論文 - 西原　広史

PDGFRβ expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic marker

Yuzawa S., Kano M., Einama T., Nishihara H.

Medical Oncology （Medical Oncology）  29 （ 4 ） 2824 - 2830 2012年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  13570560

　概要を見る

Pancreatic adenocarcinoma is a lethal disease that often develops a desmoplastic reaction in tumor stroma. In general, desmoplasia is thought to promote tumor growth. However, its molecular pathology and prognostic potential have not been fully investigated. Here, we investigate 26 cases of pancreatic ductal adenocarcinoma and examine the clinicopathological association between survival and expression levels of several molecular markers for stromal cells. These include alpha-smooth muscle actin (SMA) and platelet-derived growth factor (PDGF) receptor β (PDGFRβ). Both are markers of activated fibroblasts or pancreatic stellate cells (PSCs) that play an important role in desmoplasia. The staining patterns of both molecular markers were not uniform, so we categorized them into 3 grades (high, middle, and low) according to intensity. Interestingly, Kaplan-Meier analysis revealed that higher expression of PDGFRβ matched shorter prognosis (p = 0.0287, log-rank test) as well as lymphatic invasion and lymph node metastasis, whereas SMA did not (p = 0.6122). Our results suggest the prognostic potential of cancer stroma via PDGF-B signaling. Regulation of PDGF-B-associated signaling crosstalk between cancer cells and stroma cells, therefore, may indicate a possible therapeutic target for desmoplastic malignant tumors such as pancreatic adenocarcinoma. © 2012 Springer Science+Business Media, LLC.

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Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer

Kawamata F., Kamachi H., Einama T., Homma S., Tahara M., Miyazaki M., Tanaka S., Kamiyama T., Nishihara H., Taketomi A., Todo S.

International Journal of Oncology （International Journal of Oncology）  41 （ 6 ） 2109 - 2118 2012年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  10196439

　概要を見る

Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarcinoma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EHBDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization.

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Prognostic implication of histological oligodendroglial tumor component: Clinicopathological analysis of 111 cases of malignant gliomas

Kanno H., Nishihara H., Narita T., Yamaguchi S., Kobayashi H., Tanino M., Kimura T., Terasaka S., Tanaka S.

PLoS ONE （PLoS ONE）  7 （ 7 ） e41669 2012年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1932-6203

　概要を見る

The favorable prognosis of high-grade oligodendroglial tumor such as glioblastoma (GBM) with oligodendroglioma component (GBMO) has been suggested; however, the studies which examine the prognostic significance of oligodendroglial tumor were limited. In this study, we performed a histopathology-based reevaluation of 111 cases of high grade gliomas according to the latest World Health Organization (WHO), and compared the clinical outcomes between oligodendroglial tumors and pure astrocytic tumors. The survival analysis revealed that the patients with high grade oligodendroglial tumor including GBMO significantly indicated better prognosis compared to the patients with high grade pure astrocytic tumors (GBM and AA, anaplastic astrocytoma) as expected, and the obtained survival curves were almost identical to those from the patients with conventional Grade III or Grade IV tumors, respectively. Moreover, if the cases of oligodendroglial tumor were histopathologically excluded, the patients with AA exhibited extremely poor prognosis which was similar to that of GBM, suggesting that the histological identification of oligodendroglial tumor component, even partially, prescribe the prognosis of high grade glioma patients. This is the prominent report of retrospective clinicopathological analysis for high-grade gliomas throughout Grade III and IV, especially referring to the prognostic value of histological oligodendroglial tumor component; in addition, our results might offer an alternative aspect for the grading of high-grade astrocytic/oligodendroglial tumors. © 2012 Kanno et al.

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CD133 negatively regulates tumorigenicity via AKT pathway in synovial sarcoma

Kimura T., Wang L., Tabu K., Nishihara H., Mashita Y., Kikuchi N., Tanino M., Hiraga H., Tanaka S.

Cancer Investigation （Cancer Investigation）  30 （ 5 ） 390 - 397 2012年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  07357907

　概要を見る

Synovial sarcoma (SS) is an aggressive tumor that accounts for almost 10 of all soft tissue sarcomas. In this study, we found the expression of CD133 in human SS specimens, thus, we focused on the function of CD133 in SS. Separation of the CD133-positive and -negative subpopulations in SS cell lines clarified that the CD133-negative subpopulation exhibited enhanced growth and hyperphosphorylation of AKT. Treatment of Akt inhibitor suppressed the cell growth of CD133-negative subpopulation to the levels of CD133-positive cells. These results suggest that CD133 has negative effect on the growth of cells through AKT-dependent signalling pathway. Copyright © 2012 Informa Healthcare USA, Inc.

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STAT3 inhibition overcomes temozolomide resistance in glioblastoma by downregulating MGMT expression

Kohsaka S., Wang L., Yachi K., Mahabir R., Narita T., Itoh T., Tanino M., Kimura T., Nishihara H., Tanaka S.

Molecular Cancer Therapeutics （Molecular Cancer Therapeutics）  11 （ 6 ） 1289 - 1299 2012年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15357163

　概要を見る

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with a poor prognosis. Current standard treatment includes chemotherapy with the DNA-alkylating agent temozolomide concomitant with surgical resection and/or irradiation. However, a number of cases are resistant to temozolomide-inducedDNA damage due to elevated expression of the DNA repair enzyme O 6-methylguanine-DNA methyltransferase (MGMT). Here, we show that upregulation of both MGMT and STAT3 was accompanied with acquisition of temozolomide resistance in the GBM cell line U87. Inactivation of STAT3 by inhibitor or short hairpin RNA (shRNA) downregulated MGMT expression in GBM cell lines. MGMT upregulation was not observed by the treatment of interleukin (IL)-6 which is a strong activator of STAT3. Contrarily, forced expressedMGMTcould be downregulated by STAT3 inhibitor which was partially rescued by the proteasome inhibitor, MG132, suggesting the STAT3-mediated posttranscriptional regulation of the protein levels of MGMT. Immunohistochemical analysis of 44 malignant glioma specimens showed significant positive correlation between expression levels of MGMT and phosphorylated STAT3 (p-STAT3; P < 0.001, r = 0.58). Importantly, the levels of both MGMT and p-STAT3 were increased in the recurrence compared with the primary lesion in paired identical tumors of 12 cases. Finally, we showed that STAT3 inhibitor or STAT3 knockdown potentiated temozolomide efficacy in temozolomide-resistant GBM cell lines. Therefore, STAT3 inhibitor might be one of the candidate reagents for combination therapy with temozolomide for patients with temozolomide- resistant GBM. ©2012 AACR.

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Pericyte-coverage of human tumor vasculature and nanoparticle permeability

Zhang L., Nishihara H., Kano M.

Biological and Pharmaceutical Bulletin （Biological and Pharmaceutical Bulletin）  35 （ 5 ） 761 - 766 2012年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  09186158

　概要を見る

Nano drug delivery systems (nanoDDS) are a promising strategy for treatment of human tumors. As indicated by our previous work, the extent of pericyte-coverage of tumor vasculature is important to determining nanoDDS efficacy since intratumoral accumulation of nanoDDS is less in tumor models with pericyte- covered vasculature. Here we investigated the clinical relevance of our previous observations in animal models, by determining pericyte coverage using immunohistochemistry of smooth muscle actin (SMA) with CD34: a vascular endothelial marker, in human tumor tissue samples. The investigation revealed that tumor vasculature coverage by pericytes in pancreatic and diffuse-type gastric cancers was significantly greater than in ovarian, colon, and intestinal-type gastric cancers. The latter group of cancers is easier to treat clinically. These observations are consistent with our previous findings in animal models. On the basis of these findings we believe optimization of nanoDDS delivery should be done depend upon a clear understanding of the effects of pericyte vascular coverage. © 2012 The Pharmaceutical Society of Japan.

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A case of clear cell variant of solid-pseudopapillary tumor of the pancreas in an adult male patient

Tanino M., Kohsaka S., Kimura T., Tabu K., Nishihara H., Sawa H., Kawami H., Kamada H., Shimizu M., Tanaka S.

Annals of Diagnostic Pathology （Annals of Diagnostic Pathology）  16 （ 2 ） 134 - 140 2012年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  10929134

　概要を見る

A clear cell variant of solid-pseudopapillary tumor (SPT) of the pancreas was initially reported in 2006 as a tumor that arose in the pancreatic body and tail in young adults; to date, only 4 cases of this entity have been reported. Here, we present the case of a 58-year-old man with clear cell variant of SPT with distinctive clinicopathologic features. The tumor was well demarcated, was 2.6 cm in size and mostly composed of multivacuolated clear cells with solid growth, and exhibited the characteristic immunohistochemical positivity of β-catenin in the cytoplasm and nuclei of the neoplastic cells. In contrast to classical SPT with nuclear positivity, this case was negative for E-cadherin. Direct DNA sequencing of exon 3 of β-catenin gene demonstrated a single amino acid substitution (serine to phenylalanine) in codon 37, which is the phosphorylation site by GSKβ and frequently found in classical SPT. Electron microscopy demonstrated enlarged mitochondria and endoplasmic reticulum. Despite the fact that previous cases of clear cell variant of SPT arose mainly in the pancreatic body and tail in female young adults (age, 26-32 years), this case suggested that it is possible for a clear cell variant of SPT to arise in the pancreatic head in a middle-aged man. Because the recognition of the clear cell variant of SPT is important for the appropriate diagnosis of primary pancreatic tumor, the present case with its distinctive characteristics may provide new information for a more profound understanding of the pancreatic SPT. © 2012 Elsevier Inc. All rights reserved.

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The impact of extent of resection and histological subtype on the outcome of adult patients with high-grade gliomas

Yamaguchi S., Kobayashi H., Terasaka S., Ishii N., Ikeda J., Kanno H., Nishihara H., Tanaka S., Houkin K.

Japanese Journal of Clinical Oncology （Japanese Journal of Clinical Oncology）  42 （ 4 ） 270 - 277 2012年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  03682811

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Objective: We reviewed the relationship between extent of resection and survival of patients with high-grade gliomas with special consideration of an oligodendroglial component. Methods: A retrospective review was performed on 160 adult patients with histological diagnosis of high-grade gliomas since 2000. All histological slides were categorized as high-grade astrocytomas or oligodendroglial tumors. Extent of resection was assessed by early post-operative magnetic resonance imaging and classified as complete resection, incomplete resection and biopsy. Measured outcomes were overall survival and progression-free survival. The independent association of extent of resection and survival was analyzed by the multivariate proportional hazard model adjusting for prognostic factors. Results: The lesions were classified as high-grade astrocytomas in 93 patients and high-grade oligodendroglial tumors in 67 patients. In high-grade astrocytomas, the median survival after complete resection (n = 36), incomplete resection (n = 36) and biopsy (n = 21) was 23.4, 15.3 and 12.6 months, respectively. Complete resection was independently associated with increased overall survival (P < 0.001) and progression-free survival (P = 0.002) compared with incomplete resection, while incomplete resection was not associated with survival benefit compared with biopsy by multivariate analysis. On the other hand, in high-grade oligodendroglial tumors, the majority of patients were still alive and there is no significant difference in the survival between complete resection (n = 24) and incomplete resection (n = 33), while even incomplete resection had a significantly longer overall survival (P < 0.001) and progression-free survival (P = 0.006) compared with biopsy (n = 10). Conclusions: Maximal cytoreduction improves the survival of high-grade gliomas, although our data indicated that the impact of extent of resection in high-grade astrocytomas is different from that in high-grade oligodendroglial tumors. © The Author 2012. Published by Oxford University Press. All rights reserved.

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CRKL plays a pivotal role in tumorigenesis of head and neck squamous cell carcinoma through the regulation of cell adhesion

Yanagi H., Wang L., Nishihara H., Kimura T., Tanino M., Yanagi T., Fukuda S., Tanaka S.

Biochemical and Biophysical Research Communications （Biochemical and Biophysical Research Communications）  418 （ 1 ） 104 - 109 2012年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0006291X

　概要を見る

The signaling adapter protein CRK is an indispensable molecule involved in regulating the malignant potential of human cancers. CRK-like (CRKL) is a hematopoietic cell-dominant homologue of CRK that is reported to be phosphorylated by BCR-ABL tyrosine kinase in chronic myelogenous leukemia patients, but its biological function in non-hematopoietic tumors remains unclear. In this study, we explored the tumorigenic role of CRKL in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Immunoprecipitation analysis of HNSCC cell line, HSC-3 cells, showed that the dominant binding partner for C3G was CRKL, not CRK. To clarify the molecular function of CRKL, we established lentiviral shRNA-mediated CRKL-knockdown HNSCC cell lines. In CRKL-knockdown HSC-3 and HSC-4 cells, cell growth and motility were diminished compared to control cells. Cell adhesion assays showed that cell attachment onto both fibronectin- and collagen-coated dishes was significantly suppressed in CRKL-knockdown HSC-3 cells, while no significant change was observed for poly- l-lysine-coated dishes. Immunofluorescence staining revealed that focal adhesion was reduced in CRKL-knockdown HSC-3 cells. With a pulldown assay, CRKL-knockdown HSC-3 cells showed decreased amounts of active Rap1 compared to control cells. Moreover, in an in vivo assay, tumor formation of CRKL-knockdown HSC-3 cells in nude mice was significantly abrogated. Our results indicate that CRKL regulates HNSCC-cell growth, motility, and integrin-dependent cell adhesion, suggesting that CRKL plays a principal role in HNSCC tumorigenicity. © 2012 Elsevier Inc.

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Cyclooxygenase-2 inhibition causes antiangiogenic effects on tumor endothelial and vascular progenitor cells

Muraki C., Ohga N., Hida Y., Nishihara H., Kato Y., Tsuchiya K., Matsuda K., Totsuka Y., Shindoh M., Hida K.

International Journal of Cancer （International Journal of Cancer）  130 （ 1 ） 59 - 70 2012年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00207136

　概要を見る

Tumor angiogenesis is necessary for solid tumor progression and metastasis. Cyclooxygenase (COX)-2 is known to play an important role in cancer growth and invasion, and it activates the signaling pathways controlling cell proliferation, migration, apoptosis, and angiogenesis. COX-2 is reported to be expressed in many cancer cells. Several studies have reported successful treatment of cancer cells with COX-2 inhibitors (COX-2is). However, the effect of COX-2 inhibition on the tumor endothelium remains to be elucidated. Our study shows that COX-2 is expressed in the vasculature of surgically resected human tumors. To investigate the effects of COX-2 inhibition on the tumor endothelium in vitro, we isolated tumor endothelial cells (TECs) from human melanoma and oral carcinoma xenografts in mice, in which we confirmed that tumor growth was suppressed by inhibiting angiogenesis with the COX-2is NS398. COX-2 mRNA was upregulated in TECs compared to normal endothelial cells (NECs). Cell migration and proliferation were suppressed by NS398 in TECs but not in NECs. The effects of NS398 in vivo were consistent with the in vitro results. The number of CD133 +/vascular endothelial growth factor receptor-2 + cells in circulation was significantly suppressed by COX-2 inhibition. In addition, the number of progenitor marker-positive cells decreased in the tumor blood vessels after COX-2i treatment, which suggests that the homing of progenitor cells into the tumor was also blocked. We conclude that NS398 specifically targets both TECs and vascular progenitor cells without affecting NECs. Copyright © 2011 UICC.

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[A case of central nervous system lymphomatoid granulomatosis successfully treated with corticosteroids].

Shimada S, Ueno H, Yamasaki F, Sugiyama K, Yasutomi H, Sekine M, Ohshita T, Kurashige T, Nakamura T, Nishihara H, Yamawaki T, Kurisu K, Matsumoto M

Brain and nerve = Shinkei kenkyu no shinpo （1）  64 （ 1 ） 85 - 87 2012年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1881-6096

Tuning-up and driving a redox-active rotor

Kume S., Nishihara H.

Chemical Communications （Chemical Communications）  47 （ 1 ） 415 - 417 2011年12月

ISSN  13597345

　概要を見る

The dynamic bistable rotational behaviour of a copper(i) coordination environment can be rationally tuned with balancing the substituent size on the rotor. Such rotors are sensitive to weak interactions, and the rotation was driven by a redox reaction on a ferrocenyl moiety via reconstruction of the charge interaction between redox centres. © 2010 The Royal Society of Chemistry.

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Co-expression of mesothelin and CA125 correlates with unfavorable patient outcome in pancreatic ductal adenocarcinoma

Einama T., Kamachi H., Nishihara H., Homma S., Kanno H., Takahashi K., Sasaki A., Tahara M., Okada K., Muraoka S., Kamiyama T., Matsuno Y., Ozaki M., Todo S.

Pancreas （Pancreas）  40 （ 8 ） 1276 - 1282 2011年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  08853177

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Objectives: Recent studies have shown that the high affinity of mesothelin-CA125 interaction might cause intracavitary tumor metastasis. We examined the clinicopathologic significance and prognostic implication of mesothelin and CA125 expression in pancreatic ductal adenocarcinoma. Methods: Tissue samples from 66 pancreatic ductal adenocarcinomas were immunohistochemically examined. Proportion and intensity of constituent tumor cells with mesothelin and CA125 expression were analyzed and classified as high-level expression, defined as expression by more than 50% of tumor cells and/or moderate to strong staining, or low-level expression otherwise. Results: A high level of mesothelin was correlated with a higher histological grade (P = 0.049) and the level of blood vessel permeation (P = 0.0006), whereas a high level of CA125 expression was correlated with a higher recurrence rate (P = 0.015). The expression of mesothelin was strongly correlated with that of CA125 (P = 0.0041). Co-expression of mesothelin and CA125 were associated with an unfavorable patient outcome (P = 0.0062). Conclusions: This is the first report showing that co-expression of mesothelin and CA125 were in pancreatic ductal adenocarcinoma, and such co-expression is associated with a poor prognosis. Our finding suggests that co-expression of these two factors plays a significant role in the acquisition of aggressive clinical behavior. © 2011 by Lippincott Williams & Wilkins.

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A case of lymphoplasmacyte-rich meningioma of the jugular foramen

Kanno H., Nishihara H., Hara K., Ozaki Y., Itoh T., Kimura T., Tanino M., Tanaka S.

Brain Tumor Pathology （Brain Tumor Pathology）  28 （ 4 ） 341 - 345 2011年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  14337398

　概要を見る

Lymphoplasmacyte-rich meningioma (LPRM), the most rare variant of meningiomas, features extensive lymphoplasmacytic infiltrates. Although the jugular foramen (JF) is occasionally involved by several types of tumor, such as paragangliomas and schwannomas, meningioma in the JF is an infrequent disease. Here we present an extremely rare case of LPRM found in the JF. A 55-year-old woman complained of paresis in her right eyelid and palsy in the right side of her lip. Hoarseness and dysphagia also occurred in the following month. Radiologic examinations disclosed a mass lesion in the right JF, and the tumor was operatively removed. Microscopically, the tumor was composed of extensive lymphoplasmacytic infiltration with mild vascular proliferation and scattered sheets of epithelioid cells with plump cytoplasm. Although the obvious whorl formation or psammoma bodies were not observed, by immunochemistry the epithelioid cells were positive for epithelial membrane antigen and also progesterone receptor, indicating a meningothelial cell origin. Considering the histological and radiologic findings, we finally diagnosed the case as LPRM, making this the second reported case of LPRM in the JF. © 2011 The Japan Society of Brain Tumor Pathology.

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A population of BJ fibroblasts escaped from Ras-induced senescence susceptible to transformation

Kohsaka S., Sasai K., Takahashi K., Akagi T., Tanino M., Kimura T., Nishihara H., Tanaka S.

Biochemical and Biophysical Research Communications （Biochemical and Biophysical Research Communications）  410 （ 4 ） 878 - 884 2011年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0006291X

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Oncogenic stimuli such as H-Ras induce oncogene-induced senescence (OIS) in fibroblasts to protect against transformation. Here we found that a population of the human diploid fibroblasts can escape from OIS induced by H-RasV12. We designated these OIS-escaped cells as OISEC (OIS-escaped cells). OISEC lost the expression of p16 which plays an important role for cell cycle arrest for induction of senescence, but OISEC preserved the p16 expression machinery and exhibited senescence by the treatment with hydrogen peroxide (H2O2) as stress-induced premature senescence (SIPS). OISEC did not possess anchorage-independent growth potential, and functional disruption of p53 and Rb by SV40 early region encoding large T and small t antigens, induced the aneuploidy phenotype and colony-forming potential of OISEC together with the exhibition of in vivo tumor formation. Finally, we also found that the distinctive feature of OISEC is expression of transcription factors, Oct3/4, SOX2, and Nanog which is closely related to stem-like cell features. This study highlights the presence of a cell population which escaped from OIS, and this OISEC may transform into malignant cancer cells by the additional hits of several genes in vivo. © 2011 Elsevier Inc.

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A uniform bimetallic rhodium/iron nanoparticle catalyst for the hydrogenation of olefins and nitroarenes

Nakamula I., Yamanoi Y., Imaoka T., Yamamoto K., Nishihara H.

Angewandte Chemie - International Edition （Angewandte Chemie - International Edition）  50 （ 26 ） 5830 - 5833 2011年06月

共著,  ISSN  14337851

　概要を見る

Mix and more than match: Relative to the catalytic activity of pure Rh nanoparticles in a dendrimer cage, Rh/Fe bimetallic nanoparticles in dendrimers have improved catalytic activity towards the hydrogenation of olefins, and unlike Wilkinson catalyst could catalyze nitroarene hydrogenation (see scheme, G4=4th generation dendrimer). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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High grade meningiomaの治療成績とMib-1 indexの関係の検討

成田 拓人, 菅野 宏美, 湯澤 明夏, 寺坂 俊介, 小林 浩之, 村田 純一, 山口 秀, 西原 広史, 宝金 清博, 田中 伸哉

Brain Tumor Pathology （日本脳腫瘍病理学会）  28 （ Suppl. ） 092 - 092 2011年05月

ISSN  1433-7398

A case of atypical teratoid/rhabdoid tumor in an adult, with long survival

Takahashi K., Nishihara H., Katoh M., Yoshinaga T., Mahabir R., Kanno H., Kimura T., Tanino M., Ikeda J., Sawamura Y., Nagashima K., Tanaka S.

Brain Tumor Pathology （Brain Tumor Pathology）  28 （ 1 ） 71 - 76 2011年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  14337398

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Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that mostly occurs in early childhood and has poor prognosis despite aggressive therapy. Adult cases are rare and, as far as we are aware, only 30 cases have been reported to date. Here we present the case of a 27-year-old female with left parietal AT/RT with the chief complaint of numbness of the right superior limb. First, the tumor was surgically removed and the diagnosis was grade II glioma. With additional radiotherapy, the clinical course after surgery was favorable. After 6 years, she had an operation for recurrence and the diagnosis was grade III glioma. Temozolomide was prescribed, and a disease-free period of 2 years followed. Surgery was performed for a third time for second recurrence with histology of diffuse growth of rhabdoid cells. Immunohistochemistry was partially positive for vimentin and epithelial membrane antigen. Ki-67 labeling index was extremely high and tumor cells showed no staining of INI1 suggestive of diagnosis of AT/RT. We re-evaluated past specimens and none had immunoreactivity of INI1. Ki-67 labeling index and O-6 methylguanine DNA methyltransferase (MGMT) staining were also re-examined and both increased gradually. She is still alive without recurrence for more than 1 year. As far as we are aware, this is the second longest survival of an adult with AT/RT. © The Japan Society of Brain Tumor Pathology 2010.

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Clinicopathologic application of lectin histochemistry: Bisecting GlcNAc in glioblastoma

Aoyanagi E., Sasai K., Nodagashira M., Wang L., Nishihara H., Ihara H., Ikeda Y., Tanaka S.

Applied Immunohistochemistry and Molecular Morphology （Applied Immunohistochemistry and Molecular Morphology）  18 （ 6 ） 518 - 525 2010年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  15412016

　概要を見る

Glycosylation is one of the most common posttranslational modifications and changes in oligosaccharide structures are associated with many human diseases including a number of cancers. Thus, discovering aberrant glycosylation patterns that serve as markers for brain tumor progression and metastasis represents an attractive strategy to improve clinicopathologic diagnosis and to provide aids to the development of novel therapies. To identify glioblastoma (GBM) cells expressing glycoproteins that contain high levels of the bisecting N-acetylglucosamine (GlcNAc) structures, lectin histochemistry was carried out using erythroagglutinating phytohemagglutinin. Although GBM frequently expressed the bisecting GlcNAc, the lectin reactivity varied among tumor regions within individual specimens. Since detailed histopathologic analysis revealed that oligosaccharides with bisecting GlcNAc structures were preferably expressed in tumor regions with low KI67 immunopositivity, immunodetection of the bisecting GlcNAc could be useful to indicate less proliferative regions in human GBM. Our study highlights the potential use of lectin histochemistry to develop new methods for diagnosis that would improve future antiglioma therapy. Copyright © 2010 by Lippincott Williams & Wilkins.

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Intraductal papillary mucinous neoplasms(IPMNs)におけるMesothelinとCA125の発現様式の検討

永生 高広, 蒲池 浩文, 西原 広史, 本間 重紀, 佐々木 彩実, 田原 宗徳, 佐藤 正法, 三野 和宏, 岡田 邦明, 近藤 征文, 神山 俊哉, 松野 吉宏, 藤堂 省

日本消化器外科学会雑誌 （(一社)日本消化器外科学会）  43 （ Suppl.2 ） 366 - 366 2010年10月

ISSN  0386-9768