Faculty Profiles - NAGATSUKA Hitoshi

Papers - NAGATSUKA Hitoshi

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Primary extranodal lymphoma of the maxilla: A case report with imaging features and dynamic data analysis of magnetic resonance imaging International journal

Hidenobu Matsuzaki, Naoki Katase, Marina Hara, Jun Ichi Asaumi, Yoshinobu Yanagi, Teruhisa Unetsubo, Miki Hisatomi, Hironobu Konouchi, Toshihiko Takenobu, Hitoshi Nagatsuka

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 112 ( 3 ) e59-69 - E69 2011.9

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Malignant lymphoma is the second-most common malignancy in the head and neck region. Waldeyer's ring is the most common site of extranodal Hodgkin's lymphoma (NHL) in that region, and a small percentage of primary extranodal NHL occurs in the oral cavity. The most common sites of extranodal NHL in the oral region are the palate and maxilla, and nearly half of extranodal NHL cases arise from bone. It is difficult to diagnose extranodal NHL because of the variety of its radiological features. We report a case of primary extranodal NHL of the maxilla in a 68-year-old female patient with atypical imaging findings, along with the results of analysis of dynamic magnetic resonance imaging (MRI). © 2011 Mosby, Inc.

DOI： 10.1016/j.tripleo.2011.02.052

シェーグレン症候群患者の口唇腺におけるヒトβデフェンシンの局在と臨床応用

金田祥弘, 水川展吉, 武田斉子, 山近英樹, 喜田沙音里, 高木慎, 長塚仁, 飯田征二

日本口腔外科学会雑誌 57 ( Suppl. ) 254 - 254 2011.9

CCN2 expression in ameloblastoma

Takebe Y, Katase N, Tsujigiwa H, Lefeuvre M, Sathi GSA, Tamamura R, Sasaki A, Nagatsuka H

Journal of Hard Tissue Biology 20 ( 3 ) 267 2011.8

Strawberry gingivitis as the first presenting sign of Wegener's granulomatosis: Report of a case

C. H. Siar, K. B. Yeo, K. Nakano, H. Nagatsuka, H. Tsujigiwa, M. Tomida, K. H. Ng, Toshiyuki Kawakami

European Journal of Medical Research 16 ( 7 ) 331 - 334 2011.7

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Wegener's granulomatosis is a rare multi-system disease characterized by the classic triad of necrotizing granulomas affecting the upper and lower respiratory tracts, disseminated vasculitis and glomerulonephritis. Oral lesions as a presenting feature are only encountered in 2% of these cases. Hyperplastic gingival lesions or strawberry gingivitis, is a characteristic sign of Wegener's granulomatosis. The latter consists of reddish-purple exophytic gingival swellings with petechial haemorrhages thus resembling strawberries. Recognition of this feature is of utmost importance for timely diagnosis and definitive management of this potentially fatal disease. A case of strawberry gingivitis as the first presenting sign of Wegener's granulomatosis affecting a 50-year-old Malay male is reported here. The differential diagnosis of red lesions that may present in the gingiva is discussed. © I. Holzapfel Publishers 2011.

DOI： 10.1186/2047-783x-16-7-331

Ameloblastic carcinoma: A case report with radiological features of computed tomography and magnetic resonance imaging and positron emission tomography International journal

Hidenobu Matsuzaki, Naoki Katase, Marina Hara, Jun Ichi Asaumi, Yoshinobu Yanagi, Teruhisa Unetsubo, Miki Hisatomi, Hironobu Konouchi, Hitoshi Nagatsuka

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 112 ( 1 ) e40-7 - E47 2011.7

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Ameloblastic carcinoma is a rare malignant odontogenic carcinoma that has metastatic potential, and because of its rare incidence, there are few reports focusing on its radiologic imaging. If it shows aggressive appearances, it can be diagnosed as malignant tumor. But in case of negative appearance, it is difficult to distinguish ameloblastic carcinoma from ameloblastoma. We report a case of ameloblastic carcinoma of the maxilla in a 76-year-old female patient with radiologic images and pathologic features. © 2011 Mosby, Inc. All rights reserved.

DOI： 10.1016/j.tripleo.2011.01.023

Immunoexpression of different type stem cell marker in ameloblastoma

G. A. Sathi, R. Tamamura, T. Hidetsugu, N. Katase, M. Lefeuvre, H. Nagatsuka

ORAL ONCOLOGY 47 S54 - S54 2011.7

Effect of fluoride-substituted apatite on in vivo bone formation International journal

Miho Inoue, Andrea P. Rodriguez, Noriyuki Nagai, Hitoshi Nagatsuka, Racquel Z. Legeros, Hidetsugu Tsujigiwa, Masahisa Inoue, Etsuo Kishimoto, Shin Takagi

Journal of Biomaterials Applications 25 ( 8 ) 811 - 824 2011.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS LTD

Biological apatites are characterized by the presence of minor constituents such as magnesium (Mg), chloride (Cl), or fluoride (F) ions. These ions affect cell proliferation and osteoblastic differentiation during bone tissue formation. F-substituted apatites are being explored as potential bonegraft materials. The aim of the present study is to investigate the mechanism of bone formation induced by fluoride-substituted apatite (FAp) by analyzing the effect of FAp on the process of in vivo bone formation. FAps containing different F concentrations (l-FAp: 0.48wt%, m-FAp: 0.91wt%, h-FAp: 2.23wt%) and calcium-deficient apatite (CDA), as positive control, were implanted in rat tibia and bone formation was evaluated by histological examination, immuhistochemistry, in situ hybridization and tartrate-resistant acid phosphatase examinations. The results showed that l-FAp, m-FAp, h-FAp, and CDA biomaterials allowed migration of macrophages, attachment, proliferation, and phenotypic expression of bone cells leading to new bone formation in direct apposition to the particles. However, the l-FAp preparation allowed faster bone conduction compared to the other experimental materials. These results suggest that FAp with low F concentration may be an efficient bonegraft material for dental and medical application. © 2010 The Author(s).

DOI： 10.1177/0885328209357109

Tumor suppressor gene detection in oral tumors for new therapeutic strategy

Naoki Katase, Mathieu Lefeuvre, Mehmet Gunduz, Hidetsugu Tsujigiwa, Silvia Susana Borkosky, Gul San Ara Sathi, Ryo Tamamura, Masae Fujii, Kenji Shimizu, Hitoshi Nagatsuka

Oral Cancer: Causes, Diagnosis and Treatment 169 - 188 2011.4

Publishing type：Part of collection (book)

In head and neck, oral and maxillofacial region, there are many kinds of neoplasms, which may originate from squamous epithelium, salivary glands and tooth germ etc. Generally, neoplasm development is considered to arise due to the cumulative abnorm alities of tumor-associated genes, i.e. oncogenes and tumor suppressor genes (TSGs). As for the neoplasms in head and neck, oral and maxillofacial regions, the responsible genes specifically associated with tumorigenesis and/or invasiveness have not been well understood. Therefore the biological characteristics of these neoplasms are yet to be determined. In order to establish a new approach for the better understanding, early diagnosis and advanced therapeutic strategies, we considered application of loss of heterozygosity (LOH) analysis for detection of TSGs.LOH analysis is a highly sensitive and specific method to detect allelic deletion of specific chromosomal locations. Briefly, paired samples of genomic DNA extracted from normal and tumor tissues of the same patients are used for the study. Certain sequences on the chromosomal loci are amplified by PCR using microsatellite markers. The PCR products are loaded into polyacrylamide gel electrophoresis and visualized with various methods including silver staining and SYBR green. Then the bands from normal and tumor DNA PCR products are compared. If the band form tumor DNA are weakened or disappeared as compared to normal counterpart after normalization with a band of housekeeping gene for each of normal and tumor DNA, LOH (+) is scored. Loci with frequent LOH might harbor TSGs.Based on the idea, we have reported several candidate TSGs as a carcinogenic as well as therapeutic target, including inhibition of growth (ING) and Dickkopf (Dkk) family of genes. LOH could be observed not only in malignant tumors but also in benign tumors. In this chapter, we will show the general data of LOH analysis in head and neck squamous cell carcinoma (HNSCC) and ameloblastoma as the actual examples.HNSCC is the 6th or 7th most occurring cancer worldwide. Despite improvement in surgery, radiation and chemotherapy, often HNSCC is difficult to be controlled in the cases with lymph nodal and/or distant metastasis. Therefore, its total survival rate is yet to be improved during decades. On the other hand, ameloblastoma is the most common odontogenic tumor, which possesses strong local invasiveness, although it is a benign tumor. Ameloblastoma generally occurs in the young population, and sometimes aggressive bone resection is needed, which might result in the impaired quality of life. Therefore, establishment of new and less aggressive therapeutic approaches are needed. Application of LOH analysis and combination with statistical analysis might be a powerful tool for detection of the role of candidate TSGs as prognostic factor. © 2011 by Nova Science Publishers, Inc. All rights reserved.

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Inhibition of mammalian target of rapamycin (mTOR) signaling by Temsirolimus as a potential therapeutic strategy for esophageal cancer treatment

Munenori Takaoka, Toshio Nishikawa, Toshiaki Ohara, Yasuko Tomono, Yasuhiro Fujiwara, Yasuhiro Shirakawa, Hitoshi Nagatsuka, Takuya Fukazawa, Tomoki Yamatsuji, Xiaohong Bao, Huifang Hao, Kaori Shigemitsu, Ichiro Morita, Toshiyoshi Fujiwara, Yoshio Naomoto

CANCER RESEARCH 71 2011.4

Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium International journal

Takayuki Motoki, Yoshio Naomoto, Junji Hoshiba, Yasuhiro Shirakawa, Tomoki Yamatsuji, Junji Matsuoka, Munenori Takaoka, Yasuko Tomono, Yasuhiro Fujiwara, Hiroshi Tsuchita, Mehmet Gunduz, Hitoshi Nagatsuka, Noriaki Tanaka, Toshiyoshi Fujiwara

World Journal of Gastroenterology 17 ( 6 ) 717 - 726 2011.2

Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBLISHING GROUP INC

AIM: To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells. METHODS: We developed three kinds of artificial milk with different amounts of glutamine; Complete amino acid milk (CAM), which is based on maternal mouse milk, glutamine-depleted milk (GDM), and glutaminerich milk (GRM). GRM contains three-fold more glutamine than CAM. Eighty-seven newborn mice were divided into three groups and were fed with either of CAM, GDM, or GRM via a recently improved nipple- bottle system for seven days. After the feeding period, the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'- deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation, and for cleaved-caspase-3 as a marker of apoptosis. Moreover, IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)- 2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay, flow cytometry, and western blotting to examine the biological effect of glutamine on cell growth and apoptosis. RESULTS: During the feeding period, we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%), but not in the GRM-fed mice, with no differences in body weight gain between each group. Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice. Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining; GRM: 13.8%, CAM: 10.7%, GDM: 1.14%, GRM vs GDM: P < 0.001, CAM vs GDM: P < 0.001) and Ki-67 labeling index (the average percentage of Ki- 67-positive staining; GRM: 24.5%, CAM: 22.4% GDM: 19.4%, GRM vs GDM: P = 0.001, CAM vs GDM: P = 0.049), suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells. Glutamine deprivation further caused the deformation of the nuclear membrane and the plasma membrane, accompanied by chromatin degeneration and an absence of fat droplets from the colonic epithelia, indicating that the cells underwent apoptosis. Moreover, immunohistochemical analysis revealed the appearance of cleaved caspase-3 in colonic epithelial cells of GDM-fed mice. Finally, when IEC6 rat intestinal epithelial cells were cultured without glutamine, cell proliferation was significantly suppressed after 24 h (relative cell growth; 4 mmol/L: 100.0% ± 36.1%, 0 mmol/L: 25.3% ± 25.0%, P < 0.05), with severe cellular damage. The cells underwent apoptosis, accompanied by increased cell population in sub-G0 phase (4 mmol/L: 1.68%, 0.4 mmol/L: 1.35%, 0 mmol/L: 5.21%), where dying cells are supposed to accumulate. CONCLUSION: Glutamine is an important alimentary component for the maintenance of intestinal mucosa. Glutamine deprivation can cause instability of the intestinal epithelial alignment by increased apoptosis. © 2011 Baishideng. All rights reserved.

DOI： 10.3748/wjg.v17.i6.717

マウス骨由来間葉系幹細胞の培養におけるLifおよびb-FGFの効果

山近英樹, 松原正和, 喜多憲一郎, 武田斉子, 池谷陽子, 藤田佑貴, 松村達志, 水川展吉, 辻極秀次, 長塚仁, 飯田征二

日本口腔科学会雑誌 60 ( 1 ) 162 - 162 2011.1

Transplanted bone marrow-derived cell migration into periodontal tissues and cell differentiation

Rina Muraoka, Hidetsugu Tsujigiwa, Keisuke Nakano, Naoki Katase, Ryo Tamamura, Mihoko Tomida, Norimasa Okafuji, Hitoshi Nagatsuka, Toshiyuki Kawakami

Journal of Hard Tissue Biology 20 ( 4 ) 301 - 306 2011

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：JOURNAL HARD TISSUE BIOLOGY

We examined the transplanted bone marrow-derived cell migration into periodontal tissues. Bone marrow cells from green fluorescent protein (GFP) transgenic mice were transplanted. The immunohistochemistry (IHC) revealed that GFP-positive cells were detected in the periodontal tissues. The GFP-positive cells histopathologically differentiated into some cell types. The fluorescence IHC and TRAP staining techniques demonstrated these cells were detected as osteoclasts and macrophages. Furthermore, GFP-positive cells gathered adjacent blood vessels. The data suggest that GFP-positive bone marrow-derived cell migrate into periodontal tissues and differentiate periodontal tissue component-cells. © 2011 The Hard Tissue Biology Network Association.

DOI： 10.2485/jhtb.20.301

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Increased expression of the PRL-3 gene in human oral squamous cell carcinoma and dysplasia tissues International journal

Nur Mohammad Monsur Hassan, Jun Ichi Hamada, Takeshi Kameyama, Mitsuhiro Tada, Koji Nakagawa, Shoko Yoshida, Haruhiko Kashiwazaki, Yutaka Yamazaki, Yukiko Suzuki, Akira Sasaki, Hitoshi Nagatsuka, Nobuo Inoue, Tetsuya Moriuchi

Asian Pacific Journal of Cancer Prevention 12 ( 4 ) 947 - 951 2011

Language：English Publishing type：Research paper (scientific journal) Publisher：ASIAN PACIFIC ORGANIZATION CANCER PREVENTION

Phosphatase of regenerating liver (PRL) belongs to a class of the protein tyrosine phosphatase family, which is known so far to consist of 3 members, PRL-1, PRL-2, and PRL-3. The aim of this study was to uncover the role of PRL genes in development of oral malignancy. We analyzed expression levels of the 3 PRL genes in 50 human oral squamous cell carcinomas (OSCCs), 11 dysplasia and 12 normal mucosa tissues by a real-time RTPCR method. PRL-3 but not PRL-1 or PRL-2 expressions were significantly higher in OSCC and dysplasia than in normal mucosa tissues. Additionally, PRL-3 expressions were significantly higher in OSCC tissues harboring dominant-negative p53 or recessive p53 mutation than in those harboring wild-type p53. These results suggest that PRL-3 plays a role in oral cancer development and can be useful as a marker of pre-malignant and malignant lesion of oral mucosa.

Co-expression of BMP-2 and -7 in the tumoral epithelium of CEOT with selective BMP-7 expression in amyloid materials

Chong H. Siar, Keisuke Nakano, Phuu P. Han, Mihoko Tomida, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Kok H. Ng, Toshiyuki Kawakami

Journal of Hard Tissue Biology 20 ( 2 ) 125 - 132 2011

Language：English Publishing type：Research paper (scientific journal) Publisher：JOURNAL HARD TISSUE BIOLOGY

The calcifying epithelial odontogenic tumor (CEOT) is a benign but locally-invasive odontogenic neoplasm believed to take origin from the stratum intermedium of the developing tooth germ. Bone morphogenetic proteins (BMPs) are multifunctional signaling molecules that regulate diverse cellular processes including epithelial-mesenchymal interactions during odontogenesis. Aberrant BMP activity has been enumerated in the ameloblastoma but information about its distribution in the CEOT remains limited. The aim here was to investigate BMP expression in CEOT and to speculate on its significance. Immunolabelling for BMP-2 and BMP-7 was performed on archival tissues of six CEOT cases and the level of expression was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results disclosed that CEOT epithelium demonstrated co-expression of BMP-2 and -7 suggesting upregulation of these proteins at sites of tumor differentiation. Distribution patterns were distinct with some overlap. Their localizations were largely membranous and/or cytoplasmic. Amyloid-like materials strongly expressed BMP-7 but were nonreactive for BMP-2, implicating that these signaling proteins play differential roles in the formation of these extracellular products. Mineralized substances including Liesegang rings were mostly negative for both BMPs suggesting that calcification process is associated with repression of these molecules. Stromal endothelium and fibroblasts were stained variably positive. BMP was heterogeneously detected in the CEOT epithelium at the tumor advancing front suggesting their upregulation at active sites and downregulation in quiescent areas. Present findings suggest that BMP-2 and BMP-7 most likely play differential roles in the cellular differentiation and progression of CEOT. BMP-7 accumulation within amyloid-like protein is a novel finding. © 2011 The Hard Tissue Biology Network Association.

DOI： 10.2485/jhtb.20.125

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Transplanted bone marrow derived cells differentiated totooth, bone and connective tissues in mice

Hidetsugu Tsujigiwa, Naoki Katase, Gulsan A. Sathi, Rosario R. Buery, Yasuhisa Hirata, Midori Kubota, Keisuke Nakano, Toshiyuki Kawakami, Hitoshi Nagatsuka

Journal of Hard Tissue Biology 20 ( 2 ) 147 - 152 2011

Language：English Publishing type：Research paper (scientific journal) Publisher：JOURNAL HARD TISSUE BIOLOGY

Teeth are important structures for masticatory and phonetic purposes. Loss of teeth decreases these functions leading to impaired quality of life. Missing teeth replaced by tooth regeneration may be possible with emerging advances in stem cell biology and tissue engineering. Recent investigations have demonstrated that bone marrow derived cells (BMDC) can differentiate into cells other than blood cells. In the present study, the ability of BMDC to differentiate into tooth forming tissues was investigated using bone marrow transplantation model. BMDC from green fluorescent protein (GFP) transgenic mice were transplanted into 8-week old, C57BL/6 immunocompromised mice, which underwent 10-Gy whole body lethal irradiation. Immunohistochemical analysis revealed that bone marrow cells are positive to GFP, confirming successful bone marrow transplantation. Diffusedly GFP-positive cells were observed within the dental pulp of mouse incisor. GFP-positive cells in the dental pulp have arborescent processes resembling dendritic cell-like cells. Some odontoblast-like cells were also positive to GFP. Cells positive to GFP were observed in the cervical loop region and periodontal ligament. Langerhans cells in the oral epithelium, stromal fibroblasts, blood vessels and osteoclasts were also positive to GFP. These results indicate that BMDC have the ability to differentiate into tooth, bone and connective tissues. © 2011 The Hard Tissue Biology Network Association.

DOI： 10.2485/jhtb.20.147

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Molecular screening of anti-quorum sensing capability of Salvadora persica on Enterococcus faecalis

Afsaneh Rezaei, Glenn G. Oyong, Virgilio B. Borja, Masahisa Inoue, Tomomi Abe, Ryo Tamamura, Hitoshi Nagatsuka, Kojun Setsu, Rosario R. Buery

Journal of Hard Tissue Biology 20 ( 2 ) 115 - 124 2011

Language：English Publishing type：Research paper (scientific journal) Publisher：JOURNAL HARD TISSUE BIOLOGY

Quorum sensing (QS) refers to the phenomenon characterized by the accumulation of signaling molecules enabling a cell to sense a bacterial population triggering a coordinated response. Enterococcus faecalis is a resistant microorganism commonly found in oral infections. Salvadora persica has been traditionally used in Middle East countries to clean the teeth due to its antimicrobial activity. The study investigated the anti-quorum sensing (AQS) ability of S. persica extracts on E. faecalis. Extracts from the bark, leaves, root and shoots were tested against Chromobacterium violaceum. AQS ability was determined using differential scanning fluorimetry (DSF) and elastolytic assay to detect the level of protease and quantitative polymerase chain reaction (QPCR) to detect cytolysin (cylR1) and gelatinase (gelE) virulence factors. Preliminary disk diffusion assays revealed AQS activity by inhibiting violacein pigment production in C. violaceum without affecting its growth. Furthermore, only negligible amount of proteases was detected in DSF and elastolytic assays. CylR1 and gelE gene expression revealed no detectable signals even from the lowest possible threshold. The results indicate that S. persica has AQS ability against E. faecalis. S. persica extract can be used as alternative or in combination with other anti-microbial agents against infections caused by E. faecalis. © 2010 The Hard Tissue Biology Network Association.

DOI： 10.2485/jhtb.20.115

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The utility of three-dimensional dynamic contrast-enhanced magnetic resonance imaging in delineating vessel-rich regions: A case report of an aneurysmal bone cyst of the mandible Reviewed

Yoshinobu Yanagi, Mariko Fujita, Miki Hisatomi, Hidenobu Matsuzaki, Hironobu Konouchi, Naoki Katase, Hitoshi Nagatsuka, Jun Ichi Asaumi

Oral Radiology 26 ( 2 ) 110 - 115 2010.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Aneurysmal bone cysts (ABCs) are classified as bone-related lesions based on the 2005 World Health Organization histological classification of odontogenic tumors. Most ABCs are diagnosed using a combination of conventional radiography, computed tomography, magnetic resonance imaging (MRI), and digital subtraction angiography. ABCs should be differentiated from true cysts or other pseudocysts because their treatment is different. Additionally, unlike other cysts, ABCs pose a hemorrhagic risk in surgery; thus, preoperative evaluation of intralesional blood flow is required. Here we report a case of a mandibular ABC in a 39-year-old woman and focus on its dynamic contrast-enhanced MRI (DCE-MRI) features. On DCE-MRI, the lesion was divided into two areas according to the enhancement pattern: the bloodpooling and blood-flow areas. The series of DCE-MR images of the blood-pooling area showed marked enhancement of the margin, but no enhancement in the inner part of the cavity. Additionally, the time-signal intensity curve (TIC) demonstrated no change in the signal intensity (SI) until approximately 15 min after gadoliniumdiethylenetriamine penta-acetic acid (Gd-DTPA) administration. In contrast, the series of DCE-MR images of the blood-flow area exhibited marked enhancement in the cyst cavity in the early phase. The TIC showed a rapid increase in SI in the early phase, followed by a rapid decrease until 150 s, and finally a gradual decrease until approximately 15 min after Gd-DTPA administration. Thus, in the current patient, preoperative DCE-MRI clearly delineated the vessel-rich area within the lesion. © Japanese Society for Oral and Maxillofacial Radiology and Springer 2010.

DOI： 10.1007/s11282-010-0048-3

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Screening for DNA copy number aberrations in mucinous adenocarcinoma arising from the minor salivary gland: Two case reports International journal

Kenichiro Uchida, Atsunori Oga, Takamitsu Mano, Hitoshi Nagatsuka, Yoshiya Ueyama, Kohsuke Sasaki

Cancer Genetics and Cytogenetics 203 ( 2 ) 324 - 327 2010.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Mucinous adenocarcinoma (MAC) is a rare malignancy in the minor salivary gland. To our knowledge, genomic alterations in this tumor have not been reported previously. To identify DNA copy number aberrations, we applied comparative genomic hybridization (CGH) to four samples of MAC in minor salivary gland derived from two patients: a primary tumor and two cervical metastatic lymph nodes from one patient, and a primary tumor from the other patient. Copy number increases were commonly detected in 1q21∼q31 and 20q13, and these may play an important role in MAC carcinogenesis. Copy number increases in 1q, 12p, 12q, and 20q were commonly detected in all three samples derived from patient 1, and gain of 7p and loss of chromosome 4 were additionally detected in the two samples derived from metastatic lymph nodes. Amplifications were also detected in the chromosomal regions 8q22∼qter, 12p11∼p12, 12q11∼q21, and 20q13. Amplification of MDM2 (12q15) and of AURKA (20q13) was detected with fluorescence in situ hybridization. The DNA copy number aberrations detected in MAC in minor salivary glands were different from those reported for colorectal MAC. The present findings are novel in identifying genomic alterations of MAC arising from the minor salivary gland. © 2010 Elsevier Inc.

DOI： 10.1016/j.cancergencyto.2010.08.027

Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma International journal

Beyhan Cengiz, Esra Gunduz, Mehmet Gunduz, Levent Bekir Beder, Ryo Tamamura, Cahit Bagci, Noboru Yamanaka, Kenji Shimizu, Hitoshi Nagatsuka

International Journal of Cancer 127 ( 9 ) 2088 - 2094 2010.11

Language：English Publishing type：Research paper (scientific journal) Publisher：JOHN WILEY & SONS INC

Our previous study showed high frequency of allelic loss at chromosome 2q37 region in oral cancer. This location contains several candidate tumor suppressor genes such as PPP1R7, ILKAP, DTYMK and ING5. We previously showed 3 members of inhibitor of growth (ING) family, ING1, ING3 and ING4 as tumor suppressor gene in head and neck cancer. As ING5 shows high homology with other members of ING genes including highly conserved carboxy-terminal plant homeodomain and nuclear localization signal, we first picked up ING5 and examined it as a possible tumor suppressor in oral cancer. For this aim, mutation and mRNA expression status of ING5 in paired normal and oral squamous cell carcinoma samples were examined by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. Three missense mutations located within leucine zipper like (LZL) finger and novel conserved region (NCR) domains in ING5 protein were detected, probably abrogating its normal function. We also found 5 different alternative splicing variants of ING5. Then, we examined mRNA level of ING5 by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) analysis, which demonstrated decreased expression of ING5 mRNA in 61% of the primary tumors as compared to the matched normal samples. In conclusion, tumor-specific mutation and downregulation of ING5 mRNA suggested it as a tumor suppressor gene in oral squamous cell carcinoma. © 2010 UICC.

DOI： 10.1002/ijc.25224

Inhibitory mechanism of bone formation in ameloblastoma.

Nagatsuka H, Sathi GSA, Katase N, Tamamura R, Tsujigiwa H

Journal of Hard Tissue Biology 20 ( 1 ) 67 - 68 2010.11

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Papers - NAGATSUKA Hitoshi