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Article ; Online: Weekly paclitaxel, carboplatin and cetuximab (PCE) combination followed by nivolumab for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Takeshita, Naohiro / Enokida, Tomohiro / Okano, Susumu / Fujisawa, Takao / Wada, Akihisa / Sato, Masanobu / Tanaka, Hideki / Tanaka, Nobukazu / Onaga, Ryutaro / Hoshi, Yuta / Sakashita, Shingo / Ishii, Genichiro / Tahara, Makoto

Oral oncology

2023 Volume 147, Page(s) 106615

Abstract: ... metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, few studies have reported ... patients with R/M SCCHN from the oral cavity, oropharynx, hypopharynx, and larynx who received PCE as 1st ...

Abstract	Objectives: Cetuximab-based chemotherapy is a standard 1st-line treatment for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, few studies have reported survival data for a treatment sequence consisting of a PCE regimen (paclitaxel + carboplatin + cetuximab) followed by an immune checkpoint inhibitor. Materials and methods: We retrospectively assessed 37 patients with R/M SCCHN from the oral cavity, oropharynx, hypopharynx, and larynx who received PCE as 1st-line treatment followed by nivolumab as 2nd-line at the National Cancer Center Hospital East between December 2016 and July 2021. For comparison, we also analyzed 14 patients who did not receive nivolumab after PCE. Results: Of the 37 patients who received nivolumab, overall response rate (ORR) by PCE was 48.6%, and median time to response and median progression-free survival (PFS) were 2.1 months (range: 0.8-4.8) and 4.4 months, respectively. In the nivolumab phase, ORR was 10.8%. 23 patients received 3rd-line therapy. Median PFS2, PFS3, and overall survival (OS) were 6.8, 11.6, and 19.5 months, respectively. Subgroup analysis by PD-L1 expression showed no significant difference in OS. Analysis of the comparison group revealed a trend toward improved OS in those who received nivolumab compared to those who did not (HR 0.47, 95%CI [0.19-1.13], p = 0.084). Conclusion: PCE followed by nivolumab shows a favorable survival outcome, representing the potential for rapid tumor response with PCE and extension of OS by the addition of nivolumab regardless of combined positive score.
MeSH term(s)	Humans ; Cetuximab/therapeutic use ; Nivolumab/therapeutic use ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/etiology ; Carboplatin/therapeutic use ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/etiology ; Paclitaxel ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Recurrence, Local/pathology
Chemical Substances	Cetuximab (PQX0D8J21J) ; Nivolumab (31YO63LBSN) ; Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2023-11-04
Publishing country	England
Document type	Journal Article
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2023.106615
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Zs.A 4869: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m².

Nakatani, Shinya / Nakatani, Ayumi / Tsugawa, Naoko / Yamada, Shinsuke / Mori, Katsuhito / Imanishi, Yasuo / Ishimura, Eiji / Okano, Toshio / Inaba, Masaaki

Nephron

2015 Volume 130, Issue 2, Page(s) 119–126

Abstract: ... of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2 ... Methods: Subjects with eGFR ≥60 ml/min/1.73 m(2) (n = 20) were enrolled and their serum levels of FGF-23 ... demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m(2), FGF-23 might play an important role ...

Abstract	Background/aims: Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D), allows the distinction of the effects of FGF-23 from those of PTH. The aim of this study was to elucidate which factor, FGF-23 or PTH, plays a more important role in the regulation of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2). Methods: Subjects with eGFR ≥60 ml/min/1.73 m(2) (n = 20) were enrolled and their serum levels of FGF-23, intact PTH, and vitamin D metabolites were determined. Results: Serum FGF-23 correlated inversely with 1,25(OH)2D (r = -0.717, p = 0.0004) and the 1,25(OH)2D/25-OH-D ratio (r = -0.518, p = 0.019), compared with a significant positive correlation between serum intact PTH and the 1,25(OH)2D/25-OH-D ratio (r = 0.562, p = 0.010). Multiple regression analyses revealed serum FGF-23 as a significant factor that was associated with serum 1,25(OH)2D (β = -0.593, p = 0.018), 1,25(OH)2D/25-OH-D ratio (β = -0.521, p = 0.025), and the 24,25(OH)2D/1,25(OH)2D ratio (β = 0.632, p = 0.008), and intact PTH as a significant factor associated with the 1,25(OH)2D/25-OH-D ratio (β = 0.445, p = 0.028). Conclusions: This study demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m(2), FGF-23 might play an important role in the regulation of vitamin D metabolism. In addition to the established role of PTH, the association between FGF-23 and indices of vitamin D metabolism suggested the potential role of FGF-23 on phosphate metabolism in such patients.
MeSH term(s)	Aged ; Aged, 80 and over ; Ergocalciferols/blood ; Female ; Fibroblast Growth Factors/metabolism ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D/metabolism
Chemical Substances	Ergocalciferols ; fibroblast growth factor 23 ; Vitamin D (1406-16-2) ; 1,25-dihydroxyergocalciferol (55248-15-2) ; Fibroblast Growth Factors (62031-54-3) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000430870
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Article ; Online: Detection of chromosomal blaCTX-M-15 in Escherichia coli O25b-B2-ST131 isolates from the Kinki region of Japan.

Hirai, Itaru / Fukui, Naoki / Taguchi, Masumi / Yamauchi, Kou / Nakamura, Tatsuya / Okano, Sho / Yamamoto, Yoshimasa

International journal of antimicrobial agents

2013 Volume 42, Issue 6, Page(s) 500–506

Abstract: Escherichia coli O25b-B2-ST131 isolates harbouring bla(CTX-M-15) are distributed worldwide. The bla ... CTX-M-15) transposition unit has often been found on plasmids and the genetic contexts have been ... examined; however, less is known about the frequency and contexts of the bla(CTX-M-15) transposition unit ...

Abstract	Escherichia coli O25b-B2-ST131 isolates harbouring bla(CTX-M-15) are distributed worldwide. The bla(CTX-M-15) transposition unit has often been found on plasmids and the genetic contexts have been examined; however, less is known about the frequency and contexts of the bla(CTX-M-15) transposition unit on the chromosome. This study was performed to determine the chromosomal location of the bla(CTX-M-15) transposition unit and to analyse the molecular structure of the region surrounding the bla(CTX-M-15) transposition unit in E. coli O25b-B2-ST131 isolates. Twenty-two E. coli O25b-B2-ST131 strains harbouring bla(CTX-M-15) that had been isolated from university hospital patients and nursing home residents in the Kinki region of Japan were examined. Inverse PCR (iPCR) targeting bla(CTX-M-15) was performed to classify the molecular structure of the region surrounding the bla(CTX-M-15) transposition unit. The isolates were classified into nine types (types A-I) considering the iPCR results; type A was the most prevalent type (13/22 isolates). Sequences of the iPCR-amplified DNA fragments showed that the bla(CTX-M-15) transposition unit consisted of ISEcp1, bla(CTX-M-15) and orf477Δ. A homology search of the obtained sequences showed that the bla(CTX-M-15) transposition unit was inserted into different chromosomal regions in eight of the nine classified types. Although 21 of the 22 E. coli isolates possessed chromosomally located bla(CTX-M-15) transposition units, clonal spread was not evident on pulsed-field gel electrophoresis (PFGE) analysis. Taken together, these data indicate that certain E. coli O25b-B2-ST131 strains harbouring chromosomal bla(CTX-M-15) have emerged and spread in the Kinki region of Japan.
MeSH term(s)	Aged ; Chromosomes, Bacterial ; DNA Transposable Elements ; DNA, Bacterial/chemistry ; DNA, Bacterial/genetics ; Electrophoresis, Gel, Pulsed-Field ; Escherichia coli/classification ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Escherichia coli/isolation & purification ; Escherichia coli Infections/microbiology ; Genetic Loci ; Humans ; Japan ; Molecular Sequence Data ; Molecular Typing ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; beta-Lactamases/genetics ; beta-Lactamases/secretion
Chemical Substances	DNA Transposable Elements ; DNA, Bacterial ; beta-lactamase CTX-M-15 (EC 3.5.2.-) ; beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2013-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2013.08.005
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Zs.A 3368: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m

Nakatani, Shinya / Nakatani, Ayumi / Tsugawa, Naoko / Yamada, Shinsuke / Mori, Katsuhito / Imanishi, Yasuo / Ishimura, Eiji / Okano, Toshio / Inaba, Masaaki

Nephron

2015 Volume 130, Issue 2, Page(s) 119–126

Abstract: Background/Aims: Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), ... ...

Institution	Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka Department of Hygienic Sciences, Kobe Pharmaceutical University, Hyogo, Japan
Abstract	Background/Aims: Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D), allows the distinction of the effects of FGF-23 from those of PTH. The aim of this study was to elucidate which factor, FGF-23 or PTH, plays a more important role in the regulation of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m2Methods: Subjects with eGFR ≥60 ml/min/1.73 m2 (n = 20) were enrolled and their serum levels of FGF-23, intact PTH, and vitamin D metabolites were determined. Results: Serum FGF-23 correlated inversely with 1,25(OH)2D (r = -0.717, p = 0.0004) and the 1,25(OH)2D/25-OH-D ratio (r = -0.518, p = 0.019), compared with a significant positive correlation between serum intact PTH and the 1,25(OH)2D/25-OH-D ratio (r = 0.562, p = 0.010). Multiple regression analyses revealed serum FGF-23 as a significant factor that was associated with serum 1,25(OH)2D (β = -0.593, p = 0.018), 1,25(OH)2D/25-OH-D ratio (β = -0.521, p = 0.025), and the 24,25(OH)2D/1,25(OH)2D ratio (β = 0.632, p = 0.008), and intact PTH as a significant factor associated with the 1,25(OH)2D/25-OH-D ratio (β = 0.445, p = 0.028). Conclusions: This study demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m2, FGF-23 might play an important role in the regulation of vitamin D metabolism. In addition to the established role of PTH, the association between FGF-23 and indices of vitamin D metabolism suggested the potential role of FGF-23 on phosphate metabolism in such patients.
Keywords	CKD-MBD ; Vitamin D ; Intact PTH ; FGF-23
Language	English
Publishing date	2015-06-09
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Clinical Practice: Original Paper
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000430870
Database	Karger publisher's database

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Article ; Online: Serial measurement of free light chain detects poor response to therapy early in three patients with multiple myeloma who have measurable M-proteins.

Fuchida, Shin-ichi / Okano, Akira / Hatsuse, Mayumi / Murakami, Satoshi / Haruyama, Harue / Itoh, Saori / Shimazaki, Chihiro

International journal of hematology

2012 Volume 96, Issue 5, Page(s) 664–668

Abstract: ... in patients who have measurable M-proteins by electrophoresis. We examined the kinetics of serum FLC in six ...

Abstract	Free light chain (FLC) assays are important in the diagnosis and monitoring of patients with multiple myeloma (MM). Serum FLC concentrations also correlate with disease course in the majority of MM patients and have been incorporated into the new response criteria. Although baseline values of FLC are prognostic in newly diagnosed MM, serial measurement of serum FLC does not appear to be of greater value in patients who have measurable M-proteins by electrophoresis. We examined the kinetics of serum FLC in six patients with newly diagnosed MM during treatment with high-dose dexamethasone (HD-DEX) and bortezomib and dexamethasone. In some cases, the involved serum FLC increased in the latter part of each chemotherapy cycle before the start of the next cycle, especially in HD-DEX, suggesting that the response to these agents may be insufficient for induction therapy for MM. Earlier disease assessment by serum FLC assays may be of value in detecting poorly responding patients who require alternative forms of therapy.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Boronic Acids/administration & dosage ; Bortezomib ; Dexamethasone/administration & dosage ; Female ; Humans ; Immunoglobulin Light Chains/blood ; Immunoglobulins/blood ; Male ; Middle Aged ; Multiple Myeloma/blood ; Multiple Myeloma/drug therapy ; Pyrazines/administration & dosage
Chemical Substances	Boronic Acids ; Immunoglobulin Light Chains ; Immunoglobulins ; M-proteins (Myeloma) ; Pyrazines ; Bortezomib (69G8BD63PP) ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2012-09-02
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-012-1164-0
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Zs.A 269: Show issues

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Article ; Online: Musashi-1 post-transcriptionally enhances phosphotyrosine-binding domain-containing m-Numb protein expression in regenerating gastric mucosa.

Takahashi, Tetsufumi / Suzuki, Hidekazu / Imai, Takao / Shibata, Shinsuke / Tabuchi, Yoshiaki / Tsuchimoto, Kanji / Okano, Hideyuki / Hibi, Toshifumi

PloS one

2013 Volume 8, Issue 1, Page(s) e53540

Abstract: ... injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb ... type ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and ... Results: We demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was ...

Abstract	Objective: Upregulation of the RNA-binding protein Musashi-1 (Msi1) has been shown to occur in rat gastric corpus mucosa after ethanol-induced mucosal injury. However, there is no direct evidence linking Msi1 with gastric regeneration. We examined the process of tissue repair after acute gastric mucosal injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb expression in regenerating gastric mucosa. Methods: Acute gastric injury was induced in Msi1-KO and wild-type ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and protein in the gastric mucosa were analyzed by quantitative RT-PCR and western blotting, respectively. Results: We demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was significantly upregulated at both the mRNA and protein levels in wild-type mice at 3 h after ethanol-induced acute gastric injury. In contrast, in Msi1-KO mice, the m-Numb protein was expressed weakly, and was associated with delayed regeneration of the injured gastric mucosal epithelium. In the Msi1-KO mouse, the ratio of m-Numb mRNA to total m-Numb mRNA in the heavy polysome fractions was lower than that in the wild-type mouse. Further, we showed that m-Numb-enhancement in gastric mucous cells induced the expression of prostate stem cell antigen and metallothionein-2. Under the m-Numb enhancing condition, the gastric cells exhibited enhanced cell proliferation and were significantly more resistant to H(2)O(2)-induced cell death than control cells. Conclusions: Msi1-dependent post-transcriptional enhancement of m-Numb is crucial in gastric epithelial regeneration.
MeSH term(s)	Alternative Splicing ; Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Burns, Chemical/genetics ; Burns, Chemical/metabolism ; Burns, Chemical/pathology ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Ethanol ; GPI-Linked Proteins/genetics ; GPI-Linked Proteins/metabolism ; Gastric Mucosa/injuries ; Gastric Mucosa/metabolism ; Gene Expression Regulation ; Hydrogen Peroxide/pharmacology ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Metallothionein/genetics ; Metallothionein/metabolism ; Mice ; Mice, Knockout ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Nerve Tissue Proteins/deficiency ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Phosphotyrosine/chemistry ; Phosphotyrosine/genetics ; Polyribosomes/genetics ; Polyribosomes/metabolism ; Protein Structure, Tertiary ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; Re-Epithelialization/genetics ; Signal Transduction
Chemical Substances	Antigens, Neoplasm ; GPI-Linked Proteins ; Membrane Proteins ; Msi1h protein, mouse ; Mt2 protein, mouse ; Neoplasm Proteins ; Nerve Tissue Proteins ; Numb protein, mouse ; Psca protein, mouse ; RNA, Messenger ; RNA-Binding Proteins ; Phosphotyrosine (21820-51-9) ; Ethanol (3K9958V90M) ; Metallothionein (9038-94-2) ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2013-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0053540
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Article: [GUIDELINE FOR ALLERGIC RHINITIS].

Okano, Mitsuhiro

Arerugi = [Allergy

2023 Volume 72, Issue 5, Page(s) 417–427

MeSH term(s)	Humans ; Rhinitis, Allergic/diagnosis ; Rhinitis, Allergic/therapy ; Rhinitis, Allergic, Seasonal ; Quality of Life
Language	Japanese
Publishing date	2023-07-17
Publishing country	Japan
Document type	Journal Article
ZDB-ID	974201-3
ISSN	0021-4884
ISSN	0021-4884
DOI	10.15036/arerugi.72.417
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Article: Differentiation of a murine intestinal epithelial cell line (MIE) toward the M cell lineage.

Kanaya, Takashi / Miyazawa, Kohtaro / Takakura, Ikuro / Itani, Wataru / Watanabe, Kouichi / Ohwada, Shyuichi / Kitazawa, Haruki / Rose, Michael T / McConochie, Huw R / Okano, Hideyuki / Yamaguchi, Takahiro / Aso, Hisashi

American journal of physiology. Gastrointestinal and liver physiology

2008 Volume 295, Issue 2, Page(s) G273–84

Abstract: M cells are a kind of intestinal epithelial cell in the follicle-associated epithelium ... the important role of M cells in mucosal immune responses, the origin and mechanisms of differentiation as well ... as cell death of M cells remain unclear. To clarify the mechanism of M cell differentiation, we established ...

Abstract	M cells are a kind of intestinal epithelial cell in the follicle-associated epithelium of Peyer's patches. These cells can transport antigens and microorganisms into underlying lymphoid tissues. Despite the important role of M cells in mucosal immune responses, the origin and mechanisms of differentiation as well as cell death of M cells remain unclear. To clarify the mechanism of M cell differentiation, we established a novel murine intestinal epithelial cell line (MIE) from the C57BL/6 mouse. MIE cells grow rapidly and have a cobblestone morphology, which is a typical feature of intestinal epithelial cells. Additionally, they express cytokeratin, villin, cell-cell junctional proteins, and alkaline phosphatase activity and can form microvilli. Their expression of Musashi-1 antigen indicates that they may be close to intestinal stem cells or transit-amplifying cells. MIE cells are able to differentiate into the M cell lineage following coculture with intestinal lymphocytes, but not with Peyer's patch lymphocytes (PPL). However, PPL costimulated with anti-CD3/CD28 MAbs caused MIE cells to display typical features of M cells, such as transcytosis activity, the disorganization of microvilli, and the expression of M cell markers. This transcytosis activity of MIE cells was not induced by T cells isolated from PPL costimulated with the same MAbs and was reduced by the depletion of the T cell population from PPL. A mixture of T cells treated with MAbs and B cells both from PPL led MIE cells to differentiate into M cells. We report here that MIE cells have the potential ability to differentiate into M cells and that this differentiation required activated T cells and B cells.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Cell Line ; Cell Lineage/physiology ; Coculture Techniques ; Intestinal Mucosa/cytology ; Intestinal Mucosa/ultrastructure ; Male ; Mice ; Mice, Inbred BALB C ; Microscopy, Phase-Contrast ; Peyer's Patches/cytology ; Specific Pathogen-Free Organisms
Language	English
Publishing date	2008-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00378.2007
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Article ; Online: Two major mechanisms regulating cell-fate decisions in the developing nervous system.

Okano, Hideyuki

Development, growth & differentiation

2023 Volume 37, Issue 6, Page(s) 619–629

Abstract: ... genes at the post-transcriptional level. We have identified its mammalian homologue, mouse-musashi-1 (m ... Msi-1). In the developing central nervous system (CNS), m-Msi-1 expression was highly enriched ... experiment, m-Msi-1 expression appears to be associated with multipotent cells that are capable of self ...

Abstract	Two types of determinants appear to be responsible for the generation of neural cell diversity: non-cell-autonomous and cell-autonomous cues. We have identified both types of determinants through the intensive screening of P-element induced Drosophila mutants affected in neural development. As a member of the first category argos (also referred to as strawberry or giant lens), which regulates cell-cell interaction in the developing nervous system, needs to be mentioned. On the basis of the phenotype on loss of function of argos. its expression pattern and the predicted structure of its product (a secreted protein with a putative epidermal growth factor (EGF) motif) we propose that argos encodes a diffusible protein with pleiotropic functions that acts as a signal involved in lateral inhibition within the developing nervous system and also as a factor involved in axonal guidance. As a member of the second category, I refer to the Drosophila musashi gene that is required for lineage formation and asymmetric division of precursor cells in the developing nervous system. The musashi gene encodes a neural RNA-biding protein and is thus likely to regulate the asymmetric cell division of neural precursor cells by controlling the expression of target genes at the post-transcriptional level. We have identified its mammalian homologue, mouse-musashi-1 (m-Msi-1). In the developing central nervous system (CNS), m-Msi-1 expression was highly enriched to neural precursor cells as is the expression of nestin. Based on the results of a single cell culture experiment, m-Msi-1 expression appears to be associated with multipotent cells that are capable of self-renewal and with the generation of committed precursor cells of both neurons and glia. However, fully differentiated neuronal and glial cells lost their m-Msi-1 expression. The expression of m-Msi protein showed a complementary pattern to that of another mammalian RNA-binding protein Hu, which is localized in differentiated neurons in the CNS. Based on such differential expression patterns and its similarity to the Drosophila musashi, we propose that a combination of neural RNA-binding proteins are required for the asymmetric distribution of intrinsic determinants in the developing mammalian nervous system. The Drosophila glial-specific homeobox protein, Repo, can also be classified as a cell-autonomous cue regulating cell-fate decision during neural development. Repo expression is required for terminal differentiation and for the survival of glial cells.
Language	English
Publishing date	2023-06-06
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	280433-5
ISSN	1440-169X ; 0012-1592
ISSN (online)	1440-169X
ISSN	0012-1592
DOI	10.1046/j.1440-169X.1995.t01-5-00001.x
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Article ; Online: Musashi-1 post-transcriptionally enhances phosphotyrosine-binding domain-containing m-Numb protein expression in regenerating gastric mucosa.

Tetsufumi Takahashi / Hidekazu Suzuki / Takao Imai / Shinsuke Shibata / Yoshiaki Tabuchi / Kanji Tsuchimoto / Hideyuki Okano / Toshifumi Hibi

PLoS ONE, Vol 8, Iss 1, p e

2013 Volume 53540

Abstract: ... injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb ... ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and ... RESULTS: We demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was ...

Abstract	OBJECTIVE: Upregulation of the RNA-binding protein Musashi-1 (Msi1) has been shown to occur in rat gastric corpus mucosa after ethanol-induced mucosal injury. However, there is no direct evidence linking Msi1 with gastric regeneration. We examined the process of tissue repair after acute gastric mucosal injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb expression in regenerating gastric mucosa. METHODS: Acute gastric injury was induced in Msi1-KO and wild-type ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and protein in the gastric mucosa were analyzed by quantitative RT-PCR and western blotting, respectively. RESULTS: We demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was significantly upregulated at both the mRNA and protein levels in wild-type mice at 3 h after ethanol-induced acute gastric injury. In contrast, in Msi1-KO mice, the m-Numb protein was expressed weakly, and was associated with delayed regeneration of the injured gastric mucosal epithelium. In the Msi1-KO mouse, the ratio of m-Numb mRNA to total m-Numb mRNA in the heavy polysome fractions was lower than that in the wild-type mouse. Further, we showed that m-Numb-enhancement in gastric mucous cells induced the expression of prostate stem cell antigen and metallothionein-2. Under the m-Numb enhancing condition, the gastric cells exhibited enhanced cell proliferation and were significantly more resistant to H(2)O(2)-induced cell death than control cells. CONCLUSIONS: Msi1-dependent post-transcriptional enhancement of m-Numb is crucial in gastric epithelial regeneration.
Keywords	Medicine ; R ; Science ; Q
Subject code	570 ; 571
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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