Kyushu University Academic Staff Educational and Research Activities Database
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Takeshi Mitsuyasu Last modified date:2019.06.26

Assistant Professor / Section of Oral and Maxillofacial Oncology Division of Maxillofacial Diagnostic and Surgical Sciences Faculty of Dental Science Kyushu University
Maxill Ofacial Surgery
Kyushu University Hospital


Other Organization


E-Mail
Phone
092-642-6446
Fax
092-642-6386
Academic Degree
Ph. D (Dentistry)
Country of degree conferring institution (Overseas)
No
Field of Specialization
oral and maxillofacial surgery
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
Research: Growth and differentiation mechanisms of ameloblastoma and odontogenic tumor. Hedgehog signaling pathway on ameloblastoma.
Education: Clinical traning for dental student and resident
Clinical: Cleft lip and palate, Reconstructive surgery, Odontogenic tumor
Research
Research Interests
  • The mechanisms of odontogenic tumor cell proliferation and differentiation.
    keyword : odontogenic tumor, ameloblastoma
    1992.04Grwth and differentiation mechanisms of odontogenic tumor..
  • Risk factors for postoperative delirium in patients with oral carcinoma
    keyword : delirium, oral carcinoma
    2011.05~2014.03.
  • Microsurgical technique and management for prevention of anastomotic thrombosis.
    keyword : microsurgery, anastomosis, anastomotic
    2008.07~2014.03.
Academic Activities
Papers
1. Nakao Yu, Takeshi Mitsuyasu, Shintaro Kawano, Norifumi Nakamura, Shiori Kanda, Seiji Nakamura, Fibroblast growth factors 7 and 10 are involved in ameloblastoma proliferation via the mitogen-activated protein kinase pathway, INTERNATIONAL JOURNAL OF ONCOLOGY 43: 1377-1384, 2013, DOI: 10.3892/ijo.2013.2081, 43, 5, 1377-1384, 2013.11, Ameloblastoma is an epithelial benign tumor of the odontogenic apparatus and its growth mechanisms are not well understood. Fibroblast growth factor (FGF) 3, FGF7 and FGF10, which are expressed by the neural crest-derived ectomesenchymal cells, induce the proliferation of odontogenic epithelial cells during tooth development. Therefore, we examined the expression and function of these FGFs in ameloblastoma. We examined 32 cases of ameloblastoma as well as AM-1 cells (an ameloblastoma cell line) and studied the expression of FGF3, FGF7, FGF10 and their specific receptors, namely, FGF receptor (FGFR) 1 and FGFR2. Proliferation, mitogen-activated protein kinase (MAPK) signaling and PI3K signaling were examined in AM-1 cells after the addition of FGF7, FGF10 and these neutralizing antibodies. The expression of FGF7, FGF10, FGFR1 and FGFR2 was detected in ameloblastoma cells and AM-1 cells, while that of FGF3 was not. FGF7 and FGF10 stimulated AM-1 cell proliferation and phosphorylation of p44/42 MAPK. However, Akt was not phosphorylated. Blocking the p44/42 MAPK pathway by using a specific mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor (U0126) completely neutralized the effects of FGF7 and FGF10 on AM-1 cell proliferation. However, Anti FGF7 and FGF10 neutralizing antibodies did not decrease cell proliferation and MAPK phosphorylation of AM-1 cells. These results suggested that FGF7 and FGF10 are involved in the proliferation of ameloblastoma cells through the MAPK pathway..
2. Shiori Kanda, Takeshi Mitsuyasu, Nakao Yu, Shintaro Kawano, Yuichi Goto, Ryota Matsubara, Seiji Nakamura, Anti-apoptotic role of the sonic hedgehog signaling pathway in the proliferation of ameloblastoma, INTERNATIONAL JOURNAL OF ONCOLOGY 43: 695-702, 2013, 43, 695-702, INTERNATIONAL JOURNAL OF ONCOLOGY 43: 695-702, 2013, 2013.07, Sonic hedgehog (SHH) signaling pathway is crucial to growth and patterning during organogenesis. Aberrant activation of the SHH signaling pathway can result in tumor formation. We examined the expression of SHH signaling molecules and investigated the involvement of the SHH pathway in the proliferation of ameloblastoma, the most common benign tumor of the jaws. We used immunohistochemistry on ameloblastoma specimens and immunocytochemistry and reverse transcription-PCR on the ameloblastoma cell line AM-1. We also used the inhibitors of SHH signaling, SHH neutralizing antibody and cyclopamine, to assess the effects of SHH on the proliferation of AM-1 cells. We detected expression of SHH, patched, GLI1, GLI2 and GLI3 in the ameloblastoma specimens and AM-1 cells. The proliferation of these cells was significantly inhibited in the presence of SHH neutralizing antibody or cyclopamine; this was confirmed by BrdU incorporation assays. Furthermore, in the presence of SHH neutralizing antibody, nuclear translocation of GLI1 and GLI2 was abolished, apoptosis was induced, BCL-2 expression decreased and BAX expression increased. Our results suggest that the SHH signaling pathway is constitutively active in ameloblastoma and plays an anti-apoptotic role in the proliferation of ameloblastoma cells through autocrine loop stimulation..
3. Nakamura N, Mitsuyasu T, Mitsuyasu Y, Taketomi T, Higuchi Y, Ohishi M., Marsupialization for odontogenic keratocysts: long-term follow-up analysis of the effects and changes in growth characteristics., Oral Surg Oral Med Oral Pathol Oral Radiol Endod., 10.1067/moe.2002.128022, 94, 5, 543-553, 94(5):543-53, 2002.11.
4. Liao J, Mitsuyasu T, Yamane K, Ohishi M., Telomerase activity in oral and maxillofacial tumors., Oral Oncol., 10.1016/S1368-8375(00)00013-0, 36, 4, 347-352, 36(4):347-52., 2000.07.
5. Harada H, Mitsuyasu T, Nakamura N, Higuchi Y, Toyoshima K, Taniguchi A, Yasumoto S., Establishment of ameloblastoma cell line, AM-1., J Oral Pathol Med., 27, 5, 207-212, 27(5):207-12., 1998.05.
6. Harada H, Mitsuyasu T, Seta Y, Maruoka Y, Toyoshima K, Yasumoto S., Overexpression of bcl-2 protein inhibits terminal differentiation of oral
keratinocytes in vitro., J Oral Pathol Med., 27(1):11-7., 1998.01.
7. Mitsuyasu T, Harada H, Higuchi Y, Kimura K, Nakamura N, Katsuki T, Kubota E, Toyoshima K, Ohishi M., Immunohistochemical demonstration of bcl-2 protein in ameloblastoma., J Oral Pathol Med., 10.1111/j.1600-0714.1997.tb00228.x, 26, 8, 345-348, 26(8):345-8., 1997.09.
Presentations
1. Bilateral cleft lip treatment protocol in Kyushu University Hospital..
2. Takeshi Mitsuyasu, Kaori Matsumura, Ami Maeno, Seiji Nakamura, Cleft lip & palate treatment team in Kyushu University Hospital, Fukuoka Japan
-Prenatal counseling and visiting on birth day-, 10th World Cleft Lip and Palate Congress, 2017.06, The team approach for managing and correcting cleft lip and palate is important for patients and families. The American Cleft Palate Association “Standards for Approval of Cleft Palate and Craniofacial Teams Commission on Approval of Teams” suggests that teams are comprised of experienced and qualified professionals from medical, surgical, dental, and allied health disciplines working in an interdisciplinary and coordinated system. Our team includes oral surgery, pediatric dentistry, pediatrics, otolaryngology, orthodontics, speech-language pathologist and nurses. Especially after getting the information of baby’s cleft lip and palate (prenatally or after birth), the parents are usually shocked. The parents’ situation is psychosocial emergency, that is disappointment, weakness and hopelessness. Often mothers feel guilty about the baby’s cleft lip and palate. During such a period, parents need to get the accurate information about malformation and its treatment and prognosis. Of course, for the duration parents are in deep anxiety and sorrow. In order to reduce their anxiety, we give the prenatal counselling and visit hospitals on the birthday. At the first communication, we give the information about the diagnosis, the treatment plan and the prognosis.
We also support the management of TSUBASA, which is a cleft lip and palate patient’s families’ community. (TSUBASA means wings in Japanese.) We hold TSUBASA meetings twice a year, a lecture meeting and Christmas meeting. Parents can exchange their information each other. And every month we hold a team meeting..
3. Syarifah Nova Amiza Zam, Takeshi Mitsuyasu, Shintaro Kawano, Kaori Matsumura, Seiji Nakamura, Effects of Sonic Hedgehog Signaling Pathway Inhibitors on Ameloblastoma Cell-lines , the 2016 IADR/APR General Session & Exhibition (June 22-25, 2016) , 2016.06, Objectives: We investigated the effects of the potent SMO inhibitors and GLI inhibitors of sonic hedgehog (SHH) on Ameloblastoma cell line.

Methods: Several Hedgehog Pathway inhibitors were used to examine. Cyclopamine and Vismodegib were used as SMO inhibitors, meanwhile GANT-61 and JQ-1 as GLI inhibitors. The human ameloblastoma cell line AM-1, was established from human plexiform type ameloblastoma tissue and immortalized by the transfection of human papillomavirus type 16 DNA, and normal oral mucosal epithelial immortalized cell line.

The expression of HH signaling pathway genes (SHH, PTCH, SMO, GLI1, GLI2, GLI3) and proteins were examined. We focused on the impact that each HH signaling pathway inhibitors have on growth in Am-1 cells by WST-8 cell proliferation assay and BrdU uptake assay.
We also detected the apoptotic cells by Annexin-V fluorescein and apoptosis related proteins (Bcl-2 and BAX) with SMO and GLI inhibitors.

Results: The hedgehog pathway inhibitors, cyclopamine, vismodegib (GDC-0449), Gant-61 and Jq-1 were used to assess. RT-PCR analysis revealed that SHH, PTCH, SMO, GLI1, GLI2, and GLI3 were expressed in AM-1 cells. Expression of SHH signaling pathway related genes and gene products were detected in AM-1 cells by immunocytochemistry.
The addition of vismodegib (GDC-0449) and cyclopamine suppressed proliferation of AM-1 cells. Gli inhibitors, Gant-61 and JQ-1, also suppressed the proliferation of AM-1 cells.
In the present of these Hedgehog pathway inhibitors, nuclear translocation of GLI1 was abolished, Annexin-V positive cells were induced, Bcl2 expression decreased and bax expression increased.

Conclusions: Our study suggests that inhibition of SHH signaling pathway is a strong candidate of the novel treatment of Ameloblastoma by growth inhibition and apoptosis induction.
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4. The effectiveness of presurgical nasoalveolar molding treatment for incomplete unilateral cleft lip patients.
Membership in Academic Society
  • Japanese Society of Pediatric Oral and Maxillofacial Surgery
  • Asian Association of Oral and Maxillofacial Surgeons
  • Japanese cleft palate association
  • Japan Society for Oral Tumors
  • Japanese society of oral and maxillofacial traumatology
  • Japanese Society of Oral and Maxillofacial Surgeons
  • Japanese Stomatological Society
  • Japanese cancer association
Awards
  • Clinicostatistical Investigation of Cleft Lip and/or Palate Patients in the Department of Oral and Maxillofacial Surgery, Kyushu University Hospital
  • Masahiro Tezuka, Yuko Ogata, Kazuhide Matsunaga, Takeshi Mitsuyasu, Sachiyo Hasegawa, Norifumi Nakamura, Perceptual and videofluoroscopic analyses of relation between backed articulation and velopharyngeal closure following cleft palate repair
  • A Study of Speech Discrimination Ability of Cleft Palate Patients with Abnormal Articulation
Educational
Educational Activities
Lecture for students.
Education for resident and post graduate students.
Other Educational Activities
  • 2019.02, SECONDARY ALVEOLAR BONE GRAFTING -For cleft lip and alveolus/palate patients-
    at University of Dental Medicine, Yangon, Myanmar..
  • 2017.02, Cleft lip & palate treatment team in
    Kyushu University Hospital, Fukuoka Japan
    -Prenatal counseling and visiting on birth day-
    Lecture at University of Dental Medicine, Mandalay.
  • 2017.05, Treatments about cleft lip and cleft palate patients.
  • 2014.05, Treatments about cleft lip and cleft palate patients.
  • 2013.04, Treatments about cleft lip and cleft palate patients.
  • 2012.04, Treatments about cleft lip and cleft palate patients.
  • 2011.08, Treatments about cleft lip and cleft palate patients in Kyushu University Hospital.
  • 2010.12, Treatments about cleft lip and cleft palate patients in Kyushu University Hospital.
  • 2010.04, Treatments about cleft lip and cleft palate patients.
  • 2011.04, For nursing staffs
    Treatments about cleft lip and cleft palate patients.
  • 2009.04, Lecture for nurses belonging to ward
    Treatments about cleft lip and palate patients..
Social
Professional and Outreach Activities
Assistance for cleft lip and palate patients group activities.
Charity operation for cleft lip and palate patients in Republic of the Union of Myanmar.
Charity operation for cleft lip and palate patients in Socialist Republic of Vietnam..