MDPI AG Acta Medica Okayama 2304-6767 12 11 2024 Coronal Cementum and Reduced Enamel Epithelium on Occlusal Surface of Impacted Wisdom Tooth in a Human 348 EN Naohiro Horie Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido Masaru Murata Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido Yasuhito Minamida Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido Hiroki Nagayasu Division of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, School of Dentistry, Health Sciences University of Hokkaido Toshiyuki Akazawa Industrial Technology and Environment Research Development, Hokkaido Research Organization Hidetsugu Tsujigiwa Department of Life Science, Faculty of Science, Okayama University of Science Youssef Haikel Department of Biomaterials and Bioengineering, Institut National de la Santé et de la Recherche médicale Unité Mixte de Recherche (INSERM UMR) _S 1121, University of Strasbourg Hitoshi Nagatsuka Department of Oral Pathology and Medicine Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 13 14 2021 The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma 3491 EN Haruka Omori Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Qiusheng Shan Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kiyofumi Takabatake Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Keisuke Nakano Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shintaro Sukegawa Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hidetsugu Tsujigiwa Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Simple Summary Normal stromal cells play a significant role in the progression of cancers but are poorly investigated in oral squamous cell carcinoma (OSCC). In this study, we found that stromal cells derived from the gingival and periodontal ligament tissues could inhibit differentiation and promote the proliferation, invasion, and migration of OSCC both in vitro and in vivo. Furthermore, microarray data suggested that genes, such as CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, probably play a role in influencing the different effects of gingival stromal tissue cells (G-SCs) and periodontal ligament stromal cells (P-SCs) on the progression of OSCC. Therefore, both G-SCs and P-SCs could promote the progression of OSCC, which could be a potential regulatory mechanism in the progression of OSCC. Normal stromal cells surrounding the tumor parenchyma, such as the extracellular matrix (ECM), normal fibroblasts, mesenchymal stromal cells, and osteoblasts, play a significant role in the progression of cancers. However, the role of gingival and periodontal ligament tissue-derived stromal cells in OSCC progression is unclear. In this study, the effect of G-SCs and P-SCs on the differentiation, proliferation, invasion, and migration of OSCC cells in vitro was examined by Giemsa staining, Immunofluorescence (IF), (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS), invasion, and migration assays. Furthermore, the effect of G-SCs and P-SCs on the differentiation, proliferation, and bone invasion by OSCC cells in vivo was examined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Finally, microarray data and bioinformatics analyses identified potential genes that caused the different effects of G-SCs and P-SCs on OSCC progression. The results showed that both G-SCs and P-SCs inhibited the differentiation and promoted the proliferation, invasion, and migration of OSCC in vitro and in vivo. In addition, genes, including CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, are probably involved in causing the different effects of G-SCs and P-SCs on OSCC progression. Therefore, as a potential regulatory mechanism, both G-SCs and P-SCs can promote OSCC progression. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 14 12 2021 Preparation of Absorption-Resistant Hard Tissue Using Dental Pulp-Derived Cells and Honeycomb Tricalcium Phosphate 3409 EN Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yasunori Inada Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Qiusheng Shan Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shigeko Fushimi Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hidetsugu Tsujigiwa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University In recent years, there has been increasing interest in the treatment of bone defects using undifferentiated mesenchymal stem cells (MSCs) in vivo. Recently, dental pulp has been proposed as a promising source of pluripotent mesenchymal stem cells (MSCs), which can be used in various clinical applications. Dentin is the hard tissue that makes up teeth, and has the same composition and strength as bone. However, unlike bone, dentin is usually not remodeled under physiological conditions. Here, we generated odontoblast-like cells from mouse dental pulp stem cells and combined them with honeycomb tricalcium phosphate (TCP) with a 300 mu m hole to create bone-like tissue under the skin of mice. The bone-like hard tissue produced in this study was different from bone tissue, i.e., was not resorbed by osteoclasts and was less easily absorbed than the bone tissue. It has been suggested that hard tissue-forming cells induced from dental pulp do not have the ability to induce osteoclast differentiation. Therefore, the newly created bone-like hard tissue has high potential for absorption-resistant hard tissue repair and regeneration procedures. No potential conflict of interest relevant to this article was reported.

Ivyspring International Acta Medica Okayama 1449-1907 18 8 2021 Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process 1824 1830 EN Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University May Wathone Oo Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetsugu Tsujigiwa Department of Life Science, Faculty of Science, Okayama University of Science Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with immunosuppressive functions; these cells play a key role in infection, immunization, chronic inflammation, and cancer. Recent studies have reported that immunosuppression plays an important role in the healing process of tissues and that Treg play an important role in fracture healing. MDSCs suppress active T cell proliferation and reduce the severity of arthritis in mice and humans. Together, these findings suggest that MDSCs play a role in bone biotransformation. In the present study, we examined the role of MDSCs in the bone healing process by creating a bone injury at the tibial epiphysis in mice. MDSCs were identified by CD11b and GR1 immunohistochemistry and their role in new bone formation was observed by detection of Runx2 and osteocalcin expression. Significant numbers of MDSCs were observed in transitional areas from the reactionary to repair stages. Interestingly, MDSCs exhibited Runx2 and osteocalcin expression in the transitional area but not in the reactionary area. And at the same area, cllagene-1 and ALP expression level increased in osteoblast progenitor cells. These data is suggesting that MDSCs emerge to suppress inflammation and support new bone formation. Here, we report, for the first time (to our knowledge), the role of MDSCs in the initiation of bone formation. MDSC appeared at the transition from inflammation to bone making and regulates bone healing by suppressing inflammation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 13 22 2020 Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation 5155 EN Kiyofumi Takabatake Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hidetsugu Tsujigiwa Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yasunori Inada Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shan Qiusheng Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shintaro Sukegawa Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shigeko Fushimi Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Recently, dental pulp has been attracting attention as a promising source of multipotent mesenchymal stem cells (MSCs) for various clinical applications of regeneration fields. To date, we have succeeded in establishing rat dental pulp-derived cells showing the characteristics of odontoblasts under in vitro conditions. We named them Tooth matrix-forming, GFP rat-derived Cells (TGC). However, though TGC form massive dentin-like hard tissues under in vivo conditions, this does not lead to the induction of polar odontoblasts. Focusing on the importance of the geometrical structure of an artificial biomaterial to induce cell differentiation and hard tissue formation, we previously have succeeded in developing a new biomaterial, honeycomb tricalcium phosphate (TCP) scaffold with through-holes of various diameters. In this study, to induce polar odontoblasts, TGC were induced to form odontoblasts using honeycomb TCP that had various hole diameters (75, 300, and 500 mu m) as a scaffold. The results showed that honeycomb TCP with 300-mu m hole diameters (300TCP) differentiated TGC into polar odontoblasts that were DSP positive. Therefore, our study indicates that 300TCP is an appropriate artificial biomaterial for dentin regeneration. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 13 21 2020 Effect of Honeycomb ƒΐ-TCP Geometrical Structure on Bone Tissue Regeneration in Skull Defect 4761 EN Toshiyuki Watanabe Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidetsugu Tsujigiwa Department of Life Science, Faculty of Science, Okayama University Science Satoko Watanabe Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Nakagiri Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The effect of the geometric structure of artificial biomaterials on skull regeneration remains unclear. In a previous study, we succeeded in developing honeycomb beta-tricalcium phosphate (beta-TCP), which has through-and-through holes and is able to provide the optimum bone microenvironment for bone tissue regeneration. We demonstrated that beta-TCP with 300-mu m hole diameters induced vigorous bone formation. In the present study, we investigated how differences in hole directions of honeycomb beta-TCP (horizontal or vertical holes) influence bone tissue regeneration in skull defects. Honeycomb beta-TCP with vertical and horizontal holes was loaded with BMP-2 using Matrigel and Collagen gel as carriers, and transplanted into skull bone defect model rats. The results showed that in each four groups (Collagen alone group, Matrigel alone group, Collagen + BMP group and Matrigel + BMP-2), vigorous bone formation was observed on the vertical beta-TCP compared with horizontal beta-TCP. The osteogenic area was larger in the Matrigel groups (with and without BMP-2) than in the Collagen group (with and without BMP-2) in both vertical beta-TCP and horizontal beta-TCP. However, when BMP-2 was added, the bone formation area was not significantly different between the Collagen group and the Matrigel group in the vertical beta-TCP. Histological finding showed that, in vertical honeycomb beta-TCP, new bone formation extended to the upper part of the holes and was observed from the dura side to the periosteum side as added to the inner walls of the holes. Therefore, we can control efficient bone formation by creating a bone microenvironment provided by vertical honeycomb beta-TCP. Vertical honeycomb beta-TCP has the potential to be an excellent biomaterial for bone tissue regeneration in skull defects and is expected to have clinical applications. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 21 20 2020 Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma 7714 EN Kiyofumi Takabatake Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Haruka Omori Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shan Qiusheng Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University May Wathone Oo Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shintaro Sukegawa Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hidetsugu Tsujigiwa Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Solid tumors consist of the tumor parenchyma and stroma. The standard concept of oncology is that the tumor parenchyma regulates the tumor stroma and promotes tumor progression, and that the tumor parenchyma represents the tumor itself and defines the biological characteristics of the tumor tissue. Thus, the tumor stroma plays a pivotal role in assisting tumor parenchymal growth and invasiveness and is regarded as a supporter of the tumor parenchyma. The tumor parenchyma and stroma interact with each other. However, the influence of the stroma on the parenchyma is not clear. Therefore, in this study, we investigated the effect of the stroma on the parenchyma in oral squamous cell carcinoma (OSCC). We isolated tumor stroma from two types of OSCCs with different invasiveness (endophytic type OSCC (ED-st) and exophytic type OSCC (EX-st)) and examined the effect of the stroma on the parenchyma in terms of proliferation, invasion, and morphology by co-culturing and co-transplanting the OSCC cell line (HSC-2) with the two types of stroma. Both types of stroma were partially positive for alpha-smooth muscle actin. The tumor stroma increased the proliferation and invasion of tumor cells and altered the morphology of tumor cells in vitro and in vivo. ED-st exerted a greater effect on the tumor parenchyma in proliferation and invasion than EX-st. Morphological analysis showed that ED-st changed the morphology of HSC-2 cells to the invasive type of OSCC, and EX-st altered the morphology of HSC-2 cells to verrucous OSCC. This study suggests that the tumor stroma influences the biological characteristics of the parenchyma and that the origin of the stroma is strongly associated with the biological characteristics of the tumor. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0001-6489 133 9 2013 The engraftment and differentiation of transplanted bone marrow-derived cells in the olfactory bulb after methimazole administration 951 956 EN Yohei Noda Kazunori Nishizaki Junko Yoshinobu Yorihisa Orita Hidetsugu Tsujigiwa Masao Yamada Conclusion: Bone marrow-derived cells can be engrafted in the olfactory bulb and a few cells can differentiate into mitral/tufted cells in the olfactory bulb. Objectives: To investigate whether bone marrow-derived cells can be engrafted into the olfactory bulb and differentiate into neurons and glial cells after methimazole administration. Methods: Bone marrow of GFP (green fluorescence protein) mice was transplanted into lethally irradiated recipient mice. Immunostaining was performed to confirm the cell types of bone marrow-derived cells expressing GFP. Results: GFP-positive cells were observed in the olfactory bulb at 2 days after methimazole administration. The number of dendritic GFP-positive cells increased up to 30 days after methimazole administration and then decreased. Double immunostaining for GFP and Iba1 or TBX21 showed that a large population of the GFP-positive cells had characteristics of microglia/macrophages and a few cells had characteristics of mitral/tufted cells. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 41 10 2005 Role of O-6-methylguanine-DNA methyltransferase and effect of O-6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines 984 993 EN Yu Maki Jun Murakami Jun-ichi Asaumi Hidetsugu Tsujigiwa Hitoshi Nagatsuka Susumu Kokeguchi Kazuhiro Fukui Noriko Kawai Yoshinobu Yanagi Masahiro Kuroda Noriaki Tanaka Nagahide Matsubara Kanji Kishi <p>The DNA repair enzyme, O-6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell tines. CDDP depleted MGMT protein and mRNA levels in all four cell tines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell tines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O-6-benzylguanine (O-6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O-6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy. (c) 2005 Elsevier Ltd. All rights reserved. </p> No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0344-5704 56 1 2005 Effects of histone deacetylase inhibitor FR901228 on expression level of telomerase reverse transcriptase in oral cancer 22 28 EN Jun Murakami Jun-ichi Asaumi Noriko Kawai Hidetsugu Tsujigiwa Yoshinobu Yanagi Hitoshi Nagatsuka Tetsuyoshi Inoue Susumu Kokeguchi Shoji Kawasaki Masahiro Kuroda Noriaki Tanaka Nagahide Matsubara Kanji Kishi We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription were analysed by RT-PCR in oral cancer cell lines. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, even in the hTERT highly expressed SAS and KB cells. Moreover, co-treatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation / deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, dependent of the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved other transcription factors except for c-myc, in addition to the inhibition of histone deacetylation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 40 6 2004 Effects of demethylating agent 5-aza-2 '-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines 597 603 EN Jun Murakami Jun-ichi Asaumi Yuu Maki Hidetsugu Tsujigiwa Masahiro Kuroda Noriyuki Nagai Yoshinobu Yanagi Tetsuyoshi Inoue Shoji Kawasaki Noriaki Tanaka Nagahide Matsubara Kanji Kishi <p>Maspin, which belongs to the serine protease inhibitor (serpin) superfamily, has been proposed as a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis. In the present study, we examined the effects of 5-aza-2'-deoxycytidine (5-aza-dC), a demethylating agent, and FR901228, a histone deacetylase (HDAC) inhibitor, on maspin expression in oral cancer cell tines. The expression levels of maspin mRNA were divided into two groups, which was the maspin tow-expressed and high-expressed cell lines in the 12 oral cancer cell lines. The maspin promoter contained only a few methylated CpG sites in the maspin low-expressed cell lines. Moreover, the methylation status was not altered after 5-aza-dC treatment. However, the transcription of the maspin gene was clearly increased following 5-aza-dC treatment in a number of oral cancer cell tines. These results imply that an action of 5-aza-dC is separate from induction of promoter demethylation. Treatment with FR901228 resulted in a time-dependent stimulation of the re-expression of maspin mRNA as early as 4 h after treatment in the maspin downregulated cells. The re-expression of the maspin gene may contribute to the recuperation of biological functions linked to FR901228 such as an inhibitory effect on tumor angiogenesis and cell invasion. These results indicate that maspin and its target genes may be excellent leads for future studies on the potential benefits of FR901228, a HDAC inhibitor, in cancer therapy.</p> No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2001 rhBMP-2/ƒRƒ‰[ƒQƒ“ŒΕ’艻‚Ι‚ζ‚ιST2Χ–E‚Φ‚Μ‰e‹Ώ‚ΖƒVƒOƒiƒ‹“`’BŒnˆβ“`Žq‚Μ”­Œ» EN No potential conflict of interest relevant to this article was reported.