| 1. |
Hiroki Inada, Miyako Udono, Kanae Matsuda-Ito, Kenichi Horisawa, Yasuyuki Ohkawa, Shizuka Miura, Takeshi Goya, Junpei Yamamoto, Masao Nagasaki, Kazuko Ueno, Daisuke Saitou, Mikita Suyama, Yoshihiko Maehara, Wataru Kumamaru, Yoshihiro Ogawa, Sayaka Sekiya & Atsushi Suzuki, Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells, Nature Communications, https://doi.org/10.1038/s41467-020-19041-z, 2020.10. |
| 2. |
Kana Ishibashi, kotaro ishii, Goro Sugiyama, Tomoki Sumida, Tsuyoshi Sugiura, Yu Kamata, Katsuhiro Seki, Takahiro Fujinaga, Kumamaru Wataru, Yosuke Kobayashi, Naomi Hiyake, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori, Deregulation of nicotinamide N-methyltransferase and gap junction protein alpha-1 causes metastasis in adenoid cystic carcinoma, Anticancer Research, 10.21873/anticanres.12207, 38, 1, 187-197, 2018.01, Background/Aim: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis. Materials and Methods: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells. Results: We examined the three cell lines. DNA microarray indicated significantly altered processes in ACCS-LN-GFP cells: particularly, the expression of nicotinamide N-methyltransferase (NNMT) was enhanced the most. NNMT is associated with tumorigenesis and is a potential tumor biomarker. Concomitantly, we found-significant down-regulation of gap junction protein alpha-1. We suggest that ACCS-LN-GFP cells acquire cancer stem cell features involving the up-regulation of NNMT and the loss of gap junction protein alpha-1, leading to epithelial-mesenchymal transition and consequent AdCC metastasis. Conclusion: NNMT is a potential biomarker of AdCC.. |
| 3. |
Kana Ishibashi, kotaro ishii, Goro Sugiyama, Yu Kamata, Azusa Suzuki, Kumamaru Wataru, Yukiko Ohyama, Hiroyuki Nakano, Tamotsu Kiyoshima, Tomoki Sumida, Tomohiro Yamada, Yoshihide Mori, Regulation of β-catenin phosphorylation by PR55β in adenoid cystic carcinoma, Cancer Genomics and Proteomics, 10.21873/cgp.20064, 15, 1, 53-60, 2018.01, Background/Aim: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. β-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. Materials and Methods: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including β-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M). Results: PR55β was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55β expression was associated with tumor grade, with ACCS-M exhibiting higher PR55β levels. More importantly, knockdown of PR55β in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of β-catenin were dependent on PR55β in ACCS-M. Finally, we confirmed a correlation between PR55β staining intensity and histopathological type in human AdCC tissues. Conclusion: Our study provides new insight into the interaction between PR55β and β-catenin and suggests that PR55β may be a target for the clinical treatment of AdCC.. |
| 4. |
Azusa Nakashima, Nakano Hiroyuki, Tomohiro Yamada, Kazuya Inoue, Goro Sugiyama, W Kumamaru , Yasumichi Nakajim, Tomoki Sumida, T Yokoyama, Katsuaki Mishiama, Yoshihide Mori, The relationship between lateral displacement of the mandible and scoliosis, Oral Maxillofac Surg, DOI 10.1007/s10006-016-0607-9, 30, 2017.03. |
| 5. |
Yu Kamata, Tomoki Sumida, Yosuke Kobayashi, Akiko Ishikawa, Kumamaru Wataru, Yoshihide Mori, Introduction of ID2 enhances invasiveness in ID2-null oral squamous cell carcinoma cells via the SNAIL axis, Cancer Genomics and Proteomics, 10.21873/cgp.20012, 13, 6, 493-498, 2016.11, Aim: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells. Materials and Methods: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP). Results: ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1). Conclusion: ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2- SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.. |
| 6. |
Minami Shibuya, Tatsuya Ikari, Goro Sugiyama, Yukiko Ohyama, Wataru Kumamaru, Koki Nagano, Tsuyoshi Sugiura, Kamemitsu Shirasuna, Yoshihide Mori, Efficient regulation of branching morphogenesis via fibroblast growth factor receptor 2c in early-stage embryonic mouse salivary glands, Differentiation, 10.1016/j.diff, 92, 4, 216-224, 2016.10. |
| 7. |
Kouhei Hayash, TATSUYA IKARI, Tsuyoshi Sugiura, Minami Shibuya, Yukiko Ohyama, Wataru Kumamaru , Yoshihide Mori, Kamemitsu Shirasuna, Involvement of the T-box transcription factor Brachyury in the early embryonic stage of mouse salivary gland, Biochemical and Biophysical Research Communications, 477, 4, 814-819, 2016.09. |
| 8. |
Rumi Yoshihama, Koujiro Yamaguchi, Ikumi Imajyo, Mariko Mine, Naomi Hiyake, Naonari Akimoto, Yosuke Kobayashi, Satomi Chigita, Wataru Kumamaru, Tamotsu Kiyoshima, Yoshihide Mori, Tsuyoshi Sugiura, Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma, ONCOLOGY LETTERS, 10.3892/ol.2015.4047, 11, 2, 1435-1446, 2016.02. |
| 9. |
K Inoue, H Nakano, T Sumida, T Yamada, N Otawa, N Fukuda, Y Nakajima, W Kumamaru , K Mishima, M Kouchi, I Takahashi, Y Mori, A novel measurement method for the morphology of the mandibular ramus using homologous modelling, Dentomaxillofacial Radiology, 10.1259/dmfr.20150062, 44, 8, 2015.07. |
| 10. |
Takahiro Fujinaga, Kumamaru Wataru, Tsuyoshi Sugiura, Yosuke Kobayashi, YUKIKO OHYAMA, TATSUYA IKARI, Mitsuho Onimaru, Naonari Akimoto, Rumi Jogo, Yoshihide Mori, Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva, International Journal of Oncology, 10.3892/ijo.2014.2332, 44, 5, 1614-1624, 2014.05, Controlling metastatic lesions is an important part of improving cancer prognosis, in addition to controlling the primary lesion. There have been numerous histological studies on primary and metastatic lesions, but little basic research has been performed using cell lines from primary and metastatic lesions belonging to the same patient. In this study, we successfully established a cell line derived from lower gingival carcinoma (WK2) as well as a line derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. We then investigated the biological characteristics of the cancer cell lines from these primary and metastatic lesions and analyzed metastasis-related genes. Comparison of the biological characteristics in vitro showed that WK3F had higher cell proliferation ability and shorter cell doubling time than WK2. WK3F also had increased cell migratory ability and higher invasive and self-replication abilities. Heterotransplantation into nude mice resulted in high tumor formation rates in the tongue and high metastasis rates in the cervical lymph nodes. Changes in WK2 and WK3F gene expression were then comprehensively analyzed using microarrays. Genes with increased expression in WK3F compared to WK2 were extracted when the Z-score was ≥2.0 and the ratio was ≥5.0, while genes with reduced expression in WK3F compared to WK2 were extracted when the Z-score was ≤ -2.0 and the ratio was ≤0.2; differences were found in 604 genes. From these, MAGEC1 (88.0 fold), MMP-7 (18.6 fold), SNAI1 (6.6 fold), MACC1 (6.2 fold), and HTRA1 (0.012 fold) were selected as metastasis-related candidate genes. The results suggest that these molecules could be important for clarifying the mechanisms that regulate metastasis and provide new therapeutic targets for inhibiting tumor invasion.. |
| 11. |
Hayashida Jun-Nosuke, Seiji Nakamura, Toyoshima Takeshi, Masafumi Moriyama, MASANORI SASAKI, E Kawamura, Yukiko Ohyama, Kumamaru Wataru, Kamemitsu Shirasuna, Possible involvement of cytokines, chemokines and chemokine receptors in the initiation and progression of chronic GVHD., Bone marrow transplantation, doi:10.1038/bmt.2012.100, Bone Marrow Transplantation (2013) 48, 115–123; doi:10.1038/bmt.2012.100; published online 4 June 2012, 2012.06. |
| 12. |
Takeshi Toyoshima, Wataru Kumamaru, Jun-nosuke Hayashida, Masahumi Moriyama, Ryoji Kitamura, Hideaki Tanaka, Akira Yamada, Kyogo Itoh, Seiji Nakamura, In vitro induction of specific CD8+ T lymphocytes by tumor-associated antigenic peptides in patients with oral squamous cell carcinoma, Cancer Letters, 2012.02, The aim of this study was to clarify candidate peptides for peptide-based specific immunotherapy of
patients with oral squamous cell carcinoma (SCC). Thirteen peptides were examined for in vitro induction of peptide-specific CD8+ T lymphocyte (CD8+TL) activity in peripheral blood mononuclear cells from 35patients with oral SCC. A correlation between the induction ability of CD8+TL and in vivo immune response of host was carried out immunohistochemically in 23 patients. Peptide-specific activities of CD8+TL for at least one peptide were detectable in 21/35 patients (60.0%). The potent peptides were SART-1690 in 9/35 (25.7%), SART-293, and ART475 in 7/35 (20.0%), respectively. In the 9 patients with SART-1690-specific activity, the whole of activities was significantly inducible for more number of other peptides compared to that in 26 patients without the activity (P = 0.035). Cellular responses in 7 patients with SART-1690-specific activity were significantly stronger than those in 16 patients without the activity (P = 0.027). Furthermore, the number of CD3+ T cells around the SCC was also significantly different between the 2 groups of patients (P = 0.041). In conclusion, SART-1690, SART-293, and ART475 could be applicable as peptide-based specific immunotherapies for the majority of patients with oral SCC.. |
| 13. |
Toyoshima T, Nakamura S, Kumamaru W, Kawamura E, Ishibashi H, Hayashida JN, Moriyama M, Ohyama Y, Sasaki M, Shirasuna K, Expression of tumor-associated antigen RCAS1 and its possible involvement in immune evasion in oral squamous cell carcinoma, Journal of Oral Pathology Medicine, 35巻 361～368頁, 2006.06. |
| 14. |
Wataru KUMAMARU, Seiji NAKAMURA, Tsutomu KADENA, Akira YAMADA, Eiji KAWAMURA, Masanori SASAKI, Yukiko OHYAMA, Takeshi TOYOSHIMA, Jun-nosuke HAYASHIDA, Kyogo ITOH and Kanemitsu SHIRASUNA, T-cell receptor Vbeta gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma, International Journal of Cancer, 108巻 5号 686～695頁
, 2004.05. |
| 15. |
Kawamura E, Nakamura S, Sasaki M, Ohyama Y, Kadena T, Kumamaru W, Shirasuna K, Accumulation of oligoclonal T cells in the infiltrating lymphocytes in oral lichen planus, Journal of Oral Pathology Medicine, 32, 5, 282-289, 2003.02. |
