Faculty Profiles - NAGATSUKA Hitoshi

Papers - NAGATSUKA Hitoshi

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Immunolocalization and distribution patterns of type IV collagen alpha chains in oral mucosal melanoma International journal

Hitoshi Nagatsuka, Rosario Santos Rivera, Mehmet Gunduz, You Jin Lee, Ryo Tamamura, Esra Gunduz, Ichiro Naito, Yoshikazu Sado, Noriyuki Nagai

Virchows Archiv 447 ( 4 ) 710 - 716 2005.10

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

The basement membrane (BM) is mainly composed of type IV collagen, which is composed of triple combinations of six distinct alpha (α) chains in a tissue-specific manner. The six collagen chain-specific antibodies (α1-α6) were used to examine the BMs of the oral epithelium (OE) and tumor clusters in oral mucosal melanoma (OMM). Eight OMM cases were examined. Results showed that the α1 and α2 chains were constantly detected at the BM of the normal OE as well as at the OE with atypical melanocytic proliferation and in invasive melanoma with nodular nests. The α1 and α2 chains were intermittently detected in in situ OMM, early invasive OMM and advanced invasive OMM with sheet-like nests. Gradual loss of α5 and α6 from the OE with atypical melanocyte through in situ OMM and early invasive OMM was observed. These findings suggest that changes in the immunolocalization and distribution patterns of type IV collagen α chains are associated with the progression of OMM. The distribution pattern of type IV collagen α chain varies depending on the architecture of the nest. © Springer-Verlag 2005.

DOI： 10.1007/s00428-005-0016-1

In vivo effect of fluoride-substituted apatite on rat bone

Miho Inoue, Hitoshi Nagatsuka, Hidetsugu Tsujigiwa, Masahisa Inoue, Racquel Z. LeGeros, Toshio Yamamoto, Noriyuki Nagai

Dental Materials Journal 24 ( 3 ) 398 - 402 2005.9

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOC DENTAL MATERIALS DEVICES

Different types of calcium phosphate compounds are commercially available for medical and dental applications as bone substitute materials. Biological apatites contain several kinds of minor elements such as carbonate (CO 3), magnesium (Mg), and fluoride (F) in enamel, dentin, and bone. It has been shown that F ion and F-substituted apatite promoted osteoblast proliferation and inhibited osteoclast cell activity. The purpose of this study was to investigate the in vivo rat tibia activity on F-substituted apatite (FAp). Apatites of unsintered calcium deficient apatite (CDA), and FAps, with low, medium, and high F concentrations, were implanted in rat tibia for 1 and 2 weeks. Implanted tissues were embedded in paraffin blocks, stained with hematoxylin-eosin and histomorphometrically observed. Results showed that low F concentration induced better and faster new bone formation in vivo compared to CDA. Therefore the results suggested that F as a minor element in bone rendered a suitable effect on bone formation in vivo.

DOI： 10.4012/dmj.24.398

A case of squamous cell carcinoma ex pleomorphic adenoma in the palate: Immunohistochemical analysis and chromosomal alteration by comparative genomic hybridization

Masamichi Ita, Kenichiro Utida, Hitoshi Nagatsuka, Toshikazu Gondo, Kohsuke Sasaki, Yoshiya Ueyama

Oral Oncology Extra 41 ( 8 ) 170 - 173 2005.9

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

Carcinoma ex pleomorphic adenoma (CXPA) is an uncommon tumor of salivary gland; moreover, histologically, squamous cell carcinoma (SCC) is exceedingly rare. This report documents a case of CXPA arising in the hard palate, which showed transformation from pleomorphic adenoma (PA) to SCC reacted to Ki-67 immunostaining. Other immunohistochemical stains also demonstrated different immunoreactivities between PA cells and SCC cells. Comparative genomic hybridization identified a chromosomal imbalance. Gain regions of the PA were 8q11-22 and 8q24 and the loss region was 13q32-34 in PA; additionally, in SCC, regions characterized by increased DNA copy number were 8p, 8q and 12q12-15. © 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ooe.2005.04.004

Analysis of amelogenin gene (AMGX, AMGY) expression in ameloblastoma International journal

Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Pwint Han Phuu, Mehmet Gunduz, Huat Siar Chong, Shinichiro Oida, Noriyuki Nagai

Oral Oncology 41 ( 8 ) 843 - 850 2005.9

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

Although the amelogenin gene is expressed in ameloblastoma, the precise expression pattern of X and Y amelogenin genes (AMGX, AMGY) in this tumor has not yet identified. In this study, we analyzed amelogenin gene expression in 19 samples (9 male, 10 female) of oral ameloblastomas by RT-PCR and detect the chromosomal origin of amelogenin mRNA by restriction enzyme digestion of the RT-PCR product. All tumor samples expressed amelogenin mRNA. We could detect increased level of AMGY expression in all male samples, higher than that of AMEX. It is an interesting finding as in normal male tooth development, the expression of AMGY is very much lower than that of AMGX. We postulate that epigenetic change of sex chromosomes may have some correlations with tumorigenesis of ameloblastoma. We also discuss the other possible mechanisms and points for future studies on this change in expression pattern. © 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2005.04.005

Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas International journal

Mehmet Gunduz, Hitoshi Nagatsuka, Kadir Demircan, Esra Gunduz, Beyhan Cengiz, Mamoru Ouchida, Hidetsugu Tsujigiwa, Eiki Yamachika, Kunihiro Fukushima, Levent Beder, Satoshi Hirohata, Yoshifumi Ninomiya, Kazunori Nishizaki, Kenji Shimizu, Noriyuki Nagai

Gene 356 ( 1-2 ) 109 - 117 2005.8

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

We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer. Progress in human genome sequencing provided additional information of the new members of the ING family genes. ING4 is localized to chromosome 12p13.31 region and harbors the PHD domain highly homologous among ING family proteins. We analyzed loss of heterozygosity at 12p12-13 region in 50 head and neck squamous cell carcinomas by using six highly polymorphic microsatellite markers and found allelic loss in 66% (33/50) of the informative cases. To clarify the role of ING4 in head and neck carcinogenesis, we first checked mutation status in tumor samples. As mutation of the ING4 gene was not found in head and neck cancers, we examined the mRNA expression level. Quantitative real-time RT-PCR analysis demonstrated decreased expression of ING4 mRNA in 76% of primary tumors as compared with that of matched normal samples. Since p53 dependent pathways of other ING family members have been shown, we examined p53 mutation status and compared with ING4 mRNA expression in tumor samples. However, no such direct relationship has been detected. In conclusion, frequent deletion and decreased mRNA expression of ING4 suggested it as a class two tumor suppressor gene and may play an important role in head and neck cancer. © 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.gene.2005.02.014

The engraftment of transplanted bone marrow-derived cells into the olfactory epithelium International journal

Hidetsugu Tsujigiwa, Kazunori Nishizaki, Takanori Teshima, Yasushi Takeda, Junko Yoshinobu, Ayako Takeuchi, Yorihisa Orita, Yuji Sugata, Hitoshi Nagatsuka, Noriyuki Nagai

Brain Research 1052 ( 1 ) 10 - 15 2005.8

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

To investigate whether bone marrow cells migrate and are engrafted into the olfactory epithelium and differentiate into olfactory neurons, bone marrow cells of green fluorescence protein (GFP) mice were transplanted into lethally irradiated recipient mice. Immunohistochemical staining was performed to evaluate the engraftment of donor bone marrow cells into the olfactory epithelium. Immunostaining for GFP was found initially in the olfactory epithelium 2 weeks after bone marrow reconstruction. The percentage of GFP positive cells increased up to 12 months after bone marrow reconstruction. Double staining for GFP and olfactory marker protein showed that a population of the GFP-positive cells had characteristics of olfactory neurons. These results demonstrate that bone marrow cells can be engrafted in the olfactory epithelium and then differentiate into olfactory neuron cells. © 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2005.05.061

Erdheim-Chester disease in a child presenting with multiple jaw lesions International journal

Hitoshi Nagatsuka, Phuu Pwint Han, Koji Taguchi, Hidetsugu Tsujigiwa, Mehmet Gunduz, Joji Fukunaga, Toshio Sugahara, Junichi Asaumi, Noriyuki Nagai

Journal of Oral Pathology and Medicine 34 ( 7 ) 420 - 422 2005.8

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

BACKGROUND: Erdheim-Chester disease is a rare histiocytic disease entity related to juvenile xanthogranuloma. It is a systemic condition, usually occurs in adult, characterized by infiltration of foamy histiocytes within the bone and soft tissues. METHODS AND RESULTS: We report a case of 13-year-old female patient who first presented with multiple osteolytic lesions of the jaws followed by bilateral symmetrical bone lesions affecting the lower extremities, as well as brain and abdominal involvement. Histological findings of the jaw lesions showed lipid-storing CD68 (+), CDIa (-) histiocytes with Touton type giant cells. CONCLUSION: To the best of our knowledge, this is the first case of Erdheim-Chester disease with jaw bone lesions occurring as initial presenting symptom. © Blackwell Munksgaard 2005 · All rights reserved.

DOI： 10.1111/j.1600-0714.2005.00320.x

Expression of Wnt5a gene in mouse embryonic orofacial development.

J Xiao, EX Zhu, N Nagai, H Nagatsuka, CG Li

DEVELOPMENTAL BIOLOGY 283 ( 2 ) 612 - 612 2005.7

Fine deletional mapping of chromosome 4q22-35 region in oral cancer. International journal

Yasuo Shinno, Esra Gunduz, Mehmet Gunduz, Hitoshi Nagatsuka, Hidetsugu Tsujigiwa, Beyhan Cengiz, You Jin Lee, Ryo Tamamura, Mamoru Ouchida, Kunihiro Fukushima, Kenji Shimizu, Noriyuki Nagai

International journal of molecular medicine 16 ( 1 ) 93 - 98 2005.7

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

We analyzed the loss of heterozygosity of the long arm of chromosome 4 in 40 oral cancers, using 16 microsatellite markers based on data from the human genome sequence, and defined the deletional mapping of the region with putative tumor suppressor genes. Our data revealed two distinct commonly deleted regions around the markers, D4S2623 and D4S1644, with an allelic deletion of 44 and 39%, respectively. Additional mapping and use of the markers near one of these hot spots narrowed down the minimally deleted region about 1.5 Mbp around the marker, D4S2623. Caspase 6 is localized 280 kb from the marker, D4S2623. Fine mapping of this region with possible tumor suppressor gene suggests caspase 6 as a putative tumor suppressor gene. Further molecular analysis of caspase 6 should be performed to clarify its role in oral carcinogenesis.

DOI： 10.3892/ijmm.16.1.93

Effects of histone deacetylase inhibitor FR901228 on the expression level of telomerase reverse transcriptase in oral cancer International journal

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

Cancer Chemotherapy and Pharmacology 56 ( 1 ) 22 - 28 2005.7

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

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 the histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription in oral cancer cell lines were analyzed by RT-PCR. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, and even SAS and KB cells expressed high levels of hTERT. Moreover, cotreatment 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, and depended on the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute to FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved transcription factors other than c-myc, in addition to inhibition of histone deacetylation. © Springer-Verlag 2005.

DOI： 10.1007/s00280-004-0976-x

Emergence of nuclear heparanase induces differentiation of human mammary cancer cells International journal

Tetsuji Nobuhisa, Yoshio Naomoto, Munenori Takaoka, Yoko Tabuchi, Keizou Ookawa, Dai Kitamoto, Esra Gunduz, Mehmet Gunduz, Hitoshi Nagatsuka, Minoru Haisa, Junji Matsuoka, Motowo Nakajima, Noriaki Tanaka

Biochemical and Biophysical Research Communications 331 ( 1 ) 175 - 180 2005.5

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

The study of epithelial differentiation touches upon many modern aspects of biology. The epithelium is in constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. Recently we reported that heparanase is expressed in nucleus as well as in the cytoplasm and that nuclear heparanase seems to be related to cell differentiation. In this study, we investigated the role of nuclear heparanase in differentiation by transducing human mammary epithelial cancer cells with heparanase which was delivered specifically into nucleus. We observed that expression of nuclear heparanase allowed the cells to differentiate with the appearance of lipid droplets. This finding supports the idea that heparanase plays a novel role in epithelial cell differentiation apart from its known enzymatic function. © 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2005.03.129

Regeneration of rat auditory ossicles using recombinant human BMP-2/collagen composites International journal

Yasushi Takeda, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Noriyuki Nagai, Junko Yoshinobu, Mitsuhiro Okano, Kunihiro Fukushima, Ayako Takeuchi, Tadashi Yoshino, Kazunori Nishizaki

Journal of Biomedical Materials Research - Part A 73 ( 2 ) 133 - 141 2005.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

Tympanoplasty operations to improve hearing impairment require a wide middle ear cavity and reconstruction of columellar formations. There is no specific material for use in the reconstruction of columellar formations. Tissue response to BMP has been employed as regenerative material. To our knowledge, however, there are no reports of the reconstruction of columellar formations using recombinant human bone morphogenetic protein-2/bovine collagen composites in the middle ear. The purpose of this study is to investigate whether recombinant human bone morphogenetic protein-2/bovine collagen composites (rhBMP-2 composites) are appropriate for use as regenerative material for tympanoplasty. In the form of pellets, rhBMP-2 composites were implanted as columellae into the tympanic cavity. At 2,4,6,8, and 12 weeks after surgery, the middle ear of the animals (n = 4 at each week) was stained with hematoxylineosin for light microscopic observation. All composites were in the process of ossification or had ossified according to their developmental stages and were covered with a single layer of squamous or cuboidal epithelium. The new bone formed in these composites was persistently stable and displayed some columellar conditions assessed by histological examination. This study led to the conclusion that rhBMP-2 composites make excellent regenerative material for auditory ossicles. © 2005 Wiley Periodicals, Inc.

DOI： 10.1002/jbm.a.30257

Regeneration of rat auditory ossicles using recombinant human BMP-2/collagen composites. International journal

Yasushi Takeda, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Noriyuki Nagai, Junko Yoshinobu, Mitsuhiro Okano, Kunihiro Fukushima, Ayako Takeuchi, Tadashi Yoshino, Kazunori Nishizaki

Journal of biomedical materials research. Part A 73 ( 2 ) 133 - 41 2005.5

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

Tympanoplasty operations to improve hearing impairment require a wide middle ear cavity and reconstruction of columellar formations. There is no specific material for use in the reconstruction of columellar formations. Tissue response to BMP has been employed as regenerative material. To our knowledge, however, there are no reports of the reconstruction of columellar formations using recombinant human bone morphogenetic protein-2/bovine collagen composites in the middle ear. The purpose of this study is to investigate whether recombinant human bone morphogenetic protein-2/bovine collagen composites (rhBMP-2 composites) are appropriate for use as regenerative material for tympanoplasty. In the form of pellets, rhBMP-2 composites were implanted as columellae into the tympanic cavity. At 2, 4, 6, 8, and 12 weeks after surgery, the middle ear of the animals (n = 4 at each week) was stained with hematoxylin-eosin for light microscopic observation. All composites were in the process of ossification or had ossified according to their developmental stages and were covered with a single layer of squamous or cuboidal epithelium. The new bone formed in these composites was persistently stable and displayed some columellar conditions assessed by histological examination. This study led to the conclusion that rhBMP-2 composites make excellent regenerative material for auditory ossicles.

Heparanase gene and protein expression in ameloblastoma: Possible role in local invasion of tumor cells International journal

Hitoshi Nagatsuka, Phuu Pwint Han, Hidetsugu Tsujigiwa, Chong Huat Siar, Mehmet Gunduz, Toshio Sugahara, Akira Sasaki, Motowo Nakajima, Yoshio Naomoto, Noriyuki Nagai

Oral Oncology 41 ( 5 ) 542 - 548 2005.5

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

Ameloblastoma is the most common odontogenic neoplasm, particularized by its local invasiveness. Heparanase is the endo-glucuronidase enzyme that specifically cleaves heparan sulfate, the important modulator of extracellular matrix, and related to invasion of tumor cells. In this study, we addressed to show the gene expression and localization of heparanase in ameloblastoma. Immunohistochemistry and in situ hybridization of heparanase were carried out in 23 ameloblastomas. Strong expression of heparanase at both mRNA and protein levels was detected in all ameloblastomas studied. Small tumor nests and budding epithelial branches showed stronger staining pattern and the stromal tissues at the immediate vicinity of the tumor nests with strong heparanase expression were loose and edematous. Cystic areas and squamous metaplastic areas of the tumor showed intense staining with heparanase antibody proposing the implication of heparanase in these processes. These results suggest the possible contribution of heparanase in the local invasiveness and secondary morphologic changes of ameloblastoma. © 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2005.01.004

Heparanase expression correlates with malignant potential in human colon cancer

T. Nobuhisa, Y. Naomoto, T. Ohkawa, M. Takaoka, R. Ono, T. Murata, M. Gunduz, Y. Shirakawa, T. Yamatsuji, M. Haisa, J. Matsuoka, H. Tsujigiwa, H. Nagatsuka, M. Nakajima, N. Tanaka

Journal of Cancer Research and Clinical Oncology 131 ( 4 ) 229 - 237 2005.4

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

Purpose: Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer. Methods: The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis. Results: Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P = 0.0481), higher Dukes stage (P = 0.0411), higher vascular infiltration (P = 0.0146), and higher lymph vessel infiltration (P = 0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P = 0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P = 0001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P = 0.017) and survival (P = 0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P = 0.003). Conclusions: Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer. © Springer-Verlag 2004.

DOI： 10.1007/s00432-004-0644-x

Basaloid squamous cell carcinoma of the tongue in a Japanese male patient: A case report

Yasuo Shinno, Hitoshi Nagatsuka, Chong Huat Siar, Hidetsugu Tsujigiwa, Ryo Tamamura, Mehmet Gunduz, You Jin Lee, Akira Sasaki, Noriyuki Nagai

Oral Oncology Extra 41 ( 4 ) 65 - 69 2005.4

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

Basaloid squamous cell carcinoma (BSCC) is a virulent variant of squamous cell carcinoma. We present a case of BSCC affecting the tongue of a 57-year old Japanese male. Microscopically, BSCC was diagnosed on the basis of presence of basaloid carcinomatous component in intimate contact with smaller areas of conventional squamous cell carcinoma. Immunohistochemistry demonstrated positive staining of tumor epithelium for pan-keratin marker MNF116, CK8, CK17, CK19 and CEA, weak immunoreactivity for CK14, EMA and S-100 protein and negative staining for CK1 and alpha-smooth muscle actin. The principal differential diagnoses considered were adenoid cystic carcinoma, adenosquamous carcinoma and polymorphous low-grade adenocarcinoma. © 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ooe.2004.12.002

Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas

Hitoshi Nagatsuka, Kazuteru Hibi, Mehmet Gunduz, Hidetsugu Tsujigiwa, Ryou Tamamura, Toshio Sugahara, Akira Sasaki, Noriyuki Nagai

Journal of Oral Pathology and Medicine 34 ( 2 ) 70 - 76 2005.2

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

BACKGROUND: Intratumoral blood vessels are known to play an important role in cancer growth and metastasis. The discrepancy in previous reports using various endothelial markers individually suggested us to investigate both normal and various tumor areas with a wide panel of vascular markers. METHODS: Here, we used a panel of three antibodies (CD31, CD34, and endoglin) as blood vessel markers to investigate the distribution and properties of blood vessels in normal oral tissues and squamous cell carcinomas. RESULTS: Many microvessels with strong remodeling activity as well as undifferentiated tumoral vascular endothelial cells and immature endothelial cells were present in the cancer cell nest and marginal area of cancer infiltration. Our results showed different vascular distribution patterns using various immunostaining markers in normal and tumoral tissues. CONCLUSION: Vascular distribution and properties of endothelial cells appear to be closely associated with metastasis.

DOI： 10.1111/j.1600-0714.2004.00227.x

Comparative Study of Two Different Structures of Collagen Scaffold for Bone Formation

Andrea Paola Rodriguez, Hitoshi Nagatsuka, Bingzhen Huang, Kan Rui, Mika Okauchi, Noriyuki Nagai, Yoshie Kagawa, Missana Liliana, Shinichiro Oida

Journal of Hard Tissue Biology 14 ( 2 ) 210 - 211 2005.1

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

It has not been determined the best scaffold-structure for bone engineering. Because of this, we compared Honeycomb porous structure (HPS) and Interconnected porous structure (IPS) with or without KUSA/ A1 cells implanted in mice. The transplants were subjected to radiological and histological examinations after 1,2,4 and 8 weeks of implantation. KUSA/A1 cells alone showed small islands of new bone. Both scaffolds alone did not reveal any bone induction. KUSA/A1-HPS presented the scaffold partially filled with new bone. In contrast, KUSA/A1-IPS showed the whole scaffold filled with new bone. Our results indicated that cotton structure plays an important role in carrying the cells giving the precise size, shape and comfortable environment. © 2005, THE SOCIETY FOR HARD TISSUE REGENERATIVE BIOLOGY. All rights reserved.

DOI： 10.2485/jhtb.14.210

Oral Potentially Malignant Epithelial Lesions and Associated Risk in the Contralateral Mucosa

Chong Huat Siar, Michelle Clare Mah, Preveen Preet Gill, Hitoshi Nagatsuka, Hidetsugu Tsujigiwa, Mehmet Gunduz, Noriyuki Nagai, Kok Han Ng

Journal of Hard Tissue Biology 14 ( 2 ) 183 - 184 2005.1

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

Statement of the problem: Early detection of potentially malignant epithelial lesions (PMELs) is aimed at improving survival rates as carcinogenesis is a multistep process and prevention is possible if these lesions are detected at an early and reversible stage of the disease. Objectives: This prospective clinical study was designed to determine the prevalence of bilateral mirror-image PMELs in patients presenting with unilateral PMELs clinically. A modified brush biopsy technique was employed to detect early cytological epithelial changes if any, in the contralateral normal oral mucosa. Materials and method: Sixty individuals presenting with unilateral PMELs were selected for this study. These comprised 30 (50%) Indians, 24 (40%) Chinese, 5 (8.3%) Malays and one (1.7%) Nepalese. All selected cases had histopathological confirmation of their primary existing lesion(s) as inclusion criteria in this study. Cases which had subsequently presented with a lesion contralateral to the existing lesion were also subjected to scalpel incisional biopsy on this second lesion. The remaining cases which presented with a unilateral PMEL at the time of this clinical study were subjected to a brush biopsy on the clinically normal looking mucosa contralateral to the existing lesion. Results: A total of 70 lesions were detected in 60 patients. The most common PMEL found was oral lichen planus. Of the 60 patients studied, 26 exhibited mirror-image lesions either metachronously (73%) or synchronously (27%). The remaining cases that had undergone brush biopsy on the contralateral side to the existing PMEL yielded normal histological results. Conclusions: Present findings demonstrated that patients presenting with PMELs in the upper aerodigestive tract are at greater risk of developing a second lesion most probably on the contralateral mirror-image site. However the efficacy of brush biopsy method in detecting epithelial changes remained inconclusive due to the small sample examined. © 2005, THE SOCIETY FOR HARD TISSUE REGENERATIVE BIOLOGY. All rights reserved.

DOI： 10.2485/jhtb.14.183

Immunolocalization of Endothelial Markers in Oral Squamous Cell Carcinoma and Their Relationship with Metastasis

Kan Rui, Hitoshi Nagatsuka, Kazuteru Hibi, Noriyuki Nagai, Chong Huat Siar, Georgina Palmario, Susan Subido Banzon, Simon M.San Miguel

Journal of Hard Tissue Biology 14 ( 2 ) 132 - 133 2005.1

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

Intratumoral blood vessels are known to play an important role in cancer growth and metastasis. The discrepancy in previous reports using various endothelial markers individually suggested us to investigate both normal and various tumor areas with a wide panel of vascular markers. We used a panel of three antibodies (CD31, CD34 and endoglin) as blood vessel markers to investigate the distribution and properties of blood vessels in normal oral tissues and squamous cell carcinomas. Many microvessels with strong remodeling activity as well as undifferentiated tumoral vascular endothelial cells and immature endothelial cells were present in the cancer cell nest and marginal area of cancer infiltration. Our results showed different vascular distribution patterns using various immunostaining markers in normal and tumoral tissues. Vascular distribution and properties of endothelial cells appear to be closely associated with metastasis. © 2005, THE SOCIETY FOR HARD TISSUE REGENERATIVE BIOLOGY. All rights reserved.

DOI： 10.2485/jhtb.14.132

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