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Article ; Online: Similarity and dissimilarity in alterations of the gene expression profile associated with inhalational anesthesia between sevoflurane and desflurane.

Nogi, Takehiro / Uranishi, Kousuke / Suzuki, Ayumu / Hirasaki, Masataka / Nakamura, Tina / Kazama, Tomiei / Nagasaka, Hiroshi / Okuda, Akihiko / Mieda, Tsutomu

PloS one

2024 Volume 19, Issue 3, Page(s) e0298264

Abstract: Although sevoflurane is one of the most commonly used inhalational anesthetic agents, the popularity of desflurane is increasing to a level similar to that of sevoflurane. Inhalational anesthesia generally activates and represses the expression of genes ... ...

Abstract	Although sevoflurane is one of the most commonly used inhalational anesthetic agents, the popularity of desflurane is increasing to a level similar to that of sevoflurane. Inhalational anesthesia generally activates and represses the expression of genes related to xenobiotic metabolism and immune response, respectively. However, there has been no comprehensive comparison of the effects of sevoflurane and desflurane on the expression of these genes. Thus, we used a next-generation sequencing method to compare alterations in the global gene expression profiles in the livers of rats subjected to inhalational anesthesia by sevoflurane or desflurane. Our bioinformatics analyses revealed that sevoflurane and, to a greater extent, desflurane significantly activated genes related to xenobiotic metabolism. Our analyses also revealed that both anesthetic agents, especially sevoflurane, downregulated many genes related to immune response.
MeSH term(s)	Animals ; Rats ; Sevoflurane/pharmacology ; Desflurane ; Isoflurane/pharmacology ; Methyl Ethers/pharmacology ; Transcriptome ; Xenobiotics ; Anesthetics, Inhalation/pharmacology ; Anesthesia, Inhalation
Chemical Substances	Sevoflurane (38LVP0K73A) ; Desflurane (CRS35BZ94Q) ; Isoflurane (CYS9AKD70P) ; Methyl Ethers ; Xenobiotics ; Anesthetics, Inhalation
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0298264
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Complete response to pembrolizumab in a patient with recurrent and metastatic urothelial bladder carcinoma reflecting coexisting sarcomatoid subtype and glandular differentiation: a case report.

Miyama, Yu / Kanao, Kent / Uranishi, Kousuke / Hirasaki, Masataka / Yasuda, Masanori

International cancer conference journal

2022 Volume 12, Issue 1, Page(s) 24–30

Abstract: In advanced urothelial carcinoma (UC), approximately 20% of patients respond to pembrolizumab, an anti-programmed cell death-1 (PD-1) antibody. Herein, we reported a single case of UC showing coexistence of sarcomatoid subtype and glandular ... ...

Abstract	In advanced urothelial carcinoma (UC), approximately 20% of patients respond to pembrolizumab, an anti-programmed cell death-1 (PD-1) antibody. Herein, we reported a single case of UC showing coexistence of sarcomatoid subtype and glandular differentiation. Notably, only glandular differentiation was recurrent, probably progressive, and metastatic, which showed complete response to pembrolizumab. An 80-year-old woman presented with hematuria and dysuria, and an intra-vesical tumor was detected on ultrasound. Transurethral resections (TUR) were performed three times. In the first TUR, a sub-pedunculated tumor and a flat lesion were closely but independently located. Pathologically, the sub-pedunculated tumor was an invasive UC, sarcomatoid subtype. Meanwhile, the flat lesion was invasive UC with glandular differentiation. Despite the second and the additional TUR, the tumor was growing and a lymph node metastasis was detected. The third TUR specimen showed UC with glandular differentiation, and a positive PD-L1 expression as well as high density CD8-positive lymphocytic cells infiltration were observed. Pembrolizumab was administered for four courses after terminating the chemotherapy. The CT scan revealed shrinkage of both primary tumor and metastases. Cystectomy and lymph nodes dissection were performed, and no residual carcinoma was detected. The therapeutic effect was regarded as pathological complete response. Pembrolizumab could be effective for special subtype or divergent differentiation of UC, particularly in an event of an 'immune hot' tumor. Supplementary information: The online version contains supplementary material available at 10.1007/s13691-022-00568-5.
Language	English
Publishing date	2022-08-06
Publishing country	Singapore
Document type	Case Reports
ISSN	2192-3183
ISSN (online)	2192-3183
DOI	10.1007/s13691-022-00568-5
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Article ; Online: MAX controls meiotic entry in sexually undifferentiated germ cells.

Suzuki, Ayumu / Uranishi, Kousuke / Nishimoto, Masazumi / Mizuno, Yosuke / Mizuno, Seiya / Takahashi, Satoru / Eisenman, Robert N / Okuda, Akihiko

Scientific reports

2024 Volume 14, Issue 1, Page(s) 5236

Abstract: Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, ...

Abstract	Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, we investigated the Max gene's role in mouse primordial germ cells. Although Max is generally ubiquitously expressed, we revealed that sexually undifferentiated male and female germ cells had abundant MAX protein because of their higher Max gene expression than somatic cells. Moreover, our data revealed that this high MAX protein level in female germ cells declined significantly around physiological meiotic onset. Max disruption in sexually undifferentiated germ cells led to ectopic and precocious expression of meiosis-related genes, including Meiosin, the gatekeeper of meiotic onset, in both male and female germ cells. However, Max-null male and female germ cells did not complete the entire meiotic process, but stalled during its early stages and were eventually eliminated by apoptosis. Additionally, our meta-analyses identified a regulatory region that supports the high Max expression in sexually undifferentiated male and female germ cells. These results indicate the strong connection between the Max gene and physiological onset of meiosis in vivo through dynamic alteration of its expression.
MeSH term(s)	Animals ; Female ; Male ; Mice ; Apoptosis ; Cell Cycle Checkpoints ; Factor X ; Germ Cells ; Meiosis/genetics
Chemical Substances	Factor X (9001-29-0) ; Max protein, mouse (137468-70-3)
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55506-7
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Article ; Online: Alternative splicing for germ cell-specific Mga transcript can be eliminated without compromising mouse viability or fertility.

Kitamura, Yuka / Suzuki, Ayumu / Uranishi, Kousuke / Nishimoto, Masazumi / Mizuno, Seiya / Takahashi, Satoru / Okuda, Akihiko

Development, growth & differentiation

2022 Volume 64, Issue 7, Page(s) 409–416

Abstract: The stimulated by retinoic acid gene 8 (STRA8)/MEIOSIN complex and polycomb repressive complex (PRC) 1.6, a PRC1 subtype, are believed to be positive and negative regulators of meiotic onset, respectively. During meiotic initiation, the transcription ... ...

Abstract	The stimulated by retinoic acid gene 8 (STRA8)/MEIOSIN complex and polycomb repressive complex (PRC) 1.6, a PRC1 subtype, are believed to be positive and negative regulators of meiotic onset, respectively. During meiotic initiation, the transcription repressive activity of PRC1.6 must be attenuated so that meiosis-related genes can be effectively activated by the STRA8/MEIOSIN complex. However, the molecular mechanisms that control the impairment of PRC1.6 function remain unclear. We recently demonstrated that the Mga gene, which encodes a scaffolding component of PRC1.6, produces variant mRNA by alternative splicing specifically during meiosis. Furthermore, the anomalous MGA protein encoded by the variant mRNA bears an intrinsic ability to function as a dominant negative regulator against the construction of PRC1.6 and is therefore assumed to be, at least in part, involved in impairment of the complex. Therefore, to unequivocally evaluate the physiological significance of Mga variant mRNA production in gametogenesis, we examined the consequences of a genetic manipulation that renders mice unable to produce Mga variant mRNA. Our data revealed that mutant mice were equivalent to wild-type mice in terms of viability and fertility. Our detailed examination of spermatogenesis also revealed that this genetic alteration is not associated with any apparent abnormalities in testis size, spermatogenic cycle, timing of meiotic onset, or marker gene expression of spermatogonia and spermatocytes. Taken together, these data indicate that the production of germ cell-specific Mga variant mRNA is dispensable not only for viability but also for gametogenesis.
MeSH term(s)	Alternative Splicing/genetics ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Fertility ; Germ Cells/metabolism ; Male ; Meiosis/genetics ; Mice ; Polycomb Repressive Complex 1/genetics ; Polycomb Repressive Complex 1/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Spermatogenesis/genetics ; Tretinoin/metabolism
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Mga protein, mouse ; RNA, Messenger ; Tretinoin (5688UTC01R) ; Polycomb Repressive Complex 1 (EC 2.3.2.27)
Language	English
Publishing date	2022-09-14
Publishing country	Japan
Document type	Journal Article
ZDB-ID	280433-5
ISSN	1440-169X ; 0012-1592
ISSN (online)	1440-169X
ISSN	0012-1592
DOI	10.1111/dgd.12806
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Zs.A 194: Show issues

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Article ; Online: Correction: PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer: a retrospective study.

Mihara, Yoshiaki / Hirasaki, Masataka / Horita, Yosuke / Fujino, Takashi / Fukushima, Hisayo / Kamakura, Yasuo / Uranishi, Kousuke / Hirano, Yasumitsu / Ryozawa, Shomei / Yasuda, Masanori / Makino, Yoshinori / Shibazaki, Satomi / Hamaguchi, Tetsuya

BMC gastroenterology

2024 Volume 24, Issue 1, Page(s) 67

Language	English
Publishing date	2024-02-06
Publishing country	England
Document type	Published Erratum
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-024-03154-6
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Article ; Online: Long noncoding RNA

Yoneda, Ryoma / Ueda, Naomi / Uranishi, Kousuke / Hirasaki, Masataka / Kurokawa, Riki

The Journal of biological chemistry

2020 Volume 295, Issue 17, Page(s) 5626–5639

Abstract: ... pncRNA- ... ...

Abstract	pncRNA-D
MeSH term(s)	Cell Cycle Checkpoints ; Cyclin D1/genetics ; Down-Regulation ; Epigenesis, Genetic ; Genes, bcl-1 ; HeLa Cells ; Humans ; Methylation ; Promoter Regions, Genetic ; RNA, Long Noncoding/genetics
Chemical Substances	CCND1 protein, human ; RNA, Long Noncoding ; Cyclin D1 (136601-57-5)
Language	English
Publishing date	2020-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.011556
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Article ; Online: Identification of germ cell-specific Mga variant mRNA that promotes meiosis via impediment of a non-canonical PRC1.

Kitamura, Yuka / Uranishi, Kousuke / Hirasaki, Masataka / Nishimoto, Masazumi / Suzuki, Ayumu / Okuda, Akihiko

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9737

Abstract: A non-canonical PRC1 (PRC1.6) prevents precocious meiotic onset. Germ cells alleviate its negative effect by reducing their amount of MAX, a component of PRC1.6, as a prerequisite for their bona fide meiosis. Here, we found that germ cells produced Mga ... ...

Abstract	A non-canonical PRC1 (PRC1.6) prevents precocious meiotic onset. Germ cells alleviate its negative effect by reducing their amount of MAX, a component of PRC1.6, as a prerequisite for their bona fide meiosis. Here, we found that germ cells produced Mga variant mRNA bearing a premature termination codon (PTC) during meiosis as an additional mechanism to impede the function of PRC1.6. The variant mRNA encodes an anomalous MGA protein that lacks the bHLHZ domain and thus functions as a dominant negative regulator of PRC1.6. Notwithstanding the presence of PTC, the Mga variant mRNA are rather stably present in spermatocytes and spermatids due to their intrinsic inefficient background of nonsense-mediated mRNA decay. Thus, our data indicate that meiosis is controlled in a multi-layered manner in which both MAX and MGA, which constitute the core of PRC1.6, are at least used as targets to deteriorate the integrity of the complex to ensure progression of meiosis.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Female ; Genetic Variation ; Germ Cells/cytology ; Germ Cells/metabolism ; HEK293 Cells ; Humans ; Male ; Meiosis ; Mice, Inbred C57BL ; Polycomb Repressive Complex 1/genetics ; RNA, Messenger/genetics ; Spermatogenesis ; Spermatozoa/cytology ; Spermatozoa/metabolism ; Mice
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Mga protein, mouse ; RNA, Messenger ; Polycomb Repressive Complex 1 (EC 2.3.2.27)
Language	English
Publishing date	2021-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-89123-5
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Article ; Online: Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells.

Uranishi, Kousuke / Hirasaki, Masataka / Kitamura, Yuka / Mizuno, Yosuke / Nishimoto, Masazumi / Suzuki, Ayumu / Okuda, Akihiko

Stem cells (Dayton, Ohio)

2021 Volume 39, Issue 11, Page(s) 1435–1446

Abstract: Although the physiological meaning of the high potential of mouse embryonic stem cells (ESCs) for meiotic entry is not understood, a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its ...

Abstract	Although the physiological meaning of the high potential of mouse embryonic stem cells (ESCs) for meiotic entry is not understood, a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively. MGA, a scaffolding component of PRC1.6, bears two distinct DNA-binding domains termed bHLHZ and T-box. However, it is unclear how this feature contributes to the functions of PRC1.6. Here, we demonstrated that both domains repress distinct sets of genes in murine ESCs, but substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that bHLHZ is crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; DNA/metabolism ; Embryonic Stem Cells/metabolism ; Germ Cells ; Meiosis/genetics ; Mice ; Mouse Embryonic Stem Cells
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Mga protein, mouse ; DNA (9007-49-2)
Language	English
Publishing date	2021-07-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.3433
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Zs.A 1894: Show issues

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Article: Discovery of a new role for the p53 family in the onset of mesendodermal differentiation of embryonic stem cells.

Okuda, Akihiko / Uranishi, Kousuke / Suzuki, Ayumu

Stem cell investigation

2017 Volume 4, Page(s) 24

Language	English
Publishing date	2017-04-07
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2884645-X
ISSN	2313-0792 ; 2306-9759
ISSN (online)	2313-0792
ISSN	2306-9759
DOI	10.21037/sci.2017.03.07
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Article ; Online: PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer: a retrospective study.

BMC gastroenterology

2023 Volume 23, Issue 1, Page(s) 339

Abstract: Background: Fluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective ... ...

Abstract	Background: Fluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. Methods: We analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates. Results: We detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher's exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1. Conclusions: The two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.
MeSH term(s)	Humans ; Retrospective Studies ; Neoplasm Recurrence, Local/genetics ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Biomarkers ; Chemotherapy, Adjuvant ; Nucleotides/therapeutic use ; Neoplasm Staging ; Fluorouracil/therapeutic use ; Biomarkers, Tumor/genetics ; PTEN Phosphohydrolase/genetics
Chemical Substances	Biomarkers ; Nucleotides ; Fluorouracil (U3P01618RT) ; Biomarkers, Tumor ; PTEN protein, human (EC 3.1.3.67) ; PTEN Phosphohydrolase (EC 3.1.3.67)
Language	English
Publishing date	2023-10-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-023-02975-1
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