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Articles by S Fujita
Total Records ( 8 ) for S Fujita
  Y Koga , M Yasunaga , A Takahashi , J Kuroda , Y Moriya , T Akasu , S Fujita , S Yamamoto , H Baba and Y. Matsumura

To reduce the colorectal cancer (CRC) mortality rate, we have reported several CRC screening methods using colonocytes isolated from feces. Expression analysis of oncogenic microRNA (miRNA) in peripheral blood was recently reported for CRC detection. In the present study, we conducted miRNA expression analysis of exfoliated colonocytes isolated from feces for CRC screening. Two hundred six CRC patients and 134 healthy volunteers were enrolled in the study. miRNA expression of the miR-17-92 cluster, miR-21, and miR-135 in colonocytes isolated from feces as well as frozen tissues was analyzed by quantitative real-time PCR. The expression of the miR-17-92 cluster, miR-21, and miR-135 was significantly higher in CRC tissues compared with normal tissues. The exfoliated colonocytes of 197 CRC patients and 119 healthy volunteers were analyzed because of the presence of sufficient miRNA concentration. miR-21 expression did not differ significantly between CRC patients and healthy volunteers (P = 0.6). The expression of miR-17-92 cluster and miR-135 was significantly higher in CRC patients than in healthy volunteers (P < 0.0001). The overall sensitivity and specificity by using miRNA expression was 74.1% (146/197; 95% confidence interval, 67.4-80.1) and 79.0% (94/119; 95% confidence interval, 70.6-85.9), respectively. Sensitivity was dependent only on tumor location (P = 0.0001). miRNA was relatively well conserved in exfoliated colonocytes from feces both of CRC patients and healthy volunteers. miRNA expression analysis of the isolated colonocytes may be a useful method for CRC screening. Furthermore, oncogenic miRNA highly expressed in CRC should be investigated for CRC screening tests in the future. Cancer Prev Res; 3(11); 1435–42. ©2010 AACR.

  N Yamamichi , R Shimomura , K. i Inada , K Sakurai , T Haraguchi , Y Ozaki , S Fujita , T Mizutani , C Furukawa , M Fujishiro , M Ichinose , K Shiogama , Y Tsutsumi , M Omata and H. Iba

Purpose: To better understand microRNA miR-21 function in carcinogenesis, we analyzed miR-21 expression patterns in different stages of colorectal cancer development using in situ hybridization (ISH).

Experimental Design: Locked nucleic acid (LNA)/DNA probes and a biotin-free tyramide signal amplification system were used in ISH analyses of miRNA expression. Conditions for specific detection of miR-21 were determined using human cell lines and miR-21–expressing lentiviral vectors. Expression was determined in 39 surgically excised colorectal tumors and 34 endoscopically resected colorectal polyps.

Results: In the surgical samples, miR-21 expression was much higher in colorectal cancers than in normal mucosa. Strong miR-21 expression was also observed in cancer-associated stromal fibroblasts, suggesting miR-21 induction by cancer-secreted cytokines. Protein expression of PDCD4, a miR-21 target, was inversely correlated with miR-21 expression, confirming that miR-21 is indeed a negative regulator of PDCD4 in vivo. In the endoscopic samples, miR-21 expression was very high in malignant adenocarcinomas but was not elevated in nontumorigenic polyps. Precancerous adenomas also frequently showed miR-21 up-regulation.

Conclusion: Using the LNA-ISH system for miRNA detection, miR-21 was detectable in precancerous adenomas. The frequency and extent of miR-21 expression increased during the transition from precancerous colorectal adenoma to advanced carcinoma. Expression patterns of miR-21 RNA and its target, tumor suppressor protein PDCD4, were mutually exclusive. This pattern may have clinical application as a biomarker for colorectal cancer development and might be emphasized by self-reinforcing regulatory systems integrated with the miR-21 gene, which has been previously shown in cell culture.

  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.

  T Wakahara , S Yamamoto , S Fujita , T Akasu , S Onouchi and Y. Moriya

Adenocarcinoid tumor most commonly occurs in the appendix and a tumor arising in the rectum is extremely rare. A 58-year-old man underwent total pelvic exenteration with extended lateral lymph node dissection for rectal adenocarcinoid tumor invading the urethra with lateral lymph node metastasis. Microscopically and immunohistochemically, the tumor consisted of carcinoid-like components and signet-ring-cell-carcinoma-like components, and an adenocarcinoid tumor was diagnosed. Postoperatively, the patient received combination chemotherapy of fluorouracil and leucovorin as an adjuvant therapy. Three years and 5 years after the initial surgery, the patient developed left groin and left external iliac lymph node recurrences, and lymphadenectomy was performed each time. As a result, the patient is alive more than 5 years after the initial surgery. There is no consensus on the indication of surgical treatment for adenocarcinoid tumor. However, in advanced cases, an aggressive surgical procedure might result in long-term survival when resectable.

  K Masago , S Fujita , K Irisa , Y. H Kim , M Ichikawa , T Mio and M. Mishima

Recently, two small-molecule kinase inhibitors targeting epidermal growth factor receptor have proven effective in the treatment of non-small cell lung cancer. There are specific activating mutations within the tyrosine kinase domain of epidermal growth factor receptor related to the sensitivity of tyrosine kinase inhibitors. However, it is unknown whether rare mutations in the N-lobe (exons 18–20) and the C-lobe (exon 21) of the epidermal growth factor receptor kinase domain other than L858R in exon 21 and the in-frame deletion in exon 19 may predict the effectiveness of epidermal growth factor receptor—tyrosine kinase inhibitors. We reported a case of non-small cell lung cancer harboring a rare epidermal growth factor somatic mutation, codon 768 AGC > ATC in exon 20 (S768I), who showed a good clinical response to gefitinib. Therefore, we may suggest that this rare mutation (S768I in exon 20) may not be an insensitive epidermal growth factor receptor somatic mutation in vivo.

  S Fujita , M Takebe , W Ushio and H. Shimoyama

The paraxial trajectory method has been generalized for the application to the cathode rays inside electron guns. The generalized method can handle rays that initially make a large angle with the optical axis with a satisfactory accuracy. The key to success of the generalization is the adoption of the trigonometric function sine for the trajectory slope specification, instead of the conventional use of the tangent. Formulas have been derived to relate the ray conditions (position and slope of the ray at reference planes) on the cathode to those at the crossover plane using third-order polynomial functions. Some of the polynomial coefficients can be used as the optical parameters in the characterization of electron sources; the electron gun focal length gives a quantitative estimate of both the crossover size and the angular current intensity. An electron gun simulation program G-optk has been developed based on the mathematical formulations presented in the article. The program calculates the principal paraxial trajectories and the relevant optical parameters from axial potentials and fields. It gives the electron-optical-column designers a clear physical picture of the electron gun in a much more faster way than the conventional ray-tracing methods.

  S Fujita , M Takebe and T. Ohye

A mathematical scheme has been proposed to extend the applicability of the generalized trajectory method to deal with curved cathodes such as cold field emitters and thermionic point cathodes. A connecting space is introduced between the cathode surface and the first reference plane, and the actual ray condition on the cathode is transformed into the trajectory condition at the reference plane: the generalized trajectory calculation is commenced from the reference plane. The electron acceleration due to the cathode surface field, which results in the increase of the transverse momentum px at the reference plane, has been found to significantly influence the estimate of the spherical aberration coefficient. The new mathematical formulation has been incorporated into the upgraded G-optk programme and enabled it to carry out precise characterization of curved cathode guns.

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