Faculty Profiles - akihide Tanimoto

Terahara M, Nagano S, Arishima Y, Zemmyo M, Yokouchi M, Yoshioka T, Tanimoto A, Komiya S . Exploration with 18F-FDG PET/CT of new ways of determination of safe surgical margins for soft tissue sarcoma. . BMC Musculoskeletal Disorders12 166 2011Reviewed

Kawaguchi Hiroaki, Miyoshi Noriaki, Miura Naoki, Horiuchi Masahisa, Ono Tomoji, Murakoshi Michiaki, Nishino Hoyoku, Nagata Ryoichi, Sahara Hisashi, Tanimoto Akihide, Yamada Kazuhiko, Yoshida Hiroki . Microminipig: research models to break through cardiovascular disease . JOURNAL OF PHARMACOLOGICAL SCIENCES115 49P 2011Reviewed

Sohsuke Yamada, Akihide Tanimoto, Ke-Yong Wang, Yan Ding, Xin Guo, Shohei Shimajiri, Hironobu Sasano, Yasuyuki Sasaguri . Non-functional adrenocortical adenoma: A unique case of combination with myelolipoma and endothelial cysts . PATHOLOGY RESEARCH AND PRACTICE207 ( 3 ) 192 - 196 2011Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER GMBH, URBAN & FISCHER VERLAG

A case of non-functioning adrenocortical adenoma combined with myelolipoma and endothelial cysts is reported. A 72-year-old Japanese female was noticed to have right renal and left adrenal tumors by an abdominal CT scan. At surgery, the mildly enlarged left adrenal gland contained a well-demarcated tumor. Macroscopically, it was yellowish to dark red or grayish in color, and was characterized by geographic appearance on the cut surface. Histopathological examination revealed a solid proliferation of clear or compact cells and a normal rim of adrenal gland, coexisting with vascular multiple cysts and myelolipomas. The cysts were filled with clotted blood, fibrinous material, or thrombi, and were partially lined with flattened endothelial cells with focal papillary hyperplasia, which were immunohistochemically positive for CD31 and CD34. These cystic walls were often thickened with hyalinized fibrosis and calcification, and were connected to myelolipomatous elements. To our knowledge, this is the first case report of adrenocortical adenoma associated with myelolipoma and endothelial cysts. It is probable that the extensive degeneration in adenoma might induce myelolipomatous metaplasia and cystic vascular formation. (C) 2010 Elsevier GmbH. All rights reserved.

DOI： 10.1016/j.prp.2010.07.008

Naoya Morisada, Masayoshi Nomura, Hisae Nishii, Yumi Furuno, Mayuko Sakanashi, Ken Sabanai, Yumiko Toyohira, Susumu Ueno, Seiji Watanabe, Masahito Tamura, Tetsuro Matsumoto, Akihide Tanimoto, Yasuyuki Sasaguri, Hiroaki Shimokawa, Koichi Kusuhara, Nobuyuki Yanagihara, Akira Shirahata, Masato Tsutsui . Complete Disruption of All Nitric Oxide Synthase Genes Causes Markedly Accelerated Renal Lesion Formation Following Unilateral Ureteral Obstruction in Mice In Vivo . JOURNAL OF PHARMACOLOGICAL SCIENCES114 ( 4 ) 379 - 389 2010.12Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

The role of nitric oxide (NO) derived from all three NO synthases (NOSs) in renal lesion formation remains to be fully elucidated We addressed this point in mice lacking all NOSs Renal injury was induced by unilateral ureteral obstruction (UUO) UUO caused significant renal lesion formation (tubular apoptosis, interstitial fibrosis, and glomerulosclerosis) in wild-type, singly, and triply NOS-/- mice However, the extents of renal lesion formation were markedly and most accelerated in the triply NOS-/- genotype UUO also elicited the infiltration of inflammatory macrophages, up-regulation of transforming growth factor (TGF)-beta 1, and induction of epithelial mesenchymal transition (EMT) in all of the genotypes, however, the extents were again largest by far in the triply NOS-/- genotype Importantly, long-term treatment with the angiotensin II type 1 (AT(1))-receptor blocker olmesartan significantly prevented the exacerbation of those renal structural changes after UUO in the triply NOS-/- genotype, along with amelioration of the macrophage infiltration, TGF-beta 1 levels, and EMT These results provide the first evidence that the complete disruption of all NOS genes results in markedly accelerated renal lesion formation in response to UUO in mice in vivo through the AT(1)-receptor pathway, demonstrating the critical renoprotective role of all NOSs-derived NO against pathological renal remodeling

DOI： 10.1254/jphs.10143FP

Hiroto Izumi, Tetsuro Wakasugi, Shohei Shimajiri, Akihide Tanimoto, Yasuyuki Sasaguri, Eiji Kashiwagi, Yoshihiro Yasuniwa, Masaki Akiyama, Bin Han, Ying Wu, Takeshi Uchiumi, Tokuzo Arao, Kazuto Nishio, Ryuta Yamazaki, Kimitoshi Kohno . Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes . CANCER SCIENCE101 ( 12 ) 2538 - 2545 2010.12Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL PUBLISHING, INC

The cell cycle is strictly regulated by numerous mechanisms to ensure cell division. The transcriptional regulation of cell-cycle-related genes is poorly understood, with the exception of the E2F family that governs the cell cycle. Here, we show that a transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-associated genes and is highly expressed in multiple solid tumors. RNA-interference (RNAi)-mediated knockdown of ZNF143 showed that expression of 152 genes was downregulated in human prostate cancer PC3 cells. Among these ZNF143 targets, 41 genes (27%) were associated with cell cycle and DNA replication including cell division cycle 6 homolog (CDC6), polo-like kinase 1 (PLK1) and minichromosome maintenance complex component (MCM) DNA replication proteins. Furthermore, RNAi of ZNF143 induced apoptosis following G2/M cell cycle arrest. Cell growth of 10 lung cancer cell lines was significantly correlated with cellular expression of ZNF143. Our data suggest that ZNF143 might be a master regulator of the cell cycle. Our findings also indicate that ZNF143 is a member of the growing list of non-oncogenes that are promising cancer drug targets. (Cancer Sci 2010; 101: 2538-2545).

DOI： 10.1111/j.1349-7006.2010.01725.x

Kiyoko Shibata, Yasuko Yatera, Yumi Furuno, Ken Sabanai, Naoya Morisada, Sei Nakata, Tsuyoshi Morishita, Fumio Yamazaki, Akihide Tanimoto, Yasuyuki Sasaguri, Hiromi Tasaki, Yasuhide Nakashima, Hiroaki Shimokawa, Nobuyuki Yanagihara, Yutaka Otsuji, Masato Tsutsui . Spontaneous Development of Left Ventricular Hypertrophy and Diastolic Dysfunction in Mice Lacking All Nitric Oxide Synthases . CIRCULATION JOURNAL74 ( 12 ) 2681 - 2692 2010.12Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE CIRCULATION SOC

Background: The role of the nitric oxide synthase (NOS) system in cardiac architecture and function remains unknown. This point was addressed in mice that lack all 3 NOS genes.
Methods and Results: Morphological, echocardiographic, and hemodynamic analyses were performed in wildtype (WT), singly nNOS(-/-), iNOS-1-, eNOS(-/-), and triply n/i/eNOS(-/-) mice. At 5 months of age, but not at 2 months of age, significant left ventricular (LV) hypertrophy was noted in n/i/eNOS(-/-) mice and to a lesser extent in eNOS(-/-) mice, but not in nNOS(-/-) or iNOS(-/-) mice, compared with WT mice. Importantly, significant LV diastolic dysfunction (as evaluated by echocardiographic E/A wave ratio and hemodynamic -dP/dt and Tau), with preserved LV systolic function (as assessed by echocardiographic fractional shortening and hemodynamic +dP/dt), was noted only in n/i/eNOS(-/-) mice, and this was associated with enhanced LV end-diastolic pressure and increased lung wet weight, all of which are characteristics consistent with diastolic heart failure in humans. Finally, long-term oral treatment with an angiotensin II type 1 (AT(1)) receptor blocker, olmesartan, significantly prevented all these abnormalities of n/i/eNOS(-/-) mice.
Conclusions: These results provide the first direct evidence that the complete disruption of all NOSs results in LV hypertrophy and diastolic dysfunction in mice in vivo through the AT(1) receptor pathway, demonstrating a pivotal role of the endogenous NOS system in maintaining cardiac homeostasis. (Cur J 2010; 74: 2681-2692)

DOI： 10.1253/circj.CJ-10-0277

Yuriz Bakhtiar, Kazunori Arita, Hirofumi Hirano, Mika Habu, Shingo Fujio, Shinichi Kitajima, Akihide Tanimoto . Prolactin-Producing Pituitary Adenoma With Abundant Spherical Amyloid Deposition Masquerading as Extensive Calcification -Case Report- . NEUROLOGIA MEDICO-CHIRURGICA50 ( 11 ) 1023 - 1026 2010.11Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN NEUROSURGICAL SOC

A 53-year-old male presented with a case of prolactin-producing pituitary adenoma with abundant spherical amylo id depositions masquerading as extensive calcification and manifesting as visual disturbance Computed tomography revealed a large high density mass suggesting calcified tumor in the intra- and supra seller regions Magnetic resonance imaging revealed a heterogeneously enhanced large pituitary tumor reaching lateral ventricle Blood prolactin level was elevated to 5971 ng/ml Cabergoline treatment for 3 months provided considerable shrinkage of the tumor but failed to improve the visual symptoms Transcranial surgery revealed that the tumor was fibrous and included abundant grayish translucent spherical granules with diameter of 0 5-1 5 mm Immunohistochemically, the tumor was strongly positive for prolactin Congo red stain and polarized light showed that these spherical bodies were amyloid depositions No calcification was noted

DOI： 10.2176/nmc.50.1023

Yan Ding, Sohsuke Yamada, Ke-Yong Wang, Shohei Shimajiri, Xin Guo, Akihide Tanimoto, Yoshitaka Murata, Shuji Kitajima, Teruo Watanabe, Hiroto Izumi, Kimitoshi Kohno, Yasuyuki Sasaguri . Overexpression of Peroxiredoxin 4 Protects Against High-Dose Streptozotocin-Induced Diabetes by Suppressing Oxidative Stress and Cytokines in Transgenic Mice . ANTIOXIDANTS & REDOX SIGNALING13 ( 10 ) 1477 - 1490 2010.11Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：MARY ANN LIEBERT, INC

Peroxiredoxin 4 (PRDX4) is one of a newly discovered family of antioxidative proteins. We generated human PRDX4 (hPRDX4) transgenic (Tg) mice, displaying a high level of hPRDX4 expression in the pancreatic islets, and then focused on the functions of PRDX4 in a type 1 diabetes mellitus (T1DM) model using a single high dose of streptozotocin (SHDS). After SHDS-injection, Tg mice showed significantly less hyperglycemia and hypoinsulinemia and a much faster response on glucose tolerance test than wild-type (WT) mice. Morphologic and immunohistochemical observation revealed that the pancreatic islet areas of Tg mice were larger along with less CD3-positive lymphocyte infiltration compared with WT mice. Upon comparison between these two mouse models, beta-cell apoptosis was also repressed, and reversely, beta-cell proliferation was enhanced in Tg mice. Real-time RT-PCR demonstrated that the expression of many inflammatory-related molecules and their receptors and transcription factors were significantly downregulated in Tg mice. These data indicate that PRDX4 can protect pancreatic islet beta-cells against injury caused by SHDS-induced insulitis, which strongly suggests that oxidative stress plays an essential role in SHDS-induced diabetes. This study, for the first time, implicates that PRDX4 has a pivotal protective function against diabetes progression in this T1DM model. Antioxid. Redox Signal. 13, 1477-1490.

DOI： 10.1089/ars.2010.3137

Michihisa Zenmyo, Akihide Tanimoto, Harutoshi Sakakima, Masahiro Yokouchi, Satoshi Nagano, Takuya Yamamoto, Yasuhiro Ishido, Setsuro Komiya, Kosei Ijiri . Gadd45 beta expression in chondrosarcoma: A pilot study for diagnostic and biological implications in histological grading . DIAGNOSTIC PATHOLOGY5 69 - 69 2010.10Reviewed International journal

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

Background: Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45 beta (GADD45 beta) is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45 beta in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45 beta in pathological grading of chondrosarcoma.
Methods: Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1) were used for immunohistochemical analysis to investigate the expression of GADD45 beta. Quantitative analysis was performed to compare the number of GADD45 beta positive cells and pathological grading.
Results: Over 70% of the cells in enchondromas expressed GADD45 beta. On the other hand, the expression of GADD45 beta decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%).
Conclusions: The association of GADD45 beta expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45 beta may be a specific diagnostic parameter for chondrosarcoma cell differentiation.

DOI： 10.1186/1746-1596-5-69

Michihisa Zenmyo, Yasuhiro Ishido, Mikio Terahara, Takuya Yamamoto, Akihide Tanimoto, Setsuro Komiya, Kosei Ijiri . Intramedullary Subependymoma of the Cervical Spinal Cord: A Case Report with lmmunohistochemical Study . INTERNATIONAL JOURNAL OF NEUROSCIENCE120 ( 10 ) 676 - 679 2010.10Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Spinal subependymomas, which have a relatively benign nature, are very rare tumors. It is difficult to distinguish spinal subependymomas from other intramedullary spinal tumors based on neuroradiological findings. A case of cervical intramedullary subependymoma in a 63-year-old female is reported. The diffused enlargement of the spinal cord at C2 level involved the lesion with isointensity on a T1-weighted MRI and relatively high intensity on a T2-weighted MRI. Enhancement in the small part of the tumor was observed on a T1-weighted MRI with gadolinium administration. The tumor occupied the left side of the spinal cord, and was totally removed through a laminoplasty of C2. Immunohistochemistry was useful for pathological diagnosis. The clinical feature of this patient is described with the review of literatures.

DOI： 10.3109/00207454.2010.509894