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Article ; Online: Corrigendum: Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19.

Yatsenko, Tetiana / Rios, Ricardo / Nogueira, Tatiane / Salama, Yousef / Takahashi, Satoshi / Tabe, Yoko / Naito, Toshio / Takahashi, Kazuhisa / Hattori, Koichi / Heissig, Beate

Frontiers in immunology

2024 Volume 15, Page(s) 1390698

Abstract: This corrects the article DOI: 10.3389/fimmu.2023.1299792.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2023.1299792.].
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1390698
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Thesis: Geschwisterkonstellation und familiäre Belastung von Patienten mit mono- und bipolaren affektiven Psychosen

Heissig, Beate

1992

Author's details	vorgelegt von Beate Heissig
Size	137 S. : graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Marburg, Univ., Diss., 1993
HBZ-ID	HT004564354
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
93 D 2400	order for loan	Magazin

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Article: [Fibrinolytic factors: novel molecular targets for cytokine storm-associated diseases].

Hattori, Koichi / Shimazu, Hiroshi / Takahashi, Satoshi / Beate, Heissig

Rinsho ketsueki] The Japanese journal of clinical hematology

2022 Volume 63, Issue 5, Page(s) 403–409

Abstract: The mortality rate due to coronavirus disease 2019 (COVID-19) reached 5.3 million. However, identifying the novel treatment targets that ultimately reduce or prevent disease aggravation will be possible by understanding the mechanism and pathophysiology ... ...

Abstract	The mortality rate due to coronavirus disease 2019 (COVID-19) reached 5.3 million. However, identifying the novel treatment targets that ultimately reduce or prevent disease aggravation will be possible by understanding the mechanism and pathophysiology underlying the COVID-19 aggravation. Authors of previous studies have identified the "cytokine storm" that constitutes the secretion of inflammatory cytokines driven by the coagulation/fibrinolytic system as an inflammatory cytodynamic control mechanism that contributes to the aggravated COVID-19 pathology and the pathophysiology of related diseases. Vasculature-lining endothelial cells are bioreactors that produce or contribute to the modulation status of cytokines and coagulation and fibrinolytic system factors. The key steps in the pathophysiology of organ damage include the destabilization of the angiocrine system triggered by vascular endothelial damage during severe COVID-19. Overproduced or imbalanced angiocrine factors and inflammatory cytokines contribute to major COVID-19 complications. Within its scope, this study outlines the significance of the fibrinolytic system in the pathophysiology of inflammatory diseases, focusing on the research results. The possibility of molecular that target these angiocrine and fibrinolytic factors for inflammatory diseases as novel treatment approaches for inflammatory diseases, such as COVID-19, was discussed.
MeSH term(s)	COVID-19/drug therapy ; Cytokine Release Syndrome/drug therapy ; Cytokines ; Endothelial Cells ; Humans ; SARS-CoV-2
Chemical Substances	Cytokines
Language	Japanese
Publishing date	2022-05-17
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.63.403
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Zs.A 1175: 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)
Zs.MO 535: Show issues

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Article ; Online: The stem cell transcription factor ZFP296 transforms NIH3T3 cells and promotes anchorage-independent growth of cancer cells.

Mizoue, Yumi / Ikeda, Tomomi / Ikegami, Takako / Riabets, Oleksandra / Oishi, Yoshie / Tobita, Morikuni / Akutsu, Hidenori / Hattori, Koichi / Heissig, Beate / Koide, Hiroshi

The International journal of developmental biology

2024 Volume 67, Issue 4, Page(s) 147–153

Abstract: Cancer cells and embryonic stem (ES) cells share several biological properties, suggesting that some genes expressed in ES cells may play an important role in cancer cell growth. In this study, we investigated the possible role of zinc finger protein 296 ...

Abstract	Cancer cells and embryonic stem (ES) cells share several biological properties, suggesting that some genes expressed in ES cells may play an important role in cancer cell growth. In this study, we investigated the possible role of zinc finger protein 296 (ZFP296), a transcription factor expressed in ES cells, in cancer development. First, we found that overexpression of
MeSH term(s)	Mice ; Animals ; Humans ; NIH 3T3 Cells ; Stem Cell Factor/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Cell Transformation, Neoplastic/genetics ; Embryonic Stem Cells/metabolism ; Neoplasms/metabolism ; DNA-Binding Proteins
Chemical Substances	zinc finger protein 296, mouse ; Stem Cell Factor ; Transcription Factors ; DNA-Binding Proteins
Language	English
Publishing date	2024-02-09
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.230143hk
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Zs.A 3202: 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 ; Online: Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19.

Yatsenko, Tetiana / Rios, Ricardo / Nogueira, Tatiane / Takahashi, Satoshi / Tabe, Yoko / Naito, Toshio / Takahashi, Kazuhisa / Hattori, Koichi / Heissig, Beate

Frontiers in immunology

2024 Volume 14, Page(s) 1299792

Abstract: Patients with coronavirus disease-2019 (COVID-19) have an increased risk of thrombosis and acute respiratory distress syndrome (ARDS). Thrombosis is often attributed to increases in plasminogen activator inhibitor-1 (PAI-1) and a shut-down of ... ...

Abstract	Patients with coronavirus disease-2019 (COVID-19) have an increased risk of thrombosis and acute respiratory distress syndrome (ARDS). Thrombosis is often attributed to increases in plasminogen activator inhibitor-1 (PAI-1) and a shut-down of fibrinolysis (blood clot dissolution). Decreased urokinase-type plasminogen activator (uPA), a protease necessary for cell-associated plasmin generation, and increased tissue-type plasminogen activator (tPA) and PAI-1 levels have been reported in COVID-19 patients. Because these factors can occur in free and complexed forms with differences in their biological functions, we examined the predictive impact of uPA, tPA, and PAI-1 in their free forms and complexes as a biomarker for COVID-19 severity and the development of ARDS. In this retrospective study of 69 Japanese adults hospitalized with COVID-19 and 20 healthy donors, we found elevated free, non-complexed PAI-1 antigen, low circulating uPA, and uPA/PAI-1 but not tPA/PAI-1 complex levels to be associated with COVID-19 severity and ARDS development. This biomarker profile was typical for patients in the complicated phase. Lack of PAI-1 activity in circulation despite free, non-complexed PAI-1 protein and plasmin/α2anti-plasmin complex correlated with suPAR and sVCAM levels, markers indicating endothelial dysfunction. Furthermore, uPA/PAI-1 complex levels positively correlated with TNFα, a cytokine reported to trigger inflammatory cell death and tissue damage. Those levels also positively correlated with lymphopenia and the pro-inflammatory factors interleukin1β (IL1β), IL6, and C-reactive protein, markers associated with the anti-viral inflammatory response. These findings argue for using uPA and uPA/PAI-1 as novel biomarkers to detect patients at risk of developing severe COVID-19, including ARDS.
MeSH term(s)	Adult ; Humans ; Urokinase-Type Plasminogen Activator/metabolism ; Plasminogen Activator Inhibitor 1 ; Retrospective Studies ; Fibrinolysin ; COVID-19 ; Biomarkers ; Respiratory Distress Syndrome ; Thrombosis
Chemical Substances	Urokinase-Type Plasminogen Activator (EC 3.4.21.73) ; Plasminogen Activator Inhibitor 1 ; Fibrinolysin (EC 3.4.21.7) ; Biomarkers
Language	English
Publishing date	2024-01-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1299792
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: siRNA against CD40 delivered via a fungal recognition receptor ameliorates murine acute graft-versus-host disease.

Heissig, Beate / Salama, Yousef / Tateno, Masatoshi / Takahashi, Satoshi / Hattori, Koichi

EJHaem

2022 Volume 3, Issue 3, Page(s) 849–861

Abstract: Acute graft-versus-host disease (aGvHD) remains a major threat to a successful outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Although antibody-based targeting of the CD40/CD40 ligand costimulatory pathway can prevent aGvHD, ... ...

Abstract	Acute graft-versus-host disease (aGvHD) remains a major threat to a successful outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Although antibody-based targeting of the CD40/CD40 ligand costimulatory pathway can prevent aGvHD, side effects hampered their clinical application, prompting a need for other ways to interfere with this important dendritic T-cell costimulatory pathway. Here, we used small interfering RNA (siRNA) complexed with β-glucan allowing the binding and uptake of the siRNA/β-glucan complex (siCD40/schizophyllan [SPG]; chemical modifications called NJA-312, NJA-302, and NJA-515) into Dectin1+ cells, which recognize this pathogen-associated molecular pattern receptor. aGvHD was induced by the transplantation of splenocytes and bone marrow cells from C57BL/6J into CBF1 mice. Splenic dendritic cells retained Dectin1 expression after HSCT but showed lower expression after irradiation. The administration of siCD40/SPG, NJA-312, and NJA-302 ameliorated aGvHD-mediated lethality and tissue damage of spleen and liver, but not skin. Multiple NJA-312high injections prevented aGvHD but resulted in early weight loss in allogeneic HSCT mice. In addition, NJA-312 treatment caused delayed initial donor T and B-cell recovery but resulted in stable chimerism in surviving mice. Mechanistically, NJA-312 reduced organ damage by suppressing CCR2+, F4/80+, and IL17A-expressing cell accumulation in spleen, liver, and thymus but not the skin of mice with aGvHD. Our work demonstrates that siRNA targeting of CD40 delivered via the PAMP-recognizing lectin Dectin1 changes the immunological niche, suppresses organ-specific murine aGvHD, and induces immune tolerance after organ transplantation. Our work charts future directions for therapeutic interventions to modulate tissue-specific immune reactions using Pathogen-associated molecular pattern (PAMP) molecules like 1,3-β-glucan for cell delivery of siRNA.
Language	English
Publishing date	2022-05-06
Publishing country	United States
Document type	Journal Article
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.439
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Article ; Online: Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling.

Salama, Yousef / Jaradat, Nidal / Hattori, Koichi / Heissig, Beate

International journal of molecular sciences

2021 Volume 22, Issue 15

Abstract: Patients diagnosed with melanoma have a poor prognosis due to regional invasion and metastases. The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is found in a subtype of melanoma with a poor prognosis and contributes to drug ... ...

Abstract	Patients diagnosed with melanoma have a poor prognosis due to regional invasion and metastases. The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is found in a subtype of melanoma with a poor prognosis and contributes to drug resistance. Aloysia citrodora essential oil (ALOC-EO) possesses an antitumor effect. Understanding signaling pathways that contribute to the antitumor of ALOC-EO is important to identify novel tumor types that can be targeted by ALOC-EO. Here, we investigated the effects of ALOC-EO on melanoma growth and tumor cell migration. ALOC-EO blocked melanoma growth in vitro and impaired primary tumor cell growth in vivo. Mechanistically, ALOC-EO blocked heparin-binding-epidermal growth factor (HB-EGF)-induced EGFR signaling and suppressed ERK1/2 phosphorylation. Myelosuppressive drugs upregulated HB-EGF and EGFR expression in melanoma cells. Cotreatment of myelosuppressive drugs with ALOC-EO improved the antitumor activity and inhibited the expression of matrix metalloproteinase-7 and -9 and a disintegrin and metalloproteinase domain-containing protein9. In summary, our study demonstrates that ALOC-EO blocks EGFR and ERK1/2 signaling, with preclinical efficacy as a monotherapy or in combination with myelosuppressive drugs in melanoma.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Bortezomib/pharmacology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Doxorubicin/pharmacology ; Drug Synergism ; ErbB Receptors/metabolism ; Heparin-binding EGF-like Growth Factor/metabolism ; Humans ; MAP Kinase Signaling System/drug effects ; Melanoma/metabolism ; Melanoma/pathology ; Mice ; Oils, Volatile/pharmacology ; Phosphorylation/drug effects ; Plant Extracts/pharmacology ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Verbenaceae/chemistry
Chemical Substances	Antineoplastic Agents ; Heparin-binding EGF-like Growth Factor ; Oils, Volatile ; Plant Extracts ; Bortezomib (69G8BD63PP) ; Doxorubicin (80168379AG) ; EGFR protein, human (EC 2.7.10.1) ; EGFR protein, mouse (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2021-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22158151
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Article: The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance.

Heissig, Beate / Salama, Yousef / Takahashi, Satoshi / Okumura, Ko / Hattori, Koichi

Cancers

2021 Volume 13, Issue 5

Abstract: Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and ...

Abstract	Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and cancer growth. Endothelial cells release growth factors such as epidermal growth factor-like protein-7 (EGFL7), which contributes to the formation of the tumor vasculature. The signaling axis formed by EGFL7 and one of its receptors, beta 3 integrin, has emerged as a key mediator in the regulation of tumor metastasis and drug resistance. Here we summarize recent studies on the role of the ECM-linked angiocrine factor EGFL7 in primary tumor growth, neoangiogenesis, tumor metastasis by enhancing epithelial-mesenchymal transition, alterations in ECM rigidity, and drug resistance. We discuss its role in cellular adhesion and migration, vascular leakiness, and the anti-cancer response and provide background on its transcriptional regulation. Finally, we discuss its potential as a drug target as an anti-cancer strategy.
Language	English
Publishing date	2021-03-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13051014
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Article ; Online: Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling

Yousef Salama / Nidal Jaradat / Koichi Hattori / Beate Heissig

International Journal of Molecular Sciences, Vol 22, Iss 8151, p

2021 Volume 8151

Abstract	Patients diagnosed with melanoma have a poor prognosis due to regional invasion and metastases. The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is found in a subtype of melanoma with a poor prognosis and contributes to drug resistance. Aloysia citrodora essential oil (ALOC-EO) possesses an antitumor effect. Understanding signaling pathways that contribute to the antitumor of ALOC-EO is important to identify novel tumor types that can be targeted by ALOC-EO. Here, we investigated the effects of ALOC-EO on melanoma growth and tumor cell migration. ALOC-EO blocked melanoma growth in vitro and impaired primary tumor cell growth in vivo. Mechanistically, ALOC-EO blocked heparin-binding-epidermal growth factor (HB-EGF)-induced EGFR signaling and suppressed ERK1/2 phosphorylation. Myelosuppressive drugs upregulated HB-EGF and EGFR expression in melanoma cells. Cotreatment of myelosuppressive drugs with ALOC-EO improved the antitumor activity and inhibited the expression of matrix metalloproteinase-7 and -9 and a disintegrin and metalloproteinase domain-containing protein9. In summary, our study demonstrates that ALOC-EO blocks EGFR and ERK1/2 signaling, with preclinical efficacy as a monotherapy or in combination with myelosuppressive drugs in melanoma.
Keywords	melanoma ; EGFR ; MMP ; Aloysia citrodora ; HB-EGF ; plant ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Multifaceted Role of Plasminogen in Cancer.

Heissig, Beate / Salama, Yousef / Osada, Taro / Okumura, Ko / Hattori, Koichi

International journal of molecular sciences

2021 Volume 22, Issue 5

Abstract: Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during ... ...

Abstract	Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. They give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. They can also directly promote primary tumor growth and metastasis, and endow tumor cells with mechanisms to evade myelosuppression, thus acquiring drug resistance. In this review, recent studies on the role fibrinolytic factors play in metastasis and controlling cell-death-associated processes are presented, along with studies that describe how cancer cells have exploited plasminogen receptors to escape myelosuppression.
MeSH term(s)	Anoikis/genetics ; Autophagy ; Cell Survival ; Cellular Senescence ; Drug Resistance, Neoplasm/genetics ; Exosomes/metabolism ; Extracellular Matrix/metabolism ; Humans ; Neoplasm Metastasis/drug therapy ; Neoplasm Metastasis/genetics ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Plasminogen/antagonists & inhibitors ; Plasminogen/metabolism ; Plasminogen Inactivators/genetics ; Plasminogen Inactivators/metabolism ; Signal Transduction/genetics
Chemical Substances	Plasminogen Inactivators ; Plasminogen (9001-91-6)
Language	English
Publishing date	2021-02-25
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/ijms22052304
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