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| 1 | Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer显示文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer. | Katsuhiko Nosho Yasutaka Sukawa Yasushi Adachi Miki Ito Kei Mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto Keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura | 2016 | World Journal of Gastroenterology2016，22，2： | 44 |
| 2 | Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats显示文摘AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy.METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler (Roche Diagnostics) and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells (hepatocytes,sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic stellate cells (HSC)) from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation,to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, respectively.RESULTS: VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter.The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction.Meanwhile, mRNA for Ang-1 and Ang-2 was foundin the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly,reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h.CONCLUSION: Ang-Tie system, together with VEGF,plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system. | Hiroaki Shimizu Noboru Mitsuhashi Masayuki Ohtsuka Hiroshi Ito Fumio Kimura Satoshi Ambiru Akira Togawa Hiroyuki Yoshidome Atsushi Kato Masaru Miyazaki | 2005 | World Journal of Gastroenterology2005，11，46： | 17 |
| 3 | MicroRNA-31 expression in colorectal serrated pathway progression显示文摘MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in CRC.Moreover,high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps(HPs).These results suggest that miR-31 may contribute to the progression of serrated lesions.At a follow-up colonoscopy,we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated features.Tissue specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP component.Higher miR-31 expression was observed in the carcinoma component(57-fold increase)and the HP component(8-fold increase)compared with the paired normal mucosa,suggesting that miR-31 may be one of the key molecules in serrated pathway progression. | Hironori Aoki Katsuhiko Nosho Hisayoshi Igarashi Miki Ito Kei Mitsuhashi Takafumi Naito Eiichiro Yamamoto Tokuma Tanuma Masafumi Nomura Hiroyuki Maguchi Toshiya Shinohara Hiromu Suzuki Hiroyuki Yamamoto Yasuhisa Shinomura | 2014 | World Journal of Gastroenterology2014，20，34： | 5 |
| 4 | Immunotherapy of solid cancer using dendritic cells pulsed with the HLA-A24-restricted peptide of carcinoembryonic antigen显示文摘 | Tsuyoshi Itoh Yuji Ueda Ichiro Kawashima Ikuei Nukaya Hitoshi Fujiwara Nobuaki Fuji Tetsuro Yamashita Tetsunori Yoshimura Kaori Okugawa Tomoko Iwasaki Mitsuko Ideno Kazutoh Takesako Masakazu Mitsuhashi Kunzo Orita Hisakazu Yamagishi | 2002 | Cancer Immunology,Immunotherapy2002，，2： | 2 |
| 5 | In vitro antibacterial activity of AM-1155, anovel 6-fluoro-8-methoxy quinolone显示文摘 | Wakabayashi E Mitsuhashi S | 1994 | Antimicrob Agents Chemother1994，38，3： | 1 |
| 6 | In vitro antibacterial activity of AM-1155,a novel 6-fluoro-8-methoxy quinolone 显示文摘 | Wakabayashi E Mitsuhashi S | 1994 | Antimicrob Agents Chemother1994，38，3： | 1 |
| 7 | Changes in the localization of heat shock protein 72 correlated with development of thermotolerance in human esophageal cancer cell line显示文摘 | Nonaka T Akimoto T Mitsuhashi N | 2003 | Anticancer Res2003，23，6： | 1 |
| 8 | Establishment and characterization of a new human lung poorly differentiated adenocarcinoma cell line,GLL-1,producing carcinoembryonic antigen(CEA) and CA19-9显示文摘 | Mitsuhashi N Takahashi T Sakurai H | 1995 | Lung Cancer1995，12，12： | 1 |
| 9 | Oxidative stress-depen-dent conversion of hydrogen sulfide to sulfite by activated neutrophils显示文摘 | Mitsuhashi H Yamashita S Ikeuchi H | 2005 | Shock2005，24，6： | 1 |
| 10 | Mutant ras oncogenes upregu- late VEGF/VPF expression:implications for induction and inhibition of tumor angiogenesis显示文摘 | Rak J Mitsuhashi Y Bayko L | 1995 | Cancer Res1995，55，20： | 1 |
| 11 | Low voltage circuit breaker using auto-puffer interuption technique显示文摘 | TSUKIMA M MITSUHASHI T TAKAHASTF M | 2002 | Transactions of the Institute Electrical Engineer of Japan2002，122，9： | 1 |
| 12 | Giant cell tumor of the thoracic spine simulating mediastinal neoplasm显示文摘 | Sakurai H Mitsuhashi N Hayakawa K | 1999 | AJNR1999，20，9： | 1 |
| 13 | Impact of Ultrasound Attenuation and Plaque Rupture as Detected by Intravascular Ultrasound on the Incidence of No-Reflow Phenomenon After Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction显示文摘 | Mitsuaki Endo Kiyoshi Hibi Tomoaki Shimizu Naohiro Komura Ikuyoshi Kusama Fumiyuki Otsuka Takayuki Mitsuhashi Noriaki Iwahashi Jun Okuda Kengo Tsukahara Masami Kosuge Toshiaki Ebina Satoshi Umemura Kazuo Kimura | 2010 | JACC: Cardiovascular Interventions2010，，5： | 1 |
| 14 | Two factors in visual fatigue caused by stereoscopic HDTV images 显示文摘 | Yano S Emoto M Mitsuhashi T | 2004 | Displays2004，25，4： | 1 |
| 15 | Sensitive spectrophotometric method for the determination of ethylenediaminetetraacetic acid in foods显示文摘 | HAMANO T MITSUHASHI Y KOJIMA N | 1993 | The Analyst1993，118，7： | 1 |
| 16 | Oxidative stress - dependent conversion of hydrogen sulfide to sulfite by activated neutrophils 显示文摘 | Mitsuhashi H Yamashita S Ikeuchi H | 2005 | Shock2005，24，6： | 1 |
| 17 | Expressin of cyclooxygenase-2 in patients with bladder carcinoma 显示文摘 | Yoshimura R Sano H Mitsuhashi M | 2001 | Uro12001，165，5： | 1 |
| 18 | Synthesis and radical polymerization of styrene derivative bearing kojie acid moieties 显示文摘 | Tomita I Mitsuhashi K Endo T | 1996 | Polym Sci A1996，34，： | 1 |
| 19 | Gas chromatographic determination of total iodine in foods 显示文摘 | Mitsuhashi T Kaneda Y | 1990 | J Assoc off Anal Chem1990，73，5： | 1 |
| 20 | Absorption,distribution and excretion of a foodstuff (Kureha M6271) derivedfrom mycelia of basidiomycetes Tricholoma matsutake after oraladministration显示文摘 | MITSUHASHI S HOSHI H MATSUNAGA K | 2003 | New Rem2003，52，6： | 1 |
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