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Search Results: 1 - 10 of 119 matches for " Yoshimitsu Abiko "
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RUNX3 Has an Oncogenic Role in Head and Neck Cancer
Takaaki Tsunematsu, Yasusei Kudo, Shinji Iizuka, Ikuko Ogawa, Tsuyoshi Fujita, Hidemi Kurihara, Yoshimitsu Abiko, Takashi Takata
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005892
Abstract: Background Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of cancer and appears to be an important component of the transforming growth factor-beta (TGF-?)-induced tumor suppression pathway. Surprisingly, we found that RUNX3 expression level in head and neck squamous cell carcinoma (HNSCC) tissues, which is one of the most common types of human cancer, was higher than that in normal tissues by a previously published microarray dataset in our preliminary study. Therefore, here we examined the oncogenic role of RUNX3 in HNSCC. Principal Findings Frequent RUNX3 expression and its correlation with malignant behavior were observed in HNSCC. Ectopic RUNX3 overexpression promoted cell growth and inhibited serum starvation-induced apoptosis and chemotherapeutic drug induced apoptosis in HNSCC cells. These findings were confirmed by RUNX3 knockdown. Moreover, RUNX3 overexpression enhanced tumorsphere formation. RUNX3 expression level was well correlated with the methylation status in HNSCC cells. Moreover, RUNX3 expression was low due to the methylation of its promoter in normal oral epithelial cells. Conclusions/Significance Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can be a useful marker for predicting malignant behavior and the effect of chemotherapeutic drugs in HNSCC.
Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker
Kusumawadee Utispan, Peti Thuwajit, Yoshimitsu Abiko, Komgrid Charngkaew, Anucha Paupairoj, Siri Chau-in, Chanitra Thuwajit
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-13
Abstract: In this study, the gene expression profile of Cfs in comparison to Lfs was performed using oligonucleotide microarrays. The common- and unique-expressed genes in Cfs and the promising roles in cancer promotion and progression were determined. PN was markedly over-expressed in Cfs confirmed by real time RT-PCR and western blot analysis. Immunohistochemistry examination of a number of patients with intrahepatic CCA showed the expression of PN solely in stromal fibroblasts, but was expressed neither in cancer cells nor immune cells. Low to no expression of PN was observed in tissues of benign liver disease and hepatocellular carcinoma. CCA patients with high levels of PN had significantly shorter survival time than those with low levels (P = 0.026). Multivariate analysis revealed high levels of PN (P = 0.045) and presence of lymph node metastasis (P = 0.002) as independent poor prognostic factors. The in vitro study revealed that recombinant PN induced CCA cell proliferation and invasion. Interestingly, interference RNA against integrin α5 significantly reduced the cellular response to PN-stimulated proliferation and invasion.The gene expression profile of fibroblasts in CCA is apparently explored for the first time and has determined the genes involving in induction of this cancer progression. High PN can be used to distinguish CCA from other related liver diseases and is proposed as a prognostic factor of poor survival. Regulation of fibroblast-derived PN in CCA proliferation and invasion may be considered as an alternative therapeutic approach.Cholangiocarcinoma (CCA) originates from biliary epithelial cells and is a unique cancer in northeastern Thailand where the prevalence of a liver fluke, Opisthorchis viverrini infection is higher than elsewhere in the country. A recent study showed a strong positive correlation of CCA incidence and the prevalence of O. viverrini infection [1]. In other countries, CCA has been shown to correlate with Clonorchis sinesis [2,3], a
An Integrated Expression Profiling Reveals Target Genes of TGF-β and TNF-α Possibly Mediated by MicroRNAs in Lung Cancer Cells
Akira Saito, Hiroshi I. Suzuki, Masafumi Horie, Mitsuhiro Ohshima, Yasuyuki Morishita, Yoshimitsu Abiko, Takahide Nagase
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056587
Abstract: EMT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-β elicited EMT in Smad-dependent manner and TNF-α accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion. TNF-α stimulated the phosphorylation of Smad2 linker region, and this effect was attenuated by inhibiting MEK or JNK pathway. Comprehensive expression analysis unraveled genes differentially regulated by TGF-β and TNF-α, such as cytokines, chemokines, growth factors and ECM (extracellular matrices), suggesting the drastic change in autocrine/paracrine signals as well as cell-to-ECM interactions. Integrated analysis of microRNA signature enabled us to identify a subset of genes, potentially regulated by microRNAs. Among them, we confirmed TGF-β-mediated induction of miR-23a in lung epithelial cell lines, target genes of which were further identified by gene expression profiling. Combined with in silico approaches, we determined HMGN2 as a downstream target of miR-23a. These findings provide a line of evidence that the effects of TGF-β and TNF-α were partially mediated by microRNAs, and shed light on the complexity of molecular events elicited by TGF-β and TNF-α.
Tissue-Engineered Products for Skin Regenerative Medicine  [PDF]
Yoshimitsu Kuroyanagi
Open Journal of Regenerative Medicine (OJRM) , 2016, DOI: 10.4236/ojrm.2016.53006
Abstract: In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditions such as burn injury and intractable skin ulcer. A major obstruction to wound healing is infection. Another obstruction to wound healing is deficiency of growth factors. The endogenous levels of growth factors are reduced in some chronic wounds. To improve these wound conditions, researchers have been trying to create several types of artificial skins. The tissue-engineered products include three prime constituents, i.e., cells, growth factors, and materials. In this review, the practical design of tissue-engineered products for skin regenerative medicine is introduced. The first design makes it possible to release silver sulfadiazine (AgSD) from a wound dressing. The second design makes it possible to release Epidermal Growth Factor (EGF) from a wound dressing or a skin care product composed of hyaluronic acid spongy sheet containing bioactive ingredients. The third design makes it possible to release several types of growth factors from allogeneic fibroblasts within cultured dermal substitute. This tissue-engineered product is prepared by seeding allogeneic fibroblasts into a collagen and hyaluronic acid spongy sheet. Although allogeneic cells are rejected gradually in immune system, they are able to release some types of growth factors, thereby regenerating a damaged tissue. The clinical study demonstrates that these tissue-engineered products are promising for the treatment of burn injury and intractable skin ulcer.
Characterization of hemin-binding protein 35 (HBP35) in Porphyromonas gingivalis: its cellular distribution, thioredoxin activity and role in heme utilization
Mikio Shoji, Yasuko Shibata, Teruaki Shiroza, Hideharu Yukitake, Benjamin Peng, Yu-Yen Chen, Keiko Sato, Mariko Naito, Yoshimitsu Abiko, Eric C Reynolds, Koji Nakayama
BMC Microbiology , 2010, DOI: 10.1186/1471-2180-10-152
Abstract: We observed that the hbp35 gene was transcribed as a 1.1-kb mRNA with subsequent translation resulting in three proteins with molecular masses of 40, 29 and 27 kDa in the cytoplasm, and one modified form of the 40-kDa protein on the cell surface. A recombinant 40-kDa HBP35 exhibited thioredoxin activity in vitro and mutation of the two putative active site cysteine residues abolished this activity. Both recombinant 40- and 27-kDa proteins had the ability to bind hemin, and growth of an hbp35 deletion mutant was substantially retarded under hemin-depleted conditions compared with growth of the wild type under the same conditions.P. gingivalis HBP35 exhibits thioredoxin and hemin-binding activities and is essential for growth in hemin-depleted conditions suggesting that the protein plays a significant role in hemin acquisition.Porphyromonas gingivalis has been implicated as a major pathogen associated with chronic periodontitis. The establishment of P. gingivalis at a periodontal site and progression of disease is dependent on the ability of the bacterium to utilize essential nutrients, of which iron (preferably in the form of heme) plays a crucial role. P. gingivalis lacks the majority of enzymes in the biosynthetic pathway for the porphyrin ring, hence it is unable to synthesize protoporphyrin IX, the precursor of heme [1-3]; and unlike other Gram-negative bacteria, P. gingivalis does not produce siderophores [3]. Although several studies have shown that P. gingivalis acquires heme from the host environment using gingipains, lipoproteins and specific outer-membrane receptors [3-5], the precise mechanisms by which P. gingivalis acquires heme are still unknown.The gene encoding the P. gingivalis outer membrane 40-kDa protein (OMP40) was first cloned by Abiko et al. [6]. As the recombinant OMP40 protein was demonstrated to exhibit hemin binding ability, and the molecular mass of the mature polypeptide determined by mass spectrometric analysis was 35.3 kDa, the protein
Issues of Transformation in the Ideas of Curriculum Reform, Curriculum Standards and Textbooks -A Japanese Perspective
Tadahiko Abiko
Journal of Textbook Research , 2010,
Abstract: In recent times, the Japanese government has faced difficulties in reforming school and social education despite the amendment of the Fundamental Law of Education 2006. With the revision of the main laws of education, the government has been transforming the public education system in terms of “educational accountability” by establishing a national test related to national curriculum standards. However, in Japan, there has been much less criticism of standard-oriented education than there has been in the U.S. or Europe.Interestingly enough, the educational problems in public schools are almost all found at the upper grades of elementary school and all grades of junior high school with young adolescent students aged 10-15. In the past two decades, Japan has been in the midst of a so-called “Age of the 3rd Educational Reform.” We have been coping with school refusal, bullying, and delinquency, along with lower than expected student scores on OECD/PISA 2003 and 2006, which mostly occur among students of the age range mentioned above.Therefore, in 2008, the government revised the National Course of Study, the national curriculum standards, in order to raise thinking abilities effectively as the core of the “Zest for Living” campaign. Under the new laws concerning public education, the revised curriculum standards stressed compulsory education, moral education, language activities, mathematics and science education, traditional culture education, experiential activities, and foreign language activities in the elementary curriculum.In addition, mastering basic knowledge and skills, increasing the number of hours of instruction per week, enhancing learning motivation, and establishing learning habits are all emphasized. All of these should help reach the final objective of improving thinking abilities. However, the Central Council for Education has not discussed our middle level education in any thorough way, though junior high school students are standing at the crossroads of their lives and suffer considerable stress.
MMP-10/Stromelysin-2 Promotes Invasion of Head and Neck Cancer
Elsayed Mohamed Deraz, Yasusei Kudo, Maki Yoshida, Mariko Obayashi, Takaaki Tsunematsu, Hirotaka Tani, Samadarani B. S. M. Siriwardena, Mohammad Reza Kiekhaee, Guangying Qi, Shinji Iizuka, Ikuko Ogawa, Giuseppina Campisi, Lorenzo Lo Muzio, Yoshimitsu Abiko, Akira Kikuchi, Takashi Takata
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025438
Abstract: Background Periostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma (HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data sets. In this study, we investigated the roles of MMP-10 in the invasion of HNSCC. Methods and Findings We examined the expression of MMP-10 in HNSCC cases by immunohistochemistry. High expression of MMP-10 was frequently observed and was significantly correlated with the invasiveness and metastasis in HNSCC cases. Next, we examined the roles of MMP-10 in the invasion of HNSCC cells in vitro. Ectopic overexpression of MMP-10 promoted the invasion of HNSCC cells, and knockdown of MMP-10 suppressed the invasion of HNSCC cells. Moreover, MMP-10 knockdown suppressed Periostin and Wnt-5b-promoted invasion. Interestingly, MMP-10 overexpression induced the decreased p38 activity and MMP-10 knockdown induced the increased p38 activity. In addition, treatment with a p38 inhibitor SB203580 in HNSCC cells inhibited the invasion. Conclusions These results suggest that MMP-10 plays an important role in the invasion and metastasis of HNSCC, and that invasion driven by MMP-10 is partially associated with p38 MAPK inhibition. We suggest that MMP-10 can be used as a marker for prediction of metastasis in HNSCC.
Comparison of Fatigue Properties and Fatigue Crack Growth Rates of Various Implantable Metals
Yoshimitsu Okazaki
Materials , 2012, DOI: 10.3390/ma5122981
Abstract: The fatigue strength, effects of a notch on the fatigue strength, and fatigue crack growth rate of Ti-15Zr-4Nb-4Ta alloy were compared with those of other implantable metals. Zr, Nb, and Ta are important alloying elements for Ti alloys for attaining superior long-term corrosion resistance and biocompatibility. The highly biocompatible Ti-15Zr-4Nb-4Ta alloy exhibited an excellent balance between strength and ductility. Its notched tensile strength was much higher than that of a smooth specimen. The strength of 20% cold-worked commercially pure (C.P.) grade 4 Ti was close to that of Ti alloy. The tension-to-tension fatigue strength of an annealed Ti-15Zr-4Nb-4Ta rod at 10 7 cycles was approximately 740 MPa. The fatigue strength of this alloy was much improved by aging treatment after solution treatment. The fatigue strengths of C.P. grade 4 Ti and stainless steel were markedly improved by 20% cold working. The fatigue strength of Co-Cr-Mo alloy was markedly increased by hot forging. The notch fatigue strengths of 20% cold-worked C.P. grade 4 Ti, and annealed and aged Ti-15Zr-4Nb-4Ta, and annealed Ti-6Al-4V alloys were less than those of the smooth specimens. The fatigue crack growth rate of Ti-15Zr-4Nb-4Ta was the same as that of Ti-6Al-4V. The fatigue crack growth rate in 0.9% NaCl was the same as that in air. Stainless steel and Co-Cr-Mo-Ni-Fe alloy had a larger stress-intensity factor range (ΔK) than Ti alloy.
On the Effects of Hot Forging and Hot Rolling on the Microstructural Development and Mechanical Response of a Biocompatible Ti Alloy
Yoshimitsu Okazaki
Materials , 2012, DOI: 10.3390/ma5081439
Abstract: Zr, Nb, and Ta as alloying elements for Ti alloys are important for attaining superior corrosion resistance and biocompatibility in the long term. However, note that the addition of excess Nb and Ta to Ti alloys leads to higher manufacturing cost. To develop low-cost manufacturing processes, the effects of hot-forging and continuous-hot-rolling conditions on the microstructure, mechanical properties, hot forgeability, and fatigue strength of Ti-15Zr-4Nb-4Ta alloy were investigated. The temperature dependences with a temperature difference (ΔT) from β-transus temperature (Tβ) for the volume fraction of the α- and β-phases were almost the same for both Ti-15Zr-4Nb-4Ta and Ti-6Al-4V alloys. In the α-β-forged Ti-15Zr-4Nb-4Ta alloy, a fine granular α-phase structure containing a fine granular β-phase at grain boundaries of an equiaxed α-phase was observed. The Ti-15Zr-4Nb-4Ta alloy billet forged at Tβ-(30 to 50) °C exhibited high strength and excellent ductility. The effects of forging ratio on mechanical strength and ductility were small at a forging ratio of more than 3. The maximum strength (σ max) markedly increased with decreasing testing temperature below Tβ. The reduction in area (R.A.) value slowly decreased with decreasing testing temperature below Tβ. The temperature dependences of σ max for the Ti-15Zr-4Nb-4Ta and Ti-6Al-4V alloys show the same tendency and might be caused by the temperature difference (ΔT) from Tβ. It was clarified that Ti-15Zr-4Nb-4Ta alloy could be manufactured using the same manufacturing process as for previously approved Ti-6Al-4V alloy, taking into account the difference (ΔT) between Tβ and heat treatment temperature. Also, the manufacturing equivalency of Ti-15Zr-4Nb-4Ta alloy to obtain marketing approval of implants was established. Thus, it was concluded that continuous hot rolling is useful for manufacturing α-β-type Ti alloy.
Syntheses of two deacetyl-thymosin β4 analogs and their anti-inflammatory effect on carrageenin-induced edema in the mouse paw
T. Abiko,R. Ogawa
Mediators of Inflammation , 2001, DOI: 10.1080/09629350120054563
Abstract: Two {Met(0)6}deacetyl-thymosin β4 analogs containing Phe(4F) or Tyr(Me) at position 12 were synthesized by the manual solid-phase method, and their anti-inflammatory effect on carrageenin-induced edema in the mouse paw was studied. Fluorination of the para-position of Phe12 resulted in a marked antiinflammatory effect on carrageenin-induced edema in the mouse paw compared with that of our synthetic {Met(0)6}deacetyl-thymosin β4, but the other analog, {Met(0)6, Tyr(Me)12}deacetyl-thymosin β4, showed a marked reduction of the anti-inflammatory effect.
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