Institution
Kumamoto University
Education•Kumamoto, Kumamoto, Japan•
About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Cancer & Population. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.
Topics: Cancer, Population, Gene, Cell culture, Receptor
Papers published on a yearly basis
Papers
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TL;DR: Results indicate that activation of CaM kinase II is involved in the induction of synaptic potentiation in both the postsynaptic and presynaptic regions.
221 citations
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TL;DR: Analysis of macrophage populations and phenotypes in intrahepatic cholangiocarcinoma patients provides suggestive evidence that TAMs contribute to cancer progression via Stat3 activation, and CD163 is useful for evaluating M2 TAMs and predicting the clinical prognosis of ICC patients.
Abstract: Many studies have shown that tumor-associated macrophages (TAMs) contribute to tumor development and poor prognosis in various cancers. In this study, we investigated the macrophage populations and phenotypes, and their correlation to angiogenesis, immunosuppression, and clinical prognosis in intrahepatic cholangiocarcinoma (ICC). CD68 (+) and CD163 (+) macrophage infiltration was analyzed in paraffin-embedded tissue samples from 39 patients. CD163 is used as a marker of M2 macrophages. Neovascularization and infiltration of forkhead box P3 (FOXP3) (+) regulatory T cells were also evaluated. The number of CD68 (+) and CD163 (+) macrophages was positively correlated with the numbers of vessels and regulatory T cells. The number of CD163 (+) cells was more closely associated with them. Intrahepatic cholangiocarcinoma (ICC) patients with high counts of CD163 (+) macrophages showed poor disease-free survival (P = 0.0426). The macrophage density was not correlated with overall survival. In an in vitro study using ICC cell lines (HuCCT1, RBE, and MEC) and human macrophages, tumor cell supernatant (TCS) from cell lines induced an activation of signal transducers and activators of transcription-3 (Stat3) and macrophage polarization toward the M2 phenotype. Tumor cell supernatant (TCS) from HuCCT1 most strongly induced Stat3 activation and production of cytokines and other bioactive molecules such as interleukin (IL)-10, vascular endothelial growth factor (VEGF)-A, transforming growth factor (TGF)-beta, and matrix metalloproteinase (MMP)-2. Down-regulation of Stat3 by siRNA significantly suppressed the production of IL-10 and VEGF-A. These results provide suggestive evidence that TAMs contribute to cancer progression via Stat3 activation, and CD163 is useful for evaluating M2 TAMs and predicting the clinical prognosis of ICC patients.
221 citations
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TL;DR: It is demonstrated here that poly(ethylene glycol)-conjugated ZnPP (PEG-ZnPP), a water-soluble derivative of Zn PP, exhibited potent HO inhibitory activity and had an antitumor effect in vivo, suggesting that tumor-targeted inhibition of HO activity could be achieved by using PEG-znPP, which induces apoptosis in solid tumors, probably through increased oxidative stress.
Abstract: High expression of the inducible isoform of heme oxygenase (HO-1) is now well known in solid tumors in humans and experimental animal models. We reported previously that HO-1 may be involved in tumor growth (Tanaka et al., Br. J. Cancer, 88: 902-909, 2003), in that inhibition of HO activity in tumors by using zinc protoporphyrin (ZnPP) significantly reduced tumor growth in a rat model. We demonstrate here that poly(ethylene glycol)-conjugated ZnPP (PEG-ZnPP), a water-soluble derivative of ZnPP, exhibited potent HO inhibitory activity and had an antitumor effect in vivo. In vitro studies with cultured SW480 cells, which express HO-1, showed that PEG-ZnPP induced oxidative stress, and consequently apoptotic death, of these cells. Pharmacokinetic analysis revealed that PEG-ZnPP-administered i.v. had a circulation time in blood that was 40 times longer than that for nonpegylated ZnPP. More important, PEG-ZnPP preferentially accumulated in solid tumor tissue in a murine model. In vivo treatment with PEG-ZnPP (equivalent to 1.5 or 5 mg of ZnPP/kg, i.v., injected daily for 6 days) remarkably suppressed the growth of Sarcoma 180 tumors implanted in the dorsal skin of ddY mice without any apparent side effects. In addition, this PEG-ZnPP treatment produced tumor-selective suppression of HO activity as well as induction of apoptosis. The major reason for tumor-selective targeting of PEG-ZnPP is attributed to the enhanced permeability and retention effect that is observed commonly in solid tumors for biocompatible macromolecular drugs. These findings suggest that tumor-targeted inhibition of HO activity could be achieved by using PEG-ZnPP, which induces apoptosis in solid tumors, probably through increased oxidative stress.
220 citations
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TL;DR: The involvement of nitric oxide and its reactive intermediates such as nitrogen dioxide (NO2) and peroxynitrite (ONOO-) in the activation of matrix metallo-proteinase was investigated and suggest that NO2 and ONOO- may be potent activators of human neutrophil procollagenase.
220 citations
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TL;DR: In this article, the voltammetric responses for the electrocatalytic oxidation of glucose at Au 2-nm nanoparticle-modified electrodes in both alkaline and neutral solutions were similar to those at a gold plate electrode.
219 citations
Authors
Showing all 19645 results
Name | H-index | Papers | Citations |
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Fred H. Gage | 216 | 967 | 185732 |
George D. Yancopoulos | 158 | 496 | 93955 |
Kenji Kangawa | 153 | 1117 | 110059 |
Tasuku Honjo | 141 | 712 | 88428 |
Hideo Yagita | 137 | 946 | 70623 |
Masashi Yanagisawa | 130 | 524 | 83631 |
Kazuwa Nakao | 128 | 1041 | 70812 |
Kouji Matsushima | 124 | 590 | 56995 |
Thomas E. Mallouk | 122 | 549 | 52593 |
Toshio Hirano | 120 | 401 | 55721 |
Eisuke Nishida | 112 | 349 | 45918 |
Hiroaki Shimokawa | 111 | 949 | 48822 |
Bernd Bukau | 111 | 271 | 38446 |
Kazuo Tsubota | 105 | 1379 | 48991 |
Toshio Suda | 104 | 580 | 41069 |