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Articles by H Yamamoto
Total Records ( 10 ) for H Yamamoto
  C Fujioka , J Horiguchi , M Kiguchi , H Yamamoto , T Kitagawa and K. Ito

OBJECTIVE. The purpose of this study was to investigate the feasibility of prospective ECG-triggered axial 64-MDCT angiography of the aorta and coronary arteries performed at a tube voltage of 100 kV.

SUBJECTS AND METHODS. Thirty patients with a heart rate less than 75 beats/min who were referred for aortic CT angiography were enrolled. The image quality of the ascending aorta, aortic valve, and coronary arteries was evaluated for motion artifacts. Contrast enhancement (mean attenuation) was measured in the ascending aorta, descending aorta, and bifurcation of the aorta. Aortic valve and coronary artery lesions were surveyed.

RESULTS. Acceptable image quality was achieved in 100% (30/30) of cases for the ascending aorta, 97% (29/30) of cases for the aortic valve, and 98% (442/452) of coronary arterial segments. Contrast enhancement was greater than 200 HU and was satisfactory (ascending aorta, 379 ± 80 HU; descending aorta, 354 ± 72 HU; bifurcation, 355 ± 96 HU). Lesions found in the aortic valve were plaque (n = 16) and bicuspid valve (n = 1) and in the coronary arteries were ≥ 50% luminal stenosis (n = 5), plaque (n = 21), myocardial bridge (n = 12), and anomalous origin (n = 1). The effective radiation dose was estimated to be 7.5 ± 1.7 mSv.

CONCLUSION. For patients with a heart rate less than 75 beats/min, prospective ECG-triggered axial CT angiography at a tube voltage of 100 kV has the potential to provide clinically relevant information about the aorta and coronary arteries with low radiation exposure.

  Y Adachi , R Li , H Yamamoto , Y Min , W Piao , Y Wang , A Imsumran , H Li , Y Arimura , C. T Lee , K Imai , D. P Carbone and Y. Shinomura

Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. We have previously shown significant therapeutic activity for recombinant adenoviruses expressing dominant-negative insulin-like growth factor-I receptor (IGF-IR/dn), including suppression of tumor invasion. In this study, we sought to evaluate the mechanism of inhibition of invasion and the relationship between IGF-IR and matrix metalloproteinase (MMP) activity in GI carcinomas. We analyzed the role of IGF-IR on invasion in three GI cancer cell lines, colorectal adenocarcinoma, HT29; pancreatic adenocarcinoma, BxPC3 and gastric adenocarcinoma, MKN45, using a modified Boyden chamber method and subcutaneous xenografts in nude mice. The impact of IGF-IR signaling on the expression of MMPs and the effects of blockade of matrilysin or IGF-IR on invasiveness were assessed using recombinant adenoviruses, a tyrosine kinase inhibitor NVP-AEW541 and antisense matrilysin. Invasive subcutaneous tumors expressed several MMPs. IGF-IR/dn reduced the expression of these MMPs but especially matrilysin (MMP-7). Insulin-like growth factor (IGF) stimulated secretion of matrilysin and IGF-IR/dn blocked IGF-mediated matrilysin induction in three GI cancers. Both IGF-IR/dn and inhibition of matrilysin reduced in vitro invasion to the same degree. NVP-AEW541 also reduced cancer cell invasion both in vitro and in murine xenograft tumors via suppression of matrilysin. Thus, blockade of IGF-IR is involved in the suppression of cancer cell invasion through downregulation of matrilysin. Strategies of targeting IGF-IR may have significant therapeutic utility to prevent invasion and progression of human GI carcinomas.

  H Suzuki , S Igarashi , M Nojima , R Maruyama , E Yamamoto , M Kai , H Akashi , Y Watanabe , H Yamamoto , Y Sasaki , F Itoh , K Imai , T Sugai , L Shen , J. P. J Issa , Y Shinomura , T Tokino and M. Toyota

A subset of colorectal cancers (CRCs) show simultaneous methylation of multiple genes; these tumors have the CpG island methylator phenotype (CIMP). CRCs with CIMP show a specific pattern of genetic alterations, including a high frequency of BRAF mutations and a low frequency of p53 mutations. We therefore hypothesized that genes inactivated by DNA methylation are involved in the BRAF- and p53-signaling pathways. Among those, we examined the epigenetic inactivation of insulin-like growth factor-binding protein 7 (IGFBP7) expression in CRCs. We found that in CRC cell lines, the silencing of IGFBP7 expression was correlated with high levels of DNA methylation and low levels of histone H3K4 methylation. Luciferase and chromatin immunoprecipitation assays in unmethylated cells revealed that p53 induces expression of IGFBP7 upon binding to a p53 response element within intron 1 of the gene. Treating methylated CRC cell lines with 5-aza-2'-deoxycytidine restored p53-induced IGFBP7 expression. Levels of IGFBP7 methylation were also significantly higher in primary CRC specimens than in normal colonic tissue (P < 0.001). Methylation of IGFBP7 was correlated with BRAF mutations, an absence of p53 mutations and the presence of CIMP. Thus, epigenetic inactivation of IGFBP7 appears to play a key role in tumorigenesis of CRCs with CIMP by enabling escape from p53-induced senescence.

  H Suzuki , E Yamamoto , M Nojima , M Kai , H. o Yamano , K Yoshikawa , T Kimura , T Kudo , E Harada , T Sugai , H Takamaru , T Niinuma , R Maruyama , H Yamamoto , T Tokino , K Imai , M Toyota and Y. Shinomura

Altered expression of microRNA (miRNA) is strongly implicated in cancer, and recent studies have shown that the silencing of some miRNAs is associated with CpG island hypermethylation. To identify epigenetically silenced miRNAs in gastric cancer (GC), we screened for miRNAs induced by treatment with 5-aza-2’-deoxycytidine and 4-phenylbutyrate. We found that miR-34b and miR-34c are epigenetically silenced in GC and that their downregulation is associated with hypermethylation of the neighboring CpG island. Methylation of the miR-34b/c CpG island was frequently observed in GC cell lines (13/13, 100%) but not in normal gastric mucosa from Helicobacter pylori-negative healthy individuals. Transfection of a precursor of miR-34b and miR-34c into GC cells induced growth suppression and dramatically changed the gene expression profile. Methylation of miR-34b/c was found in a majority of primary GC specimens (83/118, 70%). Notably, analysis of non-cancerous gastric mucosae from GC patients (n = 109) and healthy individuals (n = 85) revealed that methylation levels are higher in gastric mucosae from patients with multiple GC than in mucosae from patients with single GC (27.3 versus 20.8%; P < 0.001) or mucosae from H. pylori-positive healthy individuals (27.3 versus 20.7%; P < 0.001). These results suggest that miR-34b and miR-34c are novel tumor suppressors frequently silenced by DNA methylation in GC, that methylation of miR-34b/c is involved in an epigenetic field defect and that the methylation might be a predictive marker of GC risk.

  M Yamaguchi , M Hayashi , S Fujita , T Yoshida , T Utsunomiya , H Yamamoto and K. Kasai

It has previously been reported that low-energy laser irradiation stimulated the velocity of tooth movement via the receptor activator of nuclear factor kappa B (RANK)/RANK ligand and the macrophage colony-stimulating factor/its receptor (c-Fms) systems. Matrix metalloproteinase (MMP)-9, cathepsin K, and alpha(v) beta(3) [(v)β3] integrin are essential for osteoclastogenesis; therefore, the present study was designed to examine the effects of low-energy laser irradiation on the expression of MMP-9, cathepsin K, and (v)β3 integrin during experimental tooth movement.

Fifty male, 6-week-old Wistar strain rats were used in the experiment. A total force of 10g was applied to the rat molars to induce tooth movement. A Ga-Al-As diode laser was used to irradiate the area around the moving tooth and, after 7 days, the amount of tooth movement was measured. To determine the amount of tooth movement, plaster models of the maxillae were made using a silicone impression material before (day 0) and after tooth movement (days 1, 2, 3, 4, and 7). The models were scanned using a contact-type three-dimensional (3-D) measurement apparatus. Immunohistochemical staining for MMP-9, cathepsin K, and integrin subunits of (v)β3 was performed. Intergroup comparisons of the average values were conducted with a Mann–Whitney U-test for tooth movement and the number of tartrate-resistant acid phosphatase (TRAP), MMP-9, cathepsin K, and integrin subunits of (v)β3-positive cells.

In the laser-irradiated group, the amount of tooth movement was significantly greater than that in the non-irradiated group at the end of the experiment (P < 0.05). Cells positively stained with TRAP, MMP-9, cathepsin K, and integrin subunits of (v)β3 were found to be significantly increased in the irradiated group on days 2–7 compared with those in the non-irradiated group (P < 0.05).

These findings suggest that low-energy laser irradiation facilitates the velocity of tooth movement and MMP-9, cathepsin K, and integrin subunits of (v)β3 expression in rats.

  M Yonemura , N Katsumata , H Hashimoto , S Satake , M Kaneko , Y Kobayashi , A Takashima , Y Kato , M Takeuchi , Y Fujiwara , H Yamamoto and T. Hojo

The aim of this study was to assess the non-inferiority of 1 mg to 3 mg granisetron (GRN) injection for the treatment of acute chemotherapy-induced nausea and vomiting (CINV) and to evaluate the tolerability of GRN given at 1 mg in Japanese cancer patients.


Patients with cancer receiving highly emetogenic chemotherapy were enrolled in this single-blind randomized controlled study. Patients were randomly assigned to receive GRN at a single dose of 1 or 3 mg. The primary endpoint was the rate of complete protection from emetic events (no vomiting, no retching and no need for rescue medication) during the first 24 h following the initiation of chemotherapy.


There were 89 patients in the 1 mg group and 90 patients in the 3 mg group. Complete protection was achieved in 70 patients (78.7%) in the 1 mg group and 73 (81.1%) patients in the 3 mg group. The one-sided test did not reveal non-inferiority of either dose of GRN to the other at a 5% significance level.


Our data failed to show the non-inferiority of 1 mg of GRN to 3 mg of GRN administered as a single dose. However, the rate of complete protection from nausea and vomiting was similar in the two groups. Given the recommended dosage in the guidelines and the economic need for reduction of medical care expenses in Japan, prophylactic administration of GRN at 1 mg may be an appropriate, alternative treatment for acute CINV in cancer patients.

  Y Ichikawa , A Goto , S Hirokawa , M Kijima , T Ishikawa , T Chishima , H Suwa , H Yamamoto , S Yamagishi , S Osada , M Ota and S. Fujii

Allergic reactions to oxaliplatin can be severe and are an important cause of discontinuation of treatment. A retrospective review was performed for 105 patients who received FOLFOX regimens between May 2005 and June 2007. Twenty-five cases (23.8%) of allergic reactions were identified, including 9 late onset reactions (8.6%) and 16 immediate reactions (15.2%). Severe allergy (Grades 3 and 4) occurred in seven patients (6.7%). Re-introduction of FOLFOX was attempted for seven immediate onset patients with a severity grade of 1 or 2, and three of these patients (42.9%) showed relapse of allergy. In ~10% of the patients, FOLFOX had to be discontinued due to allergy before the disease became refractory to the regimen. Our experience indicates that allergy to oxaliplatin may be a significant concern and that methods are required for suppression of this allergy.

  T Agatsuma , T Koizumi , M Yasuo , K Urushihata , K Tsushima , H Yamamoto , M Hanaoka , M Fukushima , T Honda and K. Kubo

The role of second-line and salvage chemotherapy in malignant pleural mesothelioma treatment is not yet established. We report a case of relapsed malignant pleural mesothelioma in which the patient failed to respond to pemetrexed-based chemotherapy but was successfully treated with gemcitabine and vinorelbine. The patient underwent a left extrapleural pneumonectomy. Three years later she developed anterior chest wall and retroperitoneal masses. Histological findings revealed metastases from the malignant pleural mesothelioma. Although two cycles of carboplatin plus pemetrexed chemotherapy were administered, she had progressive disease. Then, 1000 mg/m2 gemcitabine and 25 mg/m2 vinorelbine were administered every 2 weeks. The chemotherapy regimen was tolerated well, and the tumors were remarkably reduced. She was treated with 12 cycles of gemcitabine plus vinorelbine, and 8.5 months of progression-free survival was observed. Gemcitabine plus vinorelbine chemotherapy may be a candidate regimen for salvage chemotherapy against malignant pleural mesotheliomas.

  F Ishikawa , T Akimoto , H Yamamoto , Y Araki , T Yoshie , K Mori , H Hayashi , K Nose and M. Shibanuma

Mitochondrial dysfunction, in particular, interference in the respiratory chain, is often responsible for the toxicogenic effects of xenobiotics. In this study, changes in gene expression resulting from pharmacological inhibition of the respiratory chain were studied by DNA microarray analysis using cells treated with rotenone or antimycin A, which inhibit complexes I and III of the electron transport system, respectively. Forty-eight genes were either up- or down-regulated more than 3-fold. These included stress- and/or metabolic-related effector genes and several transcriptional regulators represented by CHOP-10. Further study using siRNA showed that among the four genes studied, up-regulation of three was dependent on CHOP-10. C/EBPβ, a dimerizing partner of CHOP-10, was also involved in two of the three genes including Trib3, implying that CHOP-10, heterodimerizing with C/EBPβ or another partner played a key role in the expression of a set of genes under stress. Although CHOP-10 and Trib3 were both ER-stress response genes, signal inducing Trib3 during mitochondrial stress was distinct from that during ER stress. Cytotoxicity caused by inhibition of the respiratory chain was attenuated by treatment with siRNA for CHOP-10. This study demonstrated the importance of CHOP-10 in coordinating individual gene expression in response to the mitochondrial stress.

  T Ohtsuki , H Yamamoto , Y Doi and M. Sisido

We present three methods relating to tRNA aminoacylation with non-natural amino acids using an Escherichia coli EF-Tu E215A/D216A mutant that can bind tightly to aa-tRNAs carrying either non-natural or natural amino acids: (i) a method for improving aminoacylation efficiency, (ii) a rapid method for analysing aminoacylation efficiency without the use of radioisotope labelling and (iii) a method for purifying aminoacyl-tRNAs. Although the EF-Tu mutant may be incompatible with some kinds of non-natural amino acids, we confirmed that the EF-Tu mutant could efficiently bind to aa-tRNAs carrying various amino acids (Arg, Ser, O-methyltyrosine, Bodipy FL-aminophenylalanine and 2-acrydonylalanine). These methods may be used for the efficient in vitro synthesis of proteins containing various non-natural amino acids.

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