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Article ; Online: Cold Preservation of Human Hepatocytes with High Viability.

Lee, Serene M L / Kern, Armin / Jauch, Karl-Walter / Thasler, Reinhard / Niess, Hanno / Thasler, Wolfgang E

2022 Volume 21, Issue 4, Page(s) 367–377

Abstract: Freshly isolated human hepatocytes are an important model for translational research, validation of experiments done in animals, and preclinical studies. Human hepatocyte isolation often cannot be carried out easily on demand in common research ... ...

Abstract	Freshly isolated human hepatocytes are an important model for translational research, validation of experiments done in animals, and preclinical studies. Human hepatocyte isolation often cannot be carried out easily on demand in common research laboratories, and researchers often collaborate to share hepatocytes or outsource hepatocyte isolations. As a prerequisite for such a strategy, hepatocytes have to maintain their phenotypes after transport. Therefore, this study aimed to determine if overnight storage or shipment of hepatocytes affects their quality when viability, adherence, and cytochrome P450 (CYP) activities are considered. Hepatocytes were stored overnight or shipped to a collaborator in a cold storage solution on wet ice. On the next day, viability of hepatocytes was assessed before plating the cells to determine adherence. Hepatocytes were also cultured in a sandwich culture to determine CYP activities and inducibility. The results showed that although viability (79% ± 0.7% on isolation) was significantly decreased by overnight storage or shipment by 11% (
MeSH term(s)	Animals ; Humans ; Female ; Male ; Hepatocytes ; Liver ; Cryopreservation ; Cytochrome P-450 Enzyme System ; Cells, Cultured ; Cell Survival
Chemical Substances	Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2022-11-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2593993-2
ISSN	1947-5543 ; 1947-5535
ISSN (online)	1947-5543
ISSN	1947-5535
DOI	10.1089/bio.2021.0173
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Neutrophil extracellular traps facilitate cancer metastasis: cellular mechanisms and therapeutic strategies.

Hu, Wenxing / Lee, Serene M L / Bazhin, Alexandr V / Guba, Markus / Werner, Jens / Nieß, Hanno

Journal of cancer research and clinical oncology

2022 Volume 149, Issue 5, Page(s) 2191–2210

Abstract: Background: The formation of neutrophil extracellular traps (NETs) was initially discovered as a novel immune response against pathogens. Recent studies have also suggested that NETs play an important role in tumor progression. This review summarizes ... ...

Abstract	Background: The formation of neutrophil extracellular traps (NETs) was initially discovered as a novel immune response against pathogens. Recent studies have also suggested that NETs play an important role in tumor progression. This review summarizes the cellular mechanisms by which NETs promote distant metastasis and discusses the possible clinical applications targeting NETs. Method: The relevant literature from PubMed and Google Scholar (2001-2021) have been reviewed for this article. Results: The presence of NETs has been detected in various primary tumors and metastatic sites. NET-associated interactions have been observed throughout the different stages of metastasis, including initial tumor cell detachment, intravasation and extravasation, the survival of circulating tumor cells, the settlement and the growth of metastatic tumor cells. Several in vitro and in vivo studies proved that inhibiting NET formation resulted in anti-cancer effects. The biosafety and efficacy of some NET inhibitors have also been demonstrated in early phase clinical trials. Conclusions: Considering the role of NETs in tumor progression, NETs could be a promising diagnostic and therapeutic target for cancer management. However, current evidence is mostly derived from experimental models and as such more clinical studies are still needed to verify the clinical significance of NETs in oncological settings.
MeSH term(s)	Humans ; Extracellular Traps ; Neutrophils ; Cell Line, Tumor ; Neoplastic Cells, Circulating/pathology ; Medical Oncology
Language	English
Publishing date	2022-09-01
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04310-9
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Article ; Online: Identification and characterization of novel splice variants of human farnesoid X receptor.

Mustonen, Enni-Kaisa / Lee, Serene M L / Nieß, Hanno / Schwab, Matthias / Pantsar, Tatu / Burk, Oliver

Archives of biochemistry and biophysics

2021 Volume 705, Page(s) 108893

Abstract: Farnesoid X receptor (FXR, NR1H4) is a ligand-activated nuclear receptor, which regulates bile acid, lipid and glucose metabolism. Due to these functions, FXR has been investigated as a potential drug target for the treatment of liver diseases, such as ... ...

Abstract	Farnesoid X receptor (FXR, NR1H4) is a ligand-activated nuclear receptor, which regulates bile acid, lipid and glucose metabolism. Due to these functions, FXR has been investigated as a potential drug target for the treatment of liver diseases, such as primary biliary cholangitis and non-alcoholic steatohepatitis. Based on the previously described four splice variants, it has been suggested that alternative promoter usage and splicing may have an impact on total FXR activity as a result of encoding functionally diverse variants. Here we aimed for a systematic analysis of human hepatic FXR splice variants. In addition to the previously described FXRα1-4, we identified four novel splice variants (FXRα5-8) in human hepatocytes, which resulted from previously undetected exon skipping events. These newly identified isoforms displayed diminished DNA binding and impaired transactivation activities. Isoform FXRα5, which suppressed the transactivation activity of the functional isoform FXRα2, was further characterized as deficient in heterodimerization, coactivator recruitment and ligand binding. These findings were further supported by molecular dynamics simulations, which offered an explanation for the behavior of this isoform on the molecular level. FXRα5 exhibited low uniform expression levels in nearly all human tissues. Our systematic analysis of FXR splice variants in human hepatocytes resulted in the identification of four novel FXR isoforms, which all proved to be functionally deficient, but one novel variant, FXRα5, also displayed dominant negative activity. The possible associations with and roles of these novel isoforms in human liver diseases require further investigation.
MeSH term(s)	Humans ; Liver/metabolism ; Mutation ; Protein Isoforms/chemistry ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Receptors, Cytoplasmic and Nuclear/chemistry ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism
Chemical Substances	Protein Isoforms ; Receptors, Cytoplasmic and Nuclear ; farnesoid X-activated receptor (0C5V0MRU6P)
Language	English
Publishing date	2021-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2021.108893
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Article ; Online: Perception of journal club seminars by medical doctoral students: results from five years of evaluation.

Taverna, Mara / Bucher, Julian Nicolaus / Weniger, Maximilian / Gropp, Roswitha / Lee, Serene M L / Mayer, Barbara / Werner, Jens / Bazhin, Alexandr V

GMS journal for medical education

2022 Volume 39, Issue 1, Page(s) Doc4

Abstract: Objectives: ...

Abstract	Objectives:
MeSH term(s)	Humans ; Perception ; Students, Medical ; Students, Pharmacy ; Surveys and Questionnaires
Language	English
Publishing date	2022-02-15
Publishing country	Germany
Document type	Journal Article
ISSN	2366-5017
ISSN (online)	2366-5017
DOI	10.3205/zma001525
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Article: Identification and characterization of novel splice variants of human farnesoid X receptor

Mustonen, Enni-Kaisa / Lee, Serene M.L / Nieß, Hanno / Schwab, Matthias / Pantsar, Tatu / Burk, Oliver

Archives of biochemistry and biophysics. 2021 July 15, v. 705

2021

Abstract	Farnesoid X receptor (FXR, NR1H4) is a ligand-activated nuclear receptor, which regulates bile acid, lipid and glucose metabolism. Due to these functions, FXR has been investigated as a potential drug target for the treatment of liver diseases, such as primary biliary cholangitis and non-alcoholic steatohepatitis. Based on the previously described four splice variants, it has been suggested that alternative promoter usage and splicing may have an impact on total FXR activity as a result of encoding functionally diverse variants. Here we aimed for a systematic analysis of human hepatic FXR splice variants. In addition to the previously described FXRα1–4, we identified four novel splice variants (FXRα5–8) in human hepatocytes, which resulted from previously undetected exon skipping events. These newly identified isoforms displayed diminished DNA binding and impaired transactivation activities. Isoform FXRα5, which suppressed the transactivation activity of the functional isoform FXRα2, was further characterized as deficient in heterodimerization, coactivator recruitment and ligand binding. These findings were further supported by molecular dynamics simulations, which offered an explanation for the behavior of this isoform on the molecular level. FXRα5 exhibited low uniform expression levels in nearly all human tissues. Our systematic analysis of FXR splice variants in human hepatocytes resulted in the identification of four novel FXR isoforms, which all proved to be functionally deficient, but one novel variant, FXRα5, also displayed dominant negative activity. The possible associations with and roles of these novel isoforms in human liver diseases require further investigation.
Keywords	DNA ; bile acids ; biophysics ; dimerization ; drugs ; exons ; fatty liver ; glucose ; hepatocytes ; humans ; ligands ; lipids ; liver ; metabolism ; molecular dynamics ; transcriptional activation
Language	English
Dates of publication	2021-0715
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2021.108893
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Nelfinavir and Its Active Metabolite M8 Are Partial Agonists and Competitive Antagonists of the Human Pregnane X Receptor.

Burk, Oliver / Kronenberger, Thales / Keminer, Oliver / Lee, Serene M L / Schiergens, Tobias S / Schwab, Matthias / Windshügel, Björn

Molecular pharmacology

2021 Volume 99, Issue 3, Page(s) 184–196

Abstract: The HIV protease inhibitor nelfinavir is currently being analyzed for repurposing as an anticancer drug for many different cancers because it exerts manifold off-target protein interactions, finally resulting in cancer cell death. Xenosensing pregnane X ... ...

Abstract	The HIV protease inhibitor nelfinavir is currently being analyzed for repurposing as an anticancer drug for many different cancers because it exerts manifold off-target protein interactions, finally resulting in cancer cell death. Xenosensing pregnane X receptor (PXR), which also participates in the control of cancer cell proliferation and apoptosis, was previously shown to be activated by nelfinavir; however, the exact molecular mechanism is still unknown. The present study addresses the effects of nelfinavir and its major and pharmacologically active metabolite nelfinavir hydroxy-
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/genetics ; Binding Sites ; Cytochrome P-450 CYP3A/genetics ; Dose-Response Relationship, Drug ; Gene Expression Regulation/drug effects ; Hep G2 Cells ; Hepatocytes/cytology ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Humans ; Models, Molecular ; Molecular Conformation ; Molecular Docking Simulation ; Nelfinavir/analogs & derivatives ; Nelfinavir/chemistry ; Nelfinavir/pharmacology ; Pregnane X Receptor/agonists ; Pregnane X Receptor/antagonists & inhibitors ; Pregnane X Receptor/chemistry ; Pregnane X Receptor/metabolism ; Primary Cell Culture
Chemical Substances	ABCB1 protein, human ; ATP Binding Cassette Transporter, Subfamily B ; NR1I2 protein, human ; Pregnane X Receptor ; hydroxy-t-butylamidenelfinavir ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; CYP3A4 protein, human (EC 1.14.14.55) ; Nelfinavir (HO3OGH5D7I)
Language	English
Publishing date	2021-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/molpharm.120.000116
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Article ; Online: Perception of journal club seminars by medical doctoral students

Taverna, Mara / Bucher, Julian Nicolaus / Weniger, Maximilian / Gropp, Roswitha / Lee, Serene M. L. / Mayer, Barbara / Werner, Jens / Bazhin, Alexandr V.

GMS Journal for Medical Education, Vol 39, Iss 1, p Doc

results from five years of evaluation

2022 Volume 4

Abstract: Objectives: A journal club is one of the well-established and popular methods of post-graduate education. In this work, we were interested to understand how the participants perceive journal club as a whole and how they evaluate their personal process of ...

Abstract	Objectives: A journal club is one of the well-established and popular methods of post-graduate education. In this work, we were interested to understand how the participants perceive journal club as a whole and how they evaluate their personal process of acquiring new scientific knowledge and development of soft-skills as an indispensable prerequisite of the lifelong learning.Project description: This study is a survey analysis examining perception of journal club sessions by post-graduate medical students. A checklist for journal club preparation as well as a questionnaire for evaluation of the journal club session by participants has been developed to determine if the journal club had met its aims. Data were collected by summing up all answers to each question of the questionnaire for each session. Qualitative data from a five-year evaluation period were compiled and analyzed. Results: The journal club checklist served as a guideline for the preparation of a journal club session as well as an evaluation questionnaire containing 24 items. Our work presents evidence that journal club seminars are well perceived by participants. Furthermore, a high percentage of participants deemed the working atmosphere to be constructive and found it worthwhile to participate in the sessions. The topics of the presentations have been positively evaluated, however only a minority of participants found that the topics of the journal club was related to their own specific research topic. Concerning the distribution of the journal article, we could show that distributing the paper one week before the journal club event provided sufficient time for preparation. Our evaluation revealed that two-thirds of the participants found discussions during journal club sessions rich and productive. The motivation to think more critically increased during journal club sessions. From our work, it is evident that the participants perceived the speakers´ soft-skills to have improved with the practice. Finally, we show a clear trend of improved ...
Keywords	journal club ; research paper ; critical thinking ; post-graduate education ; Special aspects of education ; LC8-6691 ; Medicine ; R
Subject code	050
Language	German
Publishing date	2022-02-01T00:00:00Z
Publisher	German Medical Science GMS Publishing House
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Perception of journal club seminars by medical doctoral students: results from five years of evaluation

Taverna, Mara / Bucher, Julian Nicolaus / Weniger, Maximilian / Gropp, Roswitha / Lee, Serene M. L. / Mayer, Barbara / Werner, Jens / Bazhin, Alexandr V.

GMS Journal for Medical Education

2022 Volume 39, Issue 1, Page(s) 4

Abstract: Zielsetzung: Journal Clubs sind eine etablierte und weit verbreitete Methode der Postgraduiertenausbildung. Das Ziel dieser Arbeit war es zu untersuchen, wie die Teilnehmenden Journal Clubs insgesamt wahrnehmen und wie sie ihren persönlichen Prozess der ...

Title translation	Wahrnehmung von Journal-Club-Seminaren durch medizinische Promotionsstudierende: Ergebnisse aus fünf Jahren Evaluation
Abstract	Zielsetzung: Journal Clubs sind eine etablierte und weit verbreitete Methode der Postgraduiertenausbildung. Das Ziel dieser Arbeit war es zu untersuchen, wie die Teilnehmenden Journal Clubs insgesamt wahrnehmen und wie sie ihren persönlichen Prozess der Aneignung neuen wissenschaftlichen Wissens sowie die Entwicklung ihrer Soft Skills als unverzichtbare Voraussetzung für lebenslanges Lernen bewerten. Projektbeschreibung: Bei dieser Studie handelt es sich um eine Befragungsauswertung zur Untersuchung der Wahrnehmung von Journal-Club-Seminaren durch medizinische Promotionsstudierende. Dazu wurden eine Checkliste für die Vorbereitung von Journal Clubs sowie ein Fragebogen für die Evaluation der Journal-Club-Sitzung durch die Teilnehmenden erarbeitet, um zu ermitteln, ob die Ziele des Journal Clubs erreicht wurden. Die Daten wurden durch Zusammenfassung aller Antworten auf jede Frage des Fragebogens für jede Sitzung erhoben. Qualitative Daten aus einem fünfjährigen Evaluationszeitraum wurden zusammengeführt und ausgewertet. Ergebnisse: Die Journal-Club-Checkliste diente bei der Vorbereitung der Journal-Club-Sitzungen sowie des Evaluationsfragebogens mit 24 Items als Leitfaden. Diese Arbeit liefert Belege dafür, dass Journal-Club-Seminare von den Teilnehmenden positiv wahrgenommen werden. Darüber hinaus empfand ein hoher Prozentsatz der Teilnehmenden die Arbeitsatmosphäre als konstruktiv und die Teilnahme an den Sitzungen als wertvoll. Die Themen der Präsentationen wurden positiv bewertet, auch wenn nur wenige Teilnehmende angaben, dass die Themen des Journal Club Bezug zu ihrem eigenen spezifischen Forschungsthema hatten. Es konnte gezeigt werden, dass eine Verteilung des Zeitschriftenartikels eine Woche vor der Journal-Club-Sitzung ausreichend Zeit zur Vorbereitung bot. Die Auswertung ergab, dass zwei Drittel der Teilnehmenden die Diskussionen während der Sitzungen bereichernd und fruchtbar fanden. Die Motivation für kritischeres Denken stieg während der Journal-Club-Sitzungen. Gestützt auf diese Arbeit ist es evident, dass sich die Soft Skills der Vortragenden in der Wahrnehmung der Teilnehmenden mit zunehmender Übung verbesserten. Schließlich konnte ein eindeutiger positiver Trend bei der Wahrnehmung des Nutzens von Journal-Club-Sitzungen vom Beginn bis zum Ende des Evaluationszeitraums nachgewiesen werden. Schlussfolgerung: Auf Grundlage der ausgewerteten Evaluationen kann geschlussfolgert werden, dass Journal-Club-Seminare von den Teilnehmenden sehr geschätzt werden und eine sinnvolle Möglichkeit für die Entwicklung bestimmter Soft Skills sind. ; Objectives: A journal club is one of the well-established and popular methods of post-graduate education. In this work, we were interested to understand how the participants perceive journal club as a whole and how they evaluate their personal process of acquiring new scientific knowledge and development of soft-skills as an indispensable prerequisite of the lifelong learning. Project description: This study is a survey analysis examining perception of journal club sessions by post-graduate medical students. A checklist for journal club preparation as well as a questionnaire for evaluation of the journal club session by participants has been developed to determine if the journal club had met its aims. Data were collected by summing up all answers to each question of the questionnaire for each session. Qualitative data from a five-year evaluation period were compiled and analyzed. Results: The journal club checklist served as a guideline for the preparation of a journal club session as well as an evaluation questionnaire containing 24 items. Our work presents evidence that journal club seminars are well perceived by participants. Furthermore, a high percentage of participants deemed the working atmosphere to be constructive and found it worthwhile to participate in the sessions. The topics of the presentations have been positively evaluated, however only a minority of participants found that the topics of the journal club was related to their own specific research topic. Concerning the distribution of the journal article, we could show that distributing the paper one week before the journal club event provided sufficient time for preparation. Our evaluation revealed that two-thirds of the participants found discussions during journal club sessions rich and productive. The motivation to think more critically increased during journal club sessions. From our work, it is evident that the participants perceived the speakers´ soft-skills to have improved with the practice. Finally, we show a clear trend of improved perception of the value of journal club sessions from beginning to the end of the evaluation time. Conclusion: Based on the analyzed evaluations, we can conclude that journal club events are highly valued by participants and could be a good option for the development of certain soft-skills.
Keywords	Medizin, Gesundheit ; journal club ; research paper ; critical thinking ; post-graduate education ; Journal Club ; Forschungsarbeit ; kritisches Denken ; Postgraduiertenausbildung ; journal clubs ; Journal Clubs
Publishing date	2022-02-15
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Article ; Online
ISSN	2366-5017
ISSN (online)	2366-5017
DOI	10.3205/zma001525
Database	German Medical Science

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Article: Susceptibility of Asialoglycoprotein Receptor-Deficient Mice to Lps/Galactosamine Liver Injury and Protection by Betaine Administration.

Rasineni, Karuna / Lee, Serene M L / McVicker, Benita L / Osna, Natalia A / Casey, Carol A / Kharbanda, Kusum K

Biology

2020 Volume 10, Issue 1

Abstract: Background: Work from our laboratory has shown that the ethanol-induced increase in apoptotic hepatocellular death is closely related to the impairment in the ability of the asialoglycoprotein receptor (ASGP-R) to remove neighboring apoptotic cells. In ... ...

Abstract	Background: Work from our laboratory has shown that the ethanol-induced increase in apoptotic hepatocellular death is closely related to the impairment in the ability of the asialoglycoprotein receptor (ASGP-R) to remove neighboring apoptotic cells. In this study, we assessed the role of ASGP-R in fulminant liver failure and investigated whether prior treatment with betaine (a naturally occurring tertiary amine) is protective. Methods: Lipopolysaccharide (LPS; 50 μg/kg BW) and galactosamine (GalN; 350 mg/kg BW) were injected together to wild-type and ASGP-R-deficient mice that were treated for two weeks prior with or without 2% betaine in drinking water. The mice were sacrificed 1.5, 3, or 4.5 h post-injection, and tissue samples were collected. Results: LPS/GalN injection generate distinct molecular processes, which includes increased production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thus causing apoptosis as evident by increased caspase-3 activity. ASGP-R deficient animals showed increased liver caspase activities, serum TNF-α and IL-6 levels, as well as more pronounced liver damage compared with the wild-type control animals after intraperitoneal injection of LPS/GalN. In addition, prior administration of betaine was found to significantly attenuate the LPS/GalN-induced increases in liver injury parameters. Conclusion: Our work underscores the importance of normal functioning of ASGP-R in preventing severe liver damage and signifies a therapeutic role of betaine in prevention of liver injuries from toxin-induced fulminant liver failure.
Language	English
Publishing date	2020-12-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10010019
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Article: Establishment of an Endoscopy-Guided Minimally Invasive Orthotopic Mouse Model of Colorectal Cancer.

Chen, Chen / Neumann, Jens / Kühn, Florian / Lee, Serene M L / Drefs, Moritz / Andrassy, Joachim / Werner, Jens / Bazhin, Alexandr V / Schiergens, Tobias S

Cancers

2020 Volume 12, Issue 10

Abstract: Open orthotopic mouse models of colorectal cancer have disadvantages such as the requirement for advanced surgical skills or the trauma caused by laparotomy. To overcome these drawbacks, this study aimed to evaluate the establishment of a minimally ... ...

Abstract	Open orthotopic mouse models of colorectal cancer have disadvantages such as the requirement for advanced surgical skills or the trauma caused by laparotomy. To overcome these drawbacks, this study aimed to evaluate the establishment of a minimally invasive model using murine colonoscopy. CT26 and MC38 CRC cells of different concentrations were injected into BALB/C and C57BL/6J mice, respectively. Follow-up endoscopies were performed to assign an endoscopic score to tumor growth. Gross autopsy, histologic and immuno-histochemical evaluation, and immune scoring were performed. To describe the learning curve of the procedures, a performance score was given. Local tumor growth with colorectal wall infiltration, luminal ulceration, the presence of tumor-infiltrating lymphocytes, lympho-vascular invasion, and early spontaneous lymph node, peritoneal, and hepatic metastases were observed. The tumors showed cytoplasmic immuno-staining for CK20. Compared to the MC38/C57BL/6J model, tumorigenicity and immunogenicity of the CT26/BALB/C model were higher. Tumor volume correlated with the endoscopic score. This endoscopy-guided orthotopic mouse model is easy to learn and quick to establish. It features early metastasis and enables the study of interactions with the immune system. When specific cell concentrations and cell lines are applied, controlled local tumor growth and metastasis can be achieved within short observation periods.
Language	English
Publishing date	2020-10-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12103007
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