Fumiko Shimizu

Showa Women's University

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Akikazu Takada

Hamamatsu University School of Medicine

Tetsuya Takao

Osaka City General Hospital

Yukie Ishii

Showa Women's University

Viviane Tabar

Memorial Sloan Kettering Cancer Center

Mutsumi Ogawa

Showa Women's University

Koos E. Hovinga

Maastricht University Medical Centre

Masahiro Ogawa

Kagawa University

Leif A. Droms

Memorial Sloan Kettering Cancer Center

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Antonio Omuro

Yale Cancer Center

Cooperative Institutions

National Institute of Diabetes and Digestive and Kidney Diseases

205

ProQuest (United States)

196

Memorial Sloan Kettering Cancer Center

152

University of Washington

137

University of Nebraska Medical Center

127

University of California, Irvine Medical Center

120

Seattle Cancer Care Alliance

119

Sheffield Teaching Hospitals NHS Foundation Trust

117

Fred Hutch Cancer Center

115

The University of Texas MD Anderson Cancer Center

103

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Calcium-bound recoverin targets rhodopsin kinase to membranes to inhibit rhodopsin phosphorylation

FEBS Letters (1996)

Kamon Sanada Fumiko Shimizu Kimihiko Kameyama Kazuko Haga Tatsuya Haga

In rod photoreceptor cells, Ca 2+ ‐bound recoverin associates with disk membranes and inhibits light‐dependent phosphorylation of rhodopsin. However, the functional significance of Ca 2+ ‐induced membrane association of recoverin has not been fully evaluated. We found that Ca 2+ ‐bound recoverin forms a complex with rhodopsin kinase preferentially at the membrane surface. Addition of increasing amounts of membranes promoted the membrane association of recoverin, and remarkably suppressed rhodopsin kinase activity. It was concluded that the Ca 2+ ‐recoverin‐rhodopsin kinase complex is stabilized by membrane association, leading to effective suppression of the kinase activity.

Recoverin

10.1016/0014-5793(96)00318-3

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Citations (30)

Measurement of Plasma Tryptophan Metabolites: Clinical and Experimental Application for Depression and Stress States Assessment

IntechOpen eBooks (2018)

Akikazu Takada Fumiko Shimizu Junichi Masuda

There are three pathways in tryptophan (TRP) metabolism. Serotonin (5-hydroxytryptamine; 5-HT) pathway is important in mood, anxiety, memory, and cognition and is impaired in depression. Kynurenine (KYN) pathways are involved in immunity, inflammation, muscles movement, and mental health. We investigated changes in TRP metabolites in plasmas of stressed rats and in depressive patients. TRP metabolite levels in 5-HT and KYN pathways in various brain areas and plasma were increased soon after electric foot shock given to rats but returned to normal 24 h later. Plasma levels of 5-HT were very low or undetectable in patients of monopolar depression. 5-hydroxyindole acetic acid (5-HIAA)/TRP ratios or KYN/TRP ratios were not different between healthy controls and depressive patients, indicating 5-HT quickly being degraded into 5-HIAA in patients of depression but KYN levels were not changed in depression. These results indicate that TRP metabolism changes upon stress application and in patients of depression.

Depression

10.5772/intechopen.78560

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Citations (7)

Inhibition of Notch Signaling in Glioblastoma Targets Cancer Stem Cells via an Endothelial Cell Intermediate

Stem Cells (2010)

Koos E. Hovinga Fumiko Shimizu Rong Wang Georgia Panagiotakos Maartje van der Heijden

Abstract Glioblastoma multiforme (GBM) is a highly heterogeneous malignant tumor. Recent data suggests the presence of a hierarchical organization within the GBM cell population that involves cancer cells with stem-like behavior, capable of repopulating the tumor and contributing to its resistance to therapy. Tumor stem cells are thought to reside within a vascular niche that provides structural and functional support. However, most GBM studies involve isolated tumor cells grown under various culture conditions. Here, we use a novel three-dimensional organotypic “explant” system of surgical GBM specimens that preserves cytoarchitecture and tumor stroma along with tumor cells. Notch inhibition in explants results in decreased proliferation and self-renewal of tumor cells but is also associated with a decrease in endothelial cells. When endothelial cells are selectively eliminated from the explants via a toxin conjugate, we also observed a decrease in self-renewal of tumor stem cells. These findings support a critical role for tumor endothelial cells in GBM stem cell maintenance, mediated at least in part by Notch signaling. The explant system further highlighted differences in the response to radiation between explants and isolated tumor neurospheres. Combination treatment with Notch blockade and radiation resulted in a substantial decrease in proliferation and in self-renewal in tumor explants while radiation alone was less effective. This data suggests that the Notch pathway plays a critical role in linking angiogenesis and cancer stem cell self-renewal and is thus a potential therapeutic target. Three-dimensional explant systems provide a novel approach for the study of tumor and microenvironment interactions.

Neurosphere

10.1002/stem.429

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Citations (288)

The epichaperome is an integrated chaperome network that facilitates tumour survival

Nature (2016)

Anna Rodina Tai Wang Pengrong Yan Erica DaGama Gomes Mark Dunphy

Crosstalk

Proteostasis

Chaperone (clinical)

10.1038/nature19807

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Citations (251)

Plasma Fatty Acid Composition in Men over 50 in the USA and Japan

Food and Nutrition Sciences (2018)

Akikazu Takada Fumiko Shimizu Yuji Ishii Masahiro Ogawa Tetsuya Takao

Background: Coronary heart disease (CHD) rates differ markedly between the US and Japan. Fatty acid profiles have been linked to risk for CHD. Few studies have compared the plasma fatty acid composition, including trans fatty acids, in Japanese and US subjects. Methods: Fasting blood samples were taken from healthy older (>age 50) American (n = 76) and Japanese (n = 44) men, and plasma levels of 23 fatty acids were analyzed by gas chromatography and expressed as a percent of total fatty acids. Results: As expected, plasma levels of long-chain ω3 fatty acids (docosahexaenoic and eicosapentaenoic acids, DHA and EPA) were higher in Japanese men and ω6 fatty acids (e.g., arachidonic acid, AA) were lower compared with American men. Plasma levels of the major industrially-produced trans fatty acids (IP-TFAs; elaidic and linoelaidic acids) were far higher in American men, and levels of the potentially cardioprotective, primarily ruminant-derived trans fatty acid palmitoelaidic acid (POA) were higher in Japanese. Plasma levels of saturated or monounsaturated fatty acids were also higher in the American men. Conclusion: There are multiple differences in plasma fatty acid profiles between American and Japanese older men. The higher levels of DHA and EPA, along with the lower levels of the IP-TFAs, are consistent with the markedly lower risk for coronary heart disease in Japan vs. the US.

Elaidic acid

10.4236/fns.2018.96054

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Citations (5)

Comparison of plasma levels of different species of trans fatty acids in Japanese male patients with acute coronary syndrome versus healthy men

Atherosclerosis (2019)

Shinji Koba Tetsuya Takao Fumiko Shimizu Mutsumi Ogawa Yukie Ishii

Background and aimsIt remains unclear how trans fatty acid (TFA) at low-level intake affect lipid levels and the development of acute coronary syndrome (ACS). The study aimed to investigate how plasma TFA composition differs between male patients with ACS and healthy men.MethodsPlasma fatty acid (FA) composition (as determined by gas chromatography) was analyzed in ACS patients on hospital admission and compared to that of age-adjusted healthy men.ResultsTotal FA and TFA levels were similar between ACS and control subjects. Palmitelaidic acid, ruminant-derived TFA (R-TFA), levels were lower in ACS patients (0.17 ± 0.06 vs. 0.20 ± 0.06 of total FA, in ACS and control, respectively, p<0.01), and were significantly directly associated with HDL cholesterol (HDL-C) (rho = 0.269) and n-3 polyunsaturated FA (n-3 PUFA) (rho = 0.442). Linoleic trans isomers (total C18:2 TFA), primary industrially-produced TFA (IP-TFAs), were significantly higher in ACS patients (0.68 ± 0.17 vs. 0.60 ± 0.20 of total FA, in ACS and control, respectively). Total trans-C18:1 isomers were comparable between ACS and control. Differences between ACS and controls in C18:1 trans varied by specific C18:1 trans species. Absolute concentrations of trans-C18:2 isomers were significantly directly associated with LDL-C and non-HDL-C in ACS men. The ACS patients showed significantly lower levels of both n-6 and n-3 PUFA (i.e., eicosapentaenoic, docosahexaenoic and arachidonic acids).ConclusionsThere were several case-control differences in specific TFA that could potential affect risk for ACS. Japanese ACS patients, especially middle-aged patients, may consume less R-TFA.

10.1016/j.atherosclerosis.2019.02.025

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Citations (12)

Resolution of fibrosis by siRNA HSP47 in vitamin A‐coupled liposomes induces regeneration of chronically injured livers

Journal of Gastroenterology and Hepatology (2021)

Yasushi Sato Akihiro Yoneda Fumiko Shimizu Miyuki Nishimura Rai Shimoyama

In chronic hepatic diseases where treatment strategies are not available, deposited fibrotic tissues deteriorate the intrinsic regeneration capacity of the liver by creating special restrictions. Thus, if the anti-fibrosis modality is efficiently applied, the regeneration capacity of the liver should be reactivated even in such refractory hepatic diseases.Rat liver fibrosis was induced by dimethyl-nitrosamine (DMN). Another liver fibrosis model was established in CCl4 treated Sox9CreERT2ROSA26: YFP mice. To resolve hepatic fibrosis, vitamin A-coupled liposomes containing siRNA HSP47 (VA-liposome siHSP47) were employed. EpCAM + hepatic progenitor cells from GFP rats were transplanted to DMN rat liver to examine their trans-differentiation into hepatic cells after resolution of liver fibrosis.Even under continuous exposure to such strong hepatotoxin as DMN, rats undergoing VA-liposome siHSP47 treatment showed an increment of DNA synthesis of hepatocytes with the concomitant restoration of impaired liver weight and normalization of albumin levels. These results were consistent with the observation that GFP + EpCAM hepatic progenitor cells transplanted to DMN rat liver, trans-differentiated into GFP + mature hepatic cells after VA-liposome siHSP47 treatment. Another rodent model also proved regeneration potential of the fibrotic liver in CCl4 administered Sox9CreERT2ROSA26: YFP mice, VA-liposome siHSP47 treatment-induced restoration of liver weight and trans-differentiation of YEP + Sox9 + cells into YFP + hepatic cells, although because of relatively mild hepatotoxicity of CCl4, undamaged hepatocytes also proliferated.These results demonstrated that regeneration of chronically damaged liver indeed occurs after anti-fibrosis treatment even under continuous exposure to hepatotoxin, which promises a significant benefit of the anti-fibrosis therapy for refractory liver diseases.

Hepatotoxin

Liver Regeneration

Hepatic fibrosis

10.1111/jgh.15587

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Citations (9)

Data from Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial

Ran Xu Fumiko Shimizu Koos E. Hovinga Kathryn Beal Sasan Karimi

<div>AbstractPurpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.Experimental Design: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood–brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment.Results: Treatment was well tolerated and no dose-limiting toxicities were observed. IHC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133+ CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors.Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood–brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. Clin Cancer Res; 22(19); 4786–96. ©2016 AACR.</div>

Temozolomide

Anaplastic astrocytoma

10.1158/1078-0432.c.6526635

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Organotypic Explant Culture of Glioblastoma Multiforme and Subsequent Single‐Cell Suspension

Current Protocols in Stem Cell Biology (2011)

Fumiko Shimizu Koos E. Hovinga Michael Metzner Denis Soulet Viviane Tabar

Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM cell lines used in laboratory studies are frequently passaged in various culture media at high proliferation rates, resulting in significant genetic and molecular alterations. Thus, data obtained in cell lines are often inapplicable to patient tumors. Furthermore, recent studies suggest that there is a stem cell-like hierarchy among GBM cell populations and a crucial role for tumor vasculature in stem cells, as well as tumor growth, which cannot be reproduced in cell line cultures. Our laboratory has developed a novel three-dimensional (3D) organotypic "explant" system of surgical GBM specimens that preserves tumor cells in their original milieu, as well as the cytoarchitecture of the tumor stroma. Our previous study on the role of Notch inhibition has demonstrated a definitive effect on the tumor endothelium that could only be highlighted by this system. In this unit, we describe a detailed protocol for preparing GBM explants, and discuss strengths, as well as limitations of the explant system as an in vitro 3D model of GBM.

Cytoarchitecture

10.1002/9780470151808.sc0305s19

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Citations (19)

[Symposium: Function structure of the cells of microorganisms].

PubMed (1969)

Fumiko Shimizu Masaru Koike Masamiki Masui Sugio Ōtani Kenta Kato

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