Faculty Profiles - TANUMA Junichi

Papers - TANUMA Junichi

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Hypomineralized Enamel of Dens Invaginatus: Its distinct images and pathogenesis of the Type III invagination using micro-focusing computed tomography Reviewed

Maiko Yamada, Motohiko Nagayama, Akitoshi Katsumata, Satoshi Kawano, Keika Gen, Michiko Ehara, Juna Nakao, Jun-ichi Tanuma, Takakazu Yoshida

JOURNAL OF HARD TISSUE BIOLOGY 23 ( 4 ) 449 - 453 2014.10

Pthlh, a promising cancer modifier gene in rat tongue carcinogenesis. Reviewed International journal

Hirohiko Suwa, Masato Hirano, Kouji Kawarada, Motohiko Nagayama, Michiko Ehara, Tomonari Muraki, Hayase Shisa, Aiko Sugiyama, Masahiro Sugimoto, Hiroshi Hiai, Motoo Kitano, Jun-Ichi Tanuma

Oncology reports 31 ( 1 ) 3 - 12 2014.1

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

Susceptibly to the induction of rat tongue cancer (TC) by oral 4-nitroquinoline 1-oxide (4NQO) exposure is a polygenic trait. Among several quantitative trait loci identified by crosses between TC-susceptible Dark Agouti (DA) rats and TC-resistant Wistar-Furth (WF) rats, we focused on tongue cancer susceptibility locus (Tcas3) of chromosome 4. We examined tongue carcinogenesis in the reciprocal congenic strains DA.WF-Tcas3 and WF.DA-Tcas3 and in their parental strains. The Tcas3DA allele, and not the Tcas3WF allele, significantly favored tumor latency, incidence and TC number/size. In genomic DNA of TCs induced in (DA x WF) F1 rats, the resistant Tcas3WF allele was frequently and selectively lost, particularly in larger tumors. Thus, we searched the possible candidate genes in the Tcas3 region using microarray analysis of TCs in F1 rats and revealed significant upregulation of 2 cancer-related genes, parathyroid hormone-like hormone (Pthlh) and Kras2. The relevance of the WF allele of Pthlh as a cancer modifier was indicated by 3 single nucleotide polymorphisms specific to this strain. In contrast, no consistent strain-specific variations were found in Kras2. Moreover, the plasma Ca2+ level was consistently higher in DA rats when compared to the level in WF rats bearing TCs; moreover, the Pthlh-mRNA expression level was >30-fold higher in TCs when compared to this level in the normal tongue mucosa. Immunostaining experiments showed strong PTHrP protein expression in TCs of DA rats, and the signal was intensified in larger TCs. Kras2 was also upregulated in TCs, but to a lesser degree than PTHrP. Thus, Pthlh is a promising candidate modifier gene in the development and progression of rat TCs.

DOI： 10.3892/or.2013.2859

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Intraneural perineurioma arising in the lateral border of the tongue. Reviewed International journal

Masato Hirano, Tomonori Muraki, Motohiko Nagayama, Michiko Ehara, Kouji Kawarada, Hirohiko Suwa, Motoo Kitano, Jun-ichi Tanuma

Pathology international 63 ( 12 ) 619 - 21 2013.12

Basaloid squamous cell carcinoma of the tongue: a case report. Reviewed

Matsui R, Tanuma J, Kwashima K, Miyahara M, Semba I, Sugihara K

Oral Medicine & Oral Pathology 15 117 - 122 2011.2

FGFR4 polymorphism, TP53 mutation, and their combinations are prognostic factors for oral squamous cell carcinoma. Reviewed International journal

Jun-Ichi Tanuma, Toshiyuki Izumo, Masato Hirano, Yoshitaka Oyazato, Fumiya Hori, Eri Umemura, Hayase Shisa, Hiroshi Hiai, Motoo Kitano

Oncology reports 23 ( 3 ) 739 - 44 2010.3

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

The genotype of the fibroblast growth factor receptor 4 (FGFR4) gene and TP53 mutation have been reported as prognostic factors for cancers of the head and neck, bladder, breast and colon. To determine whether they are applicable for oral squamous cell carcinoma (OSCC), we investigated these two genes in OSCC samples from 150 patients who had undergone radical surgery and in 100 cancer-free individuals. In OSCC, the FGFR4 Gly388Arg polymorphism and the presence or absence of mutation in TP53 did not show a significant association with the clinicopathological features of the tumors at surgery. However, the FGFR4 Arg388 allele, as well as mutations in TP53, was found to be closely associated with poor prognosis. Moreover, these two parameters synergistically affected the survival of OSCC patients. During 60 months of observation after radical surgery, a majority of patients with homozygous Arg388 FGFR4 plus mutated TP53 died of cancer, whereas >90% patients carrying homozygous Gly388 FGFR4 plus wild-type TP53 survived. Therefore, the FGFR4 Gly388Arg polymorphism and TP53 mutations, as well as their combinations, are excellent predictors of the prognosis for OSCC patients.

DOI： 10.3892/or-00000692

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Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Reviewed International journal

Mayumi Miyahara, Jun-Ichi Tanuma, Kazumasa Sugihara, Ichiro Semba

Cancer 110 ( 6 ) 1287 - 94 2007.9

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

BACKGROUND: Lymphatic vessel density (LVD) and microvessel density (MVD) are important parameters for assessing the malignant potential of tumors and patient survival. In this report, the authors defined LVD as the density of D2-40-positive lymphatic vessels and MVD as the density of CD105-positive microvessels per unit area of tissue. It was reported previously that vascular endothelial growth factor C (VEGF-C) is a major modulator of LVD and MVD. The objectives of this study were to clarify the clinical and prognostic significance of both LVD and MVD in oral squamous cell carcinoma (OSCC) and to elucidate the lymphangiogenic and angiogenic activities of VEGF-C in cancer tissues. METHODS: In total, 110 OSCC tissue samples were evaluated for LVD, MVD, and expression of VEGF-C using immunohistochemistry. Correlations among these parameters and clinicopathologic factors were examined. RESULTS: LVD was significantly higher in tumors that had very high expression of VEGF-C compared with tumors that had no/weak expression of VEGF-C. LVD correlated well with lymph node metastasis (P < .001). MVD was correlated significantly with positive lymph node metastasis (P < .001) but not with VEGF-C expression. In contrast, high expression of VEGF-C was correlated significantly with advanced tumor status (P = .041). Survival rates were lower in patients who had higher LVD (P < .001), higher MVD (P = .0028), and strong VEGF-C expression (P = .048). CONCLUSIONS: Lymphangiogenesis predominantly influenced metastasis-free survival. The current results suggested that LVD is a more useful tool than MVD and VEGF-C for deciding on therapeutic strategies in patients with OSCC.

DOI： 10.1002/cncr.22900

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DRH strains: genetic resistance to chemical hepatocarcinogenesis. Reviewed

Hiai H, Liu H, Omi N, Tanuma J, Higashi K

Trends in Cancer Research 2 127 - 134 2007.4

Pleomorphic adenoma presenting low T-2 signal-intensity on magnetic resonance imaging Reviewed

H. Indo, S. Suenaga, E. Nozoe, N. Nakamura, J. Tanuma, I. Semba, H. J. Majima

DENTOMAXILLOFACIAL RADIOLOGY 35 ( 5 ) 380 - 382 2006.9

Selective loss of resistant alleles at p15INK4B and p16INK4A genes in chemically-induced rat tongue cancers. Reviewed International journal

Kotaro Ogawa, Jun-ichi Tanuma, Masato Hirano, Yoshikazu Hirayama, Ichiro Semba, Hayase Shisa, Motoo Kitano

Oral oncology 42 ( 7 ) 710 - 7 2006.8

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

We previously reported that susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer in Dark-Agouti (DA) and Wistar/Furth (WF) rats was determined by a number of quantitative trait loci. In this article, we further scrutinized one of the quantitative trait loci at a suggestive level on rat chromosome 5. Analyzing a DNA panel of 130 (DAxWF) F2 rats treated with 4NQO showed a quantitative trait loci, containing p15INK4B and p16INK4A. To study the possible relevance of these genes in the development of tongue cancer, we examined 45 4NQO-induced tongue cancers in 100 (DAxWF) F1 rats for loss of heterozygosity. The incidence of loss of heterozygosity at p15INK4B and p16INK4A genes in large advanced tongue cancers was 37.8% and 40.0%, respectively, and the WF allele was selectively lost. Accumulation of loss of heterozygosity and methylation of the promoter regions in the tumour suppressor genes in advanced tumours suggests that they may play a role in tongue cancer progression.

DOI： 10.1016/j.oraloncology.2005.11.011

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Immunohistological evaluation of Ki-67, p63, CK 19 and pS3 expression in oral epithelial dysplasias Reviewed

T. Takeda, K. Sugihara, Y. Hirayama, M. Hirano, J-I Tanuma, I. Semba

JOURNAL OF ORAL PATHOLOGY & MEDICINE 35 ( 6 ) 369 - 375 2006.7

Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias Reviewed

T. Takeda, K. Sugihara, Y. Hirayama, M. Hirano, J. I. Tanuma, I. Semba

Journal of Oral Pathology and Medicine 35 ( 6 ) 369 - 375 2006.7

A speed congenic rat strain bearing the tongue cancer susceptibility locus Tscc1 from Dark-Agouti rats. Reviewed International journal

Masato Hirano, Jun-Ichi Tanuma, Yoshikazu Hirayama, Masanobu Ohyama, Ichiro Semba, Shinya Wakusawa, Hayase Shisa, Hiroshi Hiai, Motoo Kitano

Cancer letters 231 ( 2 ) 185 - 91 2006.1

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

We previously reported that Dark-Agouti (DA) rats are highly susceptible to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer (TC), whereas Wistar/Furth (WF) rats are barely susceptible. Linkage analysis of reciprocal (DAxWF)F2 rats demonstrated five quantitative trait loci, Tongue squamous cell carcinoma 1-5 (Tscc1-5) determining the size and number of the TCs. The major susceptibility locus Tscc1 is mapped on rat chromosome 19. In the present study, we used a marker-assisted speed congenic procedure to construct WF.DA-Tscc1 (WF-T1D) rats, i.e. WF rats carrying a DA-derived Tscc1 chromosomal segment, and evaluated the effect of a single Tscc1 on 4NQO-induced tongue carcinogenesis. In WF-T1D rats, the incidence, number and size of 4NQO-induced TCs were significantly higher than those in WF rats, indicating that the introgressed segment contains one of the susceptibility loci for 4NQO-induced TCs from DA rats. Detection of a single nucleotide polymorphism in NQO1, one of the Tscc1 candidate genes, enabled us to map NQO1 in the Tscc1 segment between D19Wox8 and D19Wox7 on chromosome 19. Possible relevance of NQO1 polymorphism to TC susceptibility is discussed.

DOI： 10.1016/j.canlet.2005.01.043

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FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer. Reviewed International journal

Monica Spinola, Vera Piera Leoni, Jun-Ichi Tanuma, Angela Pettinicchio, Milo Frattini, Stefano Signoroni, Roberto Agresti, Riccardo Giovanazzi, Silvana Pilotti, Lucio Bertario, Fernando Ravagnani, Tommaso A Dragani

Oncology reports 14 ( 2 ) 415 - 9 2005.8

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

A functional Gly388Arg variation in the FGFR4 gene has been reported to be associated with breast and colorectal cancer prognostic parameters. To further examine the functional role of this genetic polymorphism at the population level, we assessed the presence of the Arg388 allele in 142 breast carcinoma patients, 179 colorectal carcinoma patients and 220 general population controls with respect to an association with cancer prognosis and/or risk. No significant association with cancer risk, survival or any other prognostic parameters was observed in either breast or colorectal cancer. A pooled analysis of the present and published data on nodal status by FGFR4 genotypes revealed no association in either breast cancer [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.7-1.4; 702 subjects] or colorectal cancer (OR, 1.4; 95% CI, 0.6-3.4; 260 cases). Thus, the FGFR4 polymorphism may not be relevant in predicting nodal involvement of breast cancer or colon cancer patients.

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Genetic predisposition to 4NQO-induced tongue carcinogenesis in the rat Reviewed

J Tanuma, M Hirano, Y Hirayama, Semba, I, K Ogawa, H Shisa, H Hiai, M Kitano

MEDICAL PRINCIPLES AND PRACTICE 14 ( 5 ) 297 - 305 2005

Analysis of human cytomegalovirus UL144 variability in low-passage clinical isolates in Japan. Reviewed International journal

Tsugiya Murayama, Masataka Takegoshi, Junichi Tanuma, Yoshito Eizuru

Intervirology 48 ( 2-3 ) 201 - 6 2005

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

To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor-like receptor gene and the UL55 envelope glycoprotein B gene from 42 patients with congenital human cytomegalovirus (HCMV) infection or other diseases were sequenced. Of the 42 patients, 16 (38%) had UL144 group 1 [group 1A, 15 of 16 (94%); group 1B, 1 of 16 (6%); group 1C, 0 of 16 (0%)], 5 patients (12%) had UL144 group 2, and 21 patients (50%) had UL144 group 3. Although group 1C was not found in Japan strains (0%), it was found in USA strains (22%). Other HCMV polymorphisms should be further evaluated for their potential relevance to neonatal infection, and acquired immunodeficiency syndrome-associated HCMV diseases.

DOI： 10.1159/000081749

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Genetic predisposition to 4NQO-induced tongue carcinogenesis in the rat Reviewed

J Tanuma, M Hirano, Y Hirayama, Semba, I, K Ogawa, H Shisa, H Hiai, M Kitano

MEDICAL PRINCIPLES AND PRACTICE 14 ( 5 ) 297 - 305 2005

Expressions of junB and c-fos are enhanced in 4-nitroquinoline 1-oxide-induced rat tongue cancers Reviewed

M Ohyama, Y Hirayama, J Tanuma, M Hirano, Semba, I, H Shisa, H Hiai, K Sugihara, M Kitano

PATHOLOGY INTERNATIONAL 54 ( 1 ) 35 - 40 2004.1

Expressions of junB and c-fos are enhanced in 4-nitroquinoline 1-oxide-induced rat tongue cancers. Reviewed International journal

Masanobu Ohyama, Yoshikazu Hirayama, Jun-ichi Tanuma, Masato Hirano, Ichiro Semba, Hayase Shisa, Hiroshi Hiai, Kazumasa Sugihara, Motoo Kitano

Pathology international 54 ( 1 ) 35 - 40 2004.1

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

Activator protein-1 (AP-1) is a transcription factor activated in many tumors. Using 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue cancers (TC), the present study investigated the expression levels of genes that encode the components of AP-1, the jun gene family (c-jun, junB and junD) and the fos gene family (c-fos, fra-1, fra-2 and fosB). Expression levels of junB and c-fos mRNAs in TC were significantly elevated compared with those in epithelial tissue of control rat tongue, although only c-fos mRNA levels tended to be elevated in dysplastic tongue epithelium. Histologically, all 4NQO-induced rat TC were well-differentiated squamous cell carcinomas. Immunostaining for JunB and c-Fos proteins was positive in the nuclei of tumor cells of all TC. It is noteworthy that JunB was negative, but c-Fos was positive in the dysplastic tongue epithelium of the 4NQO-treated rats. Immunostaining for both proteins was negative in tongue mucosal epithelium of control rats. There were no mutations in the coding regions of either junB or c-fos in all the TC examined. These results suggest the possibility that the expressions of junB and c-fos were enhanced stepwise in 4NQO-induced carcinogenesis of rat tongue, and that the coexpression of JunB and c-Fos might play an important role in the establishment of TC.

DOI： 10.1046/j.1440-1827.2003.01587.x

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SCCA2-like Serpins Mediate Genetic Predisposition to Skin Tumors. Reviewed

Gariboldi M, Peissel B, Fabbri A, Saran A, Zaffarouni D, Falvella FS, Spinola M, Tanuma J, Cataltepe S, Hayashizaki Y, Okazaki Y, Dragani TA

Cancer Res 63 1871 - 1875 2003.5

Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity. Reviewed International journal

Jun-ichi Tanuma, Hiroshi Hiai, Hayase Shisa, Masato Hirano, Ichiro Semba, Shigetaka Nagaoka, Motoo Kitano

International journal of cancer 102 ( 6 ) 638 - 42 2002.12

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

Rats of the DA strain are highly susceptible to 4NQO-induced TCs, whereas WF rats are barely susceptible. In (DA x WF)F2 rats, 5 QTL, Tscc1-5, are responsible for most of the phenotypic variations, though they do not account for all of the phenotypic differences between WF and DA rats. Analysis of 40 tongue tumors >5 mm in diameter from (DA x WF)F1 rats for LOH at the Tscc loci revealed a high frequency of LOH in chromosomal regions where the Tscc2, -3 and -4 loci map. In most cases of LOH, the allele of the barely susceptible WF strain was lost, suggesting that these loci in the WF strain encode tumor-suppressor genes. Analysis of the same tumors for somatic mutations in oncogenes indicated frequent alteration of Ha-ras, which maps in the Tscc3 region, but rare mutation of the p15(INK4B) and p16(INK4A) genes or the p53 and Msh2 genes. Frequent LOH was also found on rat chromosomes 5 (RNO5) and 6 (RNO6). Tumors of large size accumulated LOH at multiple loci, suggesting the involvement of Tscc loci in tumor progression.

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Papers - TANUMA Junichi