Kyushu University Academic Staff Educational and Research Activities Database
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Tamotsu Kiyoshima Last modified date:2018.06.27

Professor / Maxillofacial Diagnostic & Surgical Sciences
Department of Dental Science
Faculty of Dental Science


Graduate School
Undergraduate School


E-Mail
Phone
092-642-6328
Fax
092-642-6329
Academic Degree
D.D.S., Ph.D.
Field of Specialization
Morphological Oral Biology, Oral pathology
Outline Activities

1.Regeneration of the tooth
Three approaches as follows is aimed at the regeneration of the tooth.
1) Elucidation of the mechanism in the odontogenesis
2) Analysis the tissue-specific mechanism in aging process
3) Isolation and identification of the tissue-specific stem cells

2.Analysis of differences between oral cancers through cellular and molecular biological approaches
This research is aimed at the development of the new gene therapy method for oral cancer using the gene considered to relate to the profiles of oral cancers.


(Undergraduate School)
Oral pathology: (Lecture) The generalities and the particulars
(Exercise) The explanation of the pathological specimens meeting each unit of a lecture, and the instruction of the observation under a microscope
Outline of the dental and medical science: Introduction of the dental science
Comprehensive dental science
Research exposure: For 3rd and sixth grades

Inspection and exercise are performed to the student who expects experience of research activities in the spring and/or summer vacations, within limited condition that is fully taken the safe side into consideration.

(Graduate School)
The graduate students will study a part of above-mentioned research and write papers on it under instruction to be a "researcher" in the future. Moreover, they will be involved also in autopsy or pathological diagnosis of the oral disease from the department of medical examination so as to understand the fundamentals of pathology.
Research
Research Interests
  • Molecular and genetic investigation on the development and regeneration of the tooth
    keyword : regeneration of the tooth, tooth development, odontogenesis, epithelial-mesenchymal interaction
    2000.01Vertebrate organs are typically composed of epithelial and mesenchymal tissues. Signaling between these tissues governs many aspects of odontogenesis, from the initiation of organ development to the terminal differentiation of organ specific cell types. As well as many other embryonic organs, the development and differentiation of the tooth germ depends on such inductive interactions. We previously demonstrated that odontogenesis occurs between embryonic day 10.5 (E10.5) and E12. Based on the histological findings, we performed cDNA subtraction between the E10.5 and E12 mandibles to detect any differentially expressed genes which might be involved in the initiation of odontogenesis. By sequencing, homology search and semi-quantitative RT-PCR, we found about twenty differentially expressed genes in the course of the early developmental stage of the mouse mandible. These genes are functionally related to protein transport, signal transduction, transcription, translation and molecular chaperon activity. To elucidation of the mechanism in the odontogenesis, we are going to characterize these functions with in situ hybridization analyses, analyses of protein interactions (yeast two-hybrid system and reporter assay) and so on. Taken together with data of analysis the tissue-specific mechanism in aging process and isolation/identification of the tissue-specific stem cells, development of method for tooth regeneration is undertaken..
  • Age-dependent change of the periodontal tissue
    keyword : tooth regeneration, periodontal tissue, aging, cell scenesence, protein interaction
    2000.01.
  • Analysis of differentially expressing genes among oral squamous cell carcinomas and gene-associated functions
    keyword : oral carcinoma, invasion, metastasis, transcriptional regulation, Protein-Protein Interaction
    2000.01We previously established a human carcinoma cell line, MISK81-5 from a metastatic lymph node of oral squamous cell carcinoma. The sMISK was derived from MISK81-5 as a subpopulation having higher tumorigenicity. The analysis of differences between characteristics of the MISK81-5 cell line and its subpopulation, sMISK will be useful for studying the biological behavior of oral squamous cell carcinoma (OSCC). We then performed cDNA subtraction between these cells to detect differentially expressed genes, some of which might be involved in the biological behavior of OSCC. By sequencing, homology search and semi-quantitative RT-PCR, we found differentially expressed genes. These genes are functionally involved in signal transduction, transcription, translation and chromatin reorganization. Compared with those genes expressed in other OSCC and gastric carcinoma cell lines and keratinocytes, expressing pattern in some of these genes was interesting. To characterize the mechanism of carcinogenesis utilized by recombinant proteins based on these genes, we are going to analyze the ability of the proteins to effect on the physical profiles of the OSCC, identify the putative proteins to interact with recombinant proteins, and characterize their promoters with mutational analysis. This research is aimed at the identification of the target genes for the development of the new gene therapy method for oral cancer..
Academic Activities
Papers
1. Yurie Mikami, Shinsuke Fujii, Kengo Nagata, Hiroko Wada, Kana Hasegawa, Misaki Abe, Reiko U Yoshimoto, Shintaro Kawano, Seiji Nakamura, Tamotsu Kiyoshima, GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas., J Cancer Res Clin Oncol, 10.1007/s00432-017-2398-2, 2017.03, PURPOSE:Keratin 17 (KRT17) has been suggested as a potential diagnostic marker of squamous cell carcinoma including oral squamous cell carcinoma (OSCC). The current study was conducted to clarify the function of KRT17 and its expression mechanism in OSCC.METHODS:Immunohistochemical analyses were carried out to examine the expression of KRT17, GLI family zinc finger (GLI)-1, GLI-2, or cleaved caspase-3 in OSCCs. The expression of KRT17, GLI-1, or GLI-2 was investigated among OSCC cell lines, and the effects of loss-of-function of KRT17 or GLI, using siRNA or inhibitor, on the cell growth of the OSCC cell line HSC-2 particularly with respect to apoptosis were examined.RESULTS:Immunohistochemical analyses of tissue specimens obtained from 78 OSCC patients revealed that KRT17 was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor regions. Knockdown of KRT17 increased the number of cleaved caspase-3-positive cells, leading to the reduction of cell number. Loss-of-function of GLI-1 or GLI-2 also increased the cell numbers of apoptotic cells positive for staining of Annexin-V and propidium iodide (PI) and the terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling (TUNEL) method, and induced DNA fragmentation. This inhibitory effect on cell growth was partially rescued by exogenous KRT17 expression. In the KRT17-positive regions in OSCCs, GLI-1 or GLI-2 was frequently detected, and the number of cells with cleaved caspase-3 positive was decreased.CONCLUSIONS:KRT17 promotes tumor cell growth, at least partially, through its anti-apoptotic effect as a result of the KRT17 overexpression by GLIs in OSCC..
2. Kana Hasegawa, Hiroko Wada, Kengo Nagata, Hiroaki Fujiwara, Naohisa Wada, Hirotaka Someya, Yurie Mikami, Hidetaka Sakai, Tamotsu Kiyoshima, Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) expression and possible function in mouse tooth germ development, Int. J. Mol. Med., 10.1007/s10735-016-9680-5, 47, 4, 375-387, 2016.08.
3. Hirotaka Someya, Fujiwara Hiroaki, Kengo Nagata, Hiroko Wada, Kana Hasegawa, Yurie Mikami, Akiko Jinno, Hidetaka Sakai, Kiyoshi Koyano, Tamotsu Kiyoshima, Thymosin beta 4 is associated with RUNX2 expression via the Smad and Akt signaling pathways in mouse dental epithelial cells., Int. J. Mol. Med., doi: 10.3892/ijmm.2015.2118., 35, 5, 1169-1178, 2015.05.
4. Makiko Kihara, Tamotsu Kiyoshima, Kengo Nagata, Hiroko Wada, Fujiwara Hiroaki, Kana Hasegawa, Hirotaka Someya, Ichiro Takahashi, Hidetaka Sakai, Itm2a expression in the developing mouse first lower molar, and the subcellular localization of itm2a in mouse dental epithelial cells., PLoS One., doi: 10.1371/journal.pone.0103928., 9, 7, e103928, 2014.07.
5. Tamotsu Kiyoshima, Fujiwara Hiroaki, Kengo Nagata, Hiroko Wada, Yukiko Okuma, Maho Shiotsuka, Makiko Kihara, Kana Hasegawa, Hirotaka Someya, Hidetaka Sakai, Induction of dental epithelial cell differentiation marker gene expression in non-odontogenic human keratinocytes by transfection with thymosin beta 4., Stem Cell Research, doi: 10.1016/j.scr.2013.11.006., 12, 1, 309-322, 2014.01.
6. Maho Shiotsuka, Hiroko Wada, Tamotsu Kiyoshima, Kengo Nagata, Fujiwara Hiroaki, Makiko Kihara, Kana Hasegawa, Hirotaka Someya, Ichiro Takahashi, Hidetaka Sakai, The expression and function of thymosin beta 10 in tooth germ development., Int J Dev Biol, doi: 10.1387/ijdb.120240hs., 57, 11-12, 873-883, 2013.12.
7. Tamotsu Kiyoshima, Hisato Yoshida, Hiroko Wada, Kengo Nagata, Fujiwara Hiroaki, Makiko Kihara, Kana Hasegawa, Hirotaka Someya, Hidetaka Sakai, Chemoresistance to Concanamycin A1 in Human Oral Squamous Cell Carcinoma Is Attenuated by an HDAC Inhibitor Partly via Suppression of Bcl-2 Expression, PLOS ONE, 10.1371/journal.pone.0080998, 8, 11, 2013.11.
8. Tamotsu Kiyoshima, Kengo Nagata, Hiroko Wada, Fujiwara Hiroaki, Maho Shiotsuka, Makiko Kihara, Kana Hasegawa, Hirotaka Someya, Hidetaka Sakai, Immunohistochemical Expression of Thymosin β4 in Ameloblastomas and Odontomas., Histol. Histopathol., doi: 10.3892/ijo.2012.1594., 28, 6, 775-786, 2013.06.
9. Yukiko Okuma, Tamotsu Kiyoshima, Ieyoshi Kobayashi, Kengo Nagata, Hiroko Wada, Fujiwara Hiroaki, Haruyoshi Yamaza, Kazuaki Nonaka, Hidetaka Sakai, Multiple functional involvement of Thymosin beta-4 in tooth germ development, HISTOCHEMISTRY AND CELL BIOLOGY, 10.1007/s00418-012-1033-1, 139, 2, 355-370, 2013.02.
10. Tamotsu Kiyoshima, Norio Enoki, Ieyoshi Kobayashi, Takako Sakai, Kengo Nagata, Hiroko Wada, Fujiwara Hiroaki, 大隈 由紀子, Hidetaka Sakai, Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts., Int. J. Mol. Med., doi: 10.3892/ijmm.2012.1102., 30, 5, 1007-1012, 2012.11.
11. Lutfun Naher, Tamotsu Kiyoshima, Ieyoshi Kobayashi, Hiroko Wada, Kengo Nagata, Fujiwara Hiroaki, 大隈 由紀子, Satoru Ozeki, Seiji Nakamura, Hidetaka Sakai, STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma., Int. J. Oncol., doi: 10.3892/ijo.2012.1594., 41, 5, 1577-1586, 2012.11.
12. Takahashi KF, Kiyoshima T, Kobayashi I, Xie M, Yamaza H, Fujiwara H, Ookuma Y, Nagata K, Wada H, Sakai T, Terada Y, Sakai H., Protogenin, a new member of the immunoglobulin superfamily, is implicated in the development of the mouse lower first molar., BMC Dev Biol., 10:115-129, 2010.11.
13. Hideaki Fukuzawa, Tamotsu Kiyoshima, Ieyoshi Kobayashi, Satoru Ozeki, Hidetaka Sakai, Transcription promoter activity of the human S100A7 gene in oral squamous cell carcinoma cell lines., Biochem, Biophys.Acta, 1759: 171-176,, 2006.04.
14. Ken-ichiro Hashimoto, Tamotsu Kiyoshima, Kou Matsuo, Satoru Ozeki, Hidetaka Sakai, Effect of SCCA1 and SCCA2 on the suppression of TNF-a-induced cell death by impeding the release of mitochondrial cytochrome c in oral squamous cell carcinoma cell line., Tumor Biol., 10.1159/000086949, 26, 4, 165-172, 26:165-172, 2005.07.
15. Ogasawara T, Yoshimine Y, Kiyoshima T, Kobayashi I, Matsuo K, Akamine A, Sakai H, In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue., J Periodontal Res., 10.1111/j.1600-0765.2004.00699.x, 39, 1, 42-49, Vol.39, pp.42-9., 2004.01.
16. Kiyoshima T, Yamauchi M, Wong C, Jheon A, Ganss B, Sodek J., An L1 element disrupts human bone sialoprotein promoter: lack of tissue-specific regulation by distalless5 (Dlx5) and runt homeodomain protein2 (Runx2)/core binding factor a1 (Cbfa1) elements., Gene, Vol.299, pp.205-17., 2002.10.
17. Okamura K, Kiyoshima T, Shima K, Kobayashi I, Matsuo K, Ishibashi H, Komatsu S, Rasul AM, Sakai H., Immunohistochemical expression of CA19-9 and CA125 in mucoepidermoid and adenoid cystic carcinomas of the salivary gland., Oral Oncol., 10.1016/S1368-8375(01)00049-5, 38, 3, 244-250, Vol.38, pp.244-50., 2002.04.
18. Wada H, Kobayashi I, Yamaza H, Matsuo K, Kiyoshima T, Akhtar M, Sakai T, Koyano K, Sakai H., In situ expression of heat shock proteins, Hsc73, Hsj2 and Hsp86 in the developing tooth germ of mouse lower first molar., Histochem J., 10.1023/A:1020930228303, 34, 3-4, 105-109, Vol.34, pp.105-9., 2002.03.
19. Yamaza H, Matsuo K, Kobayashi I, Wada H, Kiyoshima T, Akhtar M, Ishibashi Y, Sakai T, Akamine A, Sakai H., Expression of Set-alpha during morphogenesis of mouse lower first molar, Histochem J., 10.1023/A:1014491111628, 33, 8, 437-441, Vol.33,pp.437-41, 2001.08.
20. Kiyoshima T, Shima K, Kobayashi I, Matsuo K, Okamura K, Komatsu S, Rasul AM, Sakai H., Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid carcinomas of the salivary glands, Oral Oncol., 10.1016/S1368-8375(00)00083-X, 37, 3, 315-322, Vol.37,pp.315-22, 2001.04.
21. Shigemura N, Kiyoshima T, Sakai T, Matsuo K, Momoi T, Yamaza H, Kobayashi I, Wada H, Akamine A, Sakai H., Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar, Histochem J., 10.1023/A:1017900305661, 33, 5, 253-258, Vol.33,pp.253-8, 2001.03.
22. Yamaza H, Matsuo K, Kiyoshima T, Shigemura N, Kobayashi I, Wada H, Akamime A, Sakai H., Detection of differentially expressed genes in the early developmental stage of the mouse mandible, Int J Dev Biol., 45, 4, 675-680, Vol.45,pp.675-80, 2001.01.
23. Shima K, Kobayashi I, Saito I, Kiyoshima T, Matsuo K, Ozeki S, Ohishi M, Sakai H., Incidence of human papillomavirus 16 and 18 infection and p53 mutation in patients with oral squamous cell carcinoma in Japan, Br J Oral Maxillofac Surg., Vol.38,pp.445-50, 2000.10.
24. Li C.Y., Shirasuna K., Ishibashi H., Nakayama H. and Kiyoshima T., Epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the palate., Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 10.1067/moe.2000.108099, 90, 4, 460-465, 2000.10.
25. Sakai T, Kiyoshima T, Kobayashi I, Moroi R, Ibuki T, Nagadome M, Terada Y, Sakai H., Age-dependent changes in the distribution of BrdU- and TUNEL-positive cells in the murine gingival tissue, J Periodontol., 10.1902/jop.1999.70.9.973, 70, 9, 973-981, Vol.70,pp.973-81, 1999.09.
26. Kobayashi I, Shima K, Saito I, Kiyoshima T, Matsuo K, Ozeki S, Ohishi M, Sakai H., Prevalence of Epstein-Barr virus in oral squamous cell carcinoma, J Pathol., 10.1002/(SICI)1096-9896(199909)189:1<34::AID-PATH391>3.0.CO;2-4, 189, 1, 34-39, Vol.189,pp.34-9, 1999.09.
27. Shigemura N, Kiyoshima T, Kobayashi I, Matsuo K, Yamaza H, Akamine A, Sakai H., The distribution of BrdU- and TUNEL-positive cells during odontogenesis in mouse lower first molars, Histochem J., 10.1023/A:1003796023992, 31, 6, 367-377, Vol.31,pp.367-77, 1999.07.
28. Kobayashi I., Kiyoshima T., Ozeki S., Shima K., Shigemura N., Matsuo K. and Sakai H., Immunohistochemical and ultrastructural study of a papillary cystadenocarcinoma arising from the sublingual gland., J. Oral Pathol. Med., 28, 6, 282-286, 1999.07.
29. Kiyoshima T., Kobayashi, I., Matsuo K., Ishibashi Y., Miyoshi A., Akashi Y. and Sakai H., Immunohistochemical localization of laminin, collagen type IV and heparan sulfate proteoglycan in human colorectal adenocarcinoma: correlation with local invasive pattern and lymph node metastasis, Acta Histochemica et Cytochemica, 31, 1, 39-47, Vol.31,pp.39-47, 1998.01.
30. Kazuhiko Okamura, Ieyoshi Kobayashi, Kou Matsuo, Tamotsu Kiyoshima, Kenji Yamamoto, Akira Miyoshi, Hidetaka Sakai, Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser: correlation with histological grade and metastatic behaviour, HISTOPATHOLOGY, 31, 6, 540-548, 1997.12.
31. Kobayashi I., Matsuo K., Kiyoshima T., Shinohara M. and Sakai H., Salivary Duct Carcinoma with Sebaceous Cell Differentiation arising from Parotid Gland: Histological, Immunohistochemical and Ultrastructural Analyses of a Case., Oral Med. Pathol., 2, 89-93, 1997.03.
32. Okamura K., Kobayashi I., Matsuo K., Kiyoshima T., Yamamoto K., Miyoshi A. and Sakai H., Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analyzed by computor image analyzer: correlation with the histological grade and the metastatic activity of carcinoma., Histopathology, 31, 540-548, 1997.03.
33. Kou Matsuo, Ieyoshi Kobayashi, Takayuki TSUKUBA, Tamotsu Kiyoshima, Yukiko Ishibashi, Akira Miyoshi, Kenji Yamamoto, Hidetaka Sakai, Immunohistochemical localization of cathepsins D and E in human gastric cancer: A possible correlation with local invasive and metastatic activities of carcinoma cells, HUMAN PATHOLOGY, 27, 2, 184-190, 1996.02.
Presentations
1. Hiroko Wada, Kana Hasegawa, Kengo Nagata, Naohisa Wada, Yurie Mikami, Hidetaka Sakai, Tamotsu Kiyoshima, The expression pattern of the FRG1 in the mouse developing tooth germ., The 95th General Session & Exhibition of the IADR, 2017.03.
2. Hiroko Wada, Aki Kinjo, Yurie Mikami, Tuyoshi Sugiura, Tamotsu Kiyoshima, Mandibular tumor, The 27th Annual Meeting of the Japanese Society of Oral Pathology, 2016.08.
3. Reiko U. Yoshimoto, Reona Aijima, Yasuyoshi Ohsaki, Zhang J.Q., Cao A.L., Tamotsu Kiyoshima, Kido M.A., Temperature changes effect on intercellular adhesion of oral epithelial cells., The 15th International Symposium on Molecular and Neural Mechanism of Taste and Olfactory Perception., 2016.06.
4. 吉田 寿人, Ying Wang, 清島 保, 坂井 英隆, Analysis of the Anti-tumor Effects of V-ATPase inhibitor, Concanamycin A1, on Oral Squamous Cell Carcinoma, 103rd USCAP (United States & Canadian Academy of Pathology) Annual Meeting, 2014.03.
5. 木原 槇子, 清島 保, 永田 健吾, 和田 裕子, 藤原 弘明, 長谷川 佳那, 染矢 祐孝, 髙橋 一郎, 坂井 英隆, Itm2a Expression during the Tooth Germ Development, Kyudai Oral Bioscience (KOB), 2014.02.
6. Pathological study of biopsied minor salivary glands in IgG4-related sclerosing disease. -Report of a case- .
7. Transcriptional Regulation of S100A7 in Oral Squamous Cell Carcinoma.
Membership in Academic Society
  • Japanese Stomatological Society
  • The Japanese Society of Conservative Dentistry
  • Japanese Society of Pediatric Oral and Maxillofacial Surgery
  • The Japanese Society of Pathology
  • The Japanese Society for Oral Pathology
  • Japanese Cancer Association
  • Japanese Society for Oral Tumors
  • Japanese Society of Oral and Maxillofacial Surgeon
  • Japanese Association for Oral Biology
  • The Japanese Society for the Temporomandibular Joint
Educational
Educational Activities

Pathology/Oral pathology: (Lecture/Exercise) The explanation of the typical pathological specimens based on the lecture, and the instruction of the observation under a microscope
Comprehensive dental science
Research exposure: For fourth and sixth grades, the instruction and the exercise of the molecular biological examination concerning the above-mentioned research as well as pathological diagnosis.


The graduate students will study a part of above-mentioned research and write papers on it under instruction to be a "researcher" in the future. Moreover, they will be involved also in autopsy or pathological diagnosis of the oral disease from the department of medical examination so as to understand the fundamentals of pathology.
Other Educational Activities
  • 2016.02.
  • 2015.04.
Social
Professional and Outreach Activities
I work as a members in the dental educational course of JICA in Faculty of Dental Science, Kyushu University, and have the class for the oral pathology and recent data associated with the oral diseases according to the course curriculum ..