LIVIVO - Search results -

Search results

Result 1 - 10 of total 41

Search options

Article ; Online: Destined for the intestine: thymic selection of TCRαβ CD8αα intestinal intraepithelial lymphocytes.

Joannou, Kevin / Baldwin, Troy A

2023 Volume 213, Issue 1, Page(s) 67–75

Abstract: The immune system is composed of a variety of different T-cell lineages distributed through both secondary lymphoid tissue and non-lymphoid tissue. The intestinal epithelium is a critical barrier surface that contains numerous intraepithelial lymphocytes ...

Abstract	The immune system is composed of a variety of different T-cell lineages distributed through both secondary lymphoid tissue and non-lymphoid tissue. The intestinal epithelium is a critical barrier surface that contains numerous intraepithelial lymphocytes that aid in maintaining homeostasis at that barrier. This review focuses on T-cell receptor αβ (TCRαβ) CD8αα intraepithelial lymphocytes, and how recent advances in the field clarify how this unique T-cell subset is selected, matures, and functions in the intestines. We consider how the available evidence reveals a story of ontogeny starting from agonist selection of T cells in the thymus and finishing through the specific signaling environment of the intestinal epithelium. We conclude with how this story raises further key questions about the development of different ontogenic waves of TCRαβ CD8αα IEL and their importance for intestinal epithelial homeostasis.
MeSH term(s)	Animals ; Mice ; CD8-Positive T-Lymphocytes ; CD8 Antigens ; Intraepithelial Lymphocytes ; Receptors, Antigen, T-Cell, alpha-beta ; Intestines ; Intestinal Mucosa ; Lymphocytes ; Mice, Inbred C57BL
Chemical Substances	CD8 Antigens ; Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2023-05-01
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad049
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 337: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Establishment of CD8+ T Cell Thymic Central Tolerance to Tissue-Restricted Antigen Requires PD-1.

May, Julia F / Kelly, Rees G / Suen, Alexander Y W / Kim, Jeongbee / Kim, Jeongwoo / Anderson, Colin C / Rayat, Gina R / Baldwin, Troy A

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 212, Issue 2, Page(s) 271–283

Abstract: Highly self-reactive T cells are censored from the repertoire by both central and peripheral tolerance mechanisms upon receipt of high-affinity TCR signals. Clonal deletion is considered a major driver of central tolerance; however, other mechanisms such ...

Abstract	Highly self-reactive T cells are censored from the repertoire by both central and peripheral tolerance mechanisms upon receipt of high-affinity TCR signals. Clonal deletion is considered a major driver of central tolerance; however, other mechanisms such as induction of regulatory T cells and functional impairment have been described. An understanding of the interplay between these different central tolerance mechanisms is still lacking. We previously showed that impaired clonal deletion to a model tissue-restricted Ag did not compromise tolerance. In this study, we determined that murine T cells that failed clonal deletion were rendered functionally impaired in the thymus. Programmed cell death protein 1 (PD-1) was induced in the thymus and was required to establish cell-intrinsic tolerance to tissue-restricted Ag in CD8+ thymocytes independently of clonal deletion. In bone marrow chimeras, tolerance was not observed in PD-L1-deficient recipients, but tolerance was largely maintained following adoptive transfer of tolerant thymocytes or T cells to PD-L1-deficient recipients. However, CRISPR-mediated ablation of PD-1 in tolerant T cells resulted in broken tolerance, suggesting different PD-1 signaling requirements for establishing versus maintaining tolerance. Finally, we showed that chronic exposure to high-affinity Ag supported the long-term maintenance of tolerance. Taken together, our study identifies a critical role for PD-1 in establishing central tolerance in autoreactive T cells that escape clonal deletion. It also sheds light on potential mechanisms of action of anti-PD-1 pathway immune checkpoint blockade and the development of immune-related adverse events.
MeSH term(s)	Mice ; Animals ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor/genetics ; Central Tolerance ; CD8-Positive T-Lymphocytes ; Thymus Gland ; Antigens ; Immune Tolerance
Chemical Substances	B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Antigens
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200775
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Are sensory neurons exquisitely sensitive to interleukin 1β?

Stemkowski, Patrick L / Bukhanova-Schulz, Nataliya / Baldwin, Troy / de Chaves, Elena Posse / Smith, Peter A

Journal of neuroimmunology

2021 Volume 354, Page(s) 577529

Abstract: Peripheral nerve injury frequently evokes chronic neuropathic pain. This is initiated by a transient inflammatory response that leads to persistent excitation of dorsal root ganglion (DRG) neurons by inflammatory cytokines such as interleukin 1β(IL-1β). ... ...

Abstract	Peripheral nerve injury frequently evokes chronic neuropathic pain. This is initiated by a transient inflammatory response that leads to persistent excitation of dorsal root ganglion (DRG) neurons by inflammatory cytokines such as interleukin 1β(IL-1β). In non-neuronal cells such as lymphocytes, interleukin 1 exerts actions at attomolar (aM; 10
MeSH term(s)	Animals ; Ganglia, Spinal/drug effects ; Ganglia, Spinal/metabolism ; Interleukin-1beta/metabolism ; Interleukin-1beta/pharmacology ; Mice ; Neuralgia/metabolism ; Rats ; Rats, Sprague-Dawley ; Sensory Receptor Cells/drug effects ; Sensory Receptor Cells/metabolism
Chemical Substances	Interleukin-1beta
Language	English
Publishing date	2021-02-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2021.577529
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1646: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology.

Odagiu, Livia / May, Julia / Boulet, Salix / Baldwin, Troy A / Labrecque, Nathalie

Frontiers in endocrinology

2021 Volume 11, Page(s) 624122

Abstract: The nuclear orphan receptors NR4A1, NR4A2, and NR4A3 are immediate early genes that are induced by various signals. They act as transcription factors and their activity is not regulated by ligand binding and are thus ... ...

Abstract	The nuclear orphan receptors NR4A1, NR4A2, and NR4A3 are immediate early genes that are induced by various signals. They act as transcription factors and their activity is not regulated by ligand binding and are thus regulated
MeSH term(s)	Animals ; DNA-Binding Proteins/physiology ; Humans ; Nuclear Receptor Subfamily 4, Group A, Member 1/physiology ; Nuclear Receptor Subfamily 4, Group A, Member 2/physiology ; Receptors, Antigen, T-Cell/physiology ; Receptors, Steroid/physiology ; Receptors, Thyroid Hormone/physiology ; Signal Transduction/physiology ; T-Lymphocytes/physiology ; Thymus Gland/cytology ; Thymus Gland/physiology
Chemical Substances	DNA-Binding Proteins ; NR4A1 protein, human ; NR4A2 protein, human ; NR4A3 protein, human ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; Receptors, Antigen, T-Cell ; Receptors, Steroid ; Receptors, Thyroid Hormone
Language	English
Publishing date	2021-02-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2020.624122
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Sex differences in peripheral immune cell activation: Implications for pain and pain resolution.

Friedman, Timothy N / La Caprara, Olivia / Zhang, Celine / Lee, Kelly / May, Julia / Faig, Christian A / Baldwin, Troy / Plemel, Jason R / Taylor, Anna M W / Kerr, Bradley J

Brain, behavior, and immunity

2023 Volume 114, Page(s) 80–93

Abstract: Decades of research into chronic pain has deepened our understanding of the cellular mechanisms behind this process. However, a failure to consider the biological variable of sex has limited the application of these breakthroughs into clinical ... ...

Abstract	Decades of research into chronic pain has deepened our understanding of the cellular mechanisms behind this process. However, a failure to consider the biological variable of sex has limited the application of these breakthroughs into clinical application. In the present study, we investigate fundamental differences in chronic pain between male and female mice resulting from inflammatory activation of the innate immune system. We provide evidence that female mice are more sensitive to the effects of macrophages. Injecting small volumes of media conditioned by either unstimulated macrophages or macrophages stimulated by the inflammatory molecule TNFα lead to increased pain sensitivity only in females. Interestingly, we find that TNFα conditioned media leads to a more rapid resolution of mechanical hypersensitivity and altered immune cell recruitment to sites of injury. Furthermore, male and female macrophages exhibit differential polarization characteristics and motility after TNFα stimulation, as well as a different profile of cytokine secretions. Finally, we find that the X-linked gene Tlr7 is critical in the facilitating the adaptive resolution of pain in models of acute and chronic inflammation in both sexes. Altogether, these findings suggest that although the cellular mechanisms of pain resolution may differ between the sexes, the study of these differences may yield more targeted approaches with clinical applications.
Language	English
Publishing date	2023-08-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.07.029
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2276: 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.MO 327: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Differential roles for Bim and Nur77 in thymocyte clonal deletion induced by ubiquitous self-antigen.

Hu, Qian Nancy / Baldwin, Troy A

Journal of immunology (Baltimore, Md. : 1950)

2015 Volume 194, Issue 6, Page(s) 2643–2653

Abstract: Negative selection, primarily mediated through clonal deletion of self-reactive thymocytes, is critical for establishing self-tolerance and preventing autoimmunity. Recent studies suggest that the molecular mechanisms of negative selection differ ... ...

Abstract	Negative selection, primarily mediated through clonal deletion of self-reactive thymocytes, is critical for establishing self-tolerance and preventing autoimmunity. Recent studies suggest that the molecular mechanisms of negative selection differ depending on the thymic compartment and developmental stage at which thymocytes are deleted. Using the physiological HY(cd4) TCR transgenic model of negative selection against ubiquitous self-antigen, we previously found that one of the principal mediators implicated in clonal deletion, Bim, is required for caspase-3 activation but is ultimately dispensable for negative selection. On the basis of these data, we hypothesized that Nur77, another molecule thought to be a key mediator of clonal deletion, could be responsible for Bim-independent deletion. Despite comparable Nur77 induction in thymocytes during negative selection, Bim deficiency resulted in an accumulation of high-affinity-signaled thymocytes as well as impairment in caspase-mediated and caspase-independent cell death. Although these data suggested that Bim may be required for Nur77-mediated cell death, we found that transgenic Nur77 expression was sufficient to induce apoptosis independently of Bim. However, transgenic Nur77-induced apoptosis was significantly inhibited in the context of TCR signaling, suggesting that endogenous Nur77 could be similarly regulated during negative selection. Although Nur77 deficiency alone did not alter positive or negative selection, combined deficiency in Bim and Nur77 impaired clonal deletion efficiency and significantly increased positive selection efficiency. Collectively, these data shed light on the different roles for Bim and Nur77 during ubiquitous Ag-mediated clonal deletion and highlight potential differences from their reported roles in tissue-restricted Ag-mediated clonal deletion.
MeSH term(s)	Animals ; Antigens, CD/immunology ; Antigens, CD/metabolism ; Antigens, Differentiation, T-Lymphocyte/immunology ; Antigens, Differentiation, T-Lymphocyte/metabolism ; Apoptosis/genetics ; Apoptosis/immunology ; Apoptosis Regulatory Proteins/deficiency ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/immunology ; Autoantigens/immunology ; Bcl-2-Like Protein 11 ; Caspase 3/immunology ; Caspase 3/metabolism ; Cells, Cultured ; Clonal Deletion/genetics ; Clonal Deletion/immunology ; Enzyme Activation/immunology ; Female ; Flow Cytometry ; Lectins, C-Type/immunology ; Lectins, C-Type/metabolism ; Male ; Membrane Proteins/deficiency ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Nuclear Receptor Subfamily 4, Group A, Member 1/deficiency ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics ; Nuclear Receptor Subfamily 4, Group A, Member 1/immunology ; Proto-Oncogene Proteins/deficiency ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/immunology ; Proto-Oncogene Proteins c-bcl-2/immunology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology ; Thymocytes/cytology ; Thymocytes/immunology ; Thymocytes/metabolism
Chemical Substances	Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; Apoptosis Regulatory Proteins ; Autoantigens ; Bcl-2-Like Protein 11 ; Bcl2l11 protein, mouse ; CD69 antigen ; Lectins, C-Type ; Membrane Proteins ; Nr4a1 protein, mouse ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Receptors, Antigen, T-Cell ; Caspase 3 (EC 3.4.22.-)
Language	English
Publishing date	2015-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1400030
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: γδ Thymocyte Maturation and Emigration in Adult Mice.

Joannou, Kevin / Golec, Dominic P / Wang, Haiguang / Henao-Caviedes, Laura M / May, Julia F / Kelly, Rees G / Chan, Rigel / Jameson, Stephen C / Baldwin, Troy A

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 208, Issue 9, Page(s) 2131–2140

Abstract: Several unique waves of γδ T cells are generated solely in the fetal/neonatal thymus, whereas additional γδ T cell subsets are generated in adults. One intriguing feature of γδ T cell development is the coordination of differentiation and acquisition of ... ...

Abstract	Several unique waves of γδ T cells are generated solely in the fetal/neonatal thymus, whereas additional γδ T cell subsets are generated in adults. One intriguing feature of γδ T cell development is the coordination of differentiation and acquisition of effector function within the fetal thymus; however, it is less clear whether this paradigm holds true in adult animals. In this study, we investigated the relationship between maturation and thymic export of adult-derived γδ thymocytes in mice. In the Rag2pGFP model, immature (CD24
MeSH term(s)	Animals ; Emigration and Immigration ; Lymphocyte Activation ; Mice ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocyte Subsets ; Thymocytes
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100360
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Coordinated changes in glycosylation regulate the germinal center through CD22.

Enterina, Jhon R / Sarkar, Susmita / Streith, Laura / Jung, Jaesoo / Arlian, Britni M / Meyer, Sarah J / Takematsu, Hiromu / Xiao, Changchun / Baldwin, Troy A / Nitschke, Lars / Shlomchick, Mark J / Paulson, James C / Macauley, Matthew S

Cell reports

2022 Volume 38, Issue 11, Page(s) 110512

Abstract: Germinal centers (GCs) are essential for antibody affinity maturation. GC B cells have a unique repertoire of cell surface glycans compared with naive B cells, yet functional roles for changes in glycosylation in the GC have yet to be ascribed. Detection ...

Abstract	Germinal centers (GCs) are essential for antibody affinity maturation. GC B cells have a unique repertoire of cell surface glycans compared with naive B cells, yet functional roles for changes in glycosylation in the GC have yet to be ascribed. Detection of GCs by the antibody GL7 reflects a downregulation in ligands for CD22, an inhibitory co-receptor of the B cell receptor. To test a functional role for downregulation of CD22 ligands in the GC, we generate a mouse model that maintains CD22 ligands on GC B cells. With this model, we demonstrate that glycan remodeling plays a critical role in the maintenance of B cells in the GC. Sustained expression of CD22 ligands induces higher levels of apoptosis in GC B cells, reduces memory B cell and plasma cell output, and delays affinity maturation of antibodies. These defects are CD22 dependent, demonstrating that downregulation of CD22 ligands on B cells plays a critical function in the GC.
MeSH term(s)	Animals ; B-Lymphocytes ; Germinal Center ; Glycosylation ; Ligands ; Mice ; Polysaccharides/metabolism ; Receptors, Antigen, B-Cell/metabolism
Chemical Substances	Ligands ; Polysaccharides ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110512
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Cutting Edge: Intestinal Mucus Limits the Clonal Deletion of Developing T Cells Specific for an Oral Antigen.

Tsai, Kevin / Huang, Yu-Hsuan / Ma, Caixia / Baldwin, Troy A / Harder, Kenneth W / Vallance, Bruce A / Priatel, John J

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 205, Issue 2, Page(s) 329–334

Abstract: A layer of mucus functions to segregate contents of the intestinal lumen from the intestinal epithelium. The MUC2 mucin is the primary constituent of intestinal mucus and plays critical protective roles against luminal microbes and other noxious agents. ... ...

Abstract	A layer of mucus functions to segregate contents of the intestinal lumen from the intestinal epithelium. The MUC2 mucin is the primary constituent of intestinal mucus and plays critical protective roles against luminal microbes and other noxious agents. In this study, we investigated whether MUC2 helps maintain CD8 T cell tolerance toward intestinal luminal Ags by gavaging wild-type and
MeSH term(s)	Administration, Oral ; Animals ; Antigens/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cell Proliferation ; Clonal Deletion ; Immune Tolerance ; Intestines/physiology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mucin-2/genetics ; Mucin-2/metabolism ; Mucus/metabolism
Chemical Substances	Antigens ; MUC2 protein, human ; Mucin-2
Language	English
Publishing date	2020-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1900687
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Activation of the Anaphase Promoting Complex Reverses Multiple Drug Resistant Cancer in a Canine Model of Multiple Drug Resistant Lymphoma.

Arnason, Terra G / MacDonald-Dickinson, Valerie / Gaunt, Matthew Casey / Davies, Gerald F / Lobanova, Liubov / Trost, Brett / Gillespie, Zoe E / Waldner, Matthew / Baldwin, Paige / Borrowman, Devon / Marwood, Hailey / Vizeacoumar, Frederick S / Vizeacoumar, Franco J / Eskiw, Christopher H / Kusalik, Anthony / Harkness, Troy A A

Cancers

2022 Volume 14, Issue 17

Abstract: Like humans, canine lymphomas are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make canines excellent models to study MDR mechanisms. Insulin- ... ...

Abstract	Like humans, canine lymphomas are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make canines excellent models to study MDR mechanisms. Insulin-sensitizers have been shown to reduce the incidence of cancer in humans prescribed them, and we previously demonstrated that they also reverse and delay MDR development in vitro. Here, we treated canines with MDR lymphoma with metformin to assess clinical and tumoral responses, including changes in MDR biomarkers, and used mRNA microarrays to determine differential gene expression. Metformin reduced MDR protein markers in all canines in the study. Microarrays performed on mRNAs gathered through longitudinal tumor sampling identified a 290 gene set that was enriched in Anaphase Promoting Complex (APC) substrates and additional mRNAs associated with slowed mitotic progression in MDR samples compared to skin controls. mRNAs from a canine that went into remission showed that APC substrate mRNAs were decreased, indicating that the APC was activated during remission. In vitro validation using canine lymphoma cells selected for resistance to chemotherapeutic drugs confirmed that APC activation restored MDR chemosensitivity, and that APC activity was reduced in MDR cells. This supports the idea that rapidly pushing MDR cells that harbor high loads of chromosome instability through mitosis, by activating the APC, contributes to improved survival and disease-free duration.
Language	English
Publishing date	2022-08-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14174215
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito