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Article ; Online: Cell Damage Mechanisms during Cryopreservation in a Zwitterion Solution and Its Alleviation by DMSO.

Ishizaki, Takeru / Tanaka, Daisuke / Ishibashi, Kojiro / Takahashi, Kenji / Hirata, Eishu / Kuroda, Kosuke

The journal of physical chemistry. B

2024 Volume 128, Issue 16, Page(s) 3904–3909

Abstract: Recently, zwitterions have been proposed as novel cryoprotectants. However, some cells are difficult to cryopreserve using aqueous zwitterion solutions alone. We investigated here the reason for cell damage in such cells, and it was the osmotic pressure ... ...

Abstract	Recently, zwitterions have been proposed as novel cryoprotectants. However, some cells are difficult to cryopreserve using aqueous zwitterion solutions alone. We investigated here the reason for cell damage in such cells, and it was the osmotic pressure after freeze concentration. Furthermore, the addition of dimethyl sulfoxide (DMSO) has been reported to improve the cryoprotective effect in such cells: the zwitterion/DMSO aqueous solution shows a higher cryoprotective effect than the commercial cryoprotectant. This study also clarified the mechanisms underlying the improvement in a cryoprotective effect. The addition of cell-permeable DMSO alleviated the osmotic pressure after the freeze concentration. This alleviation was also found to be a key factor for cryopreserving cell spheroids, while there has been no insight into this phenomenon.
MeSH term(s)	Dimethyl Sulfoxide/chemistry ; Dimethyl Sulfoxide/pharmacology ; Cryopreservation ; Cryoprotective Agents/chemistry ; Cryoprotective Agents/pharmacology ; Osmotic Pressure/drug effects ; Humans ; Solutions ; Cell Survival/drug effects
Chemical Substances	Dimethyl Sulfoxide (YOW8V9698H) ; Cryoprotective Agents ; Solutions
Language	English
Publishing date	2024-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.3c07773
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Profile of miRNAs in small extracellular vesicles released from glioblastoma cells treated by boron neutron capture therapy.

Kondo, Natsuko / Kinouchi, Tadatoshi / Natsumeda, Manabu / Matsuzaki, Juntaro / Hirata, Eishu / Sakurai, Yoshinori / Okada, Masayasu / Suzuki, Minoru

Journal of neuro-oncology

2024

Abstract: Purpose: Boron neutron capture therapy (BNCT) is a tumor cell-selective particle-radiation therapy. In BNCT, administered p-boronophenylalanine (BPA) is selectively taken up by tumor cells, and the tumor is irradiated with thermal neutrons. High-LET α- ... ...

Abstract	Purpose: Boron neutron capture therapy (BNCT) is a tumor cell-selective particle-radiation therapy. In BNCT, administered p-boronophenylalanine (BPA) is selectively taken up by tumor cells, and the tumor is irradiated with thermal neutrons. High-LET α-particles and recoil Method: Glioblastoma U87 MG cells were treated with 25 ppm of BPA in the culture media and irradiated with thermal neutrons. After irradiation, they were plated into dishes and cultured for 3 days in the 5% CO Result: An increase in 20 individual miRNAs (ratio > 2) and a decrease in 2 individual miRNAs (ratio < 0.5) were detected in BNCT cells compared with non-irradiated cells. Among detected miRNAs, 20 miRNAs were associated with worse prognosis of glioma in Kaplan Meier Survival Analysis of overall survival in TCGA. Conclusion: These miRNA after BNCT may proceed tumors, modulate radiation resistance, or inhibit invasion and affect the prognosis of glioma.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-024-04649-8
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Article ; Online: Cryopreservation of tissues by slow-freezing using an emerging zwitterionic cryoprotectant.

Ishizaki, Takeru / Takeuchi, Yasuto / Ishibashi, Kojiro / Gotoh, Noriko / Hirata, Eishu / Kuroda, Kosuke

Scientific reports

2023 Volume 13, Issue 1, Page(s) 37

Abstract: Cryopreservation of tissues is a tough challenge. Cryopreservation is categorized into slow-freezing and vitrification, and vitrification has recently been recognized as a suitable method for tissue cryopreservation. On the contrary, some researchers ... ...

Abstract	Cryopreservation of tissues is a tough challenge. Cryopreservation is categorized into slow-freezing and vitrification, and vitrification has recently been recognized as a suitable method for tissue cryopreservation. On the contrary, some researchers have reported that slow-freezing also has potential for tissue cryopreservation. Although conventional cryoprotectants have been studied well, some novel ones may efficiently cryopreserve tissues via slow-freezing. In this study, we used aqueous solutions of an emerging cryoprotectant, an artificial zwitterion supplemented with a conventional cryoprotectant, dimethyl sulfoxide (DMSO), for cell spheroids. The zwitterion/DMSO aqueous solutions produced a better cryoprotective effect on cell spheroids, which are the smallest units of tissues, compared to that of a commercial cryoprotectant. Cryopreservation with the zwitterion/DMSO solutions not only exhibited better cell recovery but also maintained the functions of the spheroids effectively. The optimized composition of the solution was 10 wt% zwitterion, 15 wt% DMSO, and 75 wt% water. The zwitterion/DMSO solution gave a higher number of living cells for the cryopreservation of mouse tumor tissues than a commercial cryoprotectant. The zwitterion/DMSO solution was also able to cryopreserve human tumor tissue, a patient-derived xenograft.
MeSH term(s)	Humans ; Mice ; Animals ; Cryoprotective Agents/pharmacology ; Freezing ; Dimethyl Sulfoxide/pharmacology ; Cryopreservation/methods ; Vitrification
Chemical Substances	Cryoprotective Agents ; Dimethyl Sulfoxide (YOW8V9698H)
Language	English
Publishing date	2023-01-02
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/s41598-022-23913-3
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Article ; Online: MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway.

Tange, Shoichiro / Hirano, Tomomi / Idogawa, Masashi / Hirata, Eishu / Imoto, Issei / Tokino, Takashi

BMC cancer

2023 Volume 23, Issue 1, Page(s) 85

Abstract: Background: While molecular targeted drugs and other therapies are being developed for many tumors, pancreatic cancer is still considered to be the malignant tumor with the worst prognosis. We started this study to identify prognostic genes and ... ...

Abstract	Background: While molecular targeted drugs and other therapies are being developed for many tumors, pancreatic cancer is still considered to be the malignant tumor with the worst prognosis. We started this study to identify prognostic genes and therapeutic targets of pancreatic cancer. Methods: To comprehensively identify prognostic genes in pancreatic cancer, we investigated the correlation between gene expression and cancer-specific prognosis using transcriptome and clinical information datasets from The Cancer Genome Atlas (TCGA). In addition, we examined the effects of the suppression of candidate prognostic genes in pancreatic cancer cell lines. Result: We found that patients with high expression levels of MYEOV, a primate-specific gene with unknown function, had significantly shorter disease-specific survival times than those with low expression levels. Cox proportional hazards analysis revealed that high expression of MYEOV was significantly associated with poor survival and was an independent prognostic factor for disease-specific survival in pancreatic cancer patients. Analysis of multiple cancer samples revealed that the MYEOV promoter region is methylated in noncancer tissues but is demethylated in tumors, causing MYEOV overexpression in tumors. Notably, the knockdown of MYEOV suppressed the expression of MTHFD2 and other folate metabolism-related enzyme genes required for the synthesis of amino acids and nucleic acids and also restored the expression of c-Myc and mTORC1 repressors. Conclusion: There is a significant correlation between elevated MYEOV expression and poor disease-specific survival in pancreatic cancer patients. MYEOV enhances the activation of several oncogenic pathways, resulting in the induction of pancreatic cancer cell proliferation. Overall, MYEOV acts as an oncogene in pancreatic cancer. Furthermore, MYEOV may be a prognostic biomarker and serve as an 'actionable' therapeutic target for pancreatic cancers.
MeSH term(s)	Cell Line, Tumor ; Demethylation ; Folic Acid/metabolism ; Gene Expression Regulation, Neoplastic ; Neoplastic Processes ; Pancreatic Neoplasms/pathology ; Prognosis ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics ; Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Pancreatic Neoplasms
Chemical Substances	Folic Acid (935E97BOY8) ; Proto-Oncogene Proteins ; MYEOV protein, human ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-myc
Language	English
Publishing date	2023-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-022-10433-6
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Article ; Online: Optimization of Zwitterionic Polymers for Cell Cryopreservation.

Kato, Yui / Uto, Takuya / Ishizaki, Takeru / Tanaka, Daisuke / Ishibashi, Kojiro / Matsuda, Yuya / Onoda, Issei / Kobayashi, Akiko / Hazawa, Masaharu / Wong, Richard W / Takahashi, Kenji / Hirata, Eishu / Kuroda, Kosuke

Macromolecular bioscience

2024 , Page(s) e2300499

Abstract: Cryopreservation techniques are valuable for the preservation of genetic properties in cells, and the development of this technology contributes to various fields. In a previous study, an isotonic freezing medium composed of poly(zwitterion) (polyZI) has ...

Abstract	Cryopreservation techniques are valuable for the preservation of genetic properties in cells, and the development of this technology contributes to various fields. In a previous study, an isotonic freezing medium composed of poly(zwitterion) (polyZI) has been reported, which alleviates osmotic shock, unlike typical hypertonic freezing media. In this study, the primitive freezing medium composed of emerging polyZI is optimized. Imidazolium/carboxylate-type polyZI (VimC
Language	English
Publishing date	2024-02-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2039130-4
ISSN	1616-5195 ; 1616-5187
ISSN (online)	1616-5195
ISSN	1616-5187
DOI	10.1002/mabi.202300499
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Article ; Online: ERK Activity Imaging During Migration of Living Cells In Vitro and In Vivo

Eishu Hirata / Etsuko Kiyokawa

International Journal of Molecular Sciences, Vol 20, Iss 3, p

2019 Volume 679

Abstract: Extracellular signal-regulated kinase (ERK) is a major downstream factor of the EGFR-RAS-RAF signalling pathway, and thus the role of ERK in cell growth has been widely examined. The development of biosensors based on fluorescent proteins has enabled us ... ...

Abstract	Extracellular signal-regulated kinase (ERK) is a major downstream factor of the EGFR-RAS-RAF signalling pathway, and thus the role of ERK in cell growth has been widely examined. The development of biosensors based on fluorescent proteins has enabled us to measure ERK activities in living cells, both after growth factor stimulation and in its absence. Long-term imaging unexpectedly revealed the oscillative activation of ERK in an epithelial sheet or a cyst in vitro. Studies using transgenic mice expressing the ERK biosensor have revealed inhomogeneous ERK activities among various cell species. In vivo Förster (or fluorescence) resonance energy transfer (FRET) imaging shed light on a novel role of ERK in cell migration. Neutrophils and epithelial cells in various organs such as intestine, skin, lung and bladder showed spatio-temporally different cell dynamics and ERK activities. Experiments using inhibitors confirmed that ERK activities are required for various pathological responses, including epithelial repair after injuries, inflammation, and niche formation of cancer metastasis. In conclusion, biosensors for ERK will be powerful and valuable tools to investigate the roles of ERK in situ.
Keywords	biosensor ; FRET ; cell migration ; ERK ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: ERK Activity Imaging During Migration of Living Cells In Vitro and In Vivo.

Hirata, Eishu / Kiyokawa, Etsuko

International journal of molecular sciences

2019 Volume 20, Issue 3

Abstract	Extracellular signal-regulated kinase (ERK) is a major downstream factor of the EGFR-RAS-RAF signalling pathway, and thus the role of ERK in cell growth has been widely examined. The development of biosensors based on fluorescent proteins has enabled us to measure ERK activities in living cells, both after growth factor stimulation and in its absence. Long-term imaging unexpectedly revealed the oscillative activation of ERK in an epithelial sheet or a cyst in vitro. Studies using transgenic mice expressing the ERK biosensor have revealed inhomogeneous ERK activities among various cell species. In vivo Förster (or fluorescence) resonance energy transfer (FRET) imaging shed light on a novel role of ERK in cell migration. Neutrophils and epithelial cells in various organs such as intestine, skin, lung and bladder showed spatio-temporally different cell dynamics and ERK activities. Experiments using inhibitors confirmed that ERK activities are required for various pathological responses, including epithelial repair after injuries, inflammation, and niche formation of cancer metastasis. In conclusion, biosensors for ERK will be powerful and valuable tools to investigate the roles of ERK in situ.
MeSH term(s)	Animals ; Biosensing Techniques/instrumentation ; Biosensing Techniques/methods ; Cell Movement ; Cell Survival ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/analysis ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fluorescence Resonance Energy Transfer/instrumentation ; Fluorescence Resonance Energy Transfer/methods ; Humans ; Optical Imaging/instrumentation ; Optical Imaging/methods
Chemical Substances	Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2019-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20030679
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Article ; Online: Tumor Microenvironment and Differential Responses to Therapy.

Hirata, Eishu / Sahai, Erik

Cold Spring Harbor perspectives in medicine

2017 Volume 7, Issue 7

Abstract: Cancer evolution plays a key role in both the development of tumors and their response to therapy. Like all evolutionary processes, tumor evolution is shaped by the environment. In tumors, this consists of a complex mixture of nontransformed cell types ... ...

Abstract	Cancer evolution plays a key role in both the development of tumors and their response to therapy. Like all evolutionary processes, tumor evolution is shaped by the environment. In tumors, this consists of a complex mixture of nontransformed cell types and extracellular matrix. Chemotherapy or radiotherapy imposes further strong selective pressures on cancer cells during cancer treatment. Here, we review how different components of the tumor microenvironment can modulate the response to chemo- and radiotherapy. We further describe how therapeutic strategies directly alter the composition, or function, of the tumor microenvironment, thereby further altering the selective pressures to which cancer cells are exposed. Last, we explore the consequences of these interactions for therapy outcomes and how to exploit our increasing understanding of the tumor microenvironment for therapeutic benefit.
MeSH term(s)	Drug Therapy ; Extracellular Matrix ; Humans ; Neoplasms/pathology ; Neoplasms/therapy ; Radiotherapy ; Tumor Microenvironment
Language	English
Publishing date	2017-07-05
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a026781
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Article ; Online: Astrocyte-induced mGluR1 activates human lung cancer brain metastasis via glutamate-dependent stabilization of EGFR.

Ishibashi, Kojiro / Ichinose, Toshiya / Kadokawa, Riki / Mizutani, Ryo / Iwabuchi, Sadahiro / Togi, Sumihito / Ura, Hiroki / Tange, Shoichiro / Shinjo, Keiko / Nakayama, Jun / Nanjo, Shigeki / Niida, Yo / Kondo, Yutaka / Hashimoto, Shinichi / Sahai, Erik / Yano, Seiji / Nakada, Mitsutoshi / Hirata, Eishu

Developmental cell

2024 Volume 59, Issue 5, Page(s) 579–594.e6

Abstract: There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/ ...

Abstract	There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/in soft substrate (MGS), which serves well as a platform to study cancer-glia interactions. Using this method, we find that human lung cancer cells become overly dependent on metabotropic glutamate receptor 1 (mGluR1) signaling in the brain microenvironment. Mechanistically, interactions with astrocytes induce mGluR1 in cancer cells through the Wnt-5a/prickle planar cell polarity protein 1 (PRICKLE1)/RE1 silencing transcription factor (REST) axis. Induced mGluR1 directly interacts with and stabilizes the epidermal growth factor receptor (EGFR) in a glutamate-dependent manner, and these cells then become responsive to mGluR1 inhibition. Our results highlight increased dependence on mGluR1 signaling as an adaptive strategy and vulnerability of human lung cancer brain metastasis.
MeSH term(s)	Mice ; Animals ; Humans ; Glutamic Acid ; Astrocytes/metabolism ; Lung Neoplasms ; Receptors, Metabotropic Glutamate/metabolism ; Brain Neoplasms ; ErbB Receptors ; Tumor Microenvironment
Chemical Substances	metabotropic glutamate receptor type 1 ; Glutamic Acid (3KX376GY7L) ; Receptors, Metabotropic Glutamate ; ErbB Receptors (EC 2.7.10.1) ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2024.01.010
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Zs.A 5742: 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.MG 76: Show issues

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Article: Glioma Stem-Like Cells Can Be Targeted in Boron Neutron Capture Therapy with Boronophenylalanine.

Kondo, Natsuko / Hikida, Masaki / Nakada, Mitsutoshi / Sakurai, Yoshinori / Hirata, Eishu / Takeno, Satoshi / Suzuki, Minoru

Cancers

2020 Volume 12, Issue 10

Abstract: As glioma stem cells are chemo- and radio-resistant, they could be the origins of recurrent malignant glioma. Boron neutron capture therapy (BNCT) is a tumor-selective particle radiation therapy. ...

Abstract	As glioma stem cells are chemo- and radio-resistant, they could be the origins of recurrent malignant glioma. Boron neutron capture therapy (BNCT) is a tumor-selective particle radiation therapy.
Language	English
Publishing date	2020-10-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12103040
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