 30 postpartum. Concentrations of AR were higher on days 1 and 2 and rapidly declined to below 1 ng/ml on day 5, and were maintained at lower levels on day 30. Concentrations of EGF were high on day 1 (greater than 10 ng/ml) but gradually declined by days 2, 5, and 30. Concentrations of TGF-α remained at lower levels of below 1 ng/ml throughout the lactation period from days 1 to 30. These results suggested that EGF and amphiregulin in colostrum might contribute to the early stage of development of neonatal gastrointestinal function.
    Archives of Gynecology 05/2012; 286(3):643-7. · 1.28 Impact Factor
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    ABSTRACT: Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that bind to and activate the EGF receptor. HB-EGF is synthesized as a membrane-anchored protein (proHB-EGF), and then proteolytically cleaved, resulting in the mitogenically active soluble form. HB-EGF plays pivotal roles in pathophysiological processes such as development and cell proliferation. In this study, we developed an immuno-PCR system for the determination of soluble HB-EGF concentrations in human serum. Utilizing a monoclonal antibody with neutralizing activity against HB-EGF as a capture antibody resulted in increasing selectivity for an active form of HB-EGF in serum, and immuno-PCR system improved its sensitivity compared to the currently available methods. As a result of measurement of HB-EGF in 20 ovarian cancer patients and 20 healthy volunteers, ovarian cancer patients showed significantly higher concentrations than healthy volunteers (P< 0.05), which indicates that soluble HB-EGF detected by newly developed immuno-PCR system can be useful serological biomarkers such as a diagnostic biomarker for ovarian cancer, and a predictive and pharmacodynamic biomarker for anti-HB-EGF targeted therapies under development.
    American Journal of Translational Research 01/2012; 4(4):415-21. · 3.23 Impact Factor
  • Nippon rinsho. Japanese journal of clinical medicine 01/2012; 70(Suppl 4):488-492.

Publication Stats

1k Citations
290.55 Total Impact Points


  • 2006–2014
    • Fukuoka University
      • • Faculty of Medicine
      • • Department of Obstetrics and Gynecology
      • • Department of Biochemistry
      Hukuoka, Fukuoka, Japan
  • 2012
    • IIzuka Hospital
      Иидзука, Fukuoka, Japan
  • 2009
    • Osaka University
      • Division of Cell Biology
      Ōsaka-shi, Osaka-fu, Japan
  • 1988–2009
    • Kyushu University
      • • Department of Obstetrics and Gynecology
      • • Medical Institute of Bioregulation - MIB Hospital
      • • Faculty of Medical Sciences
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2008
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan
  • 2000–2001
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 1995
    • Kagoshima University
      • Department of Obstetrics and Gynecology
      Kagosima, Kagoshima, Japan